| 1 | Hum. Immunol. 2001 Jul 62: 714-24 |
|---|---|
| PMID | 11423178 |
| Title | Immune related genetic polymorphisms and schizophrenia among the Chinese. |
| Abstract | Genetic association studies were conducted among two independent cohorts of Chinese ethnicity. The samples consisted of cases and unrelated controls, ascertained from Guangzhou, China, and Singapore. The studies were prompted by our earlier report of an association between schizophrenia and HLA DQB1 alleles (HLA DQB1*0602 and HLA DQB1*0303) in the Singapore sample. Polymorphisms of HLA DQB1 and flanking markers on chromosome 6p21.3 were investigated in the first part of the study. A significant negative association with HLA DQB1*0402 was detected in the Guangzhou sample (Odds ratio, OR 0.26, 95% confidence intervals, CI 0.1, 0.6; p < 0.02, corrected for multiple comparisons). Additional analysis of the Guangzhou and Singapore samples revealed associations at three other anonymous markers flanking HLA DQB1. In the second part of the study, three polymorphisms at the Interleukin-1 gene cluster (IL-1, chromosome 2q13-q21) were investigated in both cohorts, since associations with schizophrenia have been reported in another sample. Persuasive evidence for an association at IL-1 was not detected in either sample. Our results suggest a susceptibility locus for schizophrenia in the HLA region among the Chinese, but further clarification is necessary. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Psychiatry Clin. Neurosci. 2004 Jun 58: 236-9 |
| PMID | 15149287 |
| Title | Human leukocyte antigen-DQB1 alleles are not associated with schizophrenia in Kuwaiti Arabs. |
| Abstract | schizophrenia is among the most severe and debilitating of psychiatric disorders and has a complex mode of inheritance. A susceptibility locus has been identified on chromosome 6 and some association studies involving human leukocyte antigen (HLA) genes have reported diverse results. The objective of the present study was to determine if there is an association between HLA-DQB1 alleles and schizophrenia in Kuwaiti Arabs. The frequency of HLA-DQB1 alleles was determined in a cohort of 195 Kuwaiti Arabs consisting of 81 schizophrenia patients and 114 ethnically matched healthy controls, using a polymerase chain reaction-sequence specific primers method. A total of nine DQB1 alleles were identified in this Kuwaiti cohort. The most prevalent DQB1 alleles in Kuwaiti schizophrenia patients were *0601 (28%), *0201 (23%) and *0501 (16%), respectively. However, no significant difference in the allele frequency was detected between schizophrenia patients and the controls. The DQB1*0602 allele, which has been negatively associated in African-Americans in previous reports, was not detected in the present Kuwaiti schizophrenia patients or controls. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | J Clin Psychiatry 2011 Apr 72: 458-63 |
| PMID | 20868635 |
| Title | Candidate gene analysis identifies a polymorphism in HLA-DQB1 associated with clozapine-induced agranulocytosis. |
| Abstract | Clozapine is considered to be the most efficacious drug to treat schizophrenia, although it is underutilized, partially due to a side effect of agranulocytosis. This analysis of 74 candidate genes was designed to identify an association between sequence variants and clozapine-induced agranulocytosis (CIA). Blood and medical history were collected for 33 CIA cases and 54 clozapine-treated controls enrolled between April 2002 and December 2003. Significant markers from 4 genes were then assessed in an independently collected case-control cohort (49 CIA cases, 78 controls). Sequence variants in 5 genes were found to be associated with CIA in the first cohort: HLA-DQB1, HLA-C, DRD1, NTSR1, and CSF2RB. Sequence variants in HLA-DQB1 were also found to be associated with CIA in the second cohort. After refinement analyses of sequence variants in HLA-DQB1, a single SNP (single nucleotide polymorphism), 6672G>C, was found to be associated with risk for CIA; the odds of CIA are 16.9 times greater in patients who carry this marker compared to those who do not. A sequence variant (6672G>C) in HLA-DQB1 is associated with increased risk for CIA. This marker identifies a subset of patients with an exceptionally high risk of CIA, 1,175% higher than the overall clozapine-treated population under the current blood-monitoring system. Assessing risk for CIA by testing for this and other genetic variants yet to be determined may be clinically useful when deciding whether to begin or continue treatment with clozapine. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | Curr Psychiatry Rep 2011 Apr 13: 156-65 |
| PMID | 21336863 |
| Title | Genetics of antipsychotic-induced side effects and agranulocytosis. |
| Abstract | Antipsychotic medication has been enormously helpful in the treatment of psychotic symptoms during the past several decades. Unfortunately, several important side effects that can cause significant morbidity and mortality. The two most common are abnormal involuntary movements (tardive dyskinesia) and weight gain progressing through diabetes to metabolic syndrome. A more rare and life-threatening adverse effect is clozapine-induced agranulocytosis (CIA), which has been linked to clozapine use. Clozapine itself has a unique position among antipsychotic medications, representing the treatment of choice in refractory schizophrenia. Unfortunately, the potential risk of agranulocytosis, albeit small, prevents the widespread use of clozapine. Very few genetic determinants have been clearly associated with CIA due to small sample sizes and lack of replication in subsequent studies. The HLA system has been the main hypothesized region of interest in the study of CIA, and several gene variants in this region have been implicated, particularly variants of the HLA-DQB1 locus. A preliminary genome-wide association study has been conducted on a small sample for CIA, and a signal from the HLA region was noted. However, efforts to identify key gene mechanisms that will be useful in predicting antipsychotic side effects in the clinical setting have not been fully successful, and further studies with larger sample sizes are required. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | Biol. Psychiatry 2013 Nov 74: 696-705 |
| PMID | 23664640 |
| Title | Prefrontal cortical dysfunction after overexpression of histone deacetylase 1. |
| Abstract | Postmortem brain studies have shown that HDAC1-a lysine deacetylase with broad activity against histones and nonhistone proteins-is frequently expressed at increased levels in prefrontal cortex (PFC) of subjects diagnosed with schizophrenia and related disease. However, it remains unclear whether upregulated expression of Hdac1 in the PFC could affect cognition and behavior. Using adeno-associated virus, an Hdac1 transgene was expressed in young adult mouse PFC, followed by behavioral assays for working and long-term memory, repetitive activity, and response to novelty. Prefrontal cortex transcriptomes were profiled by microarray. Antipsychotic drug effects were explored in mice treated for 21 days with haloperidol or clozapine. Hdac1 overexpression in PFC neurons and astrocytes resulted in robust impairments in working memory, increased repetitive behaviors, and abnormal locomotor response profiles in novel environments. Long-term memory remained intact. Over 300 transcripts showed subtle but significant changes in Hdac1-overexpressing PFC. Major histocompatibility complex class II (MHC II)-related transcripts, including HLA-DQA1/H2-Aa, HLA-DQB1/H2-Ab1, and HLA-DRB1/H2-Eb1, located in the chromosome 6p21.3-22.1 schizophrenia and bipolar disorder risk locus, were among the subset of genes with a more robust (>1.5-fold) downregulation in expression. Hdac1 levels declined during the course of normal PFC development. Antipsychotic drug treatment, including the atypical clozapine, did not affect Hdac1 levels in PFC but induced expression of multiple MHC II transcripts. Excessive HDAC1 activity, due to developmental defects or other factors, is associated with behavioral alterations and dysregulated expression of MHC II and other gene transcripts in the PFC. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | Schizophr. Res. 2013 Jan 143: 11-7 |
| PMID | 23177929 |
| Title | Non-random mating, parent-of-origin, and maternal-fetal incompatibility effects in schizophrenia. |
| Abstract | Although the association of common genetic variation in the extended MHC region with schizophrenia is the most significant yet discovered, the MHC region is one of the more complex regions of the human genome, with unusually high gene density and long-range linkage disequilibrium. The statistical test on which the MHC association is based is a relatively simple, additive model which uses logistic regression of SNP genotypes to predict case-control status. However, it is plausible that more complex models underlie this association. Using a well-characterized sample of trios, we evaluated more complex models by looking for evidence for: (a) non-random mating for HLA alleles, schizophrenia risk profiles, and ancestry; (b) parent-of-origin effects for HLA alleles; and (c) maternal-fetal genotype incompatibility in the HLA. We found no evidence for non-random mating in the parents of individuals with schizophrenia in terms of MHC genotypes or schizophrenia risk profile scores. However, there was evidence of non-random mating that appeared mostly to be driven by ancestry. We did not detect over-transmission of HLA alleles to affected offspring via the general TDT test (without regard to parent of origin) or preferential transmission via paternal or maternal inheritance. We evaluated the hypothesis that maternal-fetal HLA incompatibility may increase risk for schizophrenia using eight classical HLA loci. The most significant alleles were in HLA-B, HLA-C, HLA-DQB1, and HLA-DRB1 but none was significant after accounting for multiple comparisons. We did not find evidence to support more complex models of gene action, but statistical power may have been limiting. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 7 | Psychiatr. Genet. 2014 Apr 24: 81 |
| PMID | 24572971 |
| Title | No association between the HLA-DQB1*0501 variant and schizophrenia in a Chinese population. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 8 | J Clin Sleep Med 2014 Sep 10: 1011-8 |
| PMID | 25142772 |
| Title | Dual cases of type 1 narcolepsy with schizophrenia and other psychotic disorders. |
| Abstract | Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia. Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens. Ten cases were identified, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested first in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable. Narcolepsy can occur in association with schizophrenia, with significant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 9 | BMC Psychiatry 2016 -1 16: 177 |
| PMID | 27245445 |
| Title | Exploring the presence of narcolepsy in patients with schizophrenia. |
| Abstract | There are several case reports of patients with narcolepsy and schizophrenia, but a systematic examination of the association of both disorders has not been done. The aim of this work is to assess the frequency of narcolepsy with cataplexy in a large consecutive series of adult patients with schizophrenia and schizoaffective disorder. We screened 366 consecutive patients with schizophrenia or schizoaffective disorder with a sleep questionnaire and the Epworth Sleepines scale (ESS) exploring narcoleptiform symptoms. Those who screened positive were assessed by a sleep specialist, and offered an HLA determination. CSF hypocretin-1 determination was proposed to those who were HLA DQB1*06:02 positive. On the screening questionnaire, 17 patients had an ESS score ?11 without cataplexy, 15 had cataplexy-like symptoms with an ESS score?Our results suggest that narcolepsy with cataplexy is not an unrecognized disease in adult patients with schizophrenia or schizoaffective disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |