| 1 | Schizophr. Res. 2000 Sep 44: 183-6 |
|---|---|
| PMID | 10962220 |
| Title | Inverse correlation between hallucinations and serum prolactin in patients with non-affective psychoses. |
| Abstract | Serum prolactin (PRL) was correlated with clinical symptomatology in 17 drug-free patients suffering from non-affective psychoses. A clear-cut negative correlation was found between the Comprehensive Psychiatric Rating Scale (CPRS) items assessing hallucinations and serum PRL levels (r=-6.14, P=0.009). No correlation was observed between clinical measures (total CPRS score, schizophrenia subscale score or depression and anxiety subscale score) and serum PRL. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 2 | Psychoneuroendocrinology 2000 Oct 25: 741-52 |
| PMID | 10938452 |
| Title | Multihormonal responses to clonidine in patients with affective and psychotic symptoms. |
| Abstract | The neuroendocrine responses to the alpha(2)-adrenoreceptor agonist clonidine (CLO) (0.35 mg if body weight <65 kg or 0.375 mg if body weight> or =65 kg, PO) were studied in a large group of subjects: 134 drug-free inpatients--with either DSM-IV schizophrenia (SCZ, n=31), schizoaffective disorder (SAD, n=16), or major depressive episode (MDE, n=87) - and 22 hospitalized controls (HCs). Comparison with a previous placebo test performed in a subgroup of 92 subjects (46 MDEs, 20 SCZs, 8 SADs, and 18 HCs) showed that CLO induced a significant increase of growth hormone, prolactin (PRL) and thyrotropin (TSH) levels but no significant change in adrenocorticotropin and cortisol release. According to diagnostic categories, we found significantly lower GH stimulation in MDEs and in SADs compared to HCs or to SCZs. In addition, we found significantly lower CLO induced PRL and TSH stimulations in paranoid SCZ patients compared to controls and disorganized SCZ patients. Taken together, these results suggest a hyposensitivity of noradrenergic alpha(2)-receptors in patients with affective symptoms. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 3 | Clin Ther 2000 Sep 22: 1085-96 |
| PMID | 11048906 |
| Title | The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia. |
| Abstract | There is relatively little comparative information on elevations in plasma prolactin level (PRL) with conventional versus novel antipsychotic agents. This paper examines the comparative effects on PRL of olanzapine, risperidone, and haloperidol based on data from 3 multicenter, double-blind, randomized clinical trials. Magnitude of response, dose dependency, time course, effects of sex and age, and response to switching from haloperidol to olanzapine are assessed. The effects of olanzapine, risperidone, and haloperidol on PRL were assessed in patients with schizophrenia or related psychoses participating in 3 double-blind clinical trials: (1) a 6-week acute trial comparing olanzapine 5 to 20 mg/d (n = 1,336) and haloperidol 5 to 20 mg/d (n = 660), with a 1-year, open-label olanzapine extension for responders; (2) a 54-week study comparing olanzapine 5 to 20 mg/d (n = 21), risperidone 4 to 10 mg/d (n = 21), and haloperidol 5 to 20 mg/d (n = 23) in early illness; and (3) a 28-week study comparing olanzapine 10 to 20 mg/d (n = 172) and risperidone 4 to 12 mg/d (n = 167). PRL elevations were significantly greater with risperidone than with either olanzapine or haloperidol in study 2. and significantly greater than with olanzapine in study 3 (all, P < 0.001). PRL elevations were significantly greater with haloperidol than with olanzapine in study 1 (P < 0.001 ). A dose-response relationship was not consistently confirmed with any of the drug treatments. Risperidone-associated PRL elevations peaked relatively early in treatment. In haloperidol- and risperidone-treated patients, the mean change in PRL was greater in women than in men. PRL decreased significantly when treatment was switched from haloperidol to olanzapine. This side-by-side analysis of 3 independent studies suggests that with the 3 antipsychotic drugs studied, PRL is elevated moderately by olanzapine (mean change, 1-4 ng/mL), intermediately by haloperidol (mean change, approximately 17 ng/mL), and strongly by risperidone (mean change, 45-80 ng/mL). No consistent dose-response relationship was observed, and the time course and sex-dependency of the response differed between the 3 agents. Patients with haloperidol-induced hyperprolactinemia may benefit from a switch to olanzapine. Long-term studies examining the health consequences of chronic hyperprolactinemia during antipsychotic treatment are needed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 4 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2001 Apr 25: 507-18 |
| PMID | 11370994 |
| Title | Dopamine receptor responsivity in schizophrenic patients in a drug-free state and after treatment with olanzapine. |
| Abstract | 1. Olanzapine is a novel atypical antipsychotic with affinity for a number of neurotransmitter receptors including dopamine D1, D2, D4, serotonin 5HT2A, 5HT2C, histamine H1, a1-adrenergic, and muscarinic receptors. 2. A neuroendocrinological method to check the degree of dopamine receptor blocking is by measuring the prolactin (PRL) responses to acute (i.m.) administration of haloperidol (HAL). The authors applied this test in a group of male patients with DSM-IV schizophrenia in the drug-free state. The patients were subsequently treated with olanzapine (OLZ) (mean daily dose: 22.5+/-5.8) and the test was repeated six weeks later. For the HAL-test, 5mg HAL were injected i.m. and blood samples were taken at times 0, 30, 60, 90 and 120 minutes. Fourteen patients enrolled in the study. Psychopathology was assessed by means of the Brief Psychiatric Rating Scale (BPRS). 3. Six weeks treatment with OLZ resulted in significant decreases in the total BPRS score and on the score of its subscales for positive, negative, and general psychopathology. Comparison of the PRL response patterns, after HAL administration by analysis of variance for repeated measures (ANOVAR) for drug treatment and time, revealed a highly significant time effect (F=28.98, p=0.000) and a significant treatment by time interaction (F=8.27, p=0.000008). Namely, in the drug-free state significant increases were found in the PRL levels after i.m. HAL administration which were significantly reduced during treatment with OLZ, indicating moderate receptor blockade. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 5 | Psychiatry Res 2001 Jul 102: 249-54 |
| PMID | 11440775 |
| Title | Lower prolactin bioactivity in unmedicated schizophrenic patients. |
| Abstract | In previous work, prolactin (PRL) abnormalities of a lower bioassay (BA) to radioimmunoassay (RIA) ratio were found in schizophrenic patients. This line of research was extended in seven male patients with schizophrenia who were neuroleptic-free; seven male control subjects were also studied. PRL values were assessed by RIA and Nb(2) BA techniques. The schizophrenic group had a significantly lower PRL BA as compared to normal controls and a lower PRL ratio of BA/RIA. The lower ratio is consistent with an earlier finding and suggests that schizophrenic patients have different molecular forms of PRL than control subjects. This difference could be due to a disordered tuberoinfundibular dopamine system or the long-term effects of neuroleptic medications. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 6 | Neuropsychopharmacology 2001 Mar 24: 278-90 |
| PMID | 11166518 |
| Title | The blunted plasma cortisol response to apomorphine and its relationship to treatment response in patients with schizophrenia. |
| Abstract | The adrenocorticotropic hormone (ACTH) and cortisol responses to apomorphine (APO), a direct acting dopamine (DA) agonist, have been reported to be significantly blunted in neuroleptic-free patients with schizophrenia (SCH). This study primarily examined the cortisol, but also the prolactin (PRL) and growth hormone (GH), response to APO in patients with SCH compared to normal controls, as well as the relationship between endocrine measures and response to antipsychotic drug treatment. APO, 0.01 mg/kg, or placebo was administered to 51-98 patients with SCH and 15-25 normal controls. Psychopathology was assessed at the baseline and six weeks after drug treatment. The plasma cortisol response to APO was markedly blunted in patients with SCH compared to normal controls. Patients who responded to six weeks of treatment with antipsychotic drugs had a higher cortisol response to APO compared to non-responders. The plasma GH, but not PRL, response to APO was blunted in male patients with SCH. Neither plasma GH nor PRL responses to APO were related to treatment response at six weeks. These results provide further evidence of dopaminergic dysfunction in SCH. Furthermore, the APO-stimulated cortisol response may be predictive of subsequent clinical response to antipsychotic drug treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 7 | Psychiatry Res 2001 Jul 102: 249-54 |
| PMID | 11440775 |
| Title | Lower prolactin bioactivity in unmedicated schizophrenic patients. |
| Abstract | In previous work, prolactin (PRL) abnormalities of a lower bioassay (BA) to radioimmunoassay (RIA) ratio were found in schizophrenic patients. This line of research was extended in seven male patients with schizophrenia who were neuroleptic-free; seven male control subjects were also studied. PRL values were assessed by RIA and Nb(2) BA techniques. The schizophrenic group had a significantly lower PRL BA as compared to normal controls and a lower PRL ratio of BA/RIA. The lower ratio is consistent with an earlier finding and suggests that schizophrenic patients have different molecular forms of PRL than control subjects. This difference could be due to a disordered tuberoinfundibular dopamine system or the long-term effects of neuroleptic medications. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 8 | Ann Pharmacother 2001 Dec 35: 1523-7 |
| PMID | 11793612 |
| Title | Effects of risperidone on gonadal axis hormones in schizophrenia. |
| Abstract | To investigate the effects of risperidone on the hypothalamo-pituitary-gonadal (HPG) axis of chronic schizophrenic male inpatients medicated regularly. Subjects included six inpatients who were diagnosed according to the Diagnostic and Statistical Manual, Fourth Edition, criteria for schizophrenia, and were termed treatment-refractory. Each patient gave informed consent for the research involved in this study. The neuroendocrine studies were done before and during risperidone administration. Patients took a mean dose of risperidone 9.5 mg/d for a mean period of 64.2 days. Psychotic symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Prolactin (PRL) increased significantly during risperidone administration. However, luteinizing hormone, follicle-stimulating hormone, and testosterone did not show significant difference between blood concentrations before and during risperidone administration. Scores of the BPRS total, thought disturbance factor, and tension decreased significantly during risperidone administration. Throughout the study, none of the patients experienced clinically significant problems associated with elevated PRL concentrations including gynecomastia and/or sexual dysfunction. Addition of risperidone produced significant improvement of psychotic symptoms in treatment-resistant schizophrenic patients, and an increase in basal blood PRL concentrations, but not in basal blood HPG axis hormone concentrations. This preliminary result warrants further double-blind evaluation with a larger sample. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 9 | Endocr. Rev. 2001 Dec 22: 724-63 |
| PMID | 11739329 |
| Title | Dopamine as a prolactin (PRL) inhibitor. |
| Abstract | Dopamine is a small and relatively simple molecule that fulfills diverse functions. Within the brain, it acts as a classical neurotransmitter whose attenuation or overactivity can result in disorders such as Parkinson's disease and schizophrenia. Major advances in the cloning and characterization of biosynthetic enzymes, transporters, and receptors have increased our knowledge regarding the metabolism, release, reuptake, and mechanism of action of dopamine. Dopamine reaches the pituitary via hypophysial portal blood from several hypothalamic nerve tracts that are regulated by PRL itself, estrogens, and several neuropeptides and neurotransmitters. Dopamine binds to type-2 dopamine receptors that are functionally linked to membrane channels and G proteins and suppresses the high intrinsic secretory activity of the pituitary lactotrophs. In addition to inhibiting PRL release by controlling calcium fluxes, dopamine activates several interacting intracellular signaling pathways and suppresses PRL gene expression and lactotroph proliferation. Thus, PRL homeostasis should be viewed in the context of a fine balance between the action of dopamine as an inhibitor and the many hypothalamic, systemic, and local factors acting as stimulators, none of which has yet emerged as a primary PRL releasing factor. The generation of transgenic animals with overexpressed or mutated genes expanded our understanding of dopamine-PRL interactions and the physiological consequences of their perturbations. PRL release in humans, which differs in many respects from that in laboratory animals, is affected by several drugs used in clinical practice. Hyperprolactinemia is a major neuroendocrine-related cause of reproductive disturbances in both men and women. The treatment of hyperprolactinemia has greatly benefited from the generation of progressively more effective and selective dopaminergic drugs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 10 | Neuro Endocrinol. Lett. 2001 Apr 22: 137-41 |
| PMID | 11335890 |
| Title | A study of light/dark rhythm of melatonin in relation to cortisol and prolactin secretion in schizophrenia. |
| Abstract | Recent studies have suggested the involvement of the pineal gland and its main hormone melatonin (MLT) in the pathogenesis of psychiatric disturbances, namely the depressive syndrome. In contrast, the behavior of MLT secretion in schizophrenia is still controversial. The present study was carried out to analyze light/dark rhythm of MLT secretion in relation to that of cortisol and prolactin (PRL) in schizophrenic patients. The study included 13 schizophrenic patients, 8 of whom were untreated, while the other 5 patients were on neuroleptic therapy. Serum levels of MLT, PRL and cortisol were measured by RIA on venous blood samples collected at 8 A.M., 12 A.M., 8 P.M. and 1 A.M. The control group consisted of 20 age-matched healthy subjects. A physiological nocturnal increase in MLT levels occurred in 6/13 patients, whereas the other 7 patients showed an abnormally low MLT peak during the night. Moreover, both light and night mean levels of MLT were significantly lower in patients than in controls. In addition, mean nocturnal levels of MLT were significantly lower in chronic patients than in those evaluated at the onset of disease. Cortisol rhythm was normal in 11/13 patients, whereas PRL levels were abnormally high in 10/13 patients. This preliminary study would suggest that schizophrenia may be associated with a diminished secretion of MLT from the pineal gland, and pineal deficiency would be more evident in the chronic disease. Finally, pineal alterations have appeared to be associated with an altered secretion of PRL and cortisol, by suggesting that the schizophrenic disease may be characterized by marked neuroendocrine disturbances, whose physio-pathological and prognostic significance needs to be established by successive clinical investigations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 11 | Br J Clin Pharmacol 2001 Apr 51: 317-24 |
| PMID | 11318766 |
| Title | Dose requirement and prolactin elevation of antipsychotics in male and female patients with schizophrenia or related psychoses. |
| Abstract | The aim of this study was to investigate the prolactin (PRL) secretion and the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis in relation to gender and side-effects and dose of antipsychotic drugs during long-term treatment. Forty-seven patients (21 men and 26 women), diagnosed with schizophrenia or related psychoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria and treated with different classical antipsychotics, were studied. Prolactin, GH and IGF-I were measured, as well as the serum concentration of the antipsychotics. In addition, body mass index (BMI) was calculated. The median daily, as well as the median body weight, adjusted daily dose of antipsychotic drugs was twofold higher in male compared with female patients. Antipsychotic-induced hyperprolactinaemia was more frequent and occurred at a lower daily dose of antipsychotics in women. Irrespective of sex, more than half of the patients had elevated BMI. Two patients had a slight increment in IGF-I levels, whereas the GH concentration, as assessed on a single occasion, was normal in all patients. Patients on long-term antipsychotic therapy, with doses adjusted according to therapeutic efficiency, exhibited hyperprolactinaemia and elevated BMI, but no obvious influence on the GH-IGF-I axis. Furthermore, it appeared that the males required twice the dose of antipsychotic compared with females. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 12 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2001 Apr 25: 507-18 |
| PMID | 11370994 |
| Title | Dopamine receptor responsivity in schizophrenic patients in a drug-free state and after treatment with olanzapine. |
| Abstract | 1. Olanzapine is a novel atypical antipsychotic with affinity for a number of neurotransmitter receptors including dopamine D1, D2, D4, serotonin 5HT2A, 5HT2C, histamine H1, a1-adrenergic, and muscarinic receptors. 2. A neuroendocrinological method to check the degree of dopamine receptor blocking is by measuring the prolactin (PRL) responses to acute (i.m.) administration of haloperidol (HAL). The authors applied this test in a group of male patients with DSM-IV schizophrenia in the drug-free state. The patients were subsequently treated with olanzapine (OLZ) (mean daily dose: 22.5+/-5.8) and the test was repeated six weeks later. For the HAL-test, 5mg HAL were injected i.m. and blood samples were taken at times 0, 30, 60, 90 and 120 minutes. Fourteen patients enrolled in the study. Psychopathology was assessed by means of the Brief Psychiatric Rating Scale (BPRS). 3. Six weeks treatment with OLZ resulted in significant decreases in the total BPRS score and on the score of its subscales for positive, negative, and general psychopathology. Comparison of the PRL response patterns, after HAL administration by analysis of variance for repeated measures (ANOVAR) for drug treatment and time, revealed a highly significant time effect (F=28.98, p=0.000) and a significant treatment by time interaction (F=8.27, p=0.000008). Namely, in the drug-free state significant increases were found in the PRL levels after i.m. HAL administration which were significantly reduced during treatment with OLZ, indicating moderate receptor blockade. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 13 | Ann Pharmacother 2001 Dec 35: 1523-7 |
| PMID | 11793612 |
| Title | Effects of risperidone on gonadal axis hormones in schizophrenia. |
| Abstract | To investigate the effects of risperidone on the hypothalamo-pituitary-gonadal (HPG) axis of chronic schizophrenic male inpatients medicated regularly. Subjects included six inpatients who were diagnosed according to the Diagnostic and Statistical Manual, Fourth Edition, criteria for schizophrenia, and were termed treatment-refractory. Each patient gave informed consent for the research involved in this study. The neuroendocrine studies were done before and during risperidone administration. Patients took a mean dose of risperidone 9.5 mg/d for a mean period of 64.2 days. Psychotic symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Prolactin (PRL) increased significantly during risperidone administration. However, luteinizing hormone, follicle-stimulating hormone, and testosterone did not show significant difference between blood concentrations before and during risperidone administration. Scores of the BPRS total, thought disturbance factor, and tension decreased significantly during risperidone administration. Throughout the study, none of the patients experienced clinically significant problems associated with elevated PRL concentrations including gynecomastia and/or sexual dysfunction. Addition of risperidone produced significant improvement of psychotic symptoms in treatment-resistant schizophrenic patients, and an increase in basal blood PRL concentrations, but not in basal blood HPG axis hormone concentrations. This preliminary result warrants further double-blind evaluation with a larger sample. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 14 | Neuro Endocrinol. Lett. 2001 Apr 22: 137-41 |
| PMID | 11335890 |
| Title | A study of light/dark rhythm of melatonin in relation to cortisol and prolactin secretion in schizophrenia. |
| Abstract | Recent studies have suggested the involvement of the pineal gland and its main hormone melatonin (MLT) in the pathogenesis of psychiatric disturbances, namely the depressive syndrome. In contrast, the behavior of MLT secretion in schizophrenia is still controversial. The present study was carried out to analyze light/dark rhythm of MLT secretion in relation to that of cortisol and prolactin (PRL) in schizophrenic patients. The study included 13 schizophrenic patients, 8 of whom were untreated, while the other 5 patients were on neuroleptic therapy. Serum levels of MLT, PRL and cortisol were measured by RIA on venous blood samples collected at 8 A.M., 12 A.M., 8 P.M. and 1 A.M. The control group consisted of 20 age-matched healthy subjects. A physiological nocturnal increase in MLT levels occurred in 6/13 patients, whereas the other 7 patients showed an abnormally low MLT peak during the night. Moreover, both light and night mean levels of MLT were significantly lower in patients than in controls. In addition, mean nocturnal levels of MLT were significantly lower in chronic patients than in those evaluated at the onset of disease. Cortisol rhythm was normal in 11/13 patients, whereas PRL levels were abnormally high in 10/13 patients. This preliminary study would suggest that schizophrenia may be associated with a diminished secretion of MLT from the pineal gland, and pineal deficiency would be more evident in the chronic disease. Finally, pineal alterations have appeared to be associated with an altered secretion of PRL and cortisol, by suggesting that the schizophrenic disease may be characterized by marked neuroendocrine disturbances, whose physio-pathological and prognostic significance needs to be established by successive clinical investigations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 15 | Psychopharmacology (Berl.) 2001 Aug 157: 55-9 |
| PMID | 11512043 |
| Title | Neuroendocrine serotonergic and dopaminergic responsivity in male schizophrenic patients during treatment with neuroleptics and after switch to risperidone. |
| Abstract | The pharmacological profile of risperidone is that of an atypical neuroleptic regarding its serotonin 5-HT2A and dopamine D2 receptor blocking properties. Treatment with risperidone, though, results in considerably elevated plasma prolactin (PRL) levels which are not observed with other atypical neuroleptics, such as clozapine, indicating a differentiated action on receptors that are involved in PRL release, mainly dopaminergic and serotonergic. To assess the responsivity of serotonergic and dopaminergic receptors during treatment with neuroleptics and after switch to risperidone, using neuroendocrine paradigms. Two neuroendocrine challenge tests, measuring the PRL increases induced by acute administration of serotonergic (clomipramine, 25 mg i.v.) and dopaminergic (haloperidol, 5 mg i.m.) drugs were performed in 13 male schizophrenic patients during treatment with typical neuroleptics and, later, after 6 weeks of treatment with risperidone. The tests were also performed in a group of nine healthy male volunteers. PRL was estimated in blood samples taken every 15 min for 1 h for clomipramine and every 30 min for 2 h for haloperidol. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS). During treatment with neuroleptics (mean dose 1354 mg chlorpromazine equivalents, range 300-2400 mg), i.m. haloperidol caused significant elevations in plasma PRL, which were totally abolished after 6 weeks treatment with risperidone (mean dose 12.1 mg/day, range 8-16 mg/day), indicating complete D2 receptor blockade. In contrast, the PRL increases obtained after clomipramine administration during neuroleptic treatment were preserved after treatment with risperidone. Both PRL response patterns to clomipramine were similar to that of healthy controls. BPRS score was 50.2+/-9.3 points during neuroleptic treatment and was reduced after risperidone to 30.1+/-6.6 points, i.e., 40% in the mean. During treatment with typical neuroleptics, the PRL responses to clomipramine are normal, and they are preserved after switch to risperidone in doses that cause complete dopamine receptor blockade. Risperidone, a dopamine and 5-HT receptor blocker, does not affect 5-HT receptors that are involved in the PRL release by the 5-HT uptake blocker clomipramine, indicating a different behavior than other atypical neuroleptics such as clozapine or olanzapine, for which a reduction of the PRL release induced by serotonergic agents like fenfluramine or mCPP has been reported. A conclusive identification of the 5-HT receptor subtypes that are involved in this different action cannot be identified at present, but it should be taken into account that risperidone differs from clozapine, showing higher affinity for 5-HT2A than 5-HT2C receptors and lacking the marked affinity of clozapine to 5-HT1A receptors. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 16 | Psychoneuroendocrinology 2001 Aug 26: 641-7 |
| PMID | 11403983 |
| Title | Effects of olanzapine and haloperidol on serum prolactin levels in male schizophrenic patients. |
| Abstract | It has been proposed that new atypical antipsychotics cause minimal prolactin (PRL) elevation compared to traditional antipsychotic agents because they spare dopamine blockade within the brain's tuberoinfundibular tract. The aim of this study was to compare the effects of olanzapine and haloperidol on PRL secretion in male schizophrenic patients. Twenty-nine male schizophrenic inpatients were included in the study. Fifteen of them were given olanzapine in a fixed dose of 10 mg/day PO and 14 of them were given haloperidol in a fixed dose of 10 mg/day PO for 6 weeks after a 2-week drug washout period. Fifteen age-matched healthy control subjects were used as control group. PRL levels were measured both before and after the 6-week treatment period in the patients. At the end of the 6th week, the PRL values observed with olanzapine treatment were significantly less than those observed with haloperidol, but not different from those of the controls. There was a significant positive correlation between the PRL values and the severity of extrapyramidal side effects in only the haloperidol group after the six week's treatment period. Our data indicate that short-term olanzapine treatment at doses of 10 mg/day PO causes minimal elevations in PRL secretion in male schizophrenic patients in contrast to haloperidol. This finding is consistent with the previous reports and may be attributed to olanzapine's differential effects on dopamine neurotransmission. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 17 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2002 Apr 26: 579-84 |
| PMID | 11999911 |
| Title | Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients. |
| Abstract | Thyrotropin-releasing hormone (TRH) test and Dexamethasone Suppression Test (DST) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia. The objectives of this study were to investigate (1) the relationship between TRH test and DST and various psychiatric symptoms and (2) the potential value of these tests in prediction of short-term outcome in schizophrenic patients. TRH test and DST were administered to 58 patients with schizophrenia. All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year. Patients were divided into two groups as remitted (RP; n = 30) and nonremitted patients (NRP; n = 28). Baseline results of these two groups were compared with each other and 30 healthy controls. Basal levels of total T3 (T3T) and free T3 (T3F) were higher in RP group than controls. Basal prolactin (PRL) level was higher in RP group, but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid-stimulating hormone (TSH) levels of NRP were significantly higher than those of RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group. Blunted TSH response rate in RP group was higher significantly compared to other two groups. The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response, whereas higher total and free T3 levels, a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 18 | Psychiatry Res 2002 Dec 113: 41-7 |
| PMID | 12467944 |
| Title | D-fenfluramine-evoked serotonergic responses in olanzapine-treated schizophrenic patients. |
| Abstract | Antagonist activity at the 5-HT(2) receptor may contribute to the therapeutic efficacy of atypical antipsychotics in schizophrenia. This neuroendocrine study examined the in vivo functional serotonergic (5-HT) activity of the atypical antipsychotic olanzapine. We examined central 5-HT(2) responses by measuring the serum prolactin (PRL) over 5 h in response to 30 mg of D-fenfluramine (DFEN) in two groups of male schizophrenic patients. Blunted PRL responses to DFEN indicate functional 5-HT(2) receptor antagonism. Seven patients treated with olanzapine at a mean (S.D.) dose of 13.1 (4.6) for a mean of 28 weeks were compared with a matched group of eight patients who had received no antipsychotic treatment for at least 2 weeks. Baseline PRL levels did not differ significantly in the two patient groups and were within the normal range. The olanzapine-treated patients showed a significantly lower maximal DFEN-evoked PRL response and a significantly lower group x time overall PRL release compared with the untreated patient group. We have previously demonstrated a similar degree of functional in vivo 5-HT(2) antagonism with the atypical antipsychotic clozapine. This study thus suggests that this activity may not contribute to the unique clinical efficacy of clozapine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 19 | Dialogues Clin Neurosci 2002 Dec 4: 408-16 |
| PMID | 22034390 |
| Title | Research on serotonin and suicidal behavior: neuroendocrine and molecular approaches. |
| Abstract | We carried out two studies to test the hypothesis that altered central serotonergic function, as assessed by lower prolactin (PRL) response to fenfluramine (D-FEN), is more closely associated with suicidal behavior than a particular psychiatric diagnosis. A D-FEN test was performed in 85 major depressed inpatients, 33 schizophrenic inpatients, and 18 healthy controls. We showed that PRL response to D-FEN is a marker of suicidality, regardless of psychiatric disorder. We then examined the association en the serotonin (5-hydroxytryptamine) receptor 5-HT(2A) gene polymorphism (T102C) and suicide in a sample of Brazilian psychiatric inpatients (95 with schizophrenia, 78 with major depression) and 52 healthy controls. No differences were found in genotypic frequencies across patients and controls. Overall, no differences were found between patients with (n=66) and without (n=107) a history of suicide attempt. We also compared patients with a history of severe suicide attempts (lethality>3; n=32) and patients without such a history (n=107), but they did not exhibit different genotypic frequencies either. These results show thai the 5-HT(2A) gene polymorphism (T102C) may not be involved in the genetic susceptibility to suicidal behavior. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 20 | Schizophr. Res. 2002 Jul 56: 75-85 |
| PMID | 12084422 |
| Title | Serotonergic function and suicidal behavior in schizophrenia. |
| Abstract | Recent studies suggest that altered serotonergic (5-HT) function, as assessed by lower prolactin (PRL) response to fenfluramine (FEN), a specific 5-HT releaser and uptake inhibitor, is associated with suicidal behavior in either depressed and personality disordered patients. The purpose of this study was to investigate, in schizophrenic patients, the relationship between suicidal behavior and PRL response to D-fenfluramine (D-FEN). A D-FEN test was performed in 18 healthy controls and 33 drug-free DSM-IV schizophrenic patients (12 with a history of suicide attempts, 21 without it). schizophrenic patients with a history of suicide attempts showed a lower PRL response to D-FEN (Delta PRL) compared to schizophrenic patients without such history (P<0.04) and also compared to healthy controls (P<0.0003). Delta PRL did not differentiate schizophrenic patients without suicide attempts and controls. These findings could not be explained by PRL basal hormonal levels, age, sex, menstrual status, demographic or clinical characteristics. These results suggest that PRL response to D-FEN is a marker of suicidal tendencies also in schizophrenia, supporting the hypothesis that a dysfunction in serotonergic function is associated with suicidal behavior regardless of the psychiatric diagnosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 21 | Psychiatry Res 2002 Dec 113: 41-7 |
| PMID | 12467944 |
| Title | D-fenfluramine-evoked serotonergic responses in olanzapine-treated schizophrenic patients. |
| Abstract | Antagonist activity at the 5-HT(2) receptor may contribute to the therapeutic efficacy of atypical antipsychotics in schizophrenia. This neuroendocrine study examined the in vivo functional serotonergic (5-HT) activity of the atypical antipsychotic olanzapine. We examined central 5-HT(2) responses by measuring the serum prolactin (PRL) over 5 h in response to 30 mg of D-fenfluramine (DFEN) in two groups of male schizophrenic patients. Blunted PRL responses to DFEN indicate functional 5-HT(2) receptor antagonism. Seven patients treated with olanzapine at a mean (S.D.) dose of 13.1 (4.6) for a mean of 28 weeks were compared with a matched group of eight patients who had received no antipsychotic treatment for at least 2 weeks. Baseline PRL levels did not differ significantly in the two patient groups and were within the normal range. The olanzapine-treated patients showed a significantly lower maximal DFEN-evoked PRL response and a significantly lower group x time overall PRL release compared with the untreated patient group. We have previously demonstrated a similar degree of functional in vivo 5-HT(2) antagonism with the atypical antipsychotic clozapine. This study thus suggests that this activity may not contribute to the unique clinical efficacy of clozapine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 22 | Dialogues Clin Neurosci 2002 Dec 4: 408-16 |
| PMID | 22034390 |
| Title | Research on serotonin and suicidal behavior: neuroendocrine and molecular approaches. |
| Abstract | We carried out two studies to test the hypothesis that altered central serotonergic function, as assessed by lower prolactin (PRL) response to fenfluramine (D-FEN), is more closely associated with suicidal behavior than a particular psychiatric diagnosis. A D-FEN test was performed in 85 major depressed inpatients, 33 schizophrenic inpatients, and 18 healthy controls. We showed that PRL response to D-FEN is a marker of suicidality, regardless of psychiatric disorder. We then examined the association en the serotonin (5-hydroxytryptamine) receptor 5-HT(2A) gene polymorphism (T102C) and suicide in a sample of Brazilian psychiatric inpatients (95 with schizophrenia, 78 with major depression) and 52 healthy controls. No differences were found in genotypic frequencies across patients and controls. Overall, no differences were found between patients with (n=66) and without (n=107) a history of suicide attempt. We also compared patients with a history of severe suicide attempts (lethality>3; n=32) and patients without such a history (n=107), but they did not exhibit different genotypic frequencies either. These results show thai the 5-HT(2A) gene polymorphism (T102C) may not be involved in the genetic susceptibility to suicidal behavior. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 23 | Schizophr. Res. 2002 Jul 56: 75-85 |
| PMID | 12084422 |
| Title | Serotonergic function and suicidal behavior in schizophrenia. |
| Abstract | Recent studies suggest that altered serotonergic (5-HT) function, as assessed by lower prolactin (PRL) response to fenfluramine (FEN), a specific 5-HT releaser and uptake inhibitor, is associated with suicidal behavior in either depressed and personality disordered patients. The purpose of this study was to investigate, in schizophrenic patients, the relationship between suicidal behavior and PRL response to D-fenfluramine (D-FEN). A D-FEN test was performed in 18 healthy controls and 33 drug-free DSM-IV schizophrenic patients (12 with a history of suicide attempts, 21 without it). schizophrenic patients with a history of suicide attempts showed a lower PRL response to D-FEN (Delta PRL) compared to schizophrenic patients without such history (P<0.04) and also compared to healthy controls (P<0.0003). Delta PRL did not differentiate schizophrenic patients without suicide attempts and controls. These findings could not be explained by PRL basal hormonal levels, age, sex, menstrual status, demographic or clinical characteristics. These results suggest that PRL response to D-FEN is a marker of suicidal tendencies also in schizophrenia, supporting the hypothesis that a dysfunction in serotonergic function is associated with suicidal behavior regardless of the psychiatric diagnosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 24 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2002 May 26: 683-91 |
| PMID | 12188100 |
| Title | Biological markers and possibilities for predicting therapeutic results in schizophrenia: a methodological contribution. |
| Abstract | The aim of the research was to select some easily available and easily replicable biological markers that could be used as predictors of both acute and long-term therapy. A selection of state markers (structural computer tomography [CT] parameters, psychological parameters, tests concentrating on attention and memory, "soft signs"), trait markers (quantified electroencephalograph [QEEG], cortisolemia, prolactinemia [PRL], and their changes) and clinical symptoms (Positive and Negative Syndrome Scale [PANSS], Clinical Global Impression [CGI]) were determined in 52 hospitalised schizophrenic patients showing either an acute episode or an exacerbation. The evaluation was repeated after one year of outpatient therapy. The parameters studied so far are not sufficiently specific and sensitive; therefore, the prediction cannot be based on a single parameter. In order to overcome this shortcoming, we carried out the analysis by means of multidimensional statistics, applying discriminant analysis. The results of both a broader and a more specific approach are stated in the paper. In all the used examples of discriminant analysis, the optimum discriminator is cortisolemia or its changes after administering dexamethasone and structural CT parameters. The results indicate that combinations of vulnerability markers and state markers (cortisolemia) may be of predictive value and are compatible with the vulnerability-stress ethiopathogenetic model of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 25 | Psychiatry Res 2002 Apr 109: 297-302 |
| PMID | 11959366 |
| Title | Risperidone-induced increase in serum prolactin is correlated with positive symptom improvement in chronic schizophrenia. |
| Abstract | The elevation in serum prolactin (PRL) concentration in schizophrenic patients treated with typical antipsychotic drugs is well documented. Recently, increased prolactin levels have been reported in patients taking risperidone. The purpose of this study was to explore the effect of the atypical antipsychotic drug risperidone on serum prolactin, and to investigate the relationship between the change in PRL and the therapeutic outcome. In this study, 30 male inpatients with a diagnosis of chronic schizophrenia (DSM-III-R) were assigned to 12 weeks of treatment with risperidone after a 2-week washout period. The risperidone dose was fixed at 6 mg/day. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum PRL was assayed in serum by radioimmunometric assay in schizophrenic patients before and after 12-week treatment, as compared to 30 age-matched normal male subjects. The results showed that risperidone treatment significantly increased the serum PRL. A significant and positive relationship between the change in PRL at pre- and post-treatment and the reduction rate of PANSS positive subscore was observed. Risperidone treatment significantly increased the serum PRL levels of schizophrenic patients. There was a close relationship between the improvement in positive symptoms and the change of serum PRL level before and after risperidone treatment. The serum PRL levels at baseline could be used to predict the responses of schizophrenic patients to risperidone. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 26 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2002 Apr 26: 579-84 |
| PMID | 11999911 |
| Title | Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients. |
| Abstract | Thyrotropin-releasing hormone (TRH) test and Dexamethasone Suppression Test (DST) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia. The objectives of this study were to investigate (1) the relationship between TRH test and DST and various psychiatric symptoms and (2) the potential value of these tests in prediction of short-term outcome in schizophrenic patients. TRH test and DST were administered to 58 patients with schizophrenia. All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year. Patients were divided into two groups as remitted (RP; n = 30) and nonremitted patients (NRP; n = 28). Baseline results of these two groups were compared with each other and 30 healthy controls. Basal levels of total T3 (T3T) and free T3 (T3F) were higher in RP group than controls. Basal prolactin (PRL) level was higher in RP group, but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid-stimulating hormone (TSH) levels of NRP were significantly higher than those of RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group. Blunted TSH response rate in RP group was higher significantly compared to other two groups. The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response, whereas higher total and free T3 levels, a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 27 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2002 Apr 26: 579-84 |
| PMID | 11999911 |
| Title | Different neuroendocrine profiles of remitted and nonremitted schizophrenic patients. |
| Abstract | Thyrotropin-releasing hormone (TRH) test and Dexamethasone Suppression Test (DST) are two neuroendocrine tests that have been extensively used in an attempt to predict treatment response and outcome in schizophrenia. The objectives of this study were to investigate (1) the relationship between TRH test and DST and various psychiatric symptoms and (2) the potential value of these tests in prediction of short-term outcome in schizophrenic patients. TRH test and DST were administered to 58 patients with schizophrenia. All patients were evaluated with a battery of rating scales before neuroendocrine test procedures and at regular intervals for 1 year. Patients were divided into two groups as remitted (RP; n = 30) and nonremitted patients (NRP; n = 28). Baseline results of these two groups were compared with each other and 30 healthy controls. Basal levels of total T3 (T3T) and free T3 (T3F) were higher in RP group than controls. Basal prolactin (PRL) level was higher in RP group, but not in NRP, compared to controls. Basal growth hormone (GH) and thyroid-stimulating hormone (TSH) levels of NRP were significantly higher than those of RP. DST nonsuppression was observed at a significantly higher rate in RP than NRP and control group. Blunted TSH response rate in RP group was higher significantly compared to other two groups. The data implicate that higher basal TSH and GH levels may be associated with a poorer treatment response, whereas higher total and free T3 levels, a blunted TSH response to TRH and nonsuppression on the DST may indicate a better response in schizophrenics. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 28 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2002 May 26: 683-91 |
| PMID | 12188100 |
| Title | Biological markers and possibilities for predicting therapeutic results in schizophrenia: a methodological contribution. |
| Abstract | The aim of the research was to select some easily available and easily replicable biological markers that could be used as predictors of both acute and long-term therapy. A selection of state markers (structural computer tomography [CT] parameters, psychological parameters, tests concentrating on attention and memory, "soft signs"), trait markers (quantified electroencephalograph [QEEG], cortisolemia, prolactinemia [PRL], and their changes) and clinical symptoms (Positive and Negative Syndrome Scale [PANSS], Clinical Global Impression [CGI]) were determined in 52 hospitalised schizophrenic patients showing either an acute episode or an exacerbation. The evaluation was repeated after one year of outpatient therapy. The parameters studied so far are not sufficiently specific and sensitive; therefore, the prediction cannot be based on a single parameter. In order to overcome this shortcoming, we carried out the analysis by means of multidimensional statistics, applying discriminant analysis. The results of both a broader and a more specific approach are stated in the paper. In all the used examples of discriminant analysis, the optimum discriminator is cortisolemia or its changes after administering dexamethasone and structural CT parameters. The results indicate that combinations of vulnerability markers and state markers (cortisolemia) may be of predictive value and are compatible with the vulnerability-stress ethiopathogenetic model of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 29 | Psychiatry Res 2002 Apr 109: 297-302 |
| PMID | 11959366 |
| Title | Risperidone-induced increase in serum prolactin is correlated with positive symptom improvement in chronic schizophrenia. |
| Abstract | The elevation in serum prolactin (PRL) concentration in schizophrenic patients treated with typical antipsychotic drugs is well documented. Recently, increased prolactin levels have been reported in patients taking risperidone. The purpose of this study was to explore the effect of the atypical antipsychotic drug risperidone on serum prolactin, and to investigate the relationship between the change in PRL and the therapeutic outcome. In this study, 30 male inpatients with a diagnosis of chronic schizophrenia (DSM-III-R) were assigned to 12 weeks of treatment with risperidone after a 2-week washout period. The risperidone dose was fixed at 6 mg/day. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum PRL was assayed in serum by radioimmunometric assay in schizophrenic patients before and after 12-week treatment, as compared to 30 age-matched normal male subjects. The results showed that risperidone treatment significantly increased the serum PRL. A significant and positive relationship between the change in PRL at pre- and post-treatment and the reduction rate of PANSS positive subscore was observed. Risperidone treatment significantly increased the serum PRL levels of schizophrenic patients. There was a close relationship between the improvement in positive symptoms and the change of serum PRL level before and after risperidone treatment. The serum PRL levels at baseline could be used to predict the responses of schizophrenic patients to risperidone. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 30 | Psychoneuroendocrinology 2003 Jul 28: 627-42 |
| PMID | 12727131 |
| Title | Dopamine and serotonin function in untreated schizophrenia: clinical correlates of the apomorphine and d-fenfluramine tests. |
| Abstract | This study examined the prolactin (PRL), adrenocorticotropin (ACTH) and cortisol responses to the direct DA receptor agonist apomorphine (APO) and the selective 5HT-releasing agent d-fenfluramine (d-FEN) in 20 untreated inpatients with DSM-IV schizophrenia and without a history of suicide attempt, compared to 23 hospitalized healthy controls. We hypothesized that different patterns of responsiveness of the DA and 5-HT systems might be associated with specific schizophrenic symptom clusters. A positive correlation was observed between pituitary-adrenal response to APO and d-FEN tests (i.e. deltaACTH and deltacortisol) in the overall population and in schizophrenic patients. Pituitary-adrenal response to APO was lower in patients than in normal controls. Moreover, lower pituitary-adrenal response to APO and d-FEN was associated with increased severity of BPRS thought disturbance score. Lower pituitary-adrenal responses to APO (and to a lesser degree to d-FEN) differentiated paranoid from disorganized schizophrenic patients. Neither PRL suppression to APO, nor PRL stimulation to d-FEN were altered in schizophrenic patients. Our results suggest that decreased hypothalamic DA receptor activity (possibly secondary to increased presynaptic DA release) together with relatively decreased 5-HT tone characterize paranoid SCH, while normal hypothalamic DA receptor activity together with relatively increased 5-HT tone characterize the disorganized SCH subtype. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 31 | Psychoneuroendocrinology 2003 Jul 28: 627-42 |
| PMID | 12727131 |
| Title | Dopamine and serotonin function in untreated schizophrenia: clinical correlates of the apomorphine and d-fenfluramine tests. |
| Abstract | This study examined the prolactin (PRL), adrenocorticotropin (ACTH) and cortisol responses to the direct DA receptor agonist apomorphine (APO) and the selective 5HT-releasing agent d-fenfluramine (d-FEN) in 20 untreated inpatients with DSM-IV schizophrenia and without a history of suicide attempt, compared to 23 hospitalized healthy controls. We hypothesized that different patterns of responsiveness of the DA and 5-HT systems might be associated with specific schizophrenic symptom clusters. A positive correlation was observed between pituitary-adrenal response to APO and d-FEN tests (i.e. deltaACTH and deltacortisol) in the overall population and in schizophrenic patients. Pituitary-adrenal response to APO was lower in patients than in normal controls. Moreover, lower pituitary-adrenal response to APO and d-FEN was associated with increased severity of BPRS thought disturbance score. Lower pituitary-adrenal responses to APO (and to a lesser degree to d-FEN) differentiated paranoid from disorganized schizophrenic patients. Neither PRL suppression to APO, nor PRL stimulation to d-FEN were altered in schizophrenic patients. Our results suggest that decreased hypothalamic DA receptor activity (possibly secondary to increased presynaptic DA release) together with relatively decreased 5-HT tone characterize paranoid SCH, while normal hypothalamic DA receptor activity together with relatively increased 5-HT tone characterize the disorganized SCH subtype. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 32 | Psychoneuroendocrinology 2003 Apr 28 Suppl 2: 55-68 |
| PMID | 12650681 |
| Title | Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. |
| Abstract | The prevalence of hyperprolactinemia during treatment with conventional antipsychotic drugs or risperidone is under-recognized and requires further investigation. This open-label study was designed to determine the extent of this potential problem in a routine clinical setting. Four hundred and two adult inpatients or outpatients with a diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder were studied in a 1-day, point prevalence trial. Neither clinicians nor patients had any prior knowledge of serum prolactin levels or any potential associated adverse events, and patients were required to have been treated with a conventional antipsychotic drug or risperidone for a minimum of 3 months prior to study entry. Patients taking concomitant medications known to elevate prolactin were excluded. Rigorous assessment of serum prolactin was performed to estimate the prevalence rate of hyperprolactinemia, defined as a level above the upper limit of normal (>18.77 ng/ml for males, and >24.20 ng/ml for females). Patients were stratified within antipsychotic treatment by gender and, for females, by menopausal status. Serum prolactin was obtained from 147 females (age range: 21-69 years; mean age=44.51 years) and 255 males (age range: 18-66 years; mean age=40.76 years). The prevalence of hyperprolactinemia among women of reproductive age (n=90) was 65.6% (mean serum prolactin=69.0 ng/ml), and among postmenopausal women (n=51), it was 45.1% (mean serum PRL=49.0 ng/ml). The prevalence of hyperprolactinemia across all males (n=255) was 42.4% (mean serum PRL= 32.4 ng/ml). The prevalence of hyperprolactinemia among females taking risperidone (N=42) was 88% versus 47.6% of those taking conventional antipsychotic drugs (N=105), with 48% of those females of reproductive age on risperidone experiencing abnormal menstrual cycles (secondary amenorrhea, oligomenorrhea, or polymenorrhea). Of all premenopausal females with hyperprolactinemia, 31.6% had estradiol levels |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 33 | Behav. Brain Res. 2003 Jan 138: 59-69 |
| PMID | 12493630 |
| Title | Sulpiride alleviates the attentional impairments of rats with medial prefrontal cortex lesions. |
| Abstract | Recent studies have shown that medial prefrontal cortex (mPFC) lesions impair performance on a number of rodent tests of attention. Although this evidence clearly suggests a role for the rat mPFC in attentional functions, it is unclear whether subcortical changes associated with mPFC lesions might also be relevant to the neuropsychological deficits observed. Given the ample evidence suggesting increased dopaminergic mechanisms in the basal ganglia following mPFC lesions, we investigated the effects of dopamine receptor agonists and antagonists on the attentional deficits associated with mPFC lesions. Rats trained on a five-choice reaction time task received either complete mPFC lesions or lesions restricted to its ventral subregions, the prelimbic and infralimbic cortices (PRL-IL). Compared with sham-operated rats, animals in both the lesioned groups were impaired at responding correctly to the visual targets, although this deficit was more marked in mPFC-lesioned rats. In addition, both lesions were associated with increased perseverative responding. The accuracy deficits of rats with mPFC lesions were alleviated by systemic administration of the dopamine D2 receptor antagonist sulpiride. In contrast, rats with PRL-IL damage were not affected and control rats were impaired by sulpiride. Administration of either the dopamine D1 receptor antagonist SCH 23390 or of pre-synaptic doses of apomorphine had similar, albeit non-significant effects. Higher doses of any of these drugs non-specifically impaired performance. These results extend previous findings of attentional impairments in rats with mPFC lesions and are compatible with recent hypotheses concerning the role of dopaminergic dysregulation in the pathogenesis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 34 | Psychoneuroendocrinology 2003 Apr 28 Suppl 2: 55-68 |
| PMID | 12650681 |
| Title | Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. |
| Abstract | The prevalence of hyperprolactinemia during treatment with conventional antipsychotic drugs or risperidone is under-recognized and requires further investigation. This open-label study was designed to determine the extent of this potential problem in a routine clinical setting. Four hundred and two adult inpatients or outpatients with a diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder were studied in a 1-day, point prevalence trial. Neither clinicians nor patients had any prior knowledge of serum prolactin levels or any potential associated adverse events, and patients were required to have been treated with a conventional antipsychotic drug or risperidone for a minimum of 3 months prior to study entry. Patients taking concomitant medications known to elevate prolactin were excluded. Rigorous assessment of serum prolactin was performed to estimate the prevalence rate of hyperprolactinemia, defined as a level above the upper limit of normal (>18.77 ng/ml for males, and >24.20 ng/ml for females). Patients were stratified within antipsychotic treatment by gender and, for females, by menopausal status. Serum prolactin was obtained from 147 females (age range: 21-69 years; mean age=44.51 years) and 255 males (age range: 18-66 years; mean age=40.76 years). The prevalence of hyperprolactinemia among women of reproductive age (n=90) was 65.6% (mean serum prolactin=69.0 ng/ml), and among postmenopausal women (n=51), it was 45.1% (mean serum PRL=49.0 ng/ml). The prevalence of hyperprolactinemia across all males (n=255) was 42.4% (mean serum PRL= 32.4 ng/ml). The prevalence of hyperprolactinemia among females taking risperidone (N=42) was 88% versus 47.6% of those taking conventional antipsychotic drugs (N=105), with 48% of those females of reproductive age on risperidone experiencing abnormal menstrual cycles (secondary amenorrhea, oligomenorrhea, or polymenorrhea). Of all premenopausal females with hyperprolactinemia, 31.6% had estradiol levels |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 35 | J Clin Psychopharmacol 2004 Apr 24: 161-6 |
| PMID | 15206663 |
| Title | Prolactin levels and erectile function in patients treated with risperidone. |
| Abstract | Treatment with risperidone is associated with prolactin (PRL) elevation, and PRL elevations are associated with erectile dysfunction (ED). We evaluated whether the PRL elevations caused by risperidone treatment of subjects with schizophrenia are associated with objective measures of erectile function. Subjects were hospitalized for 2 nights, and serum measurements of PRL, total testosterone, and free and weakly bound testosterone were performed in the morning and afternoon of each day. Risperidone levels, parent compound, and 9-hydroxy metabolite levels were drawn on the first day. Erectile function assessments, using the RigiScan, an instrument that measures nocturnal penile tumescence and rigidity, were performed on both nights. Consistent with previous reports, the correlation between total risperidone level and PRL was very high (r = 0.92, df = 12, P < 0.0001), but risperidone did not appear to affect either testosterone (r = 0.29, df = 5, P = 0.51) or free and weakly bound testosterone (r = -0.11, df = 10, P = 0.72). Contrary to expectations, PRL levels from the second night were positively correlated with erectile function (r = 0.68, df = 9, P = 0.022). Using objective measures, we were unable to confirm a detrimental association between PRL levels and male erectile function. These results are tentative given the small sample. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 36 | Psychiatry Res 2004 Jul 127: 217-26 |
| PMID | 15296821 |
| Title | Platelet serotonin and plasma prolactin and cortisol in healthy, depressed and schizophrenic women. |
| Abstract | Serotonin (5-hydroxytryptamine, 5-HT) is involved in the regulation of hypothalamic-pituitary-adrenal axis (HPA) activity and prolactin (PRL) secretion. The present study examined the relationship between platelet 5-HT and plasma cortisol and PRL concentrations in 20 schizophrenic, 25 depressed, and 25 healthy women. At the time of blood sampling, the schizophrenic and depressed patients had been drug-free for at least 7 days. Platelet 5-HT, plasma cortisol and PRL concentrations were determined by spectrofluorimetric, radioimmunoassay and immunoradiometric methods, respectively. Platelet 5-HT concentration was significantly higher in schizophrenic patients than in depressed patients or in healthy controls, while it was significantly lower in depressed patients than in healthy controls or in schizophrenic patients. Plasma cortisol levels were significantly increased both in schizophrenic and in depressed patients compared with values in healthy controls. Values of plasma PRL were similar across groups. A significant correlation was found between platelet 5-HT and plasma cortisol, and platelet 5-HT and plasma PRL concentrations in healthy controls, but not in schizophrenic or depressed patients. There was no significant relationship between plasma PRL and cortisol levels in any of the groups. Our data, although obtained on peripheral biochemical markers, indicate that depression and schizophrenia are characterized by disturbed 5-HT transmission and dysregulated HPA axis activity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 37 | Psychiatry Res 2004 Jul 127: 217-26 |
| PMID | 15296821 |
| Title | Platelet serotonin and plasma prolactin and cortisol in healthy, depressed and schizophrenic women. |
| Abstract | Serotonin (5-hydroxytryptamine, 5-HT) is involved in the regulation of hypothalamic-pituitary-adrenal axis (HPA) activity and prolactin (PRL) secretion. The present study examined the relationship between platelet 5-HT and plasma cortisol and PRL concentrations in 20 schizophrenic, 25 depressed, and 25 healthy women. At the time of blood sampling, the schizophrenic and depressed patients had been drug-free for at least 7 days. Platelet 5-HT, plasma cortisol and PRL concentrations were determined by spectrofluorimetric, radioimmunoassay and immunoradiometric methods, respectively. Platelet 5-HT concentration was significantly higher in schizophrenic patients than in depressed patients or in healthy controls, while it was significantly lower in depressed patients than in healthy controls or in schizophrenic patients. Plasma cortisol levels were significantly increased both in schizophrenic and in depressed patients compared with values in healthy controls. Values of plasma PRL were similar across groups. A significant correlation was found between platelet 5-HT and plasma cortisol, and platelet 5-HT and plasma PRL concentrations in healthy controls, but not in schizophrenic or depressed patients. There was no significant relationship between plasma PRL and cortisol levels in any of the groups. Our data, although obtained on peripheral biochemical markers, indicate that depression and schizophrenia are characterized by disturbed 5-HT transmission and dysregulated HPA axis activity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 38 | Psychopharmacology (Berl.) 2004 Sep 175: 367-73 |
| PMID | 14997280 |
| Title | Prolactinemia is uncoupled from central D2/D3 dopamine receptor occupancy in amisulpride treated patients. |
| Abstract | Atypical antipsychotic drugs are classically associated with lower propensity to extrapyramidal symptoms (EPS) and hyperprolactinemia than typical antipsychotic drugs. It has not been clarified why some atypical antipsychotic drugs, such as amisulpride, induce prolactin plasma concentration (PRL) elevation, but little EPS. Previous studies have found an association between striatal D2/D3 receptor occupancy and PRL in typical antipsychotic treated patients suggesting that PRL is a marker of central D2/D3 receptors blockade. We have evaluated the relationship between PRL and central (striatum, temporal cortex and thalamus) D2/D3 receptor occupancy in amisulpride treated schizophrenic patients. Single photon emission tomography (SPET) and [123I]-epidepride were used to determine D2/D3 receptor occupancy in eight amisulpride treated patients. PRL was measured concurrently with the scans. The mean PRL was 1166 (range 499-1892 mIU/l) for a mean amisulpride dose of 406 mg/day (range 150-600 mg/day). Amisulpride plasma concentration and central D2/D3 receptor occupancy were positively correlated (r=0.83-0.89, df=4, P<0.05). No significant correlations were observed between PRL and amisulpride (daily dose or plasma concentration, P>0.05), or between PRL and central D2/D3 receptor occupancy (P>0.05). Our findings show that amisulpride-induced hyperprolactinemia is uncoupled from central D2/D3 receptor occupancy. Amisulpride has poor blood-brain barrier penetration and reaches much higher concentration at the pituitary, which is outside the blood-brain barrier. Higher D2/D3 receptor occupancy at the pituitary gland than at central regions is a possible explanation for amisulpride PRL elevation with low EPS. Further studies evaluating pituitary D2/D3 receptor occupancy in vivo are necessary to confirm this hypothesis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 39 | J Clin Psychiatry 2005 Jun 66: 761-7 |
| PMID | 15960571 |
| Title | Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. |
| Abstract | The aim of this cross-sectional study was to investigate the degree and frequency of prolactin (PRL) elevation and related symptoms in patients treated with 3 different atypical antipsychotics: clozapine, olanzapine, and risperidone. Twenty-eight patients receiving clozapine, 29 patients receiving olanzapine, and 18 patients receiving risperidone (all meeting DSM-IV criteria for schizophrenia, schizophreni-form disorder, or schizoaffective disorder) were studied. The median daily dose was 400 mg of clozapine, 10 mg of olanzapine, and 3 mg of risperidone. Fasting morning blood samples were analyzed for PRL, and the occurrence of hyper-prolactinemic symptoms in the patients was evaluated. Elevated PRL levels were found in 16 (89%) of the patients receiving risperidone and in 7 (24%) of the patients receiving olanzapine, but in none of the patients receiving clozapine. In addition, there was a significant difference in median PRL level among the treatment groups (p < .0001), in that the PRL level was higher both in the patients treated with risperidone and in the patients treated with olanzapine, compared to those treated with clozapine. Moreover, hyperpro-lactinemic symptoms-menstrual disturbances, galactorrhea, impotence, oligospermia, and decreased libido-were reported in 8 (44%) of the risperidone-treated patients and in 1 (3%) of the olanzapine-treated patients, but in none of the clozapine-treated patients. Treatment with risperidone was frequently associated with hyperprolactinemia and related symptoms, whereas the occurrence of PRL elevation and related symptoms was modest in patients receiving olanzapine and nonexistent in those receiving clozapine. Thus, atypical anti-psychotics in therapeutic doses differ with regard to effect on PRL secretion. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 40 | J Clin Psychiatry 2005 Jun 66: 761-7 |
| PMID | 15960571 |
| Title | Differences in prolactin elevation and related symptoms of atypical antipsychotics in schizophrenic patients. |
| Abstract | The aim of this cross-sectional study was to investigate the degree and frequency of prolactin (PRL) elevation and related symptoms in patients treated with 3 different atypical antipsychotics: clozapine, olanzapine, and risperidone. Twenty-eight patients receiving clozapine, 29 patients receiving olanzapine, and 18 patients receiving risperidone (all meeting DSM-IV criteria for schizophrenia, schizophreni-form disorder, or schizoaffective disorder) were studied. The median daily dose was 400 mg of clozapine, 10 mg of olanzapine, and 3 mg of risperidone. Fasting morning blood samples were analyzed for PRL, and the occurrence of hyper-prolactinemic symptoms in the patients was evaluated. Elevated PRL levels were found in 16 (89%) of the patients receiving risperidone and in 7 (24%) of the patients receiving olanzapine, but in none of the patients receiving clozapine. In addition, there was a significant difference in median PRL level among the treatment groups (p < .0001), in that the PRL level was higher both in the patients treated with risperidone and in the patients treated with olanzapine, compared to those treated with clozapine. Moreover, hyperpro-lactinemic symptoms-menstrual disturbances, galactorrhea, impotence, oligospermia, and decreased libido-were reported in 8 (44%) of the risperidone-treated patients and in 1 (3%) of the olanzapine-treated patients, but in none of the clozapine-treated patients. Treatment with risperidone was frequently associated with hyperprolactinemia and related symptoms, whereas the occurrence of PRL elevation and related symptoms was modest in patients receiving olanzapine and nonexistent in those receiving clozapine. Thus, atypical anti-psychotics in therapeutic doses differ with regard to effect on PRL secretion. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 41 | Psychopharmacology (Berl.) 2005 Feb 178: 35-40 |
| PMID | 15289996 |
| Title | Prolactin levels in male schizophrenic patients treated with risperidone and haloperidol: a double-blind and randomized study. |
| Abstract | There are few data from systematic, double-blind clinical trials that have compared the effect of the typical and the atypical antipsychotics on serum prolactin (PRL) levels in patients with schizophrenia. The goal of this study was to compare the effect of risperidone and haloperidol on serum PRL and investigate the relationship between serum PRL levels and clinical response in patients with schizophrenia. Seventy-eight inpatients with a diagnosis of schizophrenia (according to DSM-III-R) were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol after a 2-week washout period, using a randomized, double-blind design. Clinical efficacy was determined using the positive and negative syndrome scale (PANSS). Their serum PRL was assayed by means of radioimmunometric assay (RIA) between pre-treatment and post-treatment, and compared with 30 sex-matched and age-matched normal subjects. Both risperidone and haloperidol treatment significantly increased serum PRL levels in drug-free chronic schizophrenia patients (both P<0.001). Hyperprolactinemia induced by risperidone 6 mg/kg was comparable to levels produced by haloperidol 20 mg/day. Considering dose-adjusted serum PRL levels, risperidone treatment induced a significant elevation of PRL levels compared with haloperidol treatment at the haloperidol equivalent (P<0.001). Change in PRL levels at pre-treatment and post-treatment were related to positive symptom improvement seen in the risperidone group (r=0.51, P=0.016), but not in the haloperidol group (P>0.05). Female patients showed both a higher baseline and post-treatment PRL level and a greater increase in PRL than men (all P<0.05). Risperidone is associated with a robust effect on prolactin secretion in contrast to the conventional antipsychotic haloperidol. Prolactin monitoring during risperidone treatment should be performed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 42 | Psychopharmacology (Berl.) 2005 Feb 178: 35-40 |
| PMID | 15289996 |
| Title | Prolactin levels in male schizophrenic patients treated with risperidone and haloperidol: a double-blind and randomized study. |
| Abstract | There are few data from systematic, double-blind clinical trials that have compared the effect of the typical and the atypical antipsychotics on serum prolactin (PRL) levels in patients with schizophrenia. The goal of this study was to compare the effect of risperidone and haloperidol on serum PRL and investigate the relationship between serum PRL levels and clinical response in patients with schizophrenia. Seventy-eight inpatients with a diagnosis of schizophrenia (according to DSM-III-R) were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol after a 2-week washout period, using a randomized, double-blind design. Clinical efficacy was determined using the positive and negative syndrome scale (PANSS). Their serum PRL was assayed by means of radioimmunometric assay (RIA) between pre-treatment and post-treatment, and compared with 30 sex-matched and age-matched normal subjects. Both risperidone and haloperidol treatment significantly increased serum PRL levels in drug-free chronic schizophrenia patients (both P<0.001). Hyperprolactinemia induced by risperidone 6 mg/kg was comparable to levels produced by haloperidol 20 mg/day. Considering dose-adjusted serum PRL levels, risperidone treatment induced a significant elevation of PRL levels compared with haloperidol treatment at the haloperidol equivalent (P<0.001). Change in PRL levels at pre-treatment and post-treatment were related to positive symptom improvement seen in the risperidone group (r=0.51, P=0.016), but not in the haloperidol group (P>0.05). Female patients showed both a higher baseline and post-treatment PRL level and a greater increase in PRL than men (all P<0.05). Risperidone is associated with a robust effect on prolactin secretion in contrast to the conventional antipsychotic haloperidol. Prolactin monitoring during risperidone treatment should be performed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 43 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2007 Mar 31: 399-402 |
| PMID | 17126974 |
| Title | The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: a double blind study. |
| Abstract | Pharmacotherapy of schizophrenia is associated with the stressful side effects. Muscle rigidity causes distress, discomfort and poor compliance. The aim of the study was to determine the relationship between plasma hormones (cortisol and prolactin/PRL) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine. In a randomized, double-blind 22-weeks study, 12 patients were treated with olanzapine (5-20 mg/day) and 10 patients received fluphenazine (6-21 mg/day). Treatment with olanzapine moderately decreased, while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity. The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine, respectively. The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 44 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2007 Mar 31: 399-402 |
| PMID | 17126974 |
| Title | The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: a double blind study. |
| Abstract | Pharmacotherapy of schizophrenia is associated with the stressful side effects. Muscle rigidity causes distress, discomfort and poor compliance. The aim of the study was to determine the relationship between plasma hormones (cortisol and prolactin/PRL) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine. In a randomized, double-blind 22-weeks study, 12 patients were treated with olanzapine (5-20 mg/day) and 10 patients received fluphenazine (6-21 mg/day). Treatment with olanzapine moderately decreased, while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity. The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine, respectively. The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 45 | Neuropharmacology 2008 Sep 55: 577-83 |
| PMID | 18616955 |
| Title | Role of metabotropic glutamate receptors in the control of neuroendocrine function. |
| Abstract | Glutamate exerts its effects through binding and activation of two classes of specific receptors: ionotropic (iGluRs) and metabotropic (mGluRs). Group I mGluR includes mGluR1 and mGluR5 subtypes, group II includes mGluR2 and mGluR3 subtypes and group III includes the subtypes mGluR 4, 6, 7 and 8. Glutamate and its receptors are found in all key hypothalamic areas critically involved in reproduction and neuroendocrine function. To date, considerable data support an important role for iGluRs in the control of neuroendocrine function; however, the role of mGluRs as regulators of hypothalamic-pituitary function has not been clearly elucidated. mGluRs could be exerting a fine tune on the release of hypothalamic factors that regulate hormone release such as Substance P, GABA, alpha-MSH and CRH. Group II mGluR exert a direct inhibitory effect on anterior pituitary prolactin and GH secretion. Moreover, some group II mGluR agonists, like LY 354,740 and LY 379,268, can modulate PRL secretion from the anterior pituitary through their actions as dopamine receptor agonists. Evidence suggests a role for group III mGluR subtypes in stress-related behavioral disorders. Several reports indicate that selective ligands for mGluR subtypes have potential for the treatment of a wide variety of neurological and psychiatric disorders, including depression, anxiety disorders, schizophrenia, epilepsy and Alzheimer's disease among others. Since converging lines of evidence suggest a role for mGluRs subtypes in neuroendocrine regulation of hormone secretion, mGluRs neuroendocrine actions must be taken in consideration to insure proper treatment of these diseases. Moreover, discovery of selective agonists provides an opportunity to investigate the physiological role of mGluR subtypes and to directly test the neuroendocrine actions of mGluRs. Finally, mGluRs selective agonists may have an impact in the treatment of conditions involving chronic stress, such as depression and anxiety disorders, since they regulate neuroendocrine stress circuits involving the HPA axis and stress-sensitive hormones such as oxytocin and prolactin. This review aims to provide a survey of our current understanding of the effects of mGluR activation on neuroendocrine function. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 46 | J Clin Psychiatry 2008 Mar 69: 385-91 |
| PMID | 18278991 |
| Title | Antipsychotic-induced hyperprolactinemia inhibits the hypothalamo-pituitary-gonadal axis and reduces bone mineral density in male patients with schizophrenia. |
| Abstract | An inhibitory effect of hyperprolactinemia on the hypothalamo-pituitary-gonadal axis has been suggested as a mechanism of bone loss in schizophrenia, but this has not been confirmed. In this study, which was conducted in Tokyo, Japan, from February to May 2005, we examined the possible causes of reduced bone mineral density (BMD) in male patients with schizophrenia. The BMD of the radius of 74 male patients (aged 31-78 years) who met the diagnostic criteria for DSM-IV schizophrenia was measured by dual-energy x-ray absorptiometry. Levels of prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, and 1,25-dihydroxy vitamin D (VitD) were also measured. Pedometers were used to measure the impact of exercise. Study subjects showed lower BMD in all age groups compared with reference values in healthy persons. There was no significant difference in the Z score among low, medium, and high exercise groups. 87% of the subjects had hyperprolactinemia, and VitD levels were normal in all subjects except 1. The high PRL group had lower levels of FSH and LH, and significantly lower levels of estradiol (p < .05), compared with the normal PRL group. In the high PRL group, there was a significant negative correlation between the duration of treatment and the Z score (p < .05). Male patients with schizophrenia had lower BMD than normal individuals irrespective of the amount of exercise or the level of VitD. The results support the hypothesis that inhibition of the hypothalamo-pituitary-gonadal axis by hyperprolactinemia contributes to the mechanism of the bone loss and suggest that the longer the duration of hyperprolactinemia, the greater the reduction in BMD. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 47 | J Clin Psychopharmacol 2008 Jun 28: 264-370 |
| PMID | 18480682 |
| Title | A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia. |
| Abstract | Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD) with bromocriptine (BMT), a dopamine agonist widely used for PRL-secreting disorders, in the treatment of risperidone-induced hyperprolactinemia. Twenty schizophrenic women who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 mug/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment with PGD (45 g/d) followed by BMT (5 mg/d) or BMT followed by PGD at the same doses for 4 weeks each, with an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients during PGD treatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 48 | J Clin Psychopharmacol 2008 Jun 28: 264-370 |
| PMID | 18480682 |
| Title | A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia. |
| Abstract | Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD) with bromocriptine (BMT), a dopamine agonist widely used for PRL-secreting disorders, in the treatment of risperidone-induced hyperprolactinemia. Twenty schizophrenic women who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 mug/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment with PGD (45 g/d) followed by BMT (5 mg/d) or BMT followed by PGD at the same doses for 4 weeks each, with an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients during PGD treatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 49 | Eur Neuropsychopharmacol 2008 Sep 18: 667-72 |
| PMID | 18539008 |
| Title | Increased incidence of autoimmune thyroiditis in patients with antipsychotic-induced hyperprolactinemia. |
| Abstract | Prolactin (PRL) elevation in patients with prolactin-secreting pituitary tumors has been linked to increased prevalence of thyroid autoantibodies. However, the effects of antipsychotic drug-induced hyperprolactinemia (HPRL) on development of thyroid autoimmunity and also of other autoimmune phenomena have not been previously studied. To examine whether serum PRL levels were associated with the prevalence of thyroid autoantibodies in patients with schizophrenia receiving long-term antipsychotic treatment, we determined serum PRL, thyrotropin, free thyroxine levels, and the presence of antithyroid peroxidase and antithyroglobulin antibodies in 75 consecutive, clinically stable schizophrenic outpatients who had been on stable doses of antipsychotics for at least 3 months, and had no history of overt thyroid disease. We found that the prevalence of hyperprolactinemia was significantly higher in patients positive for thyroid autoantibodies, when compared with patients negative for them (p=0.045). Serum levels of prolactin were also significantly higher in patients with positivity for thyroid autoantibodies (p=0.039). In separate analyses for genders, a trend-level relationship was observed in females between increased levels of prolactin and the presence of thyroid autoantibodies (p=0.060). Our findings suggest that through the associated HPRL, long-term antipsychotic treatment can induce thyroid autoimmunity. Future research is required to investigate, whether other autoimmune processes might be triggered by antipsychotic drug-induced HPRL, and to what extent the immune alterations reported in patients with schizophrenia are related with this phenomenon. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 50 | Eur Neuropsychopharmacol 2008 Sep 18: 667-72 |
| PMID | 18539008 |
| Title | Increased incidence of autoimmune thyroiditis in patients with antipsychotic-induced hyperprolactinemia. |
| Abstract | Prolactin (PRL) elevation in patients with prolactin-secreting pituitary tumors has been linked to increased prevalence of thyroid autoantibodies. However, the effects of antipsychotic drug-induced hyperprolactinemia (HPRL) on development of thyroid autoimmunity and also of other autoimmune phenomena have not been previously studied. To examine whether serum PRL levels were associated with the prevalence of thyroid autoantibodies in patients with schizophrenia receiving long-term antipsychotic treatment, we determined serum PRL, thyrotropin, free thyroxine levels, and the presence of antithyroid peroxidase and antithyroglobulin antibodies in 75 consecutive, clinically stable schizophrenic outpatients who had been on stable doses of antipsychotics for at least 3 months, and had no history of overt thyroid disease. We found that the prevalence of hyperprolactinemia was significantly higher in patients positive for thyroid autoantibodies, when compared with patients negative for them (p=0.045). Serum levels of prolactin were also significantly higher in patients with positivity for thyroid autoantibodies (p=0.039). In separate analyses for genders, a trend-level relationship was observed in females between increased levels of prolactin and the presence of thyroid autoantibodies (p=0.060). Our findings suggest that through the associated HPRL, long-term antipsychotic treatment can induce thyroid autoimmunity. Future research is required to investigate, whether other autoimmune processes might be triggered by antipsychotic drug-induced HPRL, and to what extent the immune alterations reported in patients with schizophrenia are related with this phenomenon. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 51 | J Neural Transm (Vienna) 2008 Aug 115: 1189-98 |
| PMID | 18506387 |
| Title | Induction of tolerance of dopaminergic responses in man. |
| Abstract | schizophrenia may reflect a sensitization of dopaminergic (DA) function. Apomorphine (Apo), a DA receptor agonist, induces both sensitization and tolerance of DA function in rodents depending on dose intervals. We investigated sensitization and tolerance to Apo in healthy male volunteers. After a period of acclimatization to the experimental setting (Day 1) subjects were assigned randomly to two groups: Group A subjects received seven injections of placebo (physiological saline) (PLA) and Group B subjects received seven injections of Apo HCl (7 microg/kg sc) under double-blind conditions at 2 h intervals commencing at 0930 hours (Day 2) after an overnight fast. Twelve hours after the seventh injection, i.e. on Day 3, after an overnight fast all subjects received an injection of Apo. Serial samples of blood commencing at 0900 hours were drawn after the first and last injection in both groups for assay of growth hormone (GH), prolactin (PRL) and cortisol by radioimmunoassay; sleepiness was measured using the Analog Sleepiness Rating Scale and yawning recorded by video recorder. The GH response in Group B (N = 8) was (a) decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.03) and (b) decreased after the eighth injection of Apo compared with the first injection of Apo in Group A (N = 10) (P = 0.001). The number of yawns in Group B was significantly decreased after the eighth injection of Apo compared with the first injection of Apo (P = 0.042). PRL, cortisol and sleepiness were not significantly different between the first and eighth injection of Apo. Sensitization was not observed in any of the measures studied. These results are compatible with induction of acute tolerance of DA-mediated GH and yawning responses. The method used provides a safe pharmacological paradigm to examine plasticity of DA mechanisms in man. Results are discussed in the context of possible therapeutic implications for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 52 | Brain Behav. Immun. 2009 May 23: 518-26 |
| PMID | 19486644 |
| Title | Time-dependent alterations of peripheral immune parameters after nigrostriatal dopamine depletion in a rat model of Parkinson's disease. |
| Abstract | Dysfunction of the central dopaminergic system is associated with neurodegenerative disorders and mental illnesses such as Parkinson's disease and schizophrenia. Patients suffering from these diseases were reported to exhibit altered immune functions compared to healthy subjects and imbalance of the central dopaminergic system has been suggested as one causative factor for the immune disturbances. However, it is unclear whether the observed immune changes are primary or secondary to the disease. Here we demonstrate that central dopamine (DA) depletion in a rat model of Parkinson's disease induced transient changes in blood leukocyte distribution and cytokine production that were apparent until four weeks after bilateral intrastriatal administration of the neurotoxin 6-hydroxydopamine (6-OHDA). Eight weeks after treatment, no differences in blood immune parameters were anymore evident between neurotoxin-treated and control animals. Nevertheless, animals with a widespread damage of dopaminergic neurons in the nigrostriatal system showed an exacerbated pro-inflammatory response following in vivo challenge with bacterial lipopolysaccharide. Our data indicate that peripheral immune perturbations in the early phase after intrastriatal 6-OHDA administration might have been related to the neurodegenerative process itself whereas the increased sensitivity to the inflammatory stimulus seems to have resulted from an impaired dopaminergic control of prolactin (PRL) and corticosterone (CORT) secretion. The findings demonstrate that the brain dopaminergic system is involved in peripheral immune regulation and suggest that central dopaminergic hypoactivity bears the risk of excessive inflammation, e.g., during infection or tissue injury. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 53 | Hum Psychopharmacol 2009 Jan 24: 49-54 |
| PMID | 19016257 |
| Title | Ultrasound bone mass in schizophrenic patients on antipsychotic therapy. |
| Abstract | To determine bone mass using quantitative phalangeal bone ultrasound in institutionalized schizophrenic patients under chronic treatment with antipsychotic drugs. A total of 73 patients with schizophrenia (25 women, mean age 59.84 +/- 17.01 years; 48 men, mean age 61.89 +/- 12.95 years) and 73 healthy subjects (25 women, mean age 60.37 +/- 17.16 years; 48 men, mean age 61.24 +/- 13.09 years) participated in the study. Bone status was assessed using an ultrasound device that measures the amplitude-dependent speed of sound (Ad-SoS) in metres per second. Measurements were made on the phalanges (II-V) of the non-dominant hand, and the mean value was computed. The schizophrenic women had higher levels of prolactin (PRL), parathyroid hormone (PTH), alkaline phosphatase (AlPh), and tartrate-resistant acid phosphatase (TRAP) (all p < 0.0001), and lower 25-hydroxyvitamin D(25(OH)D3) levels (p < 0.0001) and Ad-SoS values (p < 0.05) than controls. Ad-SoS was higher in schizophrenic men (p < 0.05). schizophrenic women in treatment with antipsychotic drugs had a loss of phalangeal bone mass that was associated with the levels of vitamin D or PTH, and increased bone turnover. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 54 | Hum Psychopharmacol 2009 Jan 24: 49-54 |
| PMID | 19016257 |
| Title | Ultrasound bone mass in schizophrenic patients on antipsychotic therapy. |
| Abstract | To determine bone mass using quantitative phalangeal bone ultrasound in institutionalized schizophrenic patients under chronic treatment with antipsychotic drugs. A total of 73 patients with schizophrenia (25 women, mean age 59.84 +/- 17.01 years; 48 men, mean age 61.89 +/- 12.95 years) and 73 healthy subjects (25 women, mean age 60.37 +/- 17.16 years; 48 men, mean age 61.24 +/- 13.09 years) participated in the study. Bone status was assessed using an ultrasound device that measures the amplitude-dependent speed of sound (Ad-SoS) in metres per second. Measurements were made on the phalanges (II-V) of the non-dominant hand, and the mean value was computed. The schizophrenic women had higher levels of prolactin (PRL), parathyroid hormone (PTH), alkaline phosphatase (AlPh), and tartrate-resistant acid phosphatase (TRAP) (all p < 0.0001), and lower 25-hydroxyvitamin D(25(OH)D3) levels (p < 0.0001) and Ad-SoS values (p < 0.05) than controls. Ad-SoS was higher in schizophrenic men (p < 0.05). schizophrenic women in treatment with antipsychotic drugs had a loss of phalangeal bone mass that was associated with the levels of vitamin D or PTH, and increased bone turnover. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 55 | Hum Psychopharmacol 2009 Jul 24: 415-22 |
| PMID | 19551763 |
| Title | Melperone, an aytpical antipsychotic drug with clozapine-like effect on plasma prolactin: contrast with typical neuroleptics. |
| Abstract | To evaluate the effect of melperone, a butyrophenone with atypical antipsychotic properties, on plasma prolactin (PRL) concentrations compared with clozapine and typical neuroleptics. Analysis of pre- and post-treatment PRL levels collected prospectively per protocol in a non-randomized study of 26 melperone-, 76 clozapine-, and 66 neuroleptic-treated patients with schizophrenia or schizoaffective disorder. Cross-sectional analysis of a larger sample of patients with PRL data was also performed. For males, post-treatment PRL levels were significantly higher in the typical neuroleptic group compared with the melperone (p = 0.0001) and clozapine (p = 0.0001) groups, with no significant difference between clozapine and melperone. For females, post-treatment PRL levels were significantly higher in the melperone group as compared to the clozapine group (p = 0.004). There were too few typical neuroleptic-treated females to permit analysis of this sample. However, the cross-sectional analysis of PRL data confirmed the results for melperone- and clozapine-treated females, and showed higher PRL levels in typical neuroleptic-treated females as compared with those who received melperone and clozapine. Melperone did not significantly increase PRL levels in male patients. However, melperone and typical neuroleptics caused increase in PRL levels in females. Further study of melperone's effects on PRL concentration is warranted. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 56 | Psychoneuroendocrinology 2009 Jan 34: 129-39 |
| PMID | 18838228 |
| Title | Effect of risperidone and olanzapine on reproductive hormones, psychopathology and sexual functioning in male patients with schizophrenia. |
| Abstract | To study the effect of drugs on the hypothalamo-pituitary-gonadal (HPG) axis we compared the endocrine actions of two neuroleptics with different receptor affinity profiles-risperidone and olanzapine in male schizophrenic patients. We investigated the levels of prolactin, estradiol, testosterone, LH, FSH and testicular peptide hormone-inhibin B, and we assessed psychopathology (PANSS), sexual function (ASEX) and treatment adherence (DAI-10) in 89 male schizophrenic inpatients treated with olanzapine or risperidone administered orally. The initial and final evaluations were carried out at weeks 3 and 8 after the onset of treatment, respectively. At initial evaluation the mean serum prolactin and inhibin B levels were markedly higher, whereas testosterone level was lower in patients treated with risperidone, than in those treated with olanzapine. In 5 out of 50 subjects from risperidone group (10%) and in 1 from olanzapine group (2.6%) testosterone levels were below the lower limit (<241ng/ml), which reflected Leydig's cell impairment. In one patient receiving risperidone and in three receiving olanzapine, inhibin B level was below 80pg/ml, indicating Sertoli's cell dysfunction. At the final evaluation the mean serum prolactin level was markedly higher in patients taking risperidone, whereas their FSH levels were lower than in patients receiving olanzapine. In all investigated groups, except for the risperidone-hyperprolactinemic group inhibin B levels were negatively correlated with serum FSH. The mean LH, FSH, testosterone and estradiol levels were within the normal reference range at initial and final evaluation. The non-adherence to medications and ASEX scores were significantly higher in risperidone groups. Sexual dysfunction and medication non-adherence was not related to prolactin or gonadal hormone levels. Risperidone elicited higher PRL elevation than olanzapine. Treatment with this medication can be associated with disturbances in reproductive hormones (testosterone) and gonadotropins (FSH). The cause of olanzapine-elicited reduction of inhibin B level and the lack of negative correlation between FSH and inhibin B in patients with risperidone-induced hyperprolactinemia require further investigation. Patients receiving risperidone showed higher level of sexual dysfunction and treatment non-adherence than those treated with olanzapine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 57 | Psychoneuroendocrinology 2009 Jan 34: 129-39 |
| PMID | 18838228 |
| Title | Effect of risperidone and olanzapine on reproductive hormones, psychopathology and sexual functioning in male patients with schizophrenia. |
| Abstract | To study the effect of drugs on the hypothalamo-pituitary-gonadal (HPG) axis we compared the endocrine actions of two neuroleptics with different receptor affinity profiles-risperidone and olanzapine in male schizophrenic patients. We investigated the levels of prolactin, estradiol, testosterone, LH, FSH and testicular peptide hormone-inhibin B, and we assessed psychopathology (PANSS), sexual function (ASEX) and treatment adherence (DAI-10) in 89 male schizophrenic inpatients treated with olanzapine or risperidone administered orally. The initial and final evaluations were carried out at weeks 3 and 8 after the onset of treatment, respectively. At initial evaluation the mean serum prolactin and inhibin B levels were markedly higher, whereas testosterone level was lower in patients treated with risperidone, than in those treated with olanzapine. In 5 out of 50 subjects from risperidone group (10%) and in 1 from olanzapine group (2.6%) testosterone levels were below the lower limit (<241ng/ml), which reflected Leydig's cell impairment. In one patient receiving risperidone and in three receiving olanzapine, inhibin B level was below 80pg/ml, indicating Sertoli's cell dysfunction. At the final evaluation the mean serum prolactin level was markedly higher in patients taking risperidone, whereas their FSH levels were lower than in patients receiving olanzapine. In all investigated groups, except for the risperidone-hyperprolactinemic group inhibin B levels were negatively correlated with serum FSH. The mean LH, FSH, testosterone and estradiol levels were within the normal reference range at initial and final evaluation. The non-adherence to medications and ASEX scores were significantly higher in risperidone groups. Sexual dysfunction and medication non-adherence was not related to prolactin or gonadal hormone levels. Risperidone elicited higher PRL elevation than olanzapine. Treatment with this medication can be associated with disturbances in reproductive hormones (testosterone) and gonadotropins (FSH). The cause of olanzapine-elicited reduction of inhibin B level and the lack of negative correlation between FSH and inhibin B in patients with risperidone-induced hyperprolactinemia require further investigation. Patients receiving risperidone showed higher level of sexual dysfunction and treatment non-adherence than those treated with olanzapine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 58 | Expert Opin Drug Metab Toxicol 2010 Jan 6: 43-53 |
| PMID | 19929252 |
| Title | Pharmacogenetics of D2 dopamine receptor gene in prolactin-secreting pituitary adenomas. |
| Abstract | Dopamine-agonists are the treatment of choice of prolactin-secreting pituitary adenomas (PRL-omas). Their actions on D2 dopamine receptor (DRD2) and the clinical outcome may be affected by polymorphisms. PRL-omas are well-differentiated endocrine tumors expressing DRD2. The dopamine-agonist cabergoline (CB), normalizes prolactin and reduces tumor size in about 80 - 90% of patients. DRD2 polymorphisms correlate with neuropsychiatric disorders, in particular alcoholism and schizophrenia. This review describes the DRD2 polymorphisms, their functional effects, and their impact on susceptibility and response to dopamine-agonists treatment. Searching PubMed database for pertinent articles we found that some DRD2 polymorphisms, particularly TaqIA, TaqIB and NcoI, are associated with different receptor binding in brain areas. One study carried out in patients with PRL-omas found a correlation between NcoI and TaqIA and resistance to CB. In particular, resistant patients had higher prevalence of NcoI-T allele than the responsive patients, while the commonest haplotype (having TaqIA2 allele) was associated with better response. This review deals with the connection between DRD2 polymorphisms and PRL-oma treatment and suggests hypotheses for further studies. Only one study was carried out to analyze the role of DRD2 polymorphisms in PRLomas response to CB. Further studies, including pituitary and hypothalamus in vivo determination of DRD2 binding according to DRD2 genotypes, investigation of possible post-receptorial mechanisms involved, as well as population studies in collaboration with psychiatrists and neurologists, are needed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 59 | Hum Psychopharmacol 2011 Aug 26: 440-3 |
| PMID | 21823168 |
| Title | Dose-dependent effects of olanzapine on QT intervals and plasma prolactin levels in Japanese patients with stable schizophrenia. |
| Abstract | There have been few reports regarding olanzapine (OLZ)-related QT prolongation and hyperprolactinemia. This study evaluated the dose-dependent effect of OLZ on QT interval and plasma prolactin (PRL) level in a single sample of patients with schizophrenia. Twenty-six subjects treated with varying starting doses of OLZ were enrolled in the study. Following baseline assessments, which included completion of the Brief Psychiatric Rating Scale (BPRS), measurements of Body Mass Index (BMI), QT interval, electrolytes, fasting plasma glucose, PRL, hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL), the dose of OLZ was increased for each subject. The same parameters were evaluated following the increased dose treatment. A significant decrease was observed in BPRS score (p = 0.01) following treatment with an increased dose of OLZ. Significant increases were observed in BMI (p = 0.032), QTc (p = 0.031), and plasma PRL level (p = 0.028). The mean values of electrolytes, fasting plasma glucose, HbA1c, TC, TG, HDL and LDL treatment were unchanged by the switch to increased-dose OLZ treatment. We have demonstrated the dose-dependent effect of OLZ on the QT interval and the plasma PRL level of patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 60 | J. Neurosci. Methods 2011 Nov 202: 199-208 |
| PMID | 21896284 |
| Title | Tonic and phasic release of glutamate and acetylcholine neurotransmission in sub-regions of the rat prefrontal cortex using enzyme-based microelectrode arrays. |
| Abstract | The medial prefrontal cortex (mPFC) is an area of the brain critical for higher cognitive processes and implicated in disorders of the CNS such as drug addiction, depression and schizophrenia. Glutamate and acetylcholine are neurotransmitters that are essential for cortical functioning, yet little is known about the dynamic function of these neurotransmitters in subregions of the mPFC. In these studies we used a novel microelectrode array technology to measure resting levels (tonic release) of glutamate and acetylcholine as well as KCl-evoked release (stimulated phasic release) in the mPFC of the anesthetized rat to further our understanding of both tonic and phasic neurotransmission in the cingulate cortex, prelimbic cortex, and infralimbic cortex of the mPFC. Studies revealed homogeneity of tonic and phasic signaling among brain subregions for each neurotransmitter. However, resting levels of glutamate were significantly higher as compared to acetylcholine levels in all subregions. Additionally, KCl-evoked acetylcholine release in the cingulate cortex (7.1 ?M) was significantly greater than KCl-evoked glutamate release in any of the three subregions (Cg1, 2.9 ?M; PRL, 2.0 ?M; IL, 1.8 ?M). Interestingly, the time for signal decay following KCl-evoked acetylcholine release was significantly longer by an average of 240% as compared to KCL-evoked glutamate release for all three brain subregions. Finally, we observed a negative relationship between acetylcholine resting levels and KCl-evoked release in the Cg1. These data suggest a homogenous distribution of both glutamatergic and acetylcholinergic innervation in the mPFC, with alterations in tonic and phasic release regulation accounting for differences between these neurotransmitters. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 61 | Neuro Endocrinol. Lett. 2011 -1 32: 428-36 |
| PMID | 21876517 |
| Title | Effect of antipsychotic-induced hyperprolactinemia on anthropometric measures, insulin sensitivity and lipid profile in patients with schizophrenia or related psychoses. |
| Abstract | This study consisting of two subprojects was undertaken to evaluate the effects of hyperprolactinemia on cardiovascular disease (CVD) risk parameters such as anthropometric measures, insulin sensitivity and blood lipids in patients with schizophrenia or related psychoses on long term treatment with antipsychotics. In subproject ?, 45 patients receiving the 2nd generation antipsychotics risperidone, clozapine or olanzapine were compared regarding prolactin (PRL), body mass index (BMI), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood lipids. In subproject ?, 24 patients receiving 1st or 2nd generation antipsychotics were investigated with diurnal profile of PRL and oral glucose tolerance test (OGTT). Elevated PRL levels were found in about 45% of the patients and occurred more often in patients receiving risperidone or haloperidol, compared to patients receiving clozapine or olanzapine. In contrast, in subproject ?, insulin and HOMA-IR were higher and high density lipoprotein cholesterol was lower in patients receiving clozapine or olanzapine, compared with patients receiving risperidone. However, PRL levels did not correlate to BMI, insulin, HOMA-IR or lipids in any of these three treatment groups. In subproject ?, OGTT showed impaired glucose tolerance in 25% and new-onset diabetes in 4% of the 24 patients investigated. Additionally, the PRL (median 24 h) levels correlated positively to the 2 h glucose level at OGTT (rs=0.42, p=0.04). Our findings point to that hyperprolactinemia due to 1st and 2nd generation antipsychotics may decrease insulin sensitivity, whereas other mechanisms probably underlie insulin resistance induced by PRL-sparing antipsychotics such as clozapine and olanzapine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 62 | Hum Psychopharmacol 2011 Jan 26: 21-7 |
| PMID | 21305610 |
| Title | Prolactin as a biomarker for treatment response and tardive dyskinesia in schizophrenia subjects: old thoughts revisited from a genetic perspective. |
| Abstract | Previous studies investigated whether prolactin (PRL) serum level was a biomarker of antipsychotic response, schizophrenia symptomatology, and tardive dyskinesia. Most of the findings support that antipsychotic drugs modulate PRL levels but PRL is not a steady indicator. Recent results suggest a genetic effect of PRL and PRL receptor (PRLR) polymorphisms in PRL levels indicating that independently of antipsychotic therapy subjects could have altered PRL levels due to their genetic background.We evaluated whether PRL and PRLR variants were associated with treatment outcome and tardive dyskinesia. We observed no association of PRL/PRLR polymorphism with treatment response (best genotypic results include PRL rs849885 and PRLR rs4703509 permuted p=0.326). Regarding tardive dyskinesia, the major allele of PRL rs37364 was nominally associated with risk for tardive dyskinesia in the European ancestry sub-sample (permuted p=0.183). Although we reported no significant associations, it is definitely worthy of investigation to see if together (genetic variants in the PRL system and PRL serum measures) could be a reliable biomarker for antipsychotic response and TD prevalence. Our results suggest that more studies in this context are required to shed light in the molecular mechanisms underlying antipsychotic response and tardive dyskinesia occurrence. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 63 | J. Chem. Neuroanat. 2013 Sep 52: 20-4 |
| PMID | 23660497 |
| Title | Deep brain stimulation of the mediodorsal thalamic nucleus yields increases in the expression of zif-268 but not c-fos in the frontal cortex. |
| Abstract | This study explores the regions activated by deep brain stimulation of the mediodorsal thalamic nucleus through examination of immediate early genes as markers of neuronal activation. Stimulation was delivered unilaterally with constant current 100 ?s duration pulses at a frequency of 130 Hz delivered at an amplitude of 200 ?A for 3h. Brains were removed, sectioned and radio-labelled for the IEGs zif-268 and c-fos. In anaesthetised rats, deep brain stimulation of mediodorsal thalamic nucleus produced robust increases in the expression of zif-268 but not c-fos localised to regions that are reciprocally connected with the mediodorsal thalamic nucleus, including the prelimbic and orbitofrontal cortices, and the premotor cortex indicating an increase in synaptic activity in these regions. These findings map those brain regions that are persistently, rather than transiently, activated by high frequency electrical stimulation of the mediodorsal thalamic nucleus by a putatively antidromic mechanism which may be relevant to neuropsychiatric disorders such as schizophrenia in which thalamocortical systems are disrupted and in which DBS protocols are being considered. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 64 | Exp Clin Psychopharmacol 2013 Aug 21: 332-41 |
| PMID | 23834553 |
| Title | Effects of cabergoline on hyperprolactinemia, psychopathology, and sexual functioning in schizophrenic patients. |
| Abstract | Antipsychotic medications are associated to different degrees with sexual dysfunction mainly through their potential to induce hyperprolactinemia. Prolactin (PRL) secretion is mainly regulated by the hypothalamic dopaminergic systems. We conducted this 6-month, parallel-group study to prospectively investigate the effects of the dopamine agonist cabergoline on sexual dysfunction in clinically stable patients with schizophrenia (DSM-IV, AP 194) and hyperprolactinemia (PRL > 20 ng/ml for men and PRL > 25 ng/ml for women). In total 80 patients were enrolled; 33 were receiving risperidone, 17 haloperidol, 11 amisulpride, and 8 risperidone microspheres long acting. Based on PRL levels (< 50, 50-99, or > 100 ng/ml), patients were assigned in 3 cabergoline doses (0.25, 0.5, and 1 mg/day in 38, 23, and 19 patients, respectively). The psychopathology was evaluated using the Positive and Negative Syndrom Scale (PANSS), and sexual dysfunction was evaluated using the Arizona Sexual Experiences Scale (ASEX). PRL levels were reduced in all patients, from 73.3 (± 46.8) to 42.0 (± 27.8) at Month 3 and 27.1 (± 20.4) at Month 6 (p < .001). ASEX scores declined from 19.1 (± 5.1) to 17.6 (± 5.5) at Month 3 and 15.0 (± 6.5) at Month 6 (p < .001). PANSS scores were reduced in the third and in the sixth month (p = .001 at 6 month vs. baseline). The decrease in PRL was not statistically different between groups. Our data suggest that cabergoline administration to clinically stable patients with schizophrenia may improve sexual functioning without adversely affecting their psychopathologic status, provided that the dose has been suited to the severity of the hyperprolactinemia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 65 | Exp Clin Psychopharmacol 2013 Aug 21: 332-41 |
| PMID | 23834553 |
| Title | Effects of cabergoline on hyperprolactinemia, psychopathology, and sexual functioning in schizophrenic patients. |
| Abstract | Antipsychotic medications are associated to different degrees with sexual dysfunction mainly through their potential to induce hyperprolactinemia. Prolactin (PRL) secretion is mainly regulated by the hypothalamic dopaminergic systems. We conducted this 6-month, parallel-group study to prospectively investigate the effects of the dopamine agonist cabergoline on sexual dysfunction in clinically stable patients with schizophrenia (DSM-IV, AP 194) and hyperprolactinemia (PRL > 20 ng/ml for men and PRL > 25 ng/ml for women). In total 80 patients were enrolled; 33 were receiving risperidone, 17 haloperidol, 11 amisulpride, and 8 risperidone microspheres long acting. Based on PRL levels (< 50, 50-99, or > 100 ng/ml), patients were assigned in 3 cabergoline doses (0.25, 0.5, and 1 mg/day in 38, 23, and 19 patients, respectively). The psychopathology was evaluated using the Positive and Negative Syndrom Scale (PANSS), and sexual dysfunction was evaluated using the Arizona Sexual Experiences Scale (ASEX). PRL levels were reduced in all patients, from 73.3 (± 46.8) to 42.0 (± 27.8) at Month 3 and 27.1 (± 20.4) at Month 6 (p < .001). ASEX scores declined from 19.1 (± 5.1) to 17.6 (± 5.5) at Month 3 and 15.0 (± 6.5) at Month 6 (p < .001). PANSS scores were reduced in the third and in the sixth month (p = .001 at 6 month vs. baseline). The decrease in PRL was not statistically different between groups. Our data suggest that cabergoline administration to clinically stable patients with schizophrenia may improve sexual functioning without adversely affecting their psychopathologic status, provided that the dose has been suited to the severity of the hyperprolactinemia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 66 | PLoS ONE 2013 -1 8: e57257 |
| PMID | 23468948 |
| Title | The roles of reward, default, and executive control networks in set-shifting impairments in schizophrenia. |
| Abstract | Patients with schizophrenia (SZ) show deficits on tasks of rapid reinforcement learning, like probabilistic reversal learning (PRL), but the neural bases for those impairments are not known. Recent evidence of relatively intact sensitivity to negative outcomes in the ventral striatum (VS) in many SZ patients suggests that PRL deficits may be largely attributable to processes downstream from feedback processing, involving both the activation of executive control task regions and deactivation of default mode network (DMN) components. We analyzed data from 29 chronic SZ patients and 21 matched normal controls (NCs) performing a PRL task in an MRI scanner. Subjects were presented with eight pairs of fractal stimuli, for 50 trials each. For each pair, subjects learned to choose the more frequently-rewarded (better) stimulus. Each time a criterion was reached, the better stimulus became the worse one, and the worse became the better. Responses to feedback events were assessed through whole-brain and regions-of-interest (ROI) analyses in DMN. We also assessed correlations between BOLD signal contrasts and clinical measures in SZs. Relative to NCs, SZ patients showed comparable deactivation of VS in response to negative feedback, but reduced deactivation of DMN components including medial prefrontal cortex (mPFC). The magnitudes of patients' punishment-evoked deactivations in VS and ventromedial PFC correlated significantly with clinical ratings for avolition/anhedonia. These findings suggest that schizophrenia is associated with a reduced ability to deactivate components of default mode networks, following the presentation of informative feedback and that motivational deficits in SZ relate closely to feedback-evoked activity in reward circuit components. These results also confirm a role for ventrolateral and dorsomedial PFC in the execution of response-set shifts. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 67 | Schizophr. Res. 2013 Apr 145: 116-9 |
| PMID | 23375624 |
| Title | Differences in plasma prolactin levels in patients with schizophrenia treated on monotherapy with five second-generation antipsychotics. |
| Abstract | Although second-generation antipsychotics (SGAs) are characterized by fewer prolactin (PRL)-related side effects compared with first-generation antipsychotics, the detailed effects of SGAs on the plasma PRL levels still remain unclear. We examined the differences in plasma PRL levels among 268 patients treated for schizophrenia with olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), quetiapine (QTP), or perospirone (PER). The participants had received antipsychotic monotherapy with stable doses of OLZ, RIS, ARP, QTP, or PER for ? 3 weeks, and fasting blood samples were drawn to examine plasma PRL levels. The differences in median plasma PRL levels in all (P<0.001), male (P<0.001) and female patients (P<0.001) among the five SGA groups were statistically significant. A stepwise multiple regression analysis showed that ARP treatment was found to contribute to lower plasma PRL level, while female sex, RIS, OLZ and chlorpromazine equivalent dose were found to contribute to a higher plasma PRL level. The median value of plasma PRL level in the RIS group was twice as much compared with that in the OLZ group, although this was not statistically significant. In this study, OLZ had a considerable effect on plasma PRL level, similar to RIS, while PER did not affect plasma PRL levels, similar to QTP. Further studies are needed to clarify the differences in plasma PRL levels among SGAs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 68 | World J. Biol. Psychiatry 2014 Sep 15: 546-52 |
| PMID | 24959913 |
| Title | Prolactin serum levels correlate with inflammatory status in drug-naïve first-episode schizophrenia. |
| Abstract | The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naïve, first-episode schizophrenia patients with normal weight. Patients with normal weight, drug-naïve, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1? (IL-1?), tumour necrosis factor-? (TNF-?) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Sixty patients with normal weight, drug-naïve, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1?, IL-6 and TNF-? compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1?, IL-6 and TNF-? within the schizophrenia group. Within the schizophrenia group, TNF-? was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration. Patients with normal weight, drug-naïve, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 69 | Hum Psychopharmacol 2014 Mar 29: 183-9 |
| PMID | 24738111 |
| Title | Effects of antipsychotics on bone mineral density and prolactin levels in patients with schizophrenia: a 12-month prospective study. |
| Abstract | Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia. One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole) was prescribed for 12 months as appropriate. BMD and PRL were tested before and after treatment. Same measures were conducted in 90 matched healthy controls. Baseline BMD of postero-anterior L1-L4 range from 1.04 ± 0.17 to 1.42 ± 1.23, and there was no significant difference between the patients group and healthy control group. However, post-treatment BMD values in patients (ranging from 1.02 ± 0.15 to 1.23 ± 0.10) were significantly lower than that in healthy controls (ranging from 1.15 ± 0.12 to 1.42 ± 1.36). The BMD values after conventional antipsychotics were significantly lower than that after atypical antipsychotics. The PRL level after conventional antipsychotics (53.05 ± 30.25 ng/ml) was significantly higher than that after atypical antipsychotics (32.81 ± 17.42 ng/ml). Conditioned relevance analysis revealed significant negative correlations between the PRL level and the BMD values after conventional antipsychotics. The increase of PRL might be an important risk factor leading to a high prevalence of osteoporosis in patients with schizophrenia on long-term conventional antipsychotic medication. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 70 | Expert Opin Drug Saf 2014 May 13: 605-24 |
| PMID | 24697217 |
| Title | Second-generation and newly approved antipsychotics, serum prolactin levels and sexual dysfunctions: a critical literature review. |
| Abstract | Using antipsychotic (AP) medication can increase prolactin (PRL) levels and place the patient at risk of sexual dysfunction (SD). The aim of this review is to describe the PRL propensity of the different second-generation and newly approved APs. It then considers the prevalence rates of SDs associated with these compounds in patients with schizophrenia and treatment strategies for the management of SDs and/or hyperprolactinemia (HPRL). Furthermore, we address the lingering question regarding the association between SDs and PRL. SD (particularly long-term) data remain scarce for several APs. A wide variety of assessment techniques used in SD research make reliable comparisons between APs impossible. The majority of these reports do not equally allow us to distinguish between treatment (AP and co-medication)-emergent SDs and illness-related SDs. This makes it difficult to assess the degree to which these side effects are associated with 'PRL-raising' APs, and what part of this fraction is directly reducible to serum PRL levels. Also, few evidence-based treatment strategies for HPRL and associated side effects are available. Therefore, longer-term randomized controlled trials, using reliable and valid structured interviews or questionnaires, are necessary to establish the precise relationship between APs, PRL levels and SDs rates and develop valuable treatment options. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 71 | CNS Drugs 2014 May 28: 421-53 |
| PMID | 24677189 |
| Title | The effects of novel and newly approved antipsychotics on serum prolactin levels: a comprehensive review. |
| Abstract | Since the 1970s, clinicians have increasingly become more familiar with hyperprolactinemia (HPRL) as a common adverse effect of antipsychotic medication, which remains the cornerstone of pharmacological treatment for patients with schizophrenia. Although treatment with second-generation antipsychotics (SGAs) as a group is, compared with use of the first-generation antipsychotics, associated with lower prolactin (PRL) plasma levels, the detailed effects on plasma PRL levels for each of these compounds in reports often remain incomplete or inaccurate. Moreover, at this moment, no review has been published about the effect of the newly approved antipsychotics asenapine, iloperidone and lurasidone on PRL levels. The objective of this review is to describe PRL physiology; PRL measurement; diagnosis, causes, consequences and mechanisms of HPRL; incidence figures of (new-onset) HPRL with SGAs and newly approved antipsychotics in adolescent and adult patients; and revisit lingering questions regarding this hormone. A literature search, using the MEDLINE database (1966-December 2013), was conducted to identify relevant publications to report on the state of the art of HPRL and to summarize the available evidence with respect to the propensity of the SGAs and the newly approved antipsychotics to elevate PRL levels. Our review shows that although HPRL usually is defined as a sustained level of PRL above the laboratory upper limit of normal, limit values show some degree of variability in clinical reports, making the interpretation and comparison of data across studies difficult. Moreover, many reports do not provide much or any data detailing the measurement of PRL. Although the highest rates of HPRL are consistently reported in association with amisulpride, risperidone and paliperidone, while aripiprazole and quetiapine have the most favorable profile with respect to this outcome, all SGAs can induce PRL elevations, especially at the beginning of treatment, and have the potential to cause new-onset HPRL. Considering the PRL-elevating propensity of the newly approved antipsychotics, evidence seems to indicate these agents have a PRL profile comparable to that of clozapine (asenapine and iloperidone), ziprasidone and olanzapine (lurasidone). PRL elevations with antipsychotic medication generally are dose dependant. However, antipsychotics having a high potential for PRL elevation (amisulpride, risperidone and paliperidone) can have a profound impact on PRL levels even at relatively low doses, while PRL levels with antipsychotics having a minimal effect on PRL, in most cases, can remain unchanged (quetiapine) or reduce (aripiprazole) over all dosages. Although tolerance and decreases in PRL values after long-term administration of PRL-elevating antipsychotics can occur, the elevations, in most cases, remain above the upper limit of normal. PRL profiles of antipsychotics in children and adolescents seem to be the same as in adults. The hyperprolactinemic effects of antipsychotic medication are mostly correlated with their affinity for dopamine D2 receptors at the level of the anterior pituitary lactotrophs (and probably other neurotransmitter mechanisms) and their blood-brain barrier penetrating capability. Even though antipsychotics are the most common cause of pharmacologically induced HPRL, recent research has shown that HPRL can be pre-existing in a substantial portion of antipsychotic-naïve patients with first-episode psychosis or at-risk mental state. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 72 | Neuro Endocrinol. Lett. 2014 -1 35: 50-7 |
| PMID | 24625910 |
| Title | Association between serum testosterone levels, body mass index (BMI) and insulin in male patients with schizophrenia treated with atypical antipsychotics--olanzapine or risperidone. |
| Abstract | A sufficient amount of testosterone (T) is essential for adequate sexual functioning but also for cognitive and psychological well-being. Most recent studies have demonstrated that higher BMI and other symptoms of metabolic syndrome are associated with alterations in sex steroid hormone concentrations. Although, neuroleptics are known to cause a significant and sustained weight excess, the relationships between body mass index and the level of testosterone in psychiatric patients have not been thoroughly studied. The main purpose of the present study was to examine the correlations between testosterone, estradiol BMI, and insulin in male patients diagnosed with schizophrenia and treated with olanzapine or risperidone. The study included 78 males diagnosed with schizophrenia according to the DSM-IV diagnostic classification hospitalized in psychiatric inpatient units (42 on risperidone and 36 on olanzapine). The initial and final evaluation of testosterone (T), estradiol, prolactin (PRL) and insulin serum levels were performed at week 3 and 8 after the onset of the new treatment, respectively. At week 3, the mean serum prolactin was markedly higher, whereas testosterone level was lower in risperidone patients compared to those treated with olanzapine. T level was negatively affected by the studied medication (risperidone), increased prolactin and a higher BMI. At week 8, the mean serum prolactin level was markedly higher in risperidone patients. Higher values of BMI and serum insulin were the most prominent factors independently associated with decreased plasma testosterone levels at that measurement point. Individual changes of T level between week 3 and 8 were positively correlated with the corresponding changes in estradiol levels. T serum levels appear to be independently linked with BMI, insulin and prolactin in both investigated neuroleptics. Further research is needed to elucidate the relationship between reproductive hormones and metabolic parameters in patients with schizophrenia under neuroleptic treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 73 | Psychiatry Investig 2015 Oct 12: 566-8 |
| PMID | 26508971 |
| Title | One-Year Follow-Up of Serum Prolactin Level in Schizophrenia Patients Treated with Blonanserin: A Case Series. |
| Abstract | In our previous study, a prolactin elevation was more frequently in risperidone than in blonanserin; however, it was more often in blonanserin than in olanzapine. Therefore, while a rate of PRL rising is low to moderate, hyperprolactinemia is a considerable adverse effect in the blonanserin treatment. In this study, to examine detailed characteristics of hyperprolactinemia of blonanserin, we analyzed the prolactin data in six schizophrenic patients who were switched to blonanserin from other antipsychotics and followed for one year. As a result, blonanserin dose was clearly associated with serum prolactin level. The average prolactin level was almost normal when the mean blonanserin dosage was 8.0 mg/day. Regardless of the dose decrease of blonanserin, there were no remarkable changes in symptoms and social functions. Based on our findings, we conclude that low dose blonanserin medication may be useful for schizophrenia maintenance treatment without hyperprolactinemia and a high rate of relapse. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 74 | Neurosci. Lett. 2015 Oct 606: 60-5 |
| PMID | 26297122 |
| Title | Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model. |
| Abstract | Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D2 receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 75 | Psychiatry Investig 2015 Oct 12: 566-8 |
| PMID | 26508971 |
| Title | One-Year Follow-Up of Serum Prolactin Level in Schizophrenia Patients Treated with Blonanserin: A Case Series. |
| Abstract | In our previous study, a prolactin elevation was more frequently in risperidone than in blonanserin; however, it was more often in blonanserin than in olanzapine. Therefore, while a rate of PRL rising is low to moderate, hyperprolactinemia is a considerable adverse effect in the blonanserin treatment. In this study, to examine detailed characteristics of hyperprolactinemia of blonanserin, we analyzed the prolactin data in six schizophrenic patients who were switched to blonanserin from other antipsychotics and followed for one year. As a result, blonanserin dose was clearly associated with serum prolactin level. The average prolactin level was almost normal when the mean blonanserin dosage was 8.0 mg/day. Regardless of the dose decrease of blonanserin, there were no remarkable changes in symptoms and social functions. Based on our findings, we conclude that low dose blonanserin medication may be useful for schizophrenia maintenance treatment without hyperprolactinemia and a high rate of relapse. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 76 | Int Clin Psychopharmacol 2015 Mar 30: 103-8 |
| PMID | 25514607 |
| Title | Prolactin variations during risperidone therapy in a sample of drug-naive children and adolescents. |
| Abstract | The aim of this prospective observational study was to investigate the variations of serum prolactin hormone (PRL) in a sample of 34 drug-naive patients (mean age 13 years) who started risperidone therapy assuming that several factors may favor the increase in serum PRL. Serum PRL and hyperprolactinemia clinical signs were examined at baseline (T0) and after almost 3 months of treatment (T1). We considered sex, pubertal status, risperidone dosage, psychiatric diagnosis, and any personal/family history of autoimmune diseases. The mean serum PRL value increased between T0 and T1 (P=0.004). The mean serum PRL was higher in females in the pubertal/postpubertal stage and for risperidone dosage up 1?mg/day. Hyperprolactinemia was found in 20% of patients at T0 and in 38% of patients at T1 (P=0.03). The mean serum PRL increase was greater in early-onset schizophrenia spectrum psychosis patients compared with no-early-onset schizophrenia spectrum psychosis patients (P=0.04). The increase in PRL was higher in patients with a personal and a family history of autoimmune diseases. This study suggests that the increase in serum PRL in patients treated with risperidone may be linked not only to the drug and its dosage but also to several risk factors such as sex, pubertal stage, psychiatric disease, and autoimmune disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 77 | J Clin Psychopharmacol 2015 Oct 35: 583-6 |
| PMID | 26270200 |
| Title | Acute Effects of Haloperidol, Amisulpride, and Quetiapine on Bone Turnover Markers in Patients With Schizophrenia. |
| Abstract | This prospective study sought to compare the acute effects of haloperidol, amisulpride, and quetiapine on serum markers of bone formation and resorption in relatively young patients with minimal previous exposure to antipsychotic drugs. Patients included in the study were randomly assigned to receive haloperidol, amisulpride, or quetiapine monotherapy in an open-label manner. Serum osteocalcin (OC, a marker of bone formation), C-terminal peptide of type I collagen (CTX, a marker of bone resorption), prolactin (PRL), estradiol, and testosterone were measured in 70 patients at baseline and after 4 weeks of antipsychotic treatment. A repeated-measures analysis of variance revealed a significant difference in CTX levels and in the OC to CTX ratio between treatment groups (F = 4.481, P < 0.05; F = 8.114, P < 0.01). After 4 weeks of treatment, only the amisulpride group had significantly increased CTX levels and decreased OC/CTX. In addition, an obvious increase in PRL level and a reduction of sex hormone secretion after amisulpride treatment were found. No significant changes in bone turnover were observed in the haloperidol or quetiapine groups. Notably, a positive correlation between the CTX change to the change in PRL after treatment (r = 0.255, P < 0.05) was observed. The PRL-raising antipsychotic drug amisulpride influenced bone turnover balance very early in the course of treatment, which may require long-term monitoring of bone metabolism. Bone resorption marker changes induced by acute antipsychotic drug treatment are likely related to increased PRL levels. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 78 | Eur Neuropsychopharmacol 2015 Aug 25: 1045-59 |
| PMID | 25937241 |
| Title | Hyperprolactinemia and medications for bipolar disorder: systematic review of a neglected issue in clinical practice. |
| Abstract | Drug-induced changes in serum prolactin (sPRL) levels constitute a relevant issue due to the potentially severe consequences on physical health of psychiatric patients such as sexual dysfunctions, osteoporosis and PRL-sensitive tumors. Several drugs have been associated to sPRL changes. Only antipsychotics have been extensively studied as sPRL-elevating agents in schizophrenia, but the extent to which bipolar disorder (BD) treatments affect sPRL levels is much less known. The objective of this systematic review is to summarize the evidence of the effects of drugs used in BD on PRL. This review followed the PRISMA statement. The MEDLINE/PubMed/Index Medicus, EMBASE, and Cochrane Library databases were systematically searched for articles in English appearing from any time to May 30, 2014. Twenty-six studies were included. These suggest that treatments for BD are less likely to be associated with PRL elevations, with valproate, quetiapine, lurasidone, mirtazapine, and bupropion reported not to change PRL levels significantly and lithium and aripiprazole to lower them in some studies. Taking into account the effects of the different classes of drugs on PRL may improve the care of BD patients requiring long-term pharmacotherapy. Based on the results of this review, lithium and valproate appear to be safer due to their low potential to elevate sPRL; among antipsychotics, quetiapine, lurasidone and aripiprazole appear to be similarly safe. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 79 | Ann Gen Psychiatry 2015 -1 14: 1 |
| PMID | 25632293 |
| Title | Long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response-a prospective open-label study. |
| Abstract | While the frequency and importance of antipsychotic switching in patients with schizophrenia, there is insufficient evidence with regard to switching strategy. Quetiapine is one of the drugs of choice for switch because of its unique receptor profile. However, there were no data on the long-term clinical and neurocognitive effect of quetiapine in patients who had responded inadequately to prior antipsychotics. The purpose of this study is to examine the long-term efficacy and tolerability of quetiapine in patients with schizophrenia who switched from other antipsychotics because of inadequate therapeutic response. We hypothesized that quetiapine would show long-term effectiveness in broad symptom dimensions including negative and neurocognitive symptoms while having good tolerability. Twenty-nine subjects with schizophrenia who did not respond to their current monotherapy of antipsychotic or who could not tolerate the treatment were switched to quetiapine and assessed at baseline and at 3, 6, and 12 months. The outcome measures included the brief assessment of cognition in schizophrenia (BACS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), the schizophrenia Quality of Life Scale Japanese version (JSQLS), the Athens Insomnia Scale (AIS), and the Drug Attitude Inventory with 30 items (DAI-30). The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS), HbA1c, prolactin (PRL), and body weight were also evaluated. Statistically significant improvements were observed in all subscores of the PANSS, the GAF, and the symptoms and side effects subscale of the JSQLS, the DIEPSS, the AIS, and the PRL level, and nearly significant improvements were observed in the DAI-30. Quetiapine monotherapy was associated with significant improvement in the verbal memory test, even after controlling for the practice effect. Although quetiapine was well tolerated, three subjects dropped out because of the worsening of the psychotic symptoms and two additional subjects dropped out because of somnolence. In this open-label, single-arm study of 29 patients, quetiapine improved both the clinical symptoms and the neurocognitive impairment in chronic schizophrenia patients who failed to respond to prior antipsychotic treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 80 | Transl Psychiatry 2016 -1 6: e785 |
| PMID | 27093067 |
| Title | Dopamine-prolactin pathway potentially contributes to the schizophrenia and type 2 diabetes comorbidity. |
| Abstract | schizophrenia (SCZ) and type 2 diabetes (T2D) are clinically associated, and common knowledge attributes this association to side effects of antipsychotic treatment. However, even drug-naive patients with SCZ are at increased risk for T2D. Dopamine dysfunction has a central role in SCZ. It is well-known that dopamine constitutively inhibits prolactin (PRL) secretion via the dopamine receptor 2 (DR2D). If dopamine is increased or if dopamine receptors hyperfunction, PRL may be reduced. During the first SCZ episode, low PRL levels are associated with worse symptoms. PRL is essential in human and social bonding, as well as it is implicated in glucose homeostasis. Dopamine dysfunction, beyond contributing to SCZ symptoms, may lead to altered appetite and T2D. To our knowledge, there are no studies of the genetics of the SCZ-T2D comorbidity focusing jointly on the dopamine and PRL pathway in the attempt to capture molecular heterogeneity correlated to possible disease manifestation heterogeneity. In this dopamine-PRL pathway-focused-hypothesis-driven review on the association of SCZ with T2D, we report a specific revision of what it is known about PRL and dopamine in relation to what we theorize is one of the missing links between the two disorders. We suggest that new studies are necessary to establish the genetic role of PRL and dopamine pathway in SCZ-T2D comorbidity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 81 | Rev Psiquiatr Salud Ment 2016 Feb -1: -1 |
| PMID | 26927534 |
| Title | Spanish consensus on the risks and detection of antipsychotic drug-related hyperprolactinaemia. |
| Abstract | Iatrogenic hyperprolactinaemia (IHPRL) has been more frequently related to some antipsychotic drugs that provoke an intense blockade of dopamine D2 receptors. There is a wide variation in clinical practice, and perhaps some more awareness between clinicians is needed. Due to the high frequency of chronic treatment in severe mental patients, careful attention is recommended on the physical risk. IHPRL symptoms could be underestimated without routine examination. An intense scientific literature search was performed in order to draw up a multidisciplinary consensus, including different specialists of psychiatry, endocrinology, oncology and internal medicine, and looking for a consensus about clinical risk and detection of IHPRL following evidence-based medicine criteria levels (EBM I- IV). Short-term symptoms include amenorrhea, galactorrhoea, and sexual dysfunction with decrease of libido and erectile difficulties related to hypogonadism. Medium and long-term symptoms related to oestrogens are observed, including a decrease bone mass density, hypogonadism, early menopause, some types of cancer risk increase (breast and endometrial), cardiovascular risk increase, immune system disorders, lipids, and cognitive dysfunction. Prolactin level, gonadal hormones and vitamin D should be checked in all patients receiving antipsychotics at baseline although early symptoms (amenorrhea-galactorrhoea) may not be observed due to the risk of underestimating other delayed symptoms that may appear in the medium term. Routine examination of sexual dysfunction is recommended due to possible poor patient tolerance and low compliance. Special care is required in children and adolescents, as well as patients with PRL levels >50ng/ml (moderate hyperprolactinaemia). A possible prolactinoma should be investigated in patients with PRL levels >150ng/ml, with special attention to patients with breast/endometrial cancer history. Densitometry should be prescribed for males >50 years old, amenorrhea>6 months, or early menopause to avoid fracture risk. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 82 | Expert Opin Drug Saf 2016 Jun 15: 809-23 |
| PMID | 26986209 |
| Title | Relationship between antipsychotic medication, serum prolactin levels and osteoporosis/osteoporotic fractures in patients with schizophrenia: a critical literature review. |
| Abstract | Using an antipsychotic medication can increase prolactin (PRL) levels, causing hyperprolactinemia (HPRL). Although the occurrence of osteoporosis within the population of patients with schizophrenia has been recognized, the precise nature of the association between antipsychotic treatment, PRL, osteoporosis, and the disease itself seems to be elusive. The aim of this review is to critically review the literature regarding the association between osteoporosis and PRL and to summarize the available evidence with respect to the impact of PRL-elevating antipsychotics on bone mineral density (BMD) and fractures in non-elderly patients with schizophrenia. Although long-standing HPRL can have an impact on the rate of bone metabolism and, when associated with hypogonadism, may lead to decreased bone density in both female and male subjects, the relative contribution of antipsychotic-induced HPRL in bone mineral loss in patients with schizophrenia remains unclear. Methodological shortcomings of existing studies, including the lack of prospective data and the focus on measurements of BMD instead of bone turnover markers, preclude definitive conclusions regarding the relationship between PRL-raising antipsychotics and BMD loss in patients with schizophrenia. Therefore, more well conducted prospective trials of these biomarkers are necessary to establish the precise relationship between antipsychotics, PRL levels and osteoporosis/osteoporotic risk. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 83 | Clin Interv Aging 2016 -1 11: 153-7 |
| PMID | 26937181 |
| Title | Factors associated with decreased bone mineral density in postmenopausal women with schizophrenia. |
| Abstract | This study examined the risk factors for decreased bone mineral density (BMD) in postmenopausal women with schizophrenia. Cluster sampling method was adopted in this large-sample, cross-sectional study. A total of 219 postmenopausal female inpatients with schizophrenia were selected and interviewed in Beijing. The average age of the patients was 60.4±7.0 years. Clinical assessment instruments included the Positive and Negative Syndrome Scale (PANSS) and a questionnaire with detailed general information and disease-related investigations. Laboratory measurements included prolactin (PRL), estradiol, progesterone, thyroid stimulating hormone, FT3, and FT4. BMD testing was performed by dual-energy X-ray absorptiometry. The prevalence of osteoporosis or osteopenia was 66.2% (n=145). Decreased BMD was associated with age, illness duration, therapeutic dose (equivalent chlorpromazine dose), treatment duration, PANSS-negative scores, body mass index (BMI), daily exercises (min/d), drinking (unit/wk), PRL, and estradiol. Multiple logistic regression analysis revealed that age, treatment duration, PANSS-negative score, BMI, and PRL were significantly associated with decreased BMD. Prevalence of BMD loss was higher in Chinese postmenopausal women with schizophrenia compared to the normal BMD group. A combination of demographic and clinical factors play important roles in determining decreased BMD, including older age, longer treatment duration, more PANSS-negative scores, higher BMI, and higher PRL level. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 84 | Schizophr Bull 2016 Feb -1: -1 |
| PMID | 26884546 |
| Title | Probabilistic Reversal Learning in Schizophrenia: Stability of Deficits and Potential Causal Mechanisms. |
| Abstract | Although individuals with schizophrenia show impaired feedback-driven learning on probabilistic reversal learning (PRL) tasks, the specific factors that contribute to these deficits remain unknown. Recent work has suggested several potential causes including neurocognitive impairments, clinical symptoms, and specific types of feedback-related errors. To examine this issue, we administered a PRL task to 126 stable schizophrenia outpatients and 72 matched controls, and patients were retested 4 weeks later. The task involved an initial probabilistic discrimination learning phase and subsequent reversal phases in which subjects had to adjust their responses to sudden shifts in the reinforcement contingencies. Patients showed poorer performance than controls for both the initial discrimination and reversal learning phases of the task, and performance overall showed good test-retest reliability among patients. A subgroup analysis of patients (n = 64) and controls (n = 49) with good initial discrimination learning revealed no between-group differences in reversal learning, indicating that the patients who were able to achieve all of the initial probabilistic discriminations were not impaired in reversal learning. Regarding potential contributors to impaired discrimination learning, several factors were associated with poor PRL, including higher levels of neurocognitive impairment, poor learning from both positive and negative feedback, and higher levels of indiscriminate response shifting. The results suggest that poor PRL performance in schizophrenia can be the product of multiple mechanisms. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |
| 85 | Acta Psychiatr Scand 2016 Jan 133: 5-22 |
| PMID | 26114737 |
| Title | Relationship between prolactin, breast cancer risk, and antipsychotics in patients with schizophrenia: a critical review. |
| Abstract | A recent meta-analysis showed that breast cancer probably is more common in female patients with schizophrenia than in the general population (effect size = 1.25, P < 0.05). Increasing experimental and epidemiological data have alerted researchers to the influence of prolactin (PRL) in mammary carcinogenesis. We therefore investigated the possible relationship between antipsychotic-induced hyperprolactinemia (HPRL) and breast cancer risk in female patients with schizophrenia. A literature search (1950 until January 2015), using the MEDLINE database, was conducted for English-language published clinical trials to identify and synthesize data of the current state of knowledge concerning breast cancer risk (factors) in women with schizophrenia and its (their) relationship between HPRL and antipsychotic medication. Although an increasing body of evidence supports the involvement of PRL in breast carcinogenesis, results of human prospective studies are limited, equivocal, and correlative (with risk ratios ranging from 0.70 to 1.9 for premenopausal women and from 0.76 to 2.03 for postmenopausal women). Moreover, these studies equally do not take into account the local production of PRL in breast epithelium, although amplification or overexpression of the local autocrine/paracrine PRL loop may be a more important mechanism in tumorigenesis. Until now, there is also no conclusive evidence that antipsychotic medication can increase the risk of breast malignancy and mortality. Other breast risk factors than PRL, such as nulliparity, obesity, diabetes mellitus, and unhealthy lifestyle behaviours (alcohol dependence, smoking, low physical activity), probably are of greater relevance in individual breast cancer cases within the population of female patients with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias |