| 1 | J Int Neuropsychol Soc 2000 Sep 6: 649-58 |
|---|---|
| PMID | 11011511 |
| Title | The functional relevance of affect recognition errors in schizophrenia. |
| Abstract | To evaluate the clinical and ecological validity of affect recognition (AR) measures in a sample of community-dwelling schizophrenic outpatients (N = 40), we analyzed the relation of facial and vocal AR to intellectual, symptomatic, and quality-of-life criteria. Facial and vocal AR showed virtually identical patterns of association with these criteria, suggesting that both modalities of AR draw on the same underlying heteromodal capacity. Specifically, AR was correlated with a subset of intellectual abilities (verbal-semantic, executive-attentional), but was unrelated to age, education, or neuroleptic dose. In terms of clinical and ecological criteria, AR errors correlated with more severe psychotic symptoms (positive and disorganized) and with lower quality of life (relationships, community pARticipation, and richness of intrapsychic experience). Even after controlling for subjects' intellectual abilities and illness severity, inaccurate AR was associated with bizARre behaviors (involving sociosexual interactions, clothing, appeARance) and with impoverished interpersonal relations. Thus, while difficulty identifying basic affective cues is related to general cognitive and illness-severity factors, it appeARs to have specific functional implications that do not depend on generalized impairment. Assessment of AR may identify a subgroup of schizophrenic patients who have a central defect in the heteromodal monitoring of emotional-social displays, associated with dysregulation of social behaviors and disruption of interpersonal relations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 2 | J Int Neuropsychol Soc 2000 Sep 6: 649-58 |
| PMID | 11011511 |
| Title | The functional relevance of affect recognition errors in schizophrenia. |
| Abstract | To evaluate the clinical and ecological validity of affect recognition (AR) measures in a sample of community-dwelling schizophrenic outpatients (N = 40), we analyzed the relation of facial and vocal AR to intellectual, symptomatic, and quality-of-life criteria. Facial and vocal AR showed virtually identical patterns of association with these criteria, suggesting that both modalities of AR draw on the same underlying heteromodal capacity. Specifically, AR was correlated with a subset of intellectual abilities (verbal-semantic, executive-attentional), but was unrelated to age, education, or neuroleptic dose. In terms of clinical and ecological criteria, AR errors correlated with more severe psychotic symptoms (positive and disorganized) and with lower quality of life (relationships, community pARticipation, and richness of intrapsychic experience). Even after controlling for subjects' intellectual abilities and illness severity, inaccurate AR was associated with bizARre behaviors (involving sociosexual interactions, clothing, appeARance) and with impoverished interpersonal relations. Thus, while difficulty identifying basic affective cues is related to general cognitive and illness-severity factors, it appeARs to have specific functional implications that do not depend on generalized impairment. Assessment of AR may identify a subgroup of schizophrenic patients who have a central defect in the heteromodal monitoring of emotional-social displays, associated with dysregulation of social behaviors and disruption of interpersonal relations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 3 | Am. J. Med. Genet. 2000 Apr 96: 141-5 |
| PMID | 10893485 |
| Title | Novel polymorphisms of the human cholecystokinin A receptor gene: an association analysis with schizophrenia. |
| Abstract | The cholecystokinin A receptor (CCK-AR) modulates CCK-stimulated dopamine release in the posterior nucleus accumbens, and its gene is mapped to 4p15.2-15.1 with the dopamine receptor 5 (DR5) gene. We speculated that alterations in the CCK-AR lead to an increase in dopamine release, which may in turn constitute a predisposition in schizophrenia. We investigated genetic vARiations in the promoter region and the coding region of the CCK-AR gene. An association analysis was conducted between 83 unrelated schizophrenic patients and 80 healthy controls. Novel polymorphisms (201A-->G, 246G-->A in the promoter region, 1260T-->A, 1266T-->C in intron 1 within the 3' mRNA splice acceptor site consensus sequence, and Leu306Leu in exon 5) were found in addition to the vARiants (608G-->A in intron 1, 3849C-->T [Ile296Ile] in exon 5) reported previously. Significant differences were found in the allele frequencies of the 201A-->G nucleotide substitution in the promoter region between patients and controls (P = 0.0181, odds ratio: 1.972, after Bonferroni correction: P = 0.0543). These differences were also found between the patients with pARanoid type and controls (P = 0.0274, odds ratio = 3.667, after Bonferroni correction: P = 0.0822). Our analyses suggest that the 201A allele frequency was higher in the schizophrenic group, especially in the pARanoid type, than in the control group at a rate that was not quite significant after Bonferroni correction. Am J. Med Genet. (Neuropsychiatr. Genet.) 96:141-145, 2000. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 4 | Am. J. Med. Genet. 2000 Apr 96: 141-5 |
| PMID | 10893485 |
| Title | Novel polymorphisms of the human cholecystokinin A receptor gene: an association analysis with schizophrenia. |
| Abstract | The cholecystokinin A receptor (CCK-AR) modulates CCK-stimulated dopamine release in the posterior nucleus accumbens, and its gene is mapped to 4p15.2-15.1 with the dopamine receptor 5 (DR5) gene. We speculated that alterations in the CCK-AR lead to an increase in dopamine release, which may in turn constitute a predisposition in schizophrenia. We investigated genetic vARiations in the promoter region and the coding region of the CCK-AR gene. An association analysis was conducted between 83 unrelated schizophrenic patients and 80 healthy controls. Novel polymorphisms (201A-->G, 246G-->A in the promoter region, 1260T-->A, 1266T-->C in intron 1 within the 3' mRNA splice acceptor site consensus sequence, and Leu306Leu in exon 5) were found in addition to the vARiants (608G-->A in intron 1, 3849C-->T [Ile296Ile] in exon 5) reported previously. Significant differences were found in the allele frequencies of the 201A-->G nucleotide substitution in the promoter region between patients and controls (P = 0.0181, odds ratio: 1.972, after Bonferroni correction: P = 0.0543). These differences were also found between the patients with pARanoid type and controls (P = 0.0274, odds ratio = 3.667, after Bonferroni correction: P = 0.0822). Our analyses suggest that the 201A allele frequency was higher in the schizophrenic group, especially in the pARanoid type, than in the control group at a rate that was not quite significant after Bonferroni correction. Am J. Med Genet. (Neuropsychiatr. Genet.) 96:141-145, 2000. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 5 | Psychopharmacology (Berl.) 2001 Jul 156: 284-90 |
| PMID | 11549230 |
| Title | The DBA/2J strain and prepulse inhibition of startle: a model system to test antipsychotics? |
| Abstract | Prepulse inhibition (PPI) of the stARtle response in mice is increasingly used as a pARadigm of sensory gating with potential predictive and construct validity towARds schizophrenia. Establishment of a mouse PPI pARadigm in which typical and atypical antipsychotic drugs directly improve a low performance PPI. Three strains of mice--C57Bl/6J, 129S6/SvEvTac and DBA/2J--were tested in a stARtle pARadigm with three prepulse intensities, 2, 4 and 8 dB above background. Under these conditions, risperidone (0, 0.25, 0.5 and 1 mg/kg i.p.) and clozapine (0, 1, 3 and 9 mg/kg i.p.) improved PPI in all three strains, with order of effect in DBA/2J > 129S6SvEvTac > C57Bl/6J. The DBA/2J strain showed lARger PPI-enhancing effects, without disturbing the basal stARtle response. Two alpha7 nicotinic receptor agonists, GTS-21 (1-10 mg/kg i.p.) and AR-R17779 (1-10 mg/kg i.p.) were inactive in the PPI procedure in DBA/2J mice. DBA/2J mice were very sensitive to the antipsychotic-like effects of atypical (clozapine) and typical (risperidone) antipsychotics, and this strain is proposed as a model to directly measure sensory gating properties of drugs. Alpha7 Nicotinergic receptor agonists were ineffective in this PPI pARadigm. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 6 | Behav. Brain Res. 2003 May 141: 171-5 |
| PMID | 12742253 |
| Title | Removal of short-term isolation stress differentially influences prepulse inhibition in APO-SUS and APO-UNSUS rats. |
| Abstract | Epidemiological studies have reported that the risk of developing schizophrenia increases with the number of genes one shARes with patients suffering from schizophrenia [Gottesman schizophrenia Genesis, New York: Freeman; 1991]. In addition, stressful life events ARe known to increase the risk of developing schizophrenia [Schizophr Res 30 (1998) 251] resulting in the stress hypothesis of schizophrenia. RemARkably, stress increases the release of dopamine and noradrenaline in the nucleus accumbens [Brain Res 554 (1991) 217], which links the stress hypothesis with the known dopamine hypothesis of schizophrenia. Additionally an increased dopamine transmission in the nucleus accumbens (Nacc) is known to disturb prepulse inhibition (ppi) [PhARmacol Biochem Behav 49 (1994) 155], a phenomenon observed in, among others, schizophrenics [ARch Gen Psychiatry 47 (1990) 181]. Some yeARs ago we have genetically selected two rat-lines which ARe mARked by a high (APO-SUS) and by a low (APO-UNSUS) apomorphine susceptibility. SimilAR to schizophrenics the APO-SUS rat-line shows a reduced ppi [J Neurosci 15 (1995) 7604]. However, these data were obtained after a period of mild stress, namely a 24-h period of social isolation. Mild stress changes the line specific differences of APO-SUS and APO-UNSUS rats. The stress pushes the APO-SUS rat in the direction of an APO-UNSUS and vice versa, especially as fAR as it concerns the dopamine and noradrenaline activity in the nucleus accumbens [Cools AR, van-den Bos R, Ellenbroek BA, Gaiting function of noradrenaline in the ventral striatum: its role in behavioural responses to environmental and phARmacological challenges. In: Willner P, Scheel-Kruger J, editors. The mesolimbic dopamine system: from motivation to action. New York: Wiley; 1991 [Chapter 6]; Cools AR, Rots NY, De-Kloet ER, Apomorphine-susceptible and apomorphine-unsusceptible WistAR rats: a new tool in the seARch for the function of striatum in switching behavioural strategies. In: Pea G (Ed.), The basal ganglia IV, New York: Plenum Press; 1994; Brain Res Bull 24 (1990) 49; Behav Neurosci 108 (1994) 1107]. Therefore, in the present paper we investigated the ppi response in non-stressed, i.e. non-isolated APO-SUS and APO-UNSUS rats. In agreement with this hypothesis, we found that removal of the stress led to an increase of ppi in the APO-SUS, but a decrease in the APO-UNSUS. These data cleARly shows that the ppi is stress-dependent in APO-SUS and APO-UNSUS rats. It is suggested that the differential stress-induced change in the dopaminergic and the noradrenergic system influences the reaction of APO-SUS and APO-UNSUS rats on ppi. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 7 | Behav. Brain Res. 2003 May 141: 171-5 |
| PMID | 12742253 |
| Title | Removal of short-term isolation stress differentially influences prepulse inhibition in APO-SUS and APO-UNSUS rats. |
| Abstract | Epidemiological studies have reported that the risk of developing schizophrenia increases with the number of genes one shARes with patients suffering from schizophrenia [Gottesman schizophrenia Genesis, New York: Freeman; 1991]. In addition, stressful life events ARe known to increase the risk of developing schizophrenia [Schizophr Res 30 (1998) 251] resulting in the stress hypothesis of schizophrenia. RemARkably, stress increases the release of dopamine and noradrenaline in the nucleus accumbens [Brain Res 554 (1991) 217], which links the stress hypothesis with the known dopamine hypothesis of schizophrenia. Additionally an increased dopamine transmission in the nucleus accumbens (Nacc) is known to disturb prepulse inhibition (ppi) [PhARmacol Biochem Behav 49 (1994) 155], a phenomenon observed in, among others, schizophrenics [ARch Gen Psychiatry 47 (1990) 181]. Some yeARs ago we have genetically selected two rat-lines which ARe mARked by a high (APO-SUS) and by a low (APO-UNSUS) apomorphine susceptibility. SimilAR to schizophrenics the APO-SUS rat-line shows a reduced ppi [J Neurosci 15 (1995) 7604]. However, these data were obtained after a period of mild stress, namely a 24-h period of social isolation. Mild stress changes the line specific differences of APO-SUS and APO-UNSUS rats. The stress pushes the APO-SUS rat in the direction of an APO-UNSUS and vice versa, especially as fAR as it concerns the dopamine and noradrenaline activity in the nucleus accumbens [Cools AR, van-den Bos R, Ellenbroek BA, Gaiting function of noradrenaline in the ventral striatum: its role in behavioural responses to environmental and phARmacological challenges. In: Willner P, Scheel-Kruger J, editors. The mesolimbic dopamine system: from motivation to action. New York: Wiley; 1991 [Chapter 6]; Cools AR, Rots NY, De-Kloet ER, Apomorphine-susceptible and apomorphine-unsusceptible WistAR rats: a new tool in the seARch for the function of striatum in switching behavioural strategies. In: Pea G (Ed.), The basal ganglia IV, New York: Plenum Press; 1994; Brain Res Bull 24 (1990) 49; Behav Neurosci 108 (1994) 1107]. Therefore, in the present paper we investigated the ppi response in non-stressed, i.e. non-isolated APO-SUS and APO-UNSUS rats. In agreement with this hypothesis, we found that removal of the stress led to an increase of ppi in the APO-SUS, but a decrease in the APO-UNSUS. These data cleARly shows that the ppi is stress-dependent in APO-SUS and APO-UNSUS rats. It is suggested that the differential stress-induced change in the dopaminergic and the noradrenergic system influences the reaction of APO-SUS and APO-UNSUS rats on ppi. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 8 | Neuropsychopharmacology 2004 Jul 29: 1282-93 |
| PMID | 15039766 |
| Title | Alpha2A-adrenoceptors are important modulators of the effects of D-amphetamine on startle reactivity and brain monoamines. |
| Abstract | Amphetamines ARe commonly used to treat attention-deficit hyperactivity disorder, but ARe also widely abused. They ARe employed in schizophrenia-related animal models as they disrupt the prepulse inhibition (PPI) of the acoustic stARtle response. The behavioral effects of amphetamines have mainly been attributed to changes in dopamine transmission, but they also involve increases in the synaptic concentrations of norepinephrine (NE). alpha2-Adrenoceptors (alpha2-ARs) regulate the excitability and transmitter release of brain monoaminergic neurons mainly as inhibitory presynaptic auto- and heteroreceptors. Modulation of acoustic stARtle and its PPI by the alpha2A-AR subtype was investigated with mice lacking the alpha2A-AR (alpha2A-KO) and their wild-type (WT) controls, without drugs and after administration of the alpha2-AR agonist dexmedetomidine or the antagonist atipamezole. The interaction of D-amphetamine (D-amph) and the alpha2-AR-noradrenergic neuronal system in modulating stARtle reactivity and in regulating brain monoamine metabolism was assessed as the behavioral and neurochemical responses to D-amph alone, or to the combination of D-amph and dexmedetomidine or atipamezole. alpha2A-KO mice were supersensitive to both neurochemical and behavioral effects of D-amph. Brain NE stores of alpha2A-KO mice were depleted by D-amph, revealing the alpha2A-AR as essential in modulating the actions of D-amph. Also, increased stARtle responses and more pronounced disruption of PPI were noted in D-amph-treated alpha2A-KO mice. alpha2A-AR also appeARed to be responsible for the stARtle-modulating effects of alpha2-AR drugs, since the stARtle attenuation after the alpha2-AR agonist dexmedetomidine was absent in alpha2A-KO mice, and the alpha2-AR antagonist atipamezole had opposite effects on the stARtle reflex in alpha2A-KO and WT mice. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 9 | J Med Syst 2004 Oct 28: 489-95 |
| PMID | 15527036 |
| Title | An autoregressive (AR) model applied to eye tremor movement, clinical application in schizophrenia. |
| Abstract | In this study, we use a pARametric autoregressive (AR) model to obtain descriptive features of eye tremor movement during fixation. The interest consists in analyzing model pARameters to determine the information that can be used as indicator of specific pathophysiology underlying cerebral dysfunction in schizophrenic subjects. We have tested healthy volunteers and schizophrenic medicated and unmedicated patients, to evaluate the treatment effect. The AR model is applied to the eye tremor movement extracted from the eye position signal recorded when subjects ARe fixating a stationARy tARget. The analysis of the model pARameters shows distinct classes, corresponding to a population of subjects among the three kinds included in this study. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 10 | J Med Syst 2004 Oct 28: 489-95 |
| PMID | 15527036 |
| Title | An autoregressive (AR) model applied to eye tremor movement, clinical application in schizophrenia. |
| Abstract | In this study, we use a pARametric autoregressive (AR) model to obtain descriptive features of eye tremor movement during fixation. The interest consists in analyzing model pARameters to determine the information that can be used as indicator of specific pathophysiology underlying cerebral dysfunction in schizophrenic subjects. We have tested healthy volunteers and schizophrenic medicated and unmedicated patients, to evaluate the treatment effect. The AR model is applied to the eye tremor movement extracted from the eye position signal recorded when subjects ARe fixating a stationARy tARget. The analysis of the model pARameters shows distinct classes, corresponding to a population of subjects among the three kinds included in this study. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 11 | Eur. Psychiatry 2004 Sep 19: 349-53 |
| PMID | 15363473 |
| Title | A possible association between the CCK-AR gene and persistent auditory hallucinations in schizophrenia. |
| Abstract | Recent studies have suggested that DNA vARiations in the CCK-AR gene might predispose individuals to schizophrenia and pARticulARly to auditory hallucinations (AH). The aim of this study is to assess the association between AH, using a specific scale for AH in schizophrenia (PSYRATS), and the CCK-AR polymorphism at 779 in a Spanish sample. A total of 105 DSM-IV schizophrenic patients with AH and 93 unrelated controls were studied. Twenty-two patients were considered as persistent auditory hallucinators, which showed similAR clinical and demographic chARacteristic than patients with episodic AH, but with the exception of the PSYRATS values. The persistent AH group showed an excess of the A1 allele when was compARed with episodic or control groups. Our data support the possible role of the CCK-AR gene in the development of persistent AH in schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 12 | Eur. Psychiatry 2004 Sep 19: 349-53 |
| PMID | 15363473 |
| Title | A possible association between the CCK-AR gene and persistent auditory hallucinations in schizophrenia. |
| Abstract | Recent studies have suggested that DNA vARiations in the CCK-AR gene might predispose individuals to schizophrenia and pARticulARly to auditory hallucinations (AH). The aim of this study is to assess the association between AH, using a specific scale for AH in schizophrenia (PSYRATS), and the CCK-AR polymorphism at 779 in a Spanish sample. A total of 105 DSM-IV schizophrenic patients with AH and 93 unrelated controls were studied. Twenty-two patients were considered as persistent auditory hallucinators, which showed similAR clinical and demographic chARacteristic than patients with episodic AH, but with the exception of the PSYRATS values. The persistent AH group showed an excess of the A1 allele when was compARed with episodic or control groups. Our data support the possible role of the CCK-AR gene in the development of persistent AH in schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 13 | Psychoneuroendocrinology 2006 Feb 31: 270-4 |
| PMID | 16112495 |
| Title | Distribution of androgen receptor CAG repeat polymorphism in Chinese schizophrenia and its correlation with age at onset. |
| Abstract | The action of androgens is mediated by the androgen receptors (ARs), which ARe located throughout the brain. The AR gene is implicated in the pathogenesis of schizophrenia because male siblings with schizophrenia shARe alleles at this gene at a rate higher than chance predicts, and differences in sex hormone function may explain the gender difference in schizophrenic manifestations. Since the shorter alleles of the AR CAG repeat polymorphism ARe associated with increased gene expression, we tested the hypothesis that the AR CAG repeat vARiant confers susceptibility to schizophrenia using a sample of 225 people with schizophrenia and 247 normal controls. Using the median AR repeat length in the normal group as the ARbitrARy cut-off point (<24 and >25 CAG repeats), the results show no association between the AR repeat length and schizophrenia in either sex. Furthermore. AR CAG repeat length did not affect the age of symptom onset in the schizophrenic population. Our findings suggest that it is unlikely that the AR CAG repeat polymorphism plays a major role in the pathogenesis of schizophrenia. Nevertheless, given that androgens affect cognitive function, violent behavior and mood, the effect of the AR CAG polymorphism on the clinical manifestations of schizophrenia may wARrant further exploration. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 14 | Psychoneuroendocrinology 2006 Feb 31: 270-4 |
| PMID | 16112495 |
| Title | Distribution of androgen receptor CAG repeat polymorphism in Chinese schizophrenia and its correlation with age at onset. |
| Abstract | The action of androgens is mediated by the androgen receptors (ARs), which ARe located throughout the brain. The AR gene is implicated in the pathogenesis of schizophrenia because male siblings with schizophrenia shARe alleles at this gene at a rate higher than chance predicts, and differences in sex hormone function may explain the gender difference in schizophrenic manifestations. Since the shorter alleles of the AR CAG repeat polymorphism ARe associated with increased gene expression, we tested the hypothesis that the AR CAG repeat vARiant confers susceptibility to schizophrenia using a sample of 225 people with schizophrenia and 247 normal controls. Using the median AR repeat length in the normal group as the ARbitrARy cut-off point (<24 and >25 CAG repeats), the results show no association between the AR repeat length and schizophrenia in either sex. Furthermore. AR CAG repeat length did not affect the age of symptom onset in the schizophrenic population. Our findings suggest that it is unlikely that the AR CAG repeat polymorphism plays a major role in the pathogenesis of schizophrenia. Nevertheless, given that androgens affect cognitive function, violent behavior and mood, the effect of the AR CAG polymorphism on the clinical manifestations of schizophrenia may wARrant further exploration. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 15 | Psychiatr. Genet. 2007 Apr 17: 117-9 |
| PMID | 17413452 |
| Title | Association study between the cholecystokinin A receptor gene and schizophrenia in the Japanese population. |
| Abstract | Cholecystokinin A receptor (CCK-AR) has been implicated in the pathophysiology of schizophrenia through its mediation of dopamine-release in the central nervous system. Several studies have observed the association between the CCK-AR gene and schizophrenia. Especially, the association has been repeatedly observed between the 779T/C polymorphism and auditory hallucinations or positive symptoms of schizophrenia. In this study, we investigated the association between the 779T/C polymorphism of the CCK-AR gene and schizophrenia in 290 Japanese patients with schizophrenia and 290 controls. As a result, no significant difference was observed in genotypic distributions or allelic frequencies between the patients and controls, although there was a trend for the association between the C allele of the polymorphism and hallucination (P=0.024) or hallucinatory-pARanoid state (P=0.049). In conclusion, the present results may not provide evidence for the association between the CCK-AR gene and schizophrenia in the Japanese population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 16 | Psychiatr. Genet. 2007 Apr 17: 47-53 |
| PMID | 17413443 |
| Title | Association between CCK-AR gene and schizophrenia with auditory hallucinations. |
| Abstract | Previous studies on a possible association between CCK-AR polymorphisms and schizophrenia have been controversial. The aim of the present study was to assess a potential association between schizophrenic patients with auditory hallucinations and polymorphisms of the CCK-AR gene. A set of single nucleotide polymorphisms mainly located in the regulatory region of the CCK-AR gene was analysed in a sample of 163 Diagnostic and statistical manual of mental disorders-IV-diagnosed schizophrenic patients and 162 healthy controls. Significant differences in the genotype (P=0.011) and allele (P=0.0009) frequencies of the +121C/G SNP (located in the 5' regulatory region) were found between patients and controls. The excess of the C allele in the patient group remained significant after Bonferroni correction (P=0.03). However, functional in vitro assays, did not reveal significant differences on gene expression between +121G and +121C alleles of this SNP. Further investigations revealed two risk haplotypes: +121C/+978A/+984T (P=0.01) and +121C/+978T/+984C (P=0.0091) as well as a protective haplotype: +121G/+978T/+984T (P=0.0001). Our data support a possible role of the CCK-AR gene in the vulnerability to schizophrenia in patients with auditory hallucinations, and suggest remARkable allele heterogeneity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 17 | Psychiatr. Genet. 2007 Apr 17: 47-53 |
| PMID | 17413443 |
| Title | Association between CCK-AR gene and schizophrenia with auditory hallucinations. |
| Abstract | Previous studies on a possible association between CCK-AR polymorphisms and schizophrenia have been controversial. The aim of the present study was to assess a potential association between schizophrenic patients with auditory hallucinations and polymorphisms of the CCK-AR gene. A set of single nucleotide polymorphisms mainly located in the regulatory region of the CCK-AR gene was analysed in a sample of 163 Diagnostic and statistical manual of mental disorders-IV-diagnosed schizophrenic patients and 162 healthy controls. Significant differences in the genotype (P=0.011) and allele (P=0.0009) frequencies of the +121C/G SNP (located in the 5' regulatory region) were found between patients and controls. The excess of the C allele in the patient group remained significant after Bonferroni correction (P=0.03). However, functional in vitro assays, did not reveal significant differences on gene expression between +121G and +121C alleles of this SNP. Further investigations revealed two risk haplotypes: +121C/+978A/+984T (P=0.01) and +121C/+978T/+984C (P=0.0091) as well as a protective haplotype: +121G/+978T/+984T (P=0.0001). Our data support a possible role of the CCK-AR gene in the vulnerability to schizophrenia in patients with auditory hallucinations, and suggest remARkable allele heterogeneity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 18 | Curr Med Res Opin 2007 Oct 23: 2551-7 |
| PMID | 17845743 |
| Title | Reviewing CATIE for clinicians: balancing benefit and risk using evidence-based medicine tools. |
| Abstract | In order to leARn from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study and apply its results to day-to-day clinical practice, it would be useful to quantify the benefits and risks of the studied antipsychotics. Reviewing the CATIE results from the perspective of evidence-based medicine metrics of attributable risk (AR), number needed to treat (NNT), number needed to hARm (NNH), and likelihood of being helped or hARmed (LHH) helps clinicians translate the CATIE findings for individualized treatment in clinical practice. Use of these evidence-based tools demonstrates that the NNT to avoid a psychiatric hospitalization due to the exacerbation of schizophrenia ranged from 3 to 7 in favor of olanzapine compARed with the other antipsychotics. The NNH to produce one treatment-emergent adverse event of weight gain > 7% ranged from -5 to -8 (favoring compARators over olanzapine). Further, when assessing LHH - the likelihood of being helped (avoid a psychiatric hospital admission) compARed to the likelihood of being hARmed (experience weight gain > 7%) - treatment with olanzapine was consistently associated with greater expectation of benefit than hARm (LHH > 1). The use of NNT, NNH, and LHH can be helpful in balancing risk versus benefit in selecting antipsychotic treatment. NNT and NNH may vARy with baseline risk, and cannot be calculated from continuous vARiables. LHH may be influenced by an individual's perception of the value of the outcomes compARed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 19 | Schizophr. Res. 2007 Jul 93: 266-77 |
| PMID | 17467955 |
| Title | Neurocognitive deficits in the (putative) prodrome and first episode of psychosis. |
| Abstract | International reseARch programs have contributed to the creation of operationally defined criteria to identify individuals at risk for schizophrenia. Although there has been substantial progress in the prospective study of the schizophrenia prodrome, the utility of current diagnostic criteria remains questionable because of the relatively low base rates of incident psychoses, the high false-positive rate and ethical concerns regARding the treatment of individuals at risk. The identification of brain based neurocognitive vulnerability mARkers for schizophrenia may contribute to the development of an at risk algorithm with greater predictive accuracy. Forty subjects at risk (AR) for schizophrenia, 15 in their first episode (FE) of schizophrenia, and 36 healthy compARison (HC) subjects were administered a neurocognitive battery that assessed the domains of processing speed, working memory, verbal episodic memory, executive functioning and general intelligence. At baseline, AR subjects showed neurocognitive deficits across all domains compARed to HC subjects that were less severe than those observed in the FE sample. In preliminARy analyses, AR subjects who later converted to psychosis (N=5) had greater neurocognitive impairment at baseline evaluation compARed to those individuals who remained "at risk" at follow-up. Neurocognitive deficits may be important in the pathogenesis of eARly psychosis and could help to define individuals at greatest risk for schizophrenia. Continued reseARch in lARger cohorts is needed to test the validity of this neurocognitive profile and its utility as a vulnerability mARker. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 20 | J Psychiatr Res 2007 Oct 41: 680-5 |
| PMID | 16698037 |
| Title | Obstetrical complications in children at high risk for bipolar disorder. |
| Abstract | To examine obstetrical complications as a risk factor for developing bipolAR disorder (BPD). We hypothesized that children with a bipolAR pARent would be at greater risk for obstetrical complications than demographically matched children of healthy adults. Additionally, within this "at-risk" (AR) sample, we hypothesized that obstetrical complications would be associated with the development of psychiatric disorders. The Washington University in St. Louis Kiddie-Schedule for Affective Disorders and schizophrenia (WASH-U KSADS) was administered to children (AR) who had at least one pARent with BPD (N=36) and children of healthy pARents (HC) (N=27), by raters who were blind to diagnostic category. To assess obstetrical risk history, the Rochester ReseARch Obstetrical Scale (ROS) was administered to pARents of AR and HC children. Children at familial risk for BPD had greater total (p=0.02) and prenatal (p=0.006) obstetrical complication scores than children of healthy pARents. However, obstetrical complications were not associated with the development of affective, anxiety, or disruptive behavioral disorders within the at-risk group. Our data suggest that compARed with children of families without BPD, children of pARents with BPD may be at greater risk for obstetrical complications, pARticulARly those that occur during the prenatal period; however, at this eARly follow-up period factors other than obstetrical complications appeAR to contribute to the differences in rates of psychiatric disorders between these groups. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 21 | Int. J. Neuropsychopharmacol. 2008 Dec 11: 1085-96 |
| PMID | 18460229 |
| Title | Enhanced alpha1 adrenergic sensitivity in sensorimotor gating deficits in neonatal ventral hippocampus-lesioned rats. |
| Abstract | Neonatal ventral hippocampus (nVH) lesion in rats is a widely used animal model of schizophrenia due to the predominantly post-pubertal emergence of many schizophrenia-like behaviours. Our previous studies have shown increased ligand binding of alpha1 adrenergic receptors (AR) in the frontal cortex of post-pubertal, but not pre-pubertal, nVH-lesioned rats, compARed to sham-lesioned control rats. Moreover, pretreatment with the alpha1 adrenergic receptor antagonist prazosin reversed amphetamine-induced hyperlocomotion in controls, but failed to do so in lesioned animals. This led to our hypothesis that nVH lesions may lead to post-pubertal hyperactivity of alpha1 adrenergic receptors. In order to test the functional relevance of alpha1 adrenergic hyperactivity to schizophrenia-like behaviours of nVH-lesioned animals, we conducted prepulse inhibition (PPI) studies in post-pubertal (postnatal days 56-120) sham and lesioned animals in response to systemic injections of alpha1 adrenergic receptor antagonist and agonist, prazosin and cirazoline, respectively. Our results show that PPI deficits in nVH-lesioned animals were reversed with prazosin treatment, without a significant effect on PPI in sham animals. Further, at vARious doses, cirazoline had a significantly greater PPI disruptive effect in nVH-lesioned animals than in sham animals. Together, these results suggest that nVH-lesioned animals show a hyperactive alpha1 adrenergic receptor system that may mediate sensorimotor gating abnormalities reported in these animals. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 22 | Pharmacol. Biochem. Behav. 2008 Sep 90: 372-81 |
| PMID | 18456310 |
| Title | Idazoxan blocks the nicotine-induced reversal of the memory impairment caused by the NMDA glutamate receptor antagonist dizocilpine. |
| Abstract | Alpha2-adrenoreceptor (alpha(2)-AR) antagonists have been shown to improve, while alpha(2)-AR agonists impair cognitive function in subjects with functioning NMDA receptors (NMDAR). In subjects with inhibited NMDAR (a model of schizophrenia) alpha(2)-AR agonists attenuate the cognitive impairments. The effect with alpha(2)-AR antagonists remains uncleAR. We investigated the effects of the alpha(2)-AR antagonist idazoxan on memory function in rats treated/not treated with NMDAR antagonist dizocilpine or a combination of dizocilpine and nicotine to clARify noradrenergic/cholinergic regulation of memory function. Female Sprague-Dawley rats (n=12) were trained for food rewARd on the radial maze. Working and reference memory errors and response latency were assessed after injections of idazoxan (0.5, 1.0 mg/kg), dizocilpine (0.05 mg/kg), nicotine (0.2, 0.4 mg/kg) or vehicle, alone or in combination. Dizocilpine potently impaired memory. Nicotine (0.4 mg/kg) reversed this impairment. Idazoxan at the doses tested did not affect performance when given alone or with dizocilpine, but it did block the nicotine reversal of the dizocilpine-induced memory impairment. Three rats after 10-12 drug treatments developed limbic seizures. Our findings suggest that combination of drugs which block alpha(2)-AR with nicotinic agonists in schizophrenia may prevent therapeutic effect of nicotinic agonists and increase risk for convulsive activity with repeated administration. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 23 | Neuropsychopharmacology 2008 Aug 33: 2263-71 |
| PMID | 17957212 |
| Title | Stimulation of alpha2-adrenoceptors suppresses excitatory synaptic transmission in the medial prefrontal cortex of rat. |
| Abstract | Stimulation of alpha2-, especially alpha2A-adrenoceptor (AR), in the prefrontal cortex (PFC) produces a beneficial effect on cognitive functions such as working memory. Alpha2-adrenergic agonists like clonidine and guanfacine have been used experimentally and clinically for treatment of psychiatric disorders such as attention-deficit/hyperactivity disorder (ADHD) and schizophrenia. However, the neurophysiological actions of alpha2-ARs in the PFC ARe poorly understood. In the present study, we recorded field excitatory post-synaptic potential (fEPSP) and evoked excitatory post-synaptic current (eEPSC) in the medial prefrontal cortex (mPFC) of rats, using in vivo field-potential recording and in vitro whole-cell patch-clamp recording techniques, and examined the effects of the alpha2-AR agonist clonidine and the selective alpha2A-AR agonist guanfacine on fEPSP and eEPSC. Systemic or intra-mPFC application of clonidine or guanfacine significantly reduced fEPSP in the mPFC, either in anesthetized or freely moving rats. Consistently, bath-application of guanfacine suppressed eEPSC in layer V/VI pyramidal neurons, and this effect was blocked by the alpha2-AR antagonist yohimbine or the Gi inhibitor NF023. Moreover, treatment with guanfacine had no effect on paired-pulse facilitation (PPF) of fEPSP and eEPSC. The present study provides the first electrophysiological evidence that stimulation of alpha2A-AR inhibits excitatory synaptic transmission in the mPFC through a post-synaptic mechanism. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 24 | Handb Exp Pharmacol 2009 -1 -1: 471-534 |
| PMID | 19639292 |
| Title | Adenosine receptors and the central nervous system. |
| Abstract | The adenosine receptors (ARs) in the nervous system act as a kind of "go-between" to regulate the release of neurotransmitters (this includes all known neurotransmitters) and the action of neuromodulators (e.g., neuropeptides, neurotrophic factors). Receptor-receptor interactions and AR-transporter interplay occur as pARt of the adenosine's attempt to control synaptic transmission. A(2A)ARs ARe more abundant in the striatum and A(1)ARs in the hippocampus, but both receptors interfere with the efficiency and plasticity-regulated synaptic transmission in most brain AReas. The omnipresence of adenosine and A(2A) and A(1) ARs in all nervous system cells (neurons and glia), together with the intensive release of adenosine following insults, makes adenosine a kind of "maestro" of the tripARtite synapse in the homeostatic coordination of the brain function. Under physiological conditions, both A(2A) and A(1) ARs play an important role in sleep and ARousal, cognition, memory and leARning, whereas under pathological conditions (e.g., PARkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, epilepsy, drug addiction, pain, schizophrenia, depression), ARs operate a time/circumstance window where in some circumstances A(1)AR agonists may predominate as eARly neuroprotectors, and in other circumstances A(2A)AR antagonists may alter the outcomes of some of the pathological deficiencies. In some circumstances, and depending on the therapeutic window, the use of A(2A)AR agonists may be initially beneficial; however, at later time points, the use of A(2A)AR antagonists proved beneficial in several pathologies. Since selective ligands for A(1) and A(2A) ARs ARe now entering clinical trials, the time has come to determine the role of these receptors in neurological and psychiatric diseases and identify therapies that will alter the outcomes of these diseases, therefore providing a hopeful future for the patients who suffer from these diseases. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 25 | Synapse 2009 Dec 63: 1051-9 |
| PMID | 19637275 |
| Title | Altered expression and alpha-1 adrenergic receptor mediated activity of protein kinase C in the prefrontal cortex of rats with neonatal ventral hippocampus lesions. |
| Abstract | The neonatal ventral hippocampus (nVH) lesion in rats captures many features of schizophrenia at the levels of behavior and neurobiological mARkers. We have previously reported enhanced expression of alpha-1 adrenergic receptors (AR) in the prefrontal cortex (PFC) of postpubertal nVH-lesioned rats and proposed that enhanced alpha-1 AR signaling might pARticipate in some of the behavioral abnormalities observed in the nVH-lesioned rats. To assess the components of alpha-1 adrenergic signaling in nVH-lesion rats, we examined prefrontal cortical expression of protein kinase C (PKC) subtypes by Western blotting and alpha-1 AR-stimulated PKC activity by in vitro enzyme assay in postpubertal animals. Neonatal VH-lesioned animals showed significantly increased expression of membrane-bound PKC-alpha and the phosphorylated form of PKC. Cytosolic PKC-beta II and PKC-gamma expression were found to be decreased in the PFC of lesioned animals with no change in the expression of PKC-beta I either in the cytosol or membrane. PKC activity assays showed an increase in basal PKC activity in the PFC slices of nVH-lesioned animals. Stimulation of alpha-1 adrenergic receptor with different concentrations of the agonist phenylephrine (PE), while increasing PKC activity in the sham-lesioned animals surprisingly decreased the activity in nVH-lesioned animals. Increased basal levels as well as activity of prefrontal PKC and its anomalous regulation by alpha-1 adrenergic receptors may pARticipate in the cognitive and stress-induced behavioral alterations in nVH-lesioned animals. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 26 | J. Alzheimers Dis. 2010 -1 20 Suppl 1: S3-15 |
| PMID | 20164566 |
| Title | Caffeine and adenosine. |
| Abstract | Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain AReas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellulAR stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, leARning, and memory, and modifies brain dysfunctions and diseases: Alzheimer's disease, PARkinson's disease, Huntington's disease, Epilepsy, Pain/Migraine, Depression, schizophrenia. In conclusion, tARgeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 27 | Neuropsychology 2010 Jan 24: 109-20 |
| PMID | 20063952 |
| Title | Course of neurocognitive deficits in the prodrome and first episode of schizophrenia. |
| Abstract | Understanding the trajectory of cognitive changes in the development of schizophrenia may shed light on the neurodevelopmental processes in the beginning stage of illness. Subjects at risk for psychosis (AR, n = 48), patients in their first episode of schizophrenia (FE, n = 20), and normal compARison subjects (n = 29) were assessed on a neurocognitive battery at baseline and at a 6-month follow-up. There were significant group differences across all cognitive domains as well as a significant group by time interaction in the verbal leARning domain. After statistically controlling for practice effects and regression to the mean, a high proportion of FE subjects showed an improvement in verbal leARning, and a significant number of AR subjects improved in general intelligence. Moreover, a higher than expected percentage of FE subjects, as well as AR subjects who later converted to psychosis, showed a deterioration in working memory and processing speed. These inconsistent trajectories suggest that some domains may improve with stabilization in the eARly stages of psychosis, whereas others may decline with progression of the illness, indicating possible tARgets for cognitive remediation strategies and candidate vulnerability mARkers for future psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 28 | Int Clin Psychopharmacol 2010 Nov 25: 334-41 |
| PMID | 20706126 |
| Title | Tolerability of paliperidone: a meta-analysis of randomized, controlled trials. |
| Abstract | Balancing tolerability and efficacy of medications can be problematic for clinicians when assessing appropriate therapy for patients. For antipsychotic therapy, this can be especially challenging because of the hazARdous movement and metabolic effects associated with them. Paliperidone is an atypical antipsychotic used for the treatment of schizophrenia and schizoaffective disorder. A systematic review of the literature for the tolerability of the drug, paliperidone, was performed. A total of 15 ARticles met the criteria for inclusion representing a total of 3779 patients. Data combination was conducted using the Mantel-Haenszel method, random effects model at 95% confidence. Adverse events with the greatest incidence in the paliperidone population were any treatment emergent adverse event (68%), extra-pyramidal symptoms (23%), headache (14%), insomnia (11%), somnolence (9%), tachycARdia (9%) and weight gain (8%). Reported events most likely related to paliperidone [lARgest attributable risks (AR)] were extra-pyramidal symptoms (AR=10), reduction in acute psychosis (AR=8), any treatment emergent adverse event (AR=6), tachycARdia (AR=4), and weight gain (AR=4). Events where incidence was entirely because of paliperidone (incidence equals AR) were hypersalivation (3), dysARthria (2), and sexual dysfunction (1). Reported events totally unrelated to paliperidone (AR=0) included anxiety, asthenia, constipation, depression, dyspepsia, glucose related events, and vomiting. Overall, a 50% reduction in treatment emergent psychosis was seen in schizophrenic patients treated with paliperidone, however the reduction of a psychotic event is about equal to the occurrence of an adverse event with paliperidone. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 29 | Int Clin Psychopharmacol 2010 Nov 25: 334-41 |
| PMID | 20706126 |
| Title | Tolerability of paliperidone: a meta-analysis of randomized, controlled trials. |
| Abstract | Balancing tolerability and efficacy of medications can be problematic for clinicians when assessing appropriate therapy for patients. For antipsychotic therapy, this can be especially challenging because of the hazARdous movement and metabolic effects associated with them. Paliperidone is an atypical antipsychotic used for the treatment of schizophrenia and schizoaffective disorder. A systematic review of the literature for the tolerability of the drug, paliperidone, was performed. A total of 15 ARticles met the criteria for inclusion representing a total of 3779 patients. Data combination was conducted using the Mantel-Haenszel method, random effects model at 95% confidence. Adverse events with the greatest incidence in the paliperidone population were any treatment emergent adverse event (68%), extra-pyramidal symptoms (23%), headache (14%), insomnia (11%), somnolence (9%), tachycARdia (9%) and weight gain (8%). Reported events most likely related to paliperidone [lARgest attributable risks (AR)] were extra-pyramidal symptoms (AR=10), reduction in acute psychosis (AR=8), any treatment emergent adverse event (AR=6), tachycARdia (AR=4), and weight gain (AR=4). Events where incidence was entirely because of paliperidone (incidence equals AR) were hypersalivation (3), dysARthria (2), and sexual dysfunction (1). Reported events totally unrelated to paliperidone (AR=0) included anxiety, asthenia, constipation, depression, dyspepsia, glucose related events, and vomiting. Overall, a 50% reduction in treatment emergent psychosis was seen in schizophrenic patients treated with paliperidone, however the reduction of a psychotic event is about equal to the occurrence of an adverse event with paliperidone. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 30 | ORL J. Otorhinolaryngol. Relat. Spec. 2010 -1 72: 235-41 |
| PMID | 20689336 |
| Title | Psychological aspects of female patients with moderate-to-severe persistent allergic rhinitis. |
| Abstract | Allergic rhinitis (AR) has been shown to impair social life and psychological functioning. The objective of our study was to explore the relationships between moderate-to-severe persistent AR and personality traits in non-psychiatric female outpatients. Female subjects were assigned to the allergic (n = 52, 24 singletons and 28 non-singletons) or non-allergic group (n = 28, 11 singletons and 17 non-singletons) on the basis of skin prick tests (SPT) and allergic symptoms. Individuals in this study were only allergic to Dermatophagoides pteronyssinus and/or D. fARinae. The psychological aspects of the female subjects were assessed by using the Minnesota Multiphasic Personality Inventory (MMPI). The allergic group scored significantly higher than the non-allergic group on 6 clinical scales [hypochondriasis (Hs), depression (D), hysteria (Hy), psychasthenia (Pt), schizophrenia (Sc), social introversion (Si)] and 1 validity scale [infrequency (F)]. Analysis of female singleton outpatient MMPI profiles showed that allergic subjects scored significantly higher on D, Hy, masculinity/femininity (Mf), Pt, and F. In addition, the grade of skin index (resulting from an SPT) was positively correlated with T-scores on the Hs, Hy, Pt, and Sc scales. Women with moderate-to-severe persistent AR, especially singleton patients, show poorer psychological functioning, indicating the close relationship between moderate-to-severe persistent AR and psychological functioning. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 31 | Psychiatry Res 2010 Apr 176: 120-5 |
| PMID | 20202689 |
| Title | Functional significance of preserved affect recognition in schizophrenia. |
| Abstract | Affect recognition (AR) is a core component of social information processing; thus, it may be critical to understanding social behavior and functioning in broader aspects of daily living. Deficits in AR ARe well documented in schizophrenia, but there is also evidence that many individuals with schizophrenia perform AR tasks at neAR-normal levels. In the current study, we sought to evaluate the functional significance of AR deficits in schizophrenia by compARing subgroups with normal-range and impaired AR performance on proxy and interviewer-rated measures of real-world functioning. schizophrenia outpatients were classified as normal-range (N=17) and impaired (N=31) based on a logistic cut point in the sample distribution of Bell-Lysaker Emotion Recognition Task (BLERT) scores, referenced to a normative sample of healthy control subjects (N=56). The derived schizophrenia subgroups were then compARed on proxy [University of California San Diego Performance-Based Skill Assessment (UPSA), Social Skills Performance Assessment (SSPA), Medication Management Ability Assessment (MMAA)] and interviewer-rated [Quality of Life Scale (QLS), Independent Living Skills Survey (ILSS)] measures of functioning, as well as a battery of neurocognitive tests. Initial analyses indicated superior MMAA and QLS performance in the neAR-normal AR subgroup. CovARiate analyses indicated that group differences in neurocognition fully mediated the observed associations between AR and MMAA, and attenuated the observed relationships between AR classification and QLS. These results support three main conclusions. First, AR, like many other domains of psychopathology studied in schizophrenia, is preserved in select subgroups. Second, there is a positive relationship between AR performance and functional outcome measures. Third, neurocognition appeARs to mediate the relationship between AR and measures of functioning. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 32 | Proc. West. Pharmacol. Soc. 2010 -1 53: 44-5 |
| PMID | 22128452 |
| Title | Pharmacovigilance of psychoactive medications in a Mexican psychiatric hospital. |
| Abstract | PhARmacovigilance is the permanent collection and assessment of the safety data of drugs in the interest of precise knowledge of the safety profile. We monitored notifications of suspected adverse reactions (AR) produced by psychoactive medications (ARPM) in a Psychiatry Hospital, during a 4-month period. Yellow cARds for adverse reaction reporting were distributed to the medical personal at the Hospital Psiquiátrico Villa OcARanza, Pachuca Hidalgo, Mexico. For each notification, the ARPM was analyzed in order to verify causality. One hundred twelve hospitalized patients entered the study (44 male and 68 female). The mean +/- SD age of the patients was 46 +/- 4.5 yeARs. The major diagnoses found were: schizophrenia (35.7%), severe mental retARdation (17 %), moderate mental retARdation (MMR)/epilepsy (12.5%), MMR (8.03%), and others (26.7%). During the study there were 721 therapeutic regimens prescribed to patients on psychiatric service. Patients were receiving an average of 5.3 +/- 1.1 (range 4 to 8) psychiatric medications. The psychiatrists reported only 5 ARPMs in five patients (prevalence: 4.46%). Among the drugs involved were neuroleptics (47.8%), antiepileptic (39.1%), and others (13.04%). The organs and systems affected by the ARs were the central nervous system, skin, endocrinological and gastrointestinal. A causal association between the medication and the AR were classified as probable in three cases, as possible in one case, as doubtful in one case and as definite in no case. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 33 | Neuroimage 2010 Jan 49: 1875-85 |
| PMID | 19770054 |
| Title | Structural and functional brain correlates of subclinical psychotic symptoms in 11-13 year old schoolchildren. |
| Abstract | Studying children experiencing psychotic symptoms provides a unique opportunity to examine the vulnerability to psychosis within the context of development. Using neuroimaging techniques this study investigated cognitive control functions, brain volumetrics and white matter integrity in an at-risk cohort of children. Between-subjects assessment of brain function and structure among 11 school-going, non-treatment seeking children aged 11-13 who were at symptomatic risk for psychosis (AR) and 14 healthy control children aged 11-12 without subclinical psychotic symptoms (CON). MRI assessments included functional measures of response inhibition and error-related processes, whole brain voxel-based morphometry (VBM) of gray matter (GM) and diffusion tensor imaging (DTI) utilizing fractional anisotropy to probe white matter (WM) integrity. fMRI results showed reduced activity in the AR group within right frontal and bilateral temporal cortex for response inhibition and reduced activity within the anterior cingulate, insula and middle frontal gyrus for error-related processing (p<.05, corrected). VBM analysis revealed GM increases in the AR group within middle and superior temporal gyri, angulAR gyrus, orbitofrontal gyrus and GM decrease within the inferior temporal gyrus (p<.05, corrected). DTI analysis identified WM decreases in the AR group along the inferior fronto-occipital fasciculus, cingulum and inferior longitudinal fasciculus (p<.05, corrected). This multimodal investigation revealed aberrant prefrontal-temporal dysfunction in addition to cingulate and insulAR dysfunctions which provide potential eARly neurocognitive risk mARkers related to the susceptibility for developing psychosis and subsequently the neurodevelopmental trajectory leading to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 34 | J Psychiatr Res 2010 Jan 44: 99-105 |
| PMID | 19616790 |
| Title | Affective reactivity of speech disturbances in schizotypy. |
| Abstract | Speech disturbances (SD) ARe a pernicious symptom of schizophrenia that increase when negative emotion is elicited. This increase is referred to as affective reactivity (AR). Although considerable reseARch has examined SD in schizophrenia, few studies have investigated this symptom in individuals at risk for the disorder, who demonstrate schizophrenia-like, or schizotypic, traits. In the present study, we examined: (1) SD severity in schizotypy, (2) how SD vARies as a function of stress reactivity in schizotypy, and (3) the relationship between SD/AR with Quality of Life (QOL). Individuals with psychometrically-defined schizotypy (n=83) and controls (n=22) completed a laboratory procedure in which they produced speech while viewing pleasant and stressful photographs. This speech was analyzed for subtle speech disorder using a well-validated measure. We found that the schizotypy group demonstrated significant increases in SD across both baseline and stressful conditions compARed to the control group. AR was not significantly different between the groups. Within the schizotypy group, severity of disorganized schizotypy symptoms was associated with high levels of SD and AR while interpersonal schizotypy was associated with low levels of SD and AR. AR was also related to increased objective QOL in the schizotypy group. This study highlights the role of stress reactivity across the schizophrenia-spectrum. Moreover, the incongruous relationships between disorganized and interpersonal symptoms with SD underscore the mARked heterogeneity in processes across schizotypy. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 35 | J Psychiatr Res 2010 Jan 44: 99-105 |
| PMID | 19616790 |
| Title | Affective reactivity of speech disturbances in schizotypy. |
| Abstract | Speech disturbances (SD) ARe a pernicious symptom of schizophrenia that increase when negative emotion is elicited. This increase is referred to as affective reactivity (AR). Although considerable reseARch has examined SD in schizophrenia, few studies have investigated this symptom in individuals at risk for the disorder, who demonstrate schizophrenia-like, or schizotypic, traits. In the present study, we examined: (1) SD severity in schizotypy, (2) how SD vARies as a function of stress reactivity in schizotypy, and (3) the relationship between SD/AR with Quality of Life (QOL). Individuals with psychometrically-defined schizotypy (n=83) and controls (n=22) completed a laboratory procedure in which they produced speech while viewing pleasant and stressful photographs. This speech was analyzed for subtle speech disorder using a well-validated measure. We found that the schizotypy group demonstrated significant increases in SD across both baseline and stressful conditions compARed to the control group. AR was not significantly different between the groups. Within the schizotypy group, severity of disorganized schizotypy symptoms was associated with high levels of SD and AR while interpersonal schizotypy was associated with low levels of SD and AR. AR was also related to increased objective QOL in the schizotypy group. This study highlights the role of stress reactivity across the schizophrenia-spectrum. Moreover, the incongruous relationships between disorganized and interpersonal symptoms with SD underscore the mARked heterogeneity in processes across schizotypy. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 36 | Psychiatry Res 2011 Jul 188: 208-16 |
| PMID | 21555157 |
| Title | Startle reactivity and prepulse inhibition in prodromal and early psychosis: effects of age, antipsychotics, tobacco and cannabis in a vulnerable population. |
| Abstract | The use of biomARkers in the study of the prodrome and first episode of psychosis provides a means of not only identifying individuals at greatest risk for psychosis but also understanding neurodevelopmental abnormalities eARly in the course of illness. Prepulse inhibition (PPI), a mARker that is deficient in schizophrenia and after developmental manipulations in animal models, was assessed in 75 eARly psychosis (EP), 89 at risk (AR) for psychosis and 85 compARison subjects (CS) at baseline and 6 months. Consistent with findings in chronic schizophrenia, PPI was stable with repeated assessment and EP subjects had reduced PPI but this was most evident in tobacco smokers. A significant positive PPI and age association in AR and EP samples, but not CS, demonstrated potential neurodevelopmental differences in eARly psychosis. Unexpected findings included the fact that medication naive EP subjects, as well as AR subjects who later developed psychosis, had greater PPI, introducing the possibility of eARly compensatory changes that diverge from findings in chronic patients. In addition, subjects with a history of cannabis use had greater stARtle reactivity while EP and AR subjects who used cannabis and were also taking an antipsychotic had greater PPI, again highlighting the potentially important cannabis/psychosis association. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 37 | Iran J Psychiatry Behav Sci 2011 -1 5: 62-70 |
| PMID | 24644448 |
| Title | Usefulness of approximate entropy in the diagnosis of schizophrenia. |
| Abstract | Diagnosis of the psychiatric diseases is a bit challenging at the first interview due to this fact that qualitative criteria ARe not as accurate as quantitative ones. Here, the objective is to classify schizophrenic patients from the healthy subject using a quantitative index elicited from their electroencephalogram (EEG) signals. Ten right handed male patients with schizophrenia who had just auditory hallucination and did not have any other psychotic features and ten age-matched right handed normal male control pARticipants pARticipated in this study. The patients used haloperidol to minimize the drug-related affection on their EEG signals. Electrophysiological data were recorded using a Neuroscan 24 Channel Synamps system, with a signal gain equal to 75K (150 xs at the headbox). According to the observable anatomical differences in the brain of schizophrenic patients from controls, several discriminative features including AR coefficients, band power, fractal dimension, and approximation entropy (ApEn) were chosen to extract quantitative values from the EEG signals. The extracted features were applied to support vector machine (SVM) classifier that produced 88.40% accuracy for distinguishing the two groups. Incidentally, ApEn produces more discriminative information compARe to the other features. This reseARch presents a reliable quantitative approach to distinguish the control subjects from the schizophrenic patients. Moreover, other representative features ARe implemented but ApEn produces higher performance due to complex and irregulAR nature of EEG signals. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 38 | Iran J Psychiatry Behav Sci 2011 -1 5: 62-70 |
| PMID | 24644448 |
| Title | Usefulness of approximate entropy in the diagnosis of schizophrenia. |
| Abstract | Diagnosis of the psychiatric diseases is a bit challenging at the first interview due to this fact that qualitative criteria ARe not as accurate as quantitative ones. Here, the objective is to classify schizophrenic patients from the healthy subject using a quantitative index elicited from their electroencephalogram (EEG) signals. Ten right handed male patients with schizophrenia who had just auditory hallucination and did not have any other psychotic features and ten age-matched right handed normal male control pARticipants pARticipated in this study. The patients used haloperidol to minimize the drug-related affection on their EEG signals. Electrophysiological data were recorded using a Neuroscan 24 Channel Synamps system, with a signal gain equal to 75K (150 xs at the headbox). According to the observable anatomical differences in the brain of schizophrenic patients from controls, several discriminative features including AR coefficients, band power, fractal dimension, and approximation entropy (ApEn) were chosen to extract quantitative values from the EEG signals. The extracted features were applied to support vector machine (SVM) classifier that produced 88.40% accuracy for distinguishing the two groups. Incidentally, ApEn produces more discriminative information compARe to the other features. This reseARch presents a reliable quantitative approach to distinguish the control subjects from the schizophrenic patients. Moreover, other representative features ARe implemented but ApEn produces higher performance due to complex and irregulAR nature of EEG signals. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 39 | Biol. Psychiatry 2011 Oct 70: 663-71 |
| PMID | 21641581 |
| Title | Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. |
| Abstract | schizophrenia is associated with immune system dysfunction, including aberrant cytokine levels. We performed a meta-analysis of these associations, considering effects of clinical status and antipsychotic treatment following an acute illness exacerbation. We identified ARticles by seARching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies. Forty studies met the inclusion criteria. Effect sizes were similAR for studies of acutely relapsed inpatients (AR) and first-episode psychosis (FEP). Interleukin (IL)-1?, IL-6, and transforming growth factor-? (TGF-?) appeARed to be state mARkers, as they were increased in AR and FEP (p < .001 for each) and normalized with antipsychotic treatment (p < .001, p = .008, and p = .005, respectively). In contrast, IL-12, interferon-? (IFN-?), tumor necrosis factor-? (TNF-?), and soluble IL-2 receptor (sIL-2R) appeARed to be trait mARkers, as levels remained elevated in acute exacerbations and following antipsychotic treatment. There was no difference in IL-6 levels between stable medicated outpatients and control subjects (p = .69). In the cerebrospinal fluid, IL-1? was significantly decreased in schizophrenia versus controls (p = .01). SimilAR effect sizes in AR and FEP suggest that the association between cytokine abnormalities and acute exacerbations of schizophrenia is independent of antipsychotic medications. While some cytokines (IL-1?, IL-6, and TGF-?) may be state mARkers for acute exacerbations, others (IL-12, IFN-?, TNF-?, and sIL-2R) may be trait mARkers. Although these results could provide the basis for future hypothesis testing, most studies did not control for potential confounding factors such as body mass index and smoking. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 40 | J. Biol. Chem. 2011 Mar 286: 9360-72 |
| PMID | 21233214 |
| Title | Contribution of Kv1.2 voltage-gated potassium channel to D2 autoreceptor regulation of axonal dopamine overflow. |
| Abstract | Impairments in axonal dopamine release ARe associated with neurological disorders such as schizophrenia and attention deficit hyperactivity disorder and pathophysiological conditions promoting drug abuse and obesity. The D2 dopamine autoreceptor (D2-AR) exerts tight regulatory control of axonal dopamine (DA) release through a mechanism suggested to involve K(+) channels. To evaluate the contribution of Kv1 voltage-gated potassium channels of the Shaker gene family to the regulation of axonal DA release by the D2-AR, the present study employed expression analyses, real time measurements of striatal DA overflow, K(+) current measurements and immunoprecipitation assays. Kv1.1, -1.2, -1.3, and -1.6 mRNA and protein were detected in midbrain DA neurons purified by fluorescence-activated cell sorting and in primARy DA neuron cultures. In addition, Kv1.1, -1.2, and -1.6 were localized to DA axonal processes in the dorsal striatum. By means of fast scan cyclic voltammetry in striatal slice prepARations, we found that the inhibition of stimulation-evoked DA overflow by a D2 agonist was attenuated by Kv1.1, -1.2, and -1.6 toxin blockers. A pARticulAR role for the Kv1.2 subunit in the process whereby axonal D2-AR inhibits DA overflow was established with the use of a selective Kv1.2 blocker and Kv1.2 knock-out mice. Moreover, we demonstrate the ability of D2-AR activation to increase Kv1.2 currents in co-transfected cells and its reliance on G?? subunit signaling along with the physical coupling of D2-AR and Kv1.2-containing channels in striatal tissue. These findings underline the contribution of Kv1.2 in the regulation of nigrostriatal DA release by the D2-AR and thereby offer a novel mechanism by which DA release is regulated. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 41 | Int J Mol Sci 2012 -1 13: 2219-38 |
| PMID | 22408449 |
| Title | Alpha7 nicotinic acetylcholine receptor is a target in pharmacology and toxicology. |
| Abstract | Alpha7 nicotinic acetylcholine receptor (?7 nAChR) is an important pARt of the cholinergic nerve system in the brain. Moreover, it is associated with a cholinergic anti-inflammatory pathway in the termination of the pARasympathetic nervous system. Antagonists of ?7 nAChR ARe a wide group represented by conotoxin and bungARotoxin. Even Alzheimer's disease drug memantine acting as an antagonist in its side pathway belongs in this group. Agonists of ?7 nAChR ARe suitable for treatment of multiple cognitive dysfunctions such as Alzheimer's disease or schizophrenia. Inflammation or even sepsis can be ameliorated by the agonistic acting compounds. PrepARations RG3487, SEN34625/WYE-103914, SEN12333, ABT-107, Clozapine, GTS-21, CNI-1493, and AR-R17779 ARe representative examples of the novel compounds with affinity towARd the ?7 nAChR. PhARmacological, toxicological, and medicinal significance of ?7 nAChR ARe discussed throughout this paper. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 42 | BMC Neurosci 2012 -1 13: 95 |
| PMID | 22867132 |
| Title | Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra. |
| Abstract | Increased risk of schizophrenia in adolescent males indicates that a link between the development of dopamine-related psychopathology and testosterone-driven brain changes may exist. However, contradictions as to whether testosterone increases or decreases dopamine neurotransmission ARe found and most studies address this in adult animals. Testosterone-dependent actions in neurons ARe direct via activation of androgen receptors (AR) or indirect by conversion to 17?-estradiol and activation of estrogen receptors (ER). How midbrain dopamine neurons respond to sex steroids depends on the presence of sex steroid receptor(s) and the level of steroid conversion enzymes (ARomatase and 5?-reductase). We investigated whether gonadectomy and sex steroid replacement could influence dopamine levels by changing tyrosine hydroxylase (TH) protein and mRNA and/or dopamine breakdown enzyme mRNA levels [catechol-O-methyl transferase (COMT) and monoamine oxygenase (MAO) A and B] in the adolescent male rat substantia nigra. We hypothesized that adolescent testosterone would regulate sex steroid signaling through regulation of ER and AR mRNAs and through modulation of ARomatase and 5?-reductase mRNA levels. We find ER? and AR in midbrain dopamine neurons in adolescent male rats, indicating that dopamine neurons ARe poised to respond to circulating sex steroids. We report that androgens (T and DHT) increase TH protein and increase COMT, MAOA and MAOB mRNAs in the adolescent male rat substantia nigra. We report that all three sex steroids increase AR mRNA. Differential action on ER pathways, with ER? mRNA down-regulation and ER? mRNA up-regulation by testosterone was found. 5? reductase-1 mRNA was increased by AR activation, and ARomatase mRNA was decreased by gonadectomy. We conclude that increased testosterone at adolescence can shift the balance of sex steroid signaling to favor androgenic responses through promoting conversion of T to DHT and increasing AR mRNA. Further, testosterone may increase local dopamine synthesis and metabolism, thereby changing dopamine regulation within the substantia nigra. We show that testosterone action through both AR and ERs modulates synthesis of sex steroid receptor by altering AR and ER mRNA levels in normal adolescent male substantia nigra. Increased sex steroids in the brain at adolescence may alter substantia nigra dopamine pathways, increasing vulnerability for the development of psychopathology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 43 | Psychol Med 2012 Oct 42: 2167-79 |
| PMID | 22717191 |
| Title | Visual information processing dysfunction across the developmental course of early psychosis. |
| Abstract | Patients with schizophrenia consistently demonstrate information processing abnormalities assessed with visual masking (VM) tasks, and these deficits have been linked to clinical and functional severity. It has been suggested that VM impairments may be a vulnerability mARker in individuals at risk for developing psychosis. ForwARd and backwARd VM performance was assessed in 72 first-episode (FE) psychosis patients, 98 subjects at risk (AR) for psychosis and 98 healthy controls (HC) using two identification tasks (with either a high- or low-energy mask) and a location task. VM was examined for stability in a subgroup (FE, n=15; AR, n=35; HC, n=21) and assessed relative to clinical and functional measures. In the identification tasks, backwARd VM deficits were observed in both FE and AR relative to HC whereas forwARd VM deficits were only present in FE patients compARed to HC. In the location task, AR subjects demonstrated superior performance in forwARd VM relative to HC. VM performance was stable over time, and VM deficits were associated with baseline functional measures and predicted future negative symptom severity in AR subjects. Visual information processing deficits, as indexed by backwARd VM, ARe present before and after the onset of frank psychosis, and probably represent a stable vulnerability mARker that is associated with negative symptoms and functional decline. Additionally, the pARadoxically better performance of AR subjects in select forwARd tasks suggests that eARly compensatory changes may chARacterize an emerging psychotic state. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 44 | J Chem Inf Model 2013 Dec 53: 3202-11 |
| PMID | 24245825 |
| Title | Molecular modeling of the 3D structure of 5-HT(1A)R: discovery of novel 5-HT(1A)R agonists via dynamic pharmacophore-based virtual screening. |
| Abstract | The serotonin receptor subtype 1A (5-HT(1A)R) has been implicated in several neurological conditions, and potent 5-HT(1A)R agonists have therapeutic potential for the treatment of depression, anxiety, schizophrenia, and PARkinson's disease. In the present study, a homology model of 5-HT(1A)R was built based on the latest released high-resolution crystal structure of the ??AR in its active state (PDB: 3SN6). A dynamic phARmacophore model, which takes the receptor flexibility into account, was constructed, validated, and applied to our dynamic phARmacophore-based virtual screening approach with the aim to identify potential 5-5-HT(1A)R agonists. The obtained hits were subjected to 55-HT(1A)R binding and functional assays, and 10 compounds with medium or high K(i) and EC?? values were identified. Among them, FW01 (K(i) = 51.9 nM, EC?? = 7 nM) was evaluated as the strongest agonist for 5-HT(1A)R. The active 5-HT(1A)R model and dynamic phARmacophore model obtained from this study can be used for future discovery and design of novel 5-HT(1A)R agonists. Also, by integrating all computational and available experimental data, a stepwise 5-HT(1A)R signal transduction model induced by agonist FW01 was proposed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 45 | Neuropsychobiology 2013 -1 68: 139-45 |
| PMID | 24051542 |
| Title | Facial affect recognition performance and event-related potentials in violent and non-violent schizophrenia patients. |
| Abstract | We investigated whether male inpatients with schizophrenia and a history of hands-on violent offences (forensic schizophrenic, FOS) ARe more impaired in emotion recognition than matched schizophrenia patients without any history of violence (general psychiatric schizophrenic, GPS). This should become appARent in performance in psychometry and in scalp event-related brain potentials (ERPs) evoked by pictures of facial affect. FOS and GPS (each n = 19) were matched concerning age, intelligence, comorbid addiction, medication and illness duration. FOS revealed significantly poorer affect recognition (AR) performance, especially of neutral and feAR stimuli. Analysis of ERPs revealed a significant interaction of hemisphere, electrode position and group of the N250 component. Post hoc analysis of group effect showed significantly lARger amplitudes in FOS at FC3. These results support the hypothesis that in FOS emotional faces ARe more salient and evoke higher ARousal. LARger impairment in AR performance combined with higher salience and ARousal may contribute to the occurrence of violent acts in schizophrenia patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 46 | Neuropsychobiology 2013 -1 68: 139-45 |
| PMID | 24051542 |
| Title | Facial affect recognition performance and event-related potentials in violent and non-violent schizophrenia patients. |
| Abstract | We investigated whether male inpatients with schizophrenia and a history of hands-on violent offences (forensic schizophrenic, FOS) ARe more impaired in emotion recognition than matched schizophrenia patients without any history of violence (general psychiatric schizophrenic, GPS). This should become appARent in performance in psychometry and in scalp event-related brain potentials (ERPs) evoked by pictures of facial affect. FOS and GPS (each n = 19) were matched concerning age, intelligence, comorbid addiction, medication and illness duration. FOS revealed significantly poorer affect recognition (AR) performance, especially of neutral and feAR stimuli. Analysis of ERPs revealed a significant interaction of hemisphere, electrode position and group of the N250 component. Post hoc analysis of group effect showed significantly lARger amplitudes in FOS at FC3. These results support the hypothesis that in FOS emotional faces ARe more salient and evoke higher ARousal. LARger impairment in AR performance combined with higher salience and ARousal may contribute to the occurrence of violent acts in schizophrenia patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 47 | J Psychiatr Res 2013 Sep 47: 1215-21 |
| PMID | 23786914 |
| Title | Analysis of miR-137 expression and rs1625579 in dorsolateral prefrontal cortex. |
| Abstract | MicroRNAs (miRNAs) ARe small non-coding RNAs that act as potent regulators of gene expression. A recent GWAS reported the rs1625579 SNP, located downstream of miR-137, as the strongest new association with schizophrenia [Ripke S, Sanders AR, Kendler KS, Levinson DF, SklAR P, Holmans PA, et al. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011;43:969-76.]. Prior to this GWAS finding, a schizophrenia imaging-genetic study found miR-137 tARget genes significantly enriched for association with activation in the dorsolateral prefrontal cortex (DLPFC) [Potkin SG, MacciARdi F, Guffanti G, Fallon JH, Wang Q, Turner JA, et al. Identifying gene regulatory networks in schizophrenia. Neuroimage 2010;53:839-47.]. We investigated the expression levels of miR-137 and three candidate tARget genes (ZNF804A, CACNA1C, TCF4) in the DLPFC of postmortem brain tissue from 2 independent cohorts: (1) 26 subjects (10 control (CTR), 7 schizophrenia (SZ), 9 bipolAR disorder (BD)) collected at the UCI brain bank; and (2) 99 subjects (33 CTR, 35 SZ, 31 BD) obtained from the Stanley Medical ReseARch Institute (SMRI). MiR-137 expression in the DLPFC did not differ between diagnoses. We also explored the relationship between rs1625579 genotypes and miR-137 expression. Significantly lower miR-137 expression levels were observed in the homozygous TT subjects compARed to TG and GG subjects in the control group (30% decrease, p-value = 0.03). Moreover, reduced miR-137 levels in TT subjects corresponded to increased levels of the miR-137 tARget gene TCF4. The miR-137 expression pattern in 9 brain regions was significant for regional effect (ANOVA p-value = 1.83E-12), with amygdala and hippocampus having the highest miR-137 expression level. In conclusion, decreased miR-137 expression is associated with the SZ risk allele of rs1625579, and potential regulation of TCF4, another SZ candidate gene. This study offers additional support for involvement of miR-137 and downstream tARgets as mechanisms of risk for psychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 48 | Basic Clin. Pharmacol. Toxicol. 2013 Oct 113: 239-49 |
| PMID | 23718812 |
| Title | Pharmacological characterisation of a structurally novel ?2C-adrenoceptor antagonist ORM-10921 and its effects in neuropsychiatric models. |
| Abstract | The ?2-adrenoceptors (ARs) ARe important modulators of a wide ARray of physiological responses. As only a few selective compounds for the three ?2-AR subtypes (?2A , ?2B and ?2C ) have been available, the phARmacological profile of a new ?2C-selective AR antagonist ORM-10921 is reported. StandARd in vitro receptor assays and antagonism of ?2, and ?1-AR agonist-evoked responses in vivo were used to demonstrate the ?2C-AR selectivity for ORM-10921 which was tested in established behavioural models related to schizophrenia and cognitive dysfunction with an emphasis on phARmacologically induced hypoglutamatergic state by phencyclidine or MK-801. The Kb values of in vitro ?2C-AR antagonism for ORM-10921 vARied between 0.078-1.2 nM depending on the applied method. The selectivity ratios compARed to ?2A-AR subtype and other relevant receptors were 10-100 times in vitro. The in vivo experiments supported its potent ?2C-antagonism combined with only a weak ?2A-antagonism. In the phARmacodynamic microdialysis study, ORM-10921 was found to increase extracellulAR dopamine levels in prefrontal cortex in the baseline conditions. In the behavioural tests, ORM-10921 displayed potent antidepressant and antipsychotic-like effects in the forced swimming test and prepulse-inhibition models analogously with the previously reported results with structurally different ?2C-selective AR antagonist JP-1302. Our new results also indicate that ORM-10921 alleviated the NMDA-antagonist-induced impairments in social behaviour and watermaze navigation. This study extends and further validates the concept that ?2C -AR is a potential therapeutic tARget in CNS disorders such as schizophrenia or Alzheimer's disease and suggests the potential of ?2C-antagonism to treat such disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 49 | Int. J. Neuropsychopharmacol. 2013 Jun 16: 1139-51 |
| PMID | 23195622 |
| Title | Expression of ?(1)-adrenergic receptors in rat prefrontal cortex: cellular co-localization with 5-HT(2A) receptors. |
| Abstract | The prefrontal cortex (PFC) is involved in behavioural control and cognitive processes that ARe altered in schizophrenia. The brainstem monoaminergic systems control PFC function, yet the cells/networks involved ARe not fully known. Serotonin (5-HT) and norepinephrine (NE) increase PFC neuronal activity through the activation of ?(1)-adrenergic receptors (?(1)ARs) and 5-HT(2A) receptors (5-HT(2A)Rs), respectively. Neurochemical and behavioural interactions between these receptors have been reported. Further, classical and atypical antipsychotic drugs shARe nm in vitro affinity for ?(1)ARs while having preferential affinity for D(2) and 5-HT(2A)Rs, respectively. Using double in situ hybridization we examined the cellulAR expression of ?(1)ARs in pyramidal (vGluT1-positive) and GABAergic (GAD(65/67)-positive) neurons in rat PFC and their co-localization with 5-HT(2A)Rs. ?(1)ARs ARe expressed by a high proportion of pyramidal (59-85%) and GABAergic (52-79%) neurons. The expression in pyramidal neurons exhibited a dorsoventral gradient, with a lower percentage of ?(1)AR-positive neurons in infralimbic cortex compARed to anterior cingulate and prelimbic cortex. The expression of ?(1A), ?(1B) and ?(1D) adrenergic receptors was segregated in different layers and subdivisions. In all them there is a high co-expression with 5-HT(2A)Rs (?80%). These observations indicate that NE controls the activity of most PFC pyramidal neurons via ?(1)ARs, either directly or indirectly, via GABAergic interneurons. Antipsychotic drugs can thus modulate the activity of PFC via ?(1)AR blockade. The high co-expression with 5-HT(2A)Rs indicates a convergence of excitatory serotonergic and noradrenergic inputs onto the same neuronal populations. Moreover, atypical antipsychotics may exert a more powerful control of PFC function through the simultaneous blockade of ?(1)ARs and 5-HT(2A)Rs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 50 | Cogn Neuropsychiatry 2013 -1 18: 26-43 |
| PMID | 22994363 |
| Title | A developmental look at the attentional system in the at risk and first episode of psychosis: age related changes in attention along the psychosis spectrum. |
| Abstract | Neurodevelopmental processes of adolescence, when superimposed on a vulnerable brain, may produce additive effects reflecting the subthreshold psychotic symptoms, cognitive, and functional deterioration that ARe the hallmARk of the eARly stages of schizophrenia. As pARt of a longitudinal study, we investigated Continuous Performance Task, Identical Pairs Version (CPT-IP) performance in a sample of 301 pARticipants (at risk for psychosis: 109; first episode-FE: 90; and controls: 102). Performance across groups was compARed using d' of fast and slow, spatial and verbal conditions over two time points. Age effects were investigated using a regression model. Across all four CPT-IP conditions FE patients performed significantly worse than controls while AR individuals significantly differed from healthy subjects in the verbal condition. Age-related performance associations across groups significantly differed in the slow verbal condition because the FE sample did not show a significant association with increasing age like the AR and NC samples. CPT performance was stable over time. Sustained attention in the putative prodrome of psychosis is not only impaired but associated with age. ReseARch focusing on cognitive and neurobiological age-related changes can help to address fundamental questions about the nature of the disorder, including whether the underlying pathophysiology of eARly psychosis is static or deteriorating. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 51 | Int. Rev. Neurobiol. 2014 -1 119: 257-307 |
| PMID | 25175970 |
| Title | Adenosine receptor control of cognition in normal and disease. |
| Abstract | Adenosine and adenosine receptors (ARs) ARe increasingly recognized as important therapeutic tARgets for controlling cognition under normal and disease conditions for its dual roles of neuromodulation as well as of homeostatic function in the brain. This chapter first presents the unique ability of adenosine, by acting on the inhibitory A1 and facilitating A2A receptor, to integrate dopamine, glutamate, and BNDF signaling and to modulate synaptic plasticity (e.g., long-term potentiation and long-term depression) in brain regions relevant to leARning and memory, providing the moleculAR and cellulAR bases for adenosine receptor (AR) control of cognition. This led to the demonstration of AR modulation of social recognition memory, working memory, reference memory, reversal leARning, goal-directed behavior/habit formation, Pavlovian feAR conditioning, and effort-related behavior. Furthermore, human and animal studies support that AR activity can also, through cognitive enhancement and neuroprotection, reverse cognitive impairments in animal models of Alzheimer's disease (AD), PARkinson's disease (PD), Huntington's disease, and schizophrenia. Lastly, epidemiological evidence indicates that regulAR human consumption of caffeine, the most widely used psychoactive drug and nonselective AR antagonists, is associated with the reduced cognitive decline in aging and AD patients, and with the reduced risk in developing PD. Thus, there is a convergence of the moleculAR studies revealing AR as moleculAR tARgets for integrating neurotransmitter signaling and controlling synaptic plasticity, with animal studies demonstrating the strong procognitive impact upon AR antagonism in normal and disease brains and with epidemiological and clinical evidences in support of caffeine and AR drugs for therapeutic modulation of cognition. Since some of adenosine A2A receptor antagonists ARe already in phase III clinical trials for motor benefits in PD patients with remARkable safety profiles, additional animal and human studies to better understand the mechanism underlying the AR-mediated control of cognition under normal and disease conditions will provide the required rationale to stimulate the necessARy clinical investigation to rapidly translate adenosine and AR drug as a novel strategy to control memory impairment in neuropsychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 52 | Encephale 2014 Dec 40: 447-56 |
| PMID | 25127895 |
| Title | [Assessment of mental states at risk of psychotic transition: validation of the French version of the CAARMS]. |
| Abstract | This ARticle aims to present the validation study of the French version of the Comprehensive Assessment of at risk mental states (CAARMS), an interview that seeks to determine whether young adults criteria for at-risk (AR) mental states, or psychosis. We assessed 40 young subjects, 15 were considered as "prodromal" (Prd) and 10 as experiencing a first episode of psychosis (PEP) by our expert clinician at the center - centre d'évaluation des jeunes adultes et adolescents, University Hospital Centre, PARis - and 15 were healthy controls matched for age and sex. When assessed with the CAARMS, 73 % (n=11) of the prodromal subjects reached the criteria for AR mental state, four subjects did not reach the criteria for AR, nor psychosis (P) and 100 % of the PEP reached the criteria for P. The three groups were significantly different on CAARMS total score (P<0.001) and subscores ; Prd subjects had intermediate scores between PEP (P<0.001) and controls (P<0.001) scores, PEP showing the highest scores. Post-hoc analysis showed that Prd significantly differed from Controls on each subscale (P<0.001) and that Prd differed from PEP on the "positive symptoms" subscale (P<0.001), as well as on "behavioural change" (P=0.021), owing to difference on the item "impaired role function". We used the brief psychiatric rating scale 24 items with anchor (BPRS24-EA) in addition to with the CAARMS, the AR group showed intermediate scores between controls and P subjects. Total scores of both scales were correlated (r=0.408 ; P=0.043) and the BPRS24-EA "positive symptoms" score was correlated with CAARMS' scores on the "Positive symptoms" subscale (r=0.456, P=0.022), "emotional disturbance" (r=0.506, P=0.01), and "behavioural change" (r=0.666 P=0.001). We found no correlation between BPRS negative and depression subscales and any of the CAARMS' subscales. When looking at its reliability, reliability coefficients (Cronbach's alpha) showed excellent reliability for "positive symptoms", "emotional disturbance", "behavioural change" and "general psychopathology" (respectively r=0.82, 0.75, 0.78, 0.84, 0.83) and moderate reliability for "cognitive change", "negative symptoms" and "motor/physical change" (respectively r=0.39, 0.59, 0.43). Overall, analysis of the results of construct validity, concurrent validity and reliability of the CAARMS indicates that the French version is valid and reliable. It is now available to develop and implement eARly detection programs in French speaking countries. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 53 | PLoS ONE 2014 -1 9: e88864 |
| PMID | 24586419 |
| Title | Kronecker product linear exponent AR(1) correlation structures for multivariate repeated measures. |
| Abstract | Longitudinal imaging studies have moved to the forefront of medical reseARch due to their ability to chARacterize spatio-temporal features of biological structures across the lifespan. Credible models of the correlations in longitudinal imaging require two or more pattern components. Valid inference requires enough flexibility of the correlation model to allow reasonable fidelity to the true pattern. On the other hand, the existence of computable estimates demands a pARsimonious pARameterization of the correlation structure. For many one-dimensional spatial or temporal ARrays, the lineAR exponent autoregressive (LEAR) correlation structure meets these two opposing goals in one model. The LEAR structure is a flexible two-pARameter correlation model that applies to situations in which the within-subject correlation decreases exponentially in time or space. It allows for an attenuation or acceleration of the exponential decay rate imposed by the commonly used continuous-time AR(1) structure. We propose the Kronecker product LEAR correlation structure for multivARiate repeated measures data in which the correlation between measurements for a given subject is induced by two factors (e.g., spatial and temporal dependence). Excellent analytic and numerical properties make the Kronecker product LEAR model a valuable addition to the suite of pARsimonious correlation structures for multivARiate repeated measures data. Longitudinal medical imaging data of caudate morphology in schizophrenia illustrates the appeal of the Kronecker product LEAR correlation structure. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 54 | J Clin Psychiatry 2015 Dec 76: 1633-4 |
| PMID | 26717524 |
| Title | Delayed drug interactions in psychiatry: armodafinil and risperidone as a potential case in point. |
| Abstract | Modafinil or ARmodafinil (AR/mod) augmentation of antipsychotic medication in schizophrenia patients may be considered with a view to reduce negative symptoms associated with the illness or excessive daytime drowsiness due to any cause. The available data suggest that there is no role for AR/mod in reducing negative symptom burden. A recent phARmacokinetic (PK) study suggested that ARmodafinil (250 mg/d) reduces key PK pARameters of risperidone by about 50%, and key PK pARameters of 9-hydroxyrisperidone (paliperidone) by about 20%-30%, probably through induction of CYP3A4. AR/mod augmentation is therefore best avoided in patients receiving risperidone or paliperidone (and most other atypical antipsychotic drugs, as well, because most atypical antipsychotics ARe metabolized by enzymes that AR/mod induce). If the AR/mod-antipsychotic drug combination is necessARy, for whatever reason, then the dose of the atypical antipsychotic drug may need to be appropriately raised. If this is not done, relapse may occur; because the relapse may postdate the introduction of AR/mod by many months, the causal role of a metabolic drug interaction may not be suspected, and physicians may attribute the relapse to the natural course of the illness. Physicians need to be awARe that any agent that induces the metabolism of psychotropic drugs that ARe used in maintenance therapy may, through lowered psychotropic drug levels, result in a delayed drug interaction that is chARacterized by illness relapse. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 55 | Schizophr. Res. 2015 Nov 168: 649-60 |
| PMID | 26232868 |
| Title | Testosterone and reward prediction-errors in healthy men and men with schizophrenia. |
| Abstract | Sex hormones impact rewARd processing, which is dysfunctional in schizophrenia; however, the degree to which testosterone levels relate to rewARd-related brain activity in healthy men and the extent to which this relationship may be altered in men with schizophrenia has not been determined. We used functional magnetic resonance imaging (fMRI) to measure neural responses in the striatum during rewARd prediction-errors and hormone assays to measure testosterone and prolactin in serum. To determine if testosterone can have a direct effect on dopamine neurons, we also localized and measured androgen receptors in human midbrain with immunohistochemistry and quantitative PCR. We found correlations between testosterone and prediction-error related activity in the ventral striatum of healthy men, but not in men with schizophrenia, such that testosterone increased the size of positive and negative prediction-error related activity in a valence-specific manner. We also identified midbrain dopamine neurons that were androgen receptor immunoreactive, and found that androgen receptor (AR) mRNA was positively correlated with tyrosine hydroxylase (TH) mRNA in human male substantia nigra. The results suggest that sex steroid receptors can potentially influence midbrain dopamine biosynthesis, and higher levels of serum testosterone ARe linked to better discrimination of motivationally-relevant signals in the ventral striatum, putatively by modulation of the dopamine biosynthesis pathway via AR ligand binding. However, the normal relationship between serum testosterone and ventral striatum activity during rewARd leARning appeARs to be disrupted in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 56 | J Psychiatr Res 2015 Jan 60: 14-21 |
| PMID | 25306261 |
| Title | Antipsychotic augmentation with modafinil or armodafinil for negative symptoms of schizophrenia: systematic review and meta-analysis of randomized controlled trials. |
| Abstract | We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of modafinil or ARmodafinil (AR/mod) augmentation in schizophrenia. We seARched PubMed, clinical trial registries, reference lists, and other sources for pARallel group, placebo-controlled RCTs. Our primARy outcome vARiable was the effect of AR/mod on negative symptom outcomes. Eight RCTs (pooled N = 372; median duration, 8 weeks) met our selection criteria. AR/mod (200 mg/day) significantly attenuated negative symptom ratings (6 RCTs; N = 322; standARdized mean difference [SMD], -0.26; 95% CI, -0.48 to -0.04). This finding remained similAR in all but one sensitivity analysis - when the only RCT in acutely ill patients was excluded, the outcome was no longer statistically significant (SMD, -0.17; 95% CI, -0.51 to 0.06). The absolute advantage for AR/mod was small: just 0.27 points on the PANSS-N (6 RCTs). AR/mod attenuated total psychopathology ratings (7 RCTs; N = 342; SMD, -0.23; 95% CI, -0.45 to -0.02) but did not influence positive symptom ratings (5 RCTs; N = 302; mean difference, -0.58; 95% CI, -1.71 to 0.55). Although data were limited, cognition, fatigue, daytime drowsiness, adverse events, and drop out rates did not differ significantly between AR/mod and placebo groups. Fixed and random effects models yielded similAR results. There was no heterogeneity in all but one analysis. Publication bias could not be tested. We conclude that AR/mod (200 mg/day) is safe and well tolerated in the short-term treatment of schizophrenia. AR/mod reduces negative symptoms with a small effect size; the absolute advantage is also small, and the advantage disappeARs when chronically ill patients or those with high negative symptom burden ARe treated. AR/mod does not benefit or worsen other symptom dimensions in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 57 | World J. Biol. Psychiatry 2016 Jun 17: 308-15 |
| PMID | 27007576 |
| Title | Alpha2C-adrenoceptor Del322-325 polymorphism and risk of psychiatric disorders: significant association with opiate abuse and dependence. |
| Abstract | Objectives ?2C-adrenoceptors (?2C-AR) ARe involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism ?2CDel322-325-AR confers a loss-of-function phenotype. Functional human studies have associated ?2CDel322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of ?2CDel322-325-AR polymorphism with suicide completion and with related psychiatric disorders: major depression, schizophrenia, opiate and alcohol abuse and dependence. Methods Post-mortem brain DNA was extracted (n?=?516) and genotyping performed by HaeIII restriction endonuclease digestion of PCR products and DNA fragment analysis on capillARy sequencer. Amplified products were sequenced to confirm the presence of the polymorphism. Results The frequency of ?2CDel322-325-AR in suicide (9%, n?=?236) and non-suicide victims (11%, n?=?280) was similAR. Genotype frequencies for the ?2CDel322-325-AR polymorphism in depressed (15%, n?=?39) and schizophrenic subjects (18%, n?=?39) were higher than in controls (7%, n?=?187), but these differences did not reach statistical significance (P?=?0.125 and P?=?0.063, respectively). A selective and significant association of ?2CDel322-325-AR polymorphism with opiate abuse and dependence was found (23%, n?=?35, P?=?0.011). Conclusions Our results indicate that ?2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for lARger genetic associative studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |
| 58 | World J. Biol. Psychiatry 2016 Jun 17: 308-15 |
| PMID | 27007576 |
| Title | Alpha2C-adrenoceptor Del322-325 polymorphism and risk of psychiatric disorders: significant association with opiate abuse and dependence. |
| Abstract | Objectives ?2C-adrenoceptors (?2C-AR) ARe involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism ?2CDel322-325-AR confers a loss-of-function phenotype. Functional human studies have associated ?2CDel322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of ?2CDel322-325-AR polymorphism with suicide completion and with related psychiatric disorders: major depression, schizophrenia, opiate and alcohol abuse and dependence. Methods Post-mortem brain DNA was extracted (n?=?516) and genotyping performed by HaeIII restriction endonuclease digestion of PCR products and DNA fragment analysis on capillARy sequencer. Amplified products were sequenced to confirm the presence of the polymorphism. Results The frequency of ?2CDel322-325-AR in suicide (9%, n?=?236) and non-suicide victims (11%, n?=?280) was similAR. Genotype frequencies for the ?2CDel322-325-AR polymorphism in depressed (15%, n?=?39) and schizophrenic subjects (18%, n?=?39) were higher than in controls (7%, n?=?187), but these differences did not reach statistical significance (P?=?0.125 and P?=?0.063, respectively). A selective and significant association of ?2CDel322-325-AR polymorphism with opiate abuse and dependence was found (23%, n?=?35, P?=?0.011). Conclusions Our results indicate that ?2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for lARger genetic associative studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypy |