| 1 | J Clin Psychopharmacol 2000 Apr 20: 210-9 |
|---|---|
| PMID | 10770460 |
| Title | Disposition of haloperidol pyridinium and reduced haloperidol pyridinium in schizophrenic patients: no relationship with clinical variables during short-term treatment. |
| Abstract | In an open clinical trial, serum concentrations of haloperidol pyridinium (C(HP+)) and reduced haloperidol pyridinium (C(RHP+)), as well as haloperidol (CH) and reduced haloperidol (C(RH)), were measured in 57 schizophrenic and schizoaffective inpatients during 6 weeks of short-term treatment. Psychopathology was monitored with the Brief Psychiatric Rating Scale (BPRS), and extrapyramidal adverse effects were assessed with the Extrapyramidal Symptom Rating Scale (EPS). Significantly linear relationships were found between haloperidol dose (D) and pyridinium metabolite serum concentrations, as well as between C(H) and the pyridinium metabolite serum concentrations. C(HP+) (range, 0.2-4.9 ng/mL) and C(RHP+) (range, 0.03-6.23 ng/mL) were low compared with C(H) and C(RH), being as mean values approximately 7% and 14% of C(H) and C(RH), respectively. Additionally, the values of C(RHP+) and the slope of the correlation of C(H) with the C(RHP+)/C(HP+) ratio were considerably lower than in a previous report of long-term treatment with haloperidol. This is explained by the shorter time of treatment of the present study. Carbamazepine comedication was found to not influence relative pyridinium metabolite serum concentrations C(HP+)/D and C(RHP+)/D. However, the aromatization ratios of haloperidol (C(HP+)/C(H)) and reduced haloperidol (C(RHP+)/C(RH)) were increased by concomitant carbamazepine. As the main result, no relationships between the pyridinium metabolite serum concentrations and clinical variables (BPRS change, EPS, dose of biperiden) were detected. For instance, the aromatization ratios C(HP+)/C(H) and C(RHP+)/C(RH) did not predict clinical improvement or extrapyramidal adverse effects. Therefore, no confirmation of the "pyridinium hypothesis," which suggests haloperidol pyridinium metabolites to be the origin of adverse effects and decreased therapeutic effect, can be derived from this study. However, the authors emphasize that pyridinium metabolites cannot be excluded as the origin of decreased therapeutic effect in long-term treatment and of adverse effects not investigated in the present study, such as tardive dyskinesia. Finally, it is concluded that the serum concentration of the parent drug remains the main variable of interest in the therapeutic drug monitoring of haloperidol during short-term treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 2 | Neuropsychobiology 2001 -1 44: 126-8 |
| PMID | 11586051 |
| Title | Analysis of the metabolism of haloperidol and its neurotoxic pyridinium metabolite in patients with drug-induced parkinsonism. |
| Abstract | The blood levels of the neurotrophic drug haloperidol (HP) and its pyridinium metabolite, HPP(+), have been analyzed by liquid chromatography/electrospray ionization-mass spectrometry in 10 schizophrenic patients treated with HP, without carbamazepine (HP, oral daily dose of 0.3-0.5 mg/kg body weight for more than 1 year, females, aged 41 +/- 8.5 years). There was a significant difference (t-test, d.f. = 8, p (t(0) = 7.2) <0.005) in the blood HPP(+) level between the 5 patients with (18.5 +/- 6.4 ng/ml) and the 5 without (6.3 +/- 2.4 ng/ml) severe side effects such as drug-induced parkinsonism (Extrapyramidal Symptom Rating Scale (ESRS) parkinsonism severity scores 2.8 +/- 1.5 and 1.8 +/- 1.1, respectively). Moreover, it is suggested that vitamin E may be effective for drug-induced parkinsonism through a change in the blood HPP(+) level. It is necessary to investigate the HPP(+) metabolism in psychiatric patients to avoid severe side effects such as drug-induced parkinsonism and cardiac functional disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 3 | Psychiatry Res 2001 Oct 104: 1-9 |
| PMID | 11600184 |
| Title | Haptoglobin polymorphism and schizophrenia: genetic variation on chromosome 16. |
| Abstract | Recently, it was shown that schizophrenia is accompanied by an activation of the inflammatory response system with signs of an acute phase response, such as increased plasma haptoglobin (HP) concentrations. HP is characterized by a molecular variation with three known phenotypes, i.e. HP 1-1, HP 2-1 and HP 2-2. The aim of the present study was to examine HP phenotypic and genotypic frequencies in schizophrenic patients. HP phenotyping was carried out in 98 Northwestern Italian schizophrenic patients and the phenotypic and genotypic distributions were compared with the distributions established in the Northwestern Italian population. Plasma HP concentrations were determined by means of a laser nephelometric method. The allele frequency of the HP phenotypes in schizophrenia, i.e. HP 1-1 (9.2%), HP 2-1 (38.8%) and HP 2-2 (52.0%), was significantly different from that in the Northwestern Italian population, i.e. HP 1-1 (17.0%), HP 2-1 (51.3%) and HP 2-2 (38.5%). The frequency of the HP-2 gene was significantly higher in schizophrenic patients (71.7%) as compared with the observed frequency in the Northwestern Italian population (62.5%). The alterations in HP phenotypic and genotypic distribution were more pronounced in the schizo-affective, disorganized, undifferentiated and residual schizophrenic patients than in paranoid schizophrenic patients. More than a third (35.7%) of the schizophrenic patients showed plasma HP concentrations which were higher than the upper limits of normality. schizophrenia is accompanied by an altered distribution of the HP phenotypes and genotypes, suggesting that genetic variation on chromosome 16 may be associated with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 4 | Psychiatry Res 2001 Oct 104: 1-9 |
| PMID | 11600184 |
| Title | Haptoglobin polymorphism and schizophrenia: genetic variation on chromosome 16. |
| Abstract | Recently, it was shown that schizophrenia is accompanied by an activation of the inflammatory response system with signs of an acute phase response, such as increased plasma haptoglobin (HP) concentrations. HP is characterized by a molecular variation with three known phenotypes, i.e. HP 1-1, HP 2-1 and HP 2-2. The aim of the present study was to examine HP phenotypic and genotypic frequencies in schizophrenic patients. HP phenotyping was carried out in 98 Northwestern Italian schizophrenic patients and the phenotypic and genotypic distributions were compared with the distributions established in the Northwestern Italian population. Plasma HP concentrations were determined by means of a laser nephelometric method. The allele frequency of the HP phenotypes in schizophrenia, i.e. HP 1-1 (9.2%), HP 2-1 (38.8%) and HP 2-2 (52.0%), was significantly different from that in the Northwestern Italian population, i.e. HP 1-1 (17.0%), HP 2-1 (51.3%) and HP 2-2 (38.5%). The frequency of the HP-2 gene was significantly higher in schizophrenic patients (71.7%) as compared with the observed frequency in the Northwestern Italian population (62.5%). The alterations in HP phenotypic and genotypic distribution were more pronounced in the schizo-affective, disorganized, undifferentiated and residual schizophrenic patients than in paranoid schizophrenic patients. More than a third (35.7%) of the schizophrenic patients showed plasma HP concentrations which were higher than the upper limits of normality. schizophrenia is accompanied by an altered distribution of the HP phenotypes and genotypes, suggesting that genetic variation on chromosome 16 may be associated with schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 5 | IDrugs 2002 Jan 5: 84-90 |
| PMID | 12861482 |
| Title | Iloperidone (Novartis). |
| Abstract | Iloperidone (HP-873) is a mixed 5-HT(2a)/(D2) antagonist under development by Novartis for the potential treatment of schizophrenia. Phase III trials started in 1998 and the company had predicted a filing in 2001, with a possible launch in 2002 [295127], [342937], [364082]. By February 2001, the company had revised its predicted launch date to 2003 [400976]. This was further revised in November 2001, and NDA filing was anticipated for mid-2003 with launch expected in mid-2004 [429516], [431614]. Novartis was also developing a depot formulation, with the aim of providing 1 month of treatment; by March 2001, this was in phase II trials [389740], [402747]. The compound was previously being developed by its originator, Hoechst Marion Roussel, for the potential treatment of schizophrenia and psychosis. It had reached phase II trials. In May 1996, the company announced that it had discontinued further development, and in January 1997, it licensed the compound to Titan Pharmaceuticals on a worldwide exclusive basis [229500], [216445]. Subsequently, Titan granted Novartis worldwide development, manufacturing and marketing rights, excluding Japan [270037]. In April 2001, Titan executed a further development and commercialization agreement with Novartis, granting the latter rights to iloperidone in Japan [407075]. In October 2001, Lehman Brothers predicted a 60% chance of iloperidone reaching the market. The analysts predicted that launch would take place in 2004, with sales of 50 million US dollars, rising to peak sales of 400 million US dollars in 2011 [429750]. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 6 | Eur. J. Neurosci. 2004 Dec 20: 3027-34 |
| PMID | 15579157 |
| Title | Effects of ventral hippocampal lesion on thermal and mechanical nociception in neonates and adult rats. |
| Abstract | The proper maturation of the hippocampus is essential for the development of different behaviours, including memory, pain responses and avoidance. The mechanisms involved in the neurodevelopment of nociception have also been implicated in several neuropsychiatric disorders. The neonatal lesion of the ventral hippocampus (VH) in rats, an animal model of schizophrenia, can be utilized to study the developmental neurobiology of animal behaviour. We examined the nociceptive responses in this animal model at different stages of development. Rat pups were lesioned at postnatal day 7 by injecting ibotenic acid into the VH bilaterally, and then tested for thermal and mechanical nociception at the age of 35, 65 and 180 days. The nociceptive tests used were the hot plate (HP), paw pressure (PP) and tail flick (TF) tests. Another group of adult rats had the same lesion in the VH and then underwent the same tests at 28, 56 and 168 days post-lesions. When compared with sham controls, the rats with neonatal VH lesion showed decreased latency for the HP and PP tests only after puberty. The TF test showed significant increase in latency for both groups at age 65 and 180 days. The adult rats with VH lesion showed no major changes over all periods of testing. These results suggest that early lesion of VH can alter the development of the neural mechanisms involved in the processing of thermal and mechanical nociception. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 7 | Schizophr. Res. 2005 Sep 77: 229-39 |
| PMID | 15946825 |
| Title | Characterization of olfactory bulb glomeruli in schizophrenia. |
| Abstract | Olfactory deficits, observed in schizophrenia, may be associated with a disruption of synaptic transmission in the olfactory system. Using immunohistochemistry and optical densitometry, we assessed the integrity of the synaptic connection between olfactory receptor neurons and olfactory bulb target neurons in schizophrenia by comparing the level of eight proteins, expressed in the olfactory bulb glomeruli, among schizophrenia and control subjects. In schizophrenia, no change was observed in the levels of OMP, GAP43 and NCAM, proteins expressed by olfactory receptor neurons, suggesting an intact innervation of the olfactory bulb by these neurons. This was supported by the absence of change in calbindin level, which has been shown to decrease after the destruction of the olfactory epithelium. The level of synaptophysin, a pre-synaptic protein, was also unchanged. These findings suggested that axons of olfactory receptor neurons establish synapses with their olfactory bulb targets in schizophrenia. The absence of change in the level of poorly phosphorylated neurofilament of moderate and high molecular weight (NFM/HP) suggested no lack of dendritic innervation despite a previously seen reduction of glomerular MAP2 level in schizophrenia subjects. This and above findings were consistent with the absence of change in the level of beta-tubulin III, a protein expressed by neurons of both olfactory epithelium and bulb. Finally, we noted no significant decrease in trkB level, a neurotrophin receptor involved in the olfactory epithelium maintenance. This study showed no evidence of major structural alteration of the synapse between the olfactory epithelium and bulb in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 8 | Schizophr. Res. 2006 Jan 81: 277-81 |
| PMID | 16253479 |
| Title | Psychopathy and institutional outcome in patients with schizophrenia in forensic settings in the UK. |
| Abstract | This study examined the institutional outcomes (12 weeks post-admission) of 134 male patients with DSM-IV schizophrenia assessed using the Psychopathy Checklist: Screening Version (PCL: SV) in a medium secure unit in the UK. High psychopathy scorers (HP) were more likely to be violent, non-compliant with programmes, engage in substance misuse violations, have criminal attitudes/peers and have low levels of insight into risk and violence. Psychopathy was also a modest predictor of institutional outcome in these domains. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 9 | Anal Bioanal Chem 2006 Oct 386: 719-24 |
| PMID | 16957915 |
| Title | Determination of haloperidol and reduced haloperidol in human serum by liquid chromatography after fluorescence labeling based on the Suzuki coupling reaction. |
| Abstract | A simultaneous method for the determination of haloperidol (HP) and its metabolite, reduced haloperidol (RHP), in human serum was developed by means of high-performance liquid chromatography (HPLC) with fluorescence detection. Suzuki coupling reaction with a fluorescent arylboronic acid, 4-(4,5-diphenyl-1H-imidazol-2-yl)phenylboronic acid (DPA), was employed to convert HP and RHP into highly fluorescent compounds. HP and RHP were extracted from human serum by liquid-liquid extraction with a mixture of n-hexane and isoamyl alcohol (99:1, v/v) and subsequently labeled by reaction with DPA. Separation of DPA derivatives of HP and RHP was performed on a silica column with a mixture of acetonitrile and H(2)O (90:10, v/v) containing triethylamine and acetic acid as a mobile phase. The proposed method allowed sensitive detection of HP and RHP in human serum with a detection limit (at a signal to noise ratio of 3) of 0.22 and 0.20 ng/mL, respectively. The applicability of the method for therapeutic drug monitoring (TDM) was demonstrated by analyzing human serum samples from schizophrenic patients receiving HP. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 10 | Psychiatry Res 2006 Jan 141: 29-37 |
| PMID | 16343643 |
| Title | Emotional information processing in violent patients with schizophrenia: association with psychopathy and symptomatology. |
| Abstract | schizophrenia and psychopathy have been independently shown to be associated with deficits in the recognition of facial expressions. These disorders are highly co-morbid in forensic settings, and both are associated with aggressive behaviour. This study examines the relative contribution of psychopathic traits and psychotic symptoms to reported deficits in facial affect recognition in forensic patients with schizophrenia. Fifty-four male patients with schizophrenia were recruited from medium and high security hospitals. Participants were categorised into groups with high (HP), medium (MP) and low (LP) scores on the Psychopathy Checklist: Screening Version and based on symptomatology assessed using the Positive and Negative Syndrome Scale. Participants completed an animated facial affect recognition task assessing accuracy across the six basic emotions over high and low intensities. The HP group was found to have impaired recognition of sadness at low intensity compared with the LP group. In the overall sample, facial affect recognition for negatively valenced emotions was not related to positive or negative symptom scores. However, recognition accuracy for disgust was found to be negatively related to the severity of cognitive symptoms. Patients with high psychopathy scores and schizophrenia showed similar deficits in emotional information processing to those reported in the literature in non-psychotic psychopathic samples. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 11 | Neurochem. Res. 2007 Aug 32: 1343-50 |
| PMID | 17401650 |
| Title | Effects of chronic haloperidol and/or clozapine on oxidative stress parameters in rat brain. |
| Abstract | Decreased antioxidant activity is considered as one of the causes of tardive dyskinesia in schizophrenic patients in a prolonged neuroleptic treatment course. Haloperidol (HAL) has been hypothesized to increase oxidative stress, while clozapine (CLO) would produce less oxidative damage. The objective was to determine whether CLO for 28 days could reverse or attenuate HAL-induced oxidative damage in animals previously treated with HAL for 28 days. HAL significantly increased thiobarbituric acid reactive substances levels in the cortex (CX) and striatum and increased protein carbonyls in hippocampus (HP) and CX and this was not attenuated by CLO treatment. In the total radical trapping antioxidant parameter assay there was a decrease in the HP total antioxidant potential induced by HAL and by treatment with HAL + CLO. Our findings demonstrated that the atypical antipsychotic CLO could not revert oxidative damage caused by HAL. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 12 | Behav Res Ther 2007 Jun 45: 1401-8 |
| PMID | 16934218 |
| Title | Hallucination proneness, schizotypy and meta-cognition. |
| Abstract | Disordered or maladaptive meta-cognitive processing appears to be a prominent feature for some individuals with a diagnosis of schizophrenia. We sought to establish whether healthy individuals distinguished either in terms hallucination proneness (HP) or level of schizotypy could also be differentiated on the sub-scales of the Meta-cognitions Questionnaire (MCQ), or a modified version of it in which items about worry were replaced with items specifically related to thinking. A total of 106 healthy volunteers completed the Oxford and Liverpool Inventory of Feelings and Experiences and Launay-Slade hallucination scale, the schizotypal Personality Questionnaire and two versions of the MCQ: the original which assesses five domains of meta-cognition and an adapted version in which items relating to worry had been replaced by items relating to thinking or reflecting on thinking (MCQ-th). ANOVA indicated highly significant differences between three groups of individuals differentiated in terms of high, medium and low proneness to hallucinations on four of the five MCQ sub-scales, and three of the four MCQ-th factors. Regression analyses indicated that the MCQ factors encompassing (1) a sense of uncontrollability of thinking (and the perceived attendant dangers of this) and (2) negative beliefs about thinking related to suspicion and punishment were the strongest predictors of high schizotypy. Individuals who score higher on a measure of HP are more likely to display patterns of meta-cognitive processing that resemble, in certain respects, those reported in individuals with a diagnosis of schizophrenia. High schizotypy predicts a negative appraisal about both the controllability and consequences of thinking. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 13 | Behav Res Ther 2007 Jun 45: 1401-8 |
| PMID | 16934218 |
| Title | Hallucination proneness, schizotypy and meta-cognition. |
| Abstract | Disordered or maladaptive meta-cognitive processing appears to be a prominent feature for some individuals with a diagnosis of schizophrenia. We sought to establish whether healthy individuals distinguished either in terms hallucination proneness (HP) or level of schizotypy could also be differentiated on the sub-scales of the Meta-cognitions Questionnaire (MCQ), or a modified version of it in which items about worry were replaced with items specifically related to thinking. A total of 106 healthy volunteers completed the Oxford and Liverpool Inventory of Feelings and Experiences and Launay-Slade hallucination scale, the schizotypal Personality Questionnaire and two versions of the MCQ: the original which assesses five domains of meta-cognition and an adapted version in which items relating to worry had been replaced by items relating to thinking or reflecting on thinking (MCQ-th). ANOVA indicated highly significant differences between three groups of individuals differentiated in terms of high, medium and low proneness to hallucinations on four of the five MCQ sub-scales, and three of the four MCQ-th factors. Regression analyses indicated that the MCQ factors encompassing (1) a sense of uncontrollability of thinking (and the perceived attendant dangers of this) and (2) negative beliefs about thinking related to suspicion and punishment were the strongest predictors of high schizotypy. Individuals who score higher on a measure of HP are more likely to display patterns of meta-cognitive processing that resemble, in certain respects, those reported in individuals with a diagnosis of schizophrenia. High schizotypy predicts a negative appraisal about both the controllability and consequences of thinking. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 14 | Behav Res Ther 2007 Jun 45: 1401-8 |
| PMID | 16934218 |
| Title | Hallucination proneness, schizotypy and meta-cognition. |
| Abstract | Disordered or maladaptive meta-cognitive processing appears to be a prominent feature for some individuals with a diagnosis of schizophrenia. We sought to establish whether healthy individuals distinguished either in terms hallucination proneness (HP) or level of schizotypy could also be differentiated on the sub-scales of the Meta-cognitions Questionnaire (MCQ), or a modified version of it in which items about worry were replaced with items specifically related to thinking. A total of 106 healthy volunteers completed the Oxford and Liverpool Inventory of Feelings and Experiences and Launay-Slade hallucination scale, the schizotypal Personality Questionnaire and two versions of the MCQ: the original which assesses five domains of meta-cognition and an adapted version in which items relating to worry had been replaced by items relating to thinking or reflecting on thinking (MCQ-th). ANOVA indicated highly significant differences between three groups of individuals differentiated in terms of high, medium and low proneness to hallucinations on four of the five MCQ sub-scales, and three of the four MCQ-th factors. Regression analyses indicated that the MCQ factors encompassing (1) a sense of uncontrollability of thinking (and the perceived attendant dangers of this) and (2) negative beliefs about thinking related to suspicion and punishment were the strongest predictors of high schizotypy. Individuals who score higher on a measure of HP are more likely to display patterns of meta-cognitive processing that resemble, in certain respects, those reported in individuals with a diagnosis of schizophrenia. High schizotypy predicts a negative appraisal about both the controllability and consequences of thinking. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 15 | Amino Acids 2007 Jan 32: 101-8 |
| PMID | 16897611 |
| Title | Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene. |
| Abstract | In this study we focused on detecting schizophrenia related changes of plasma proteins using proteomic technology and examining the relation between schizophrenia and haptoglobin (HP) genotype. We investigated plasma proteins from schizophrenic subjects (n = 42) and healthy controls (n = 46) by two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry. To further reveal the genetic relationship between acute phase proteins (APPs) and schizophrenia disease, we tested HP alpha1/HP alpha2 (HP 1/2) polymorphism and two single nucleotide polymorphisms (SNPs) of HP, rs2070937 and rs5473, for associations with schizophrenia in the Chinese Han population. With the relatively high number of samples for 2-DE work, we found that four proteins in the family of positive APPs were all up-regulated in patients. In genetic association study, we found significant associations existing between schizophrenia and HP polymorphisms, HP 1/2 and rs2070937 variants. schizophrenia is accompanied by both an altered expression of HP protein and a different genotype distribution of HP gene, demonstrating that HP is associated with schizophrenia. The results from proteomic and genomic aspects both indicate that acute phase reaction is likely to be an aetiological agent in the pathophysiology of schizophrenia, but not just an accompanying symptom. The positive APPs are schizophrenic related proteins, with the highly concordant results on four positive APPs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 16 | Amino Acids 2007 Jan 32: 101-8 |
| PMID | 16897611 |
| Title | Abnormal changes of plasma acute phase proteins in schizophrenia and the relation between schizophrenia and haptoglobin (Hp) gene. |
| Abstract | In this study we focused on detecting schizophrenia related changes of plasma proteins using proteomic technology and examining the relation between schizophrenia and haptoglobin (HP) genotype. We investigated plasma proteins from schizophrenic subjects (n = 42) and healthy controls (n = 46) by two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry. To further reveal the genetic relationship between acute phase proteins (APPs) and schizophrenia disease, we tested HP alpha1/HP alpha2 (HP 1/2) polymorphism and two single nucleotide polymorphisms (SNPs) of HP, rs2070937 and rs5473, for associations with schizophrenia in the Chinese Han population. With the relatively high number of samples for 2-DE work, we found that four proteins in the family of positive APPs were all up-regulated in patients. In genetic association study, we found significant associations existing between schizophrenia and HP polymorphisms, HP 1/2 and rs2070937 variants. schizophrenia is accompanied by both an altered expression of HP protein and a different genotype distribution of HP gene, demonstrating that HP is associated with schizophrenia. The results from proteomic and genomic aspects both indicate that acute phase reaction is likely to be an aetiological agent in the pathophysiology of schizophrenia, but not just an accompanying symptom. The positive APPs are schizophrenic related proteins, with the highly concordant results on four positive APPs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 17 | Nat. Genet. 2008 Jul 40: 827-34 |
| PMID | 18583979 |
| Title | Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. |
| Abstract | In an effort to pinpoint potential genetic risk factors for schizophrenia, research groups worldwide have published over 1,000 genetic association studies with largely inconsistent results. To facilitate the interpretation of these findings, we have created a regularly updated online database of all published genetic association studies for schizophrenia ('SzGene'). For all polymorphisms having genotype data available in at least four independent case-control samples, we systematically carried out random-effects meta-analyses using allelic contrasts. Across 118 meta-analyses, a total of 24 genetic variants in 16 different genes (APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53 and TPH1) showed nominally significant effects with average summary odds ratios of approximately 1.23. Seven of these variants had not been previously meta-analyzed. According to recently proposed criteria for the assessment of cumulative evidence in genetic association studies, four of the significant results can be characterized as showing 'strong' epidemiological credibility. Our project represents the first comprehensive online resource for systematically synthesized and graded evidence of genetic association studies in schizophrenia. As such, it could serve as a model for field synopses of genetic associations in other common and genetically complex disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 18 | Int J Psychophysiol 2008 Oct 70: 3-15 |
| PMID | 18511139 |
| Title | Auditory hallucinations and the mismatch negativity: processing speech and non-speech sounds in schizophrenia. |
| Abstract | In line with emerging research strategies focusing on specific symptoms rather than global syndromes in psychiatric disorders, we examined the functional neural correlates of auditory verbal hallucinations (AHs) in schizophrenia. Recent neuroimaging and behavioural evidence suggest a reciprocal relationship between auditory cortex response to external sounds versus that induced by AHs. The mismatch negativity (MMN), a well established event-related potential (ERP) index of auditory cortex function, was assessed in 12 hallucinating patients (HP), 12 non-hallucinating patients (NP) and 12 healthy controls (HC). The primary endpoints, MMN amplitudes and latencies recorded from anterior and posterior scalp regions, were measured in response to non-phonetic and phonetic sounds. While schizophrenia patients as a whole differed from HCs, no significant between-group differences were observed when patients were divided into hallucinated and non-hallucinated subgroups but, compared to NPs and HCs, whose MMN amplitudes were greatest in response to across phoneme change at frontal but not temporal sites, MMN amplitudes in HPs at frontal sites were not significantly different to any of the presented stimuli, while temporal MMNs in HPs were maximally sensitive to phonetic change. These findings demonstrate that auditory verbal hallucinations are associated with impaired pre-attentive processing of speech in fronto-temporal networks, which may involve defective attribution of significance that is sensitive to resource limitations. Overall, this research suggests that MMN may be a useful non-invasive tool for probing relationships between hallucinatory and neural states within schizophrenia and the manner in which auditory processing is altered in these afflicted patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 19 | Brain Res. 2009 May 1270: 121-30 |
| PMID | 19306847 |
| Title | Region-specific susceptibilities to cuprizone-induced lesions in the mouse forebrain: Implications for the pathophysiology of schizophrenia. |
| Abstract | Cuprizone (CPZ) is a neurotoxic agent acting as a copper chelator. In our recent study, C57BL/6 mice given dietary CPZ (0.2%) showed impairments in spatial working memory, social interaction, and prepulse inhibition. These abnormalities are reminiscent of certain schizophrenia symptoms and are not likely due to damage in the whole brain or in any single white matter tract/brain region. We hypothesized that white matter damage resulting from CPZ-treatment may be site-specific rather than universal. We examined the forebrains of C57BL/6 mice given the CPZ-containing diet and compared them with those of controls. We assessed CPZ-induced demyelination in main white matter tracts of the forebrain, evaluated myelin break down in the neuropil of the main olfactory bulb (MOB), cerebral cortex (CTX), caudate putamen (CP), hippocampus (HP), thalamus (TH), and hypothalamus (HY), and counted the number of myelin sheath forming oligodendrocytes (OLs) in CTX, CP, TH, and HY. Obvious demyelination was observed in the corpus callosum, external capsule, CP, and dorsal hippocampal commissure whereas other tracts seemed to be unaffected. The neuropil of CTX, HP and MOB showed myelin break down, which was mild in TH and HY. The number of OLs was decreased in all the above regions of CPZ-treated mice although the degree of OL loss was not consistent across regions. The data provide further support for white matter abnormalities contributing to schizophrenia-like behaviors in mice. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 20 | Biol Psychol 2010 Dec 85: 417-23 |
| PMID | 20837093 |
| Title | Auditory hallucinations and the P3a: attention-switching to speech in schizophrenia. |
| Abstract | In line with emerging research strategies focusing on specific symptoms rather than global syndromes in psychiatric disorders, we examined the functional neural correlates of auditory verbal hallucinations (AHs) in schizophrenia. Recent neuroimaging and behavioural evidence suggest altered early cognitive processes may be seen in patients with AH as a result of limited processing resources. The P3a subcomponent of the P300, an event-related potential (ERP) index of early attention switching, was assessed in 12 hallucinating patients (HP), 12 non-hallucinating patients (NP) and 12 healthy controls (HC) within a passive two-tone auditory oddball paradigm using vowel phonemes. P3a amplitudes and latencies were measured in response to across-phoneme changes. Following P3a acquisition, patients indicated the duration, intensity and clarity of their auditory hallucinations during recording. Hallucinating patients exhibited smaller P3a amplitudes than non-hallucinating patients and healthy controls. In HPs, P3a amplitude was negatively correlated with AH trait scores. These findings suggest that AHs are associated with impaired processing of speech as evidenced by altered P3a amplitudes to vowel phonemes. This finding may be due to limited cognitive resources available for incoming external stimuli due to a usurping of finite resources by AHs. The P3a may be a useful non-invasive tool for probing relationships between hallucinatory and neural states within schizophrenia and the manner in which auditory processing is altered in these afflicted patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 21 | Neuroimage 2011 Aug 57: 1154-61 |
| PMID | 21571075 |
| Title | Enhanced cortical effects of auditory stimulation and auditory attention in healthy individuals prone to auditory hallucinations during partial wakefulness. |
| Abstract | Investigating auditory hallucinations that occur in health may help elucidate brain mechanisms which lead to the pathological experience of auditory hallucinations in neuropsychiatric disorders such as schizophrenia. In this study, we investigated healthy individuals who reported auditory hallucinations whilst falling asleep (hypnagogic hallucinations; HG) and waking up (hypnopompic hallucinations; HP). In an initial behavioural study, we found that subjects with a history of auditory HG/HP hallucinations (n = 26) reported significantly greater subjective sensitivity to environmental sounds than non-hallucinator controls (n = 74). Then, two fMRI experiments were performed. The first examined speech-evoked brain activation in 12 subjects with a history of auditory HG/HP hallucinations and 12 non-hallucinator controls matched for age, gender and IQ. The second fMRI experiment, in the same subjects, probed how brain activation was modulated by auditory attention using a bimodal selective attention paradigm. In the first experiment, the hallucinator group demonstrated significantly greater speech-evoked activation in the left supramarginal gyrus than the control group. In the second experiment, directing attention towards the auditory (vs. visual) modality induced significantly greater activation of the anterior cingulate gyrus in the hallucinator group than in the control group. These results suggest that hallucination proneness is associated with increased sensitivity of auditory and polysensory association cortex to auditory stimulation, an effect which might arise due to enhanced attentional bias from the anterior cingulate gyrus. Our data support the overarching hypothesis that top-down modulation of auditory cortical response characteristics may be a key mechanistic step in the generation of auditory hallucinations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 22 | Zhonghua Yi Xue Za Zhi 2012 Dec 92: 3194-8 |
| PMID | 23328465 |
| Title | [Proteomic analysis of novel serum markers in first-episode schizophrenics before versus after treatment of risperidone]. |
| Abstract | To explore the changes in serum protein levels of schizophrenics before and after treatment of risperidone and identify the potential markers of diagnosis, treatment and drug side effects of schizophrenia. Eighty first-episode schizophrenics without other concurrent diseases and with positive and negative symptom scale (PANSS) score greater than or equal to 60 were recruited. And 15 of them were measured by proteomics. Different serum levels of proteins were obtained from these patients and were separated by two-dimensional electrophoresis (2-DE) before and after a single risperidone treatment for 8 weeks. These proteins were then identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and peptide mass fingerprinting. Enzyme-linked immunosorbent assay (ELISA) was used to verify the results. Almost 1400 spots were detected by 2-DE in each gel. Of these proteins, 23 protein spots showed significant differences in abundance before and after risperidone treatment. After MALDI-TOF peptide mass fingerprinting, 9 up-regulated proteins and 8 down-regulated proteins were validated after treatment. Of these proteins, the schizophrenics showed a significantly higher content of apolipoprotein A-1 (APOA-1) than those before treatment and haptoglobin (HP) protein was down-regulated after treatment. The results of ELISA were parallel with those of proteomic (P < 0.01). The serum proteins correlated with blood glucose and lipid metabolism are altered in schizophrenia after treatment of risperidone. A clinician should monitor the side effects of antipsychotic drugs according to the changes of serum proteins. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 23 | Zhonghua Yi Xue Za Zhi 2012 Dec 92: 3194-8 |
| PMID | 23328465 |
| Title | [Proteomic analysis of novel serum markers in first-episode schizophrenics before versus after treatment of risperidone]. |
| Abstract | To explore the changes in serum protein levels of schizophrenics before and after treatment of risperidone and identify the potential markers of diagnosis, treatment and drug side effects of schizophrenia. Eighty first-episode schizophrenics without other concurrent diseases and with positive and negative symptom scale (PANSS) score greater than or equal to 60 were recruited. And 15 of them were measured by proteomics. Different serum levels of proteins were obtained from these patients and were separated by two-dimensional electrophoresis (2-DE) before and after a single risperidone treatment for 8 weeks. These proteins were then identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and peptide mass fingerprinting. Enzyme-linked immunosorbent assay (ELISA) was used to verify the results. Almost 1400 spots were detected by 2-DE in each gel. Of these proteins, 23 protein spots showed significant differences in abundance before and after risperidone treatment. After MALDI-TOF peptide mass fingerprinting, 9 up-regulated proteins and 8 down-regulated proteins were validated after treatment. Of these proteins, the schizophrenics showed a significantly higher content of apolipoprotein A-1 (APOA-1) than those before treatment and haptoglobin (HP) protein was down-regulated after treatment. The results of ELISA were parallel with those of proteomic (P < 0.01). The serum proteins correlated with blood glucose and lipid metabolism are altered in schizophrenia after treatment of risperidone. A clinician should monitor the side effects of antipsychotic drugs according to the changes of serum proteins. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 24 | Int. J. Clin. Pract. 2013 Nov 67: 1105-12 |
| PMID | 24165424 |
| Title | The characteristics and outcomes of hospitalised and outpatient-treated first-onset schizophrenia patients: a 5-year register linkage study. |
| Abstract | We compared the course and outcome of schizophrenia in two groups: (i) hospitalised patients (HP) (n = 5980) who were identified based on their first hospital admission for schizophrenia and (ii) outpatient-treated patients (OTP) who received disability pension because of schizophrenia but who had no hospital admissions for schizophrenia or other psychotic disorder before having been granted a disability pension for schizophrenia (n = 1220). Outcomes were compared using data on mortality, psychiatric hospital utilisation, relapse rate and occupational functioning. A nationwide register-based 5-year follow-up study of all first-onset schizophrenia cases between 1998 and 2003 in Finland. The data were linked with the register information of hospital admissions, disability pensions and National Causes of Death Registers. When outcome of treatment was evaluated using mortality rate, relapses, hospital treatment and involuntary admissions as outcome measures, results indicated that OTP group had got along better with their illnesses than HP group. The mortality rates, number of psychiatric treatment days and relapse rate during the 5-year follow up were significantly lower in OTP group. Within the OTP group, there was a notable subgroup of never HP (n = 737, 60.4%), who did not require any psychiatric hospitalisation during the 5-year follow up. Patients first identified as outpatients had better outcomes than patients first identified following a hospitalisation. Future studies are required to establish whether outpatient treatment is associated with more favourable prognosis, even after fully adjusting for severity of initial symptoms. The higher suicide mortality of hospital-treated patients suggests that hospital treatment of first-onset patients does not protect from suicide. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 25 | Ther Drug Monit 2013 Aug 35: 493-501 |
| PMID | 23851906 |
| Title | Monitoring haloperidol exposure in body fluids and hair of children by liquid chromatography-high-resolution mass spectrometry. |
| Abstract | Haloperidol, 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone (HP), one of the most widely used antipsychotics in the treatment of schizophrenia, mania, and other psychiatric disorders, is frequently encountered in cases of unintentional pediatric intoxication because the ingestion of a small amount can cause significant toxic effects in children. For monitoring HP in suspected ingestions, a liquid chromatography-high-resolution mass spectrometry method has been developed and validated in urine, blood, and hair samples. The analyte was extracted from 1 mL blood or urine by liquid/liquid extraction and from 5 mg of hair by micropulverized extraction; gradient elution on an Atlantis T3 column was realized using HP-d4 as an internal standard. Positive ion electrospray ionization and high-resolution mass spectrometry determination were performed in an Orbitrap mass spectrometer. The method exhibited a r > 0.999 in the studied ranges (0.1-50 ng/mL in urine and blood and 0.1-50 ng/mg in hair) and a limit of quantification of 0.1 ng/mL for urine and blood and 0.1 ng/mg for hair; intra-assay and interassay relative SDs were always more than 18%. The method was applied to determine haloperidol in 3 children who were admitted to emergency departments. HP concentrations ranged from 2 to 21 ng/mL in urine, from not detected to 4.9 ng/mL in blood, and from 0.37 to 0.73 ng/mg in hair samples. The utilization of high-resolution/high-accuracy mass spectrometry in full scan mode allowed the identification of HP metabolites in urine and blood, thus unequivocally documenting the exposure to the drug. HP metabolites were structurally characterized by high-resolution multiple mass spectrometry. For the first time, a HP metabolite was detected in hair. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 26 | Curr Drug Discov Technol 2014 -1 11: 271-8 |
| PMID | 25578059 |
| Title | Inclusion Complexes of Hydroxy Propyl-?-Cyclodextrin and Paliperidone: Preparation and Characterization. |
| Abstract | In the present investigation, an attempt has been made to improve aqueous solubility of a BCS class II drug by making an inclusion complex with Hydroxypropyl-?-cyclodextrin (HP-?-CD). Paliperidone (PALI) was selected as a model drug for the study. It is practically insoluble in water with low oral bioavailability. It is a major active metabolite of risperidone approved for the treatment of schizophrenia in adults. The inclusion complexes were prepared in 1:1 (PALI: HP-?-CD) molar ratio. Phase solubility studies were performed according to Higuchi Connors method to determine the optimum conditions for the complexation. The prepared solid inclusion complexes were characterized by Differential Scanning Calorimetry (DSC), Fourier- Transform Infrared Spectroscopy (FT-IR), Powder X-ray Diffractometry (PXRD), Scanning Electron Microscopy (SEM) and Proton Nuclear Magnetic Resonance Spectroscopy ((1)H-NMR). Dissolution study was performed using USP apparatus II in phosphate buffer, pH 6.8 (37 ± 0.5°C). The solid state characterization studies confirmed the formation of inclusion complex between PALI and HP-?-CD. The aqueous solubility and in-vitro dissolution study showed that the solubility and dissolution rate of drug were considerably improved by complexation with HP-?-CD with respect to the drug alone. The enhanced solubility and dissolution may help to improve in-vivo performance of PALI. Thus, the binary complexation of PALI with HP-?-CD can be used as an approach for its solubility enhancement. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 27 | Sci Rep 2015 -1 5: 17156 |
| PMID | 26599540 |
| Title | Copy number variations play important roles in heredity of common diseases: a novel method to calculate heritability of a polymorphism. |
| Abstract | "Missing heritability" in genome wide association studies, the failure to account for a considerable fraction of heritability by the variants detected, is a current puzzle in human genetics. For solving this puzzle the involvement of genetic variants like rare single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) has been proposed. Many papers have published estimating the heritability of sets of polymorphisms, however, there has been no paper discussing the estimation of a heritability of a single polymorphism. Here I show a simple but rational method to calculate heritability of an individual polymorphism, HP(2). Using this method, I carried out a trial calculation of HP(2) of CNVs and SNPs using published data. It turned out that HP(2) of some CNVs is quite large. Noteworthy examples were that about 25% of the heritability of type 2 diabetes mellitus and about 15% of the heritability of schizophrenia could be accounted for by one CNV and by four CNVs, respectively. The results suggest that a large part of missing heritability could be accounted for by re-evaluating the CNVs which have been already found and by searching novel CNVs with large HP(2). |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 28 | Am J Orthopsychiatry 2015 Mar 85: 139-44 |
| PMID | 25822605 |
| Title | University students' identification of stigmatizing schizophrenia in Italian newspapers. |
| Abstract | Stigma associated with mental disorders represents one main obstacle to receive appropriate care for people with mental disorders. Compared to adults, university students have higher levels of stigmatizing attitudes toward patients with schizophrenia. The primary aim of this case-control study was to assess university students' ability to identify stigma toward schizophrenia in Italian newspapers. Secondary aims were: a) to explore differences in stigmatizing attitudes among two different groups of university students (health professionals [HP] and nonhealth professionals [n-HP]) and b) to compare the attitudes of these two groups with those of a sample of expert psychiatrists. The electronic archives of two Italian newspapers were searched using the term "schizo" (as a word or part of it). One hundred seventy articles published between January and December 2011 were identified. Students from the HP group and expert psychiatrists had a higher ability to detect stigmatizing attitudes in newspapers. Students from the n-HP group had a higher concordance with the experts on the topics "characteristics of the article" and "services and rights." Our findings highlight the importance of targeting university students with correct and updated information about schizophrenia and its psychosocial consequences. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 29 | Biol. Psychiatry 2015 Jan 77: 127-36 |
| PMID | 24923619 |
| Title | Event-related potential and time-frequency endophenotypes for schizophrenia and psychotic bipolar disorder. |
| Abstract | The investigators compared event-related potential (ERP) amplitudes and event-related oscillations across a broad frequency range during an auditory oddball task using a comprehensive analysis approach to describe shared and unique neural auditory processing characteristics among healthy subjects (HP), schizophrenia probands (SZ) and their first-degree relatives, and bipolar disorder I with psychosis probands (BDP) and their first-degree relatives. This Bipolar-schizophrenia Network on Intermediate Phenotypes sample consisted of clinically stable SZ (n = 229) and BDP (n = 188), HP (n = 284), first-degree relatives of schizophrenia probands (n = 264), and first-degree relatives of bipolar disorder I with psychosis probands (n = 239). They were administered an auditory oddball task in the electroencephalography environment. Principal components analysis derived data-driven frequency bands evoked power. Spatial principal components analysis reduced ERP and frequency data to component waveforms for each subject. Clusters of time bins with significant group differences on response magnitude were assessed for proband/relative differences from HP and familiality. Nine variables survived a linear discriminant analysis between HP, SZ, and BDP. Of those, two showed evidence (deficit in relatives and familiality) as genetic risk markers more specific to SZ (N1, P3b), one was specific to BDP (P2) and one for psychosis in general (N2). This study supports for both shared and unique deficits in early sensory and late cognitive processing across psychotic diagnostic groups. Additional ERP and time-frequency component alterations (frontal N2/P2, late high, early, mid, and low frequency) may provide insight into deficits in underlying neural architecture and potential protective/compensatory mechanisms in unaffected relatives. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |
| 30 | J. Nerv. Ment. Dis. 2016 May -1: -1 |
| PMID | 27218222 |
| Title | Sound-Color Associations in Psychosis-Prone Individuals. |
| Abstract | Synesthetic-pseudosynesthetic characteristics have been hypothesized to be a schizophrenia endophenotype, a developmental feature, and/or a symptom of psychosis. Few studies to date, however, have examined whether individuals at risk for psychosis have synesthetic symptoms. We examined the relationship between hue and pitch in high psychosis prone (HP; n = 30) and low psychosis prone individuals (LP; n = 31). Synesthesia was evaluated using self-report and two performance-based tasks. Results revealed that HP subjects experienced more synesthetic experiences than the LP only on the self-report measure. These results suggest that high psychotic prone patients report unusual experiences but are no more likely to exhibit synesthesia than LP individuals. HP individuals, however, were more likely to choose shorter wavelength colors than LP individuals on performance tasks. These results are consistent with the notion that psychosis vulnerability is associated with a preference to light wavelengths associated with increasing emotional valence and negative affect. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy, schizophrenias, schizotypal |