Objective: Suicide and attempted suicide are common in individuals with schizophrenia, and evidence exists for a link between substance use disorders and suicidality in this disorder. However, ...alcohol has not been consistently implicated. We examined the relationship between substance use disorders and suicide attempts in schizophrenia.
Methods: We recruited a schizophrenia sample in Australia (n = 821) for genetic analyses. We analysed demographic and clinical variables, including substance use disorders, and their relationship to suicide attempts using generalised equation modelling.
Results: A significant association was identified between lifetime alcohol abuse/dependence and suicide attempts (OR = 1.66; 95% CI, 1.23 to 2.24; p= 0.001) after adjustment for potential confounders, but not between cannabis abuse/dependence and suicide attempts, nor between other illicit drug abuse/dependence and suicide attempts. Polysubstance abuse/dependence was also not implicated.
Conclusions: These results suggest that the presence of alcohol abuse/dependence may be a risk factor for suicide attempts in individuals with schizophrenia, independent of comorbid substance abuse/dependence.
Abstract Schizophrenia is a severe debilitating brain disorder with a poorly understood aetiology. Among the diverse aetiological clues lies evidence for immune abnormalities in some individuals. The ...aim of this study was to investigate the frequency and specificity of autoantibodies directed against the brain in people with schizophrenia. Sera were screened for reactivity against human brain tissue (hippocampus and prefrontal cortex). Neuronal cell body and filamentous patterns of brain tissue staining were observed significantly more frequently in sera from schizophrenia patients (n = 30) compared to controls (n = 24). Sera that showed a neuronal cell body pattern of staining on hippocampus reacted strongly to an extracellular epitope of the M1 muscarinic acetylcholine receptor (m1AChR) in ELISA. Both cell body staining and elevated m1AChR reactivity correlated with higher symptom scores for poverty of speech. Sera showing a filamentous staining pattern predominantly targeted microfilaments, intermediate filaments or neurofilaments, particularly neurofilament medium (NFM), which is a dopamine receptor interacting protein. By ELISA, there was strongly elevated reactivity against NFM in a subset (15%) of schizophrenia patients (n = 101) compared to healthy controls (n = 55) or patients with multiple sclerosis (n = 32). These results support the hypothesis that neurotransmitter receptors or molecules involved in regulation of neurotransmission are targets of autoantibodies in some people with schizophrenia.
The reprogramming of nonneuronal somatic cells to induced pluripotent stem cells and their derivation to functional brain cells as well as the related methods for direct conversion of somatic cells ...to neurons have opened up the possibility of conducting research on cellular disease models from living schizophrenia patients. We review the published literature on schizophrenia that has used this rapidly developing technology, highlighting the need for specific aims and reproducibility. The key issues for consideration for future schizophrenia research in this field are discussed and potential investigations using this technology are put forward for critical assessment by the reader.
ObjectiveThe Molecular Genetics of Schizophrenia (MGS2) project recruited an adult control sample of non-Hispanic European-ancestry (N=3,364) and African American (N=1,301) subjects.
MethodSubjects ...gave consent to deposit phenotypic data and blood samples into a repository for general research use, with full anonymization of the sample. The authors compared the control sample with population census data for demographic data and with previous population surveys for anthropometrics and prevalences of psychiatric disorders as estimated by an Internet-administered questionnaire.
ResultsThe full MGS2 control sample includes 4,665 subjects (European-ancestry: N=3,364; African American: N=1,301), of whom 3,626 were included in the MGS2 genome-wide association study (GWAS). The sample is generally demographically representative of the U.S. population, except for being older and more female, educated, and affluent, although all strata are represented. Self-reported ancestry was consistent with genotypic and census data. Lifetime prevalences for depressive, anxiety, and substance use diagnoses were higher than in previous population-based surveys, probably due to use of an abbreviated self-report instrument. However, patterns such as sex ratios, comorbidity, and demographic associations were consistent with previous reports. DNA quality for the Internet collected/evaluated control sample was comparable to that of the face-to-face case sample.
ConclusionsThe Internet-based methods facilitated the rapid collection of large and anonymized non-Hispanic European-ancestry and African American control samples that have been validated as being generally representative for many aspects of demography, ancestry, and morbidity. Utilization of clinical screening data shared with the scientific community may permit investigators to select appropriate controls for some studies.
Several linkage studies across multiple population groups provide convergent support for a susceptibility locus for schizophrenia—and, more recently, for bipolar disorder—on chromosome 6q13-q26. We ...genotyped 192 European-ancestry and African American (AA) pedigrees with schizophrenia from samples that previously showed linkage evidence to 6q13-q26, focusing on the
MOXD1-
STX7-
TRARs gene cluster at 6q23.2, which contains a number of prime candidate genes for schizophrenia. Thirty-one screening single-nucleotide polymorphisms (SNPs) were selected, providing a minimum coverage of at least 1 SNP/20 kb. The association observed with rs4305745 (
P=.0014) within the
TRAR4 (
trace amine receptor 4) gene remained significant after correction for multiple testing. Evidence for association was proportionally stronger in the smaller AA sample. We performed database searches and sequenced genomic DNA in a 30-proband subsample to obtain a high-density map of 23 SNPs spanning 21.6 kb of this gene. Single-SNP analyses and also haplotype analyses revealed that rs4305745 and/or two other polymorphisms in perfect linkage disequilibrium (LD) with rs4305745 appear to be the most likely variants underlying the association of the
TRAR4 region with schizophrenia. Comparative genomic analyses further revealed that rs4305745 and/or the associated polymorphisms in complete LD with rs4305745 could potentially affect gene expression. Moreover, RT-PCR studies of various human tissues, including brain, confirm that
TRAR4 is preferentially expressed in those brain regions that have been implicated in the pathophysiology of schizophrenia. These data provide strong preliminary evidence that
TRAR4 is a candidate gene for schizophrenia; replication is currently being attempted in additional clinical samples.
Objectives: Social and economic marginalization are significant problems for many people living with mental illness. Clinicians and policy-makers have increased their focus on these aspects of ...recovery. Current outcome measures, however, do not support this focus, and detailed functional measures are not suitable for routine clinical use. This report describes the development and test–retest reliability of the Activity and Participation Questionnaire (APQ6); a self-report measure of vocational activity and social participation for routine use in community mental health services.
Method: The APQ6 was developed from concepts of the Australian Bureau of Statistics Labour Force Surveys and Census. Field testing and consumer consultation were undertaken in New South Wales (NSW) mental health rehabilitation services. Test–retest reliability trials were conducted simultaneously by research teams in NSW and Queensland.
Results: Pairs of short-cycle test–retest reliability interviews were obtained from 129 mental health service consumers. Consumer feedback and test–retest reliability results at question and item levels indicate good construct validity. The measure has utility as both a telephone and a personal interview in community mental health settings.
Conclusions: The reported psychometric properties support the proposed use of the APQ6 as a recovery-orientated measure focusing on vocational activity and community participation. The APQ6 is being introduced for routine use by NSW mental health services.
ObjectiveThe authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and ...rare copy number variants (CNVs).MethodThe family sample included 2,461 individuals from 631 pedigrees (581 in the primary European-ancestry analyses). Association was tested for single SNPs and genetic pathways. Polygenic scores based on family study results were used to predict case-control status in the Schizophrenia Psychiatric GWAS Consortium (PGC) data set, and consistency of direction of effect with the family study was determined for top SNPs in the PGC GWAS analysis. Within-family segregation was examined for schizophrenia-associated rare CNVs.ResultsNo genome-wide significant associations were observed for single SNPs or for pathways. PGC case and control subjects had significantly different genome-wide polygenic scores (computed by weighting their genotypes by log-odds ratios from the family study) (best p=10−17, explaining 0.4% of the variance). Family study and PGC analyses had consistent directions for 37 of the 58 independent best PGC SNPs (p=0.024). The overall frequency of CNVs in regions with reported associations with schizophrenia (chromosomes 1q21.1, 15q13.3, 16p11.2, and 22q11.2 and the neurexin-1 gene NRXN1) was similar to previous case-control studies. NRXN1 deletions and 16p11.2 duplications (both of which were transmitted from parents) and 22q11.2 deletions (de novo in four cases) did not segregate with schizophrenia in families.ConclusionsMany common SNPs are likely to contribute to schizophrenia risk, with substantial overlap in genetic risk factors between multiply affected families and cases in large case-control studies. Our findings are consistent with a role for specific CNVs in disease pathogenesis, but the partial segregation of some CNVs with schizophrenia suggests that researchers should exercise caution in using them for predictive genetic testing until their effects in diverse populations have been fully studied.
MRI diffusion tensor imaging (DTI), optimized for measuring the trace of the diffusion tensor, was used to investigate microstructural changes in the brains of 12 individuals with schizophrenia ...compared with 12 matched control subjects. To control for the effects of anatomic variation between subject groups, all participants' diffusion images were nonlinearly registered to standard anatomical space. Significant statistical differences in mean diffusivity (MD) measures between the two groups were determined on a pixel-by-pixel basis, using Gaussian random field theory. We found significantly elevated MD measures within temporal, parietal and prefrontal cortical regions in the schizophrenia group (
P > 0.001), especially within the medial frontal gyrus and anterior cingulate. The dorsal medial and anterior nucleus of the thalamus, including the caudate, also exhibited significantly increased MD in the schizophrenia group (
P > 0.001). This study has shown for the first time that MD measures offer an alternative strategy for investigating altered prefrontal–thalamic circuitry in schizophrenia.
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