A functional polymorphism in estrogen receptor alpha gene is associated with Japanese methamphetamine induced psychosis

Background

A recent study reported an association between rs2234693, which influences enhancer activity levels in estrogen receptor alpha gene (ESR1), and schizophrenia. This study reported that schizophrenic patients with the CC genotype have significantly lower ESR1 mRNA levels in the prefrontal cortex than patients with other genotypes. The symptoms of methamphetamine induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an association analysis of rs2234693 with Japanese methamphetamine induced psychosis patients.

Method

Using rs2234693, we conducted a genetic association analysis of case-control samples (197 methamphetamine induced psychosis patients and 197 healthy controls). The age and sex of the control subjects did not differ from those of the methamphetamine induced psychosis patients.

Results

We detected a significant association between ESR1 and methamphetamine induced psychosis patients in allele/genotype-wise analysis. For further interpretation of these associations, we performed single marker analysis of subjects divided by sex. Rs2234693 was associated with male methamphetamine induced psychosis.

Discussion

Our results suggest that rs2234693 in ESR1 may play a role in the pathophysiology of Japanese methamphetamine induced psychosis patients.     

Predictors of death from natural causes in schizophrenia: 10-year follow-up of a community cohort

Purpose

People with schizophrenia have increased natural mortality. There is much speculation but little evidence about the reasons behind this. This paper describes a study designed to measure the impact of pre-selected clinical, demographic and lifestyle variables on the natural mortality of a cohort with schizophrenia.

Methods

Ten-year Cox proportional hazards regression analysis of a community cohort of 95 people with schizophrenia.

Results

Death from natural causes was significantly associated with psychosis (HR 2.62, 95% CI 1.13–6.07), age (HR 1.08, 95% CI 1.02–1.13) and cigarette smoking (HR 2.53, 95% CI 1.01–6.34) at outset. There was a trend to association with low dietary unsaturated fat (P?=?0.06).

Conclusions

Active psychosis appears to predict natural mortality in people with schizophrenia. Mental health services should prioritise the effective treatment of psychosis. Further research is needed to clarify other risk factors and evaluate health promotion interventions.     

A Novel <Emphasis Type="Italic">SYNJ1</Emphasis> Mutation in a Tunisian Family with Juvenile Parkinson’s Disease Associated with Epilepsy

We investigated the effect of a set of SNPs within 5 genes identified by GWASs as possible risk genes for schizophrenia (SCZ) in two independent samples, comprising 176 SCZ patients and 326 controls of Korean origin and 83 SCZ patients and 194 controls of Italian origin. The PANSS was used to assess psychopathology severity and antipsychotic response (AR). Several clinical features were assessed at recruitment. In the Korean sample, the SP4 gene haplotype rs2282888-rs2237304-rs10272006-rs12673091 (p?=?0.02) was associated with SCZ. In the Italian sample, PPP3CC rs11780915 (genotypic: p?=?0.006; allelic: p?=?0.001) and rs2249098 (genotypic: p?=?0.0004; allelic: p?=?0.00006) were associated with SCZ, as well as the PPP3CC rs11780915-rs10108011-rs2249098 and the ZNF804A rs7603001-rs1344706 haplotypes (p?=?0.03 and p?=?0.02). Several RORA variants were associated with AR in both the samples, although only the haplotype rs1020729-rs1871858 in the Korean sample survived to the statistical correction (p?=?0.01). Exploratory analyses suggested that: (1) PPP3CC, ST8SIA2, and SP4 genes may modulate psychotic symptoms, and (2) RORA and ZNF804A genes may influence AR. Our results partially support a role for these genes in SCZ and AR. Analyses in well phenotyped samples may help to refine the role of the genes identified by GWASs.     

ZDHHC8 as a candidate gene for schizophrenia: Analysis of a putative functional intronic marker in case-control and family-based association studies

Background

The chromosome 22q11 region is proposed as a major candidate locus for susceptibility genes to schizophrenia. Recently, the gene ZDHHC8 encoding a putative palmitoyltransferase at 22q11 was proposed to increase liability to schizophrenia based on both animal models and human association studies by significant over-transmission of allele rs175174A in female, but not male subjects with schizophrenia.

Methods

Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we examined rs175174 in 204 German proband-parent triads and in an independent case-control study (schizophrenic cases: n = 433; controls: n = 186).

Results

In the triads heterozygous parents transmitted allele G preferentially to females, and allele A to males (heterogeneity χ² = 4.43; p = 0.035). The case-control sample provided no further evidence for overall or gender-specific effects regarding allele and genotype frequency distributions.

Conclusion

The findings on rs175174 at ZDHHC8 are still far from being conclusive, but evidence for sexual dimorphism is moderate, and our data do not support a significant genetic contribution of rs175174 to the aetiopathogenesis of schizophrenia.     

Polymorphisms in FZD3 and FZD6 genes and risk of neural tube defects in a northern Han Chinese population

Neural tube defects (NTDs) are the most common and severe malformations of the central nervous system. The association of single nucleotide polymorphisms (SNPs) of the Frizzled 3 (FZD3) and Frizzled 6 (FZD6) genes and NTDs in the Han population of northern China was principally studied. One synonymous SNP (rs2241802) in FZD3 gene and three nonsynonymous SNPs (rs827528, rs3808553 and rs12549394) in FZD6 gene were analyzed by polymerase chain reaction (PCR) and sequencing methods in 135 NTD patients and 135 normal controls. The allele, genotype and haplotype frequencies were calculated and analyzed to examine the relationship between FZD3/FZD6 SNPs and NTDs. Both T allele and TT genotype frequencies of the FZD6 rs3808553 loci in the NTDs group were significantly higher than those in the controls, and children with T allele and TT genotype were associated with increased NTDs risk (OR = 1.575, 95 % CI 1.112–2.230, P = 0.010 and OR = 2.811, 95 % CI 1.325–5.967, P = 0.023, respectively). There were no differences among different genotypes or alleles in other three SNPs. Haplotypes A-G-C and A-T-C in FZD6 were found associated with NTDs in the case–control study (OR = 0.560, 95 % CI 0.378–0.830, P = 0.004 and OR = 1.670, 95 % CI 1.126–2.475, P = 0.011, respectively). The rs3808553 of FZD6 is obviously associated with NTDs in Han population of northern China. The TT genotype may increase risk for NTDs.     

Lack of association between translin-associated factor X gene (TSNAX) and methamphetamine dependence in the Japanese population

Objectives

Recently, we detected that the prokineticin 2 receptor gene was associated with not only major depressive disorder (MDD) but also methamphetamine dependence. Therefore, it is possible that mood disorders and drug addiction have shared susceptibility genes. The translin-associated factor X gene (TSNAX)/disrupted-in-schizophrenia-1 gene (DISC1) has been associated with psychiatric disorders, including schizophrenia, MDD and bipolar disorder. TSNAX is located immediately upstream of DISC1 and has been shown to undergo intergenic splicing with DISC1. Based on this evidence, we hypothesized that TSNAX might be a good candidate gene for methamphetamine dependence.

Methods

We conducted a case-control study of Japanese individuals (215 with methamphetamine dependence and 318 age- and sex-matched controls) with three tagging SNPs (rs1630250, rs766288 and rs6662926) selected by HapMap database.

Results

rs1630250 was associated in males with methamphetamine dependence in the allele analysis (P-value: 0.0253). However, these results did not remain significant after Bonferroni correction to adjust for multiple comparisons (corrected P-value: 0.152).

Conclusion

Our findings suggest that TSNAX does not play a role in methamphetamine dependence in the Japanese population. A replication study using larger samples needs to be conducted to obtain conclusive results.     

Association of CTXN3-SLC12A2 polymorphisms and schizophrenia in a Thai population

Background

A genome-wide association study (GWAS) combined with brain imaging as a quantitative trait analysis revealed that the SNPs near CTXN3-SLC12A2 region were related to forebrain development and stress response which involved in schizophrenia. In the present study, the SNPs in this region were analyzed for association with schizophrenia in a Thai population.

Methods

A total of 115 schizophrenia and 173 unrelated normal controls with mean age of 37.87?±?11.8 and 42.81?±?6.0?years, respectively, were included in this study. Genotyping was performed using polymerase chain reaction and high-resolution melting (HRM) analysis. The difference in genotype distribution between patient and control was assessed by Chi-square test of the SPSS software.

Results

We found a significant association between the GWAS-discovered SNP, rs245178, with the risk of schizophrenia in the Thai population [P?=?0.006, odds ratio for the minor G allele: 0.62(0.46?C0.83)]. Additionally, another potential SNP, rs698172, which was in moderate linkage disequilibrium with rs245178, also showed strong association with schizophrenia [P?=?0.003, odds ratio for minor T allele: 0.61(0.46?C0.82)]. This association remained significant at 5% level after the Bonferroni correction for multiple testing.

Conclusions

This study shows that two SNPs in intergenic of the CTXN3 and SLC12A2 genes, rs245178 and rs698172, are associated with risk of schizophrenia in Thai population. Further study is required for clarification the role of genetic variation around these SNPs in expression pattern of the CTXN3 and SLC12A2 genes, which may be involved in schizophrenia pathogenesis.     

Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome

Background

Attention deficits belong to the main cognitive symptoms of schizophrenia and come along with altered neural activity in previously described cerebral networks. Given the high heritability of schizophrenia the question arises if impaired function of these networks is modulated by susceptibility genes and detectable in healthy risk allele carriers.

Methods

The present event-related fMRI study investigated the effect of the single nucleotide polymorphism (SNP) rs1018381 of the DTNBP1 (dystrobrevin-binding protein 1) gene on brain activity in 80 subjects while performing the attention network test (ANT). In this reaction time task three domains of attention are probed simultaneously: alerting, orienting and executive control of attention.

Results

Risk allele carriers showed impaired performance in the executive control condition associated with reduced neural activity in the left superior frontal gyrus [Brodmann area (BA) 9]. Risk allele carriers did not show alterations in the alerting and orienting networks.

Conclusions

BA 9 is a key region of schizophrenia pathology and belongs to a network that has been shown previously to be involved in impaired executive control mechanisms in schizophrenia. Our results identified the impact of DTNBP1 on the development of a specific attention deficit via modulation of a left prefrontal network.     

Dopaminergic gene polymorphisms and cognitive function in a north Indian schizophrenia cohort

Background

Associations of polymorphisms from dopaminergic neurotransmitter pathway genes have mostly been reported in Caucasian ancestry schizophrenia (SZ) samples. As studies investigating single SNPs with SZ have been inconsistent, more detailed analyses utilizing multiple SNPs with the diagnostic phenotype as well as cognitive function may be more informative. Therefore, these analyses were conducted in a north Indian sample.

Methods

Indian SZ case-parent trios (n = 601 families); unscreened controls (n = 468) and an independent set of 118 trio families were analyzed. Representative SNPs in the Dopamine D3 receptor (DRD3), dopamine transporter (SLC6A3), vesicular monoamine transporter 2 (SLC18A2), catechol-o-methyltransferase (COMT) and dopamine beta-hydroxylase (DBH) were genotyped using SNaPshot/SNPlex assays (n = 59 SNPs). The Trail Making Test (TMT) was administered to a subset of the sample (n = 260 cases and n = 302 parents).

Results

Eight SNPs were nominally associated with SZ in either case-control or family based analyses (p < 0.05, rs7631540 and rs2046496 in DRD3; rs363399 and rs10082463 in SLC18A2; rs4680, rs4646315 and rs9332377 in COMT). rs6271 at DBH was associated in both analyses. Haplotypes of DRD3 SNPs incorporating rs7631540-rs2134655-rs3773678-rs324030-rs6280-rs905568 showed suggestive associations in both case-parent and trio samples. At SLC18A2, rs10082463 was nominally associated with psychomotor performance and rs363285 with executive functions using the TMT but did not withstand multiple corrections.

Conclusions

Suggestive associations with dopaminergic genes were detected in this study, but convincing links between dopaminergic polymorphisms and SZ or cognitive function were not observed.     

Variations in <Emphasis Type="Italic">Disrupted</Emphasis>-<Emphasis Type="Italic">in</Emphasis>-<Emphasis Type="Italic">Schizophrenia 1</Emphasis> gene modulate long-term longitudinal differences in cortical thickness in patients with a first-episode of psychosis

Schizophrenia patients typically present a widespread bilateral cortical thinning from the early stages of the illness. However, there is controversy whether this reduction in cortical thickness (CT) is static or progressive over the evolution of the disorder. Disrupted-in-Schizophrenia 1 (DISC1) is one of the main candidates genes for schizophrenia, as it has been found associated to the illness, and to several endophenotypes of the disorder including structural brain differences. This gene is known to be involved in neurodevelopment and brain maturation processes. We therefore hypothesized that variations in this gene modulate different progressions of CT in psychosis. Seventy-nine Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs6675281 (Leu607Phe) and rs821616 (Ser704Cys) SNPs of the DISC1 gene. Brain MRIs were carried out at baseline and 3 years after initiating the treatment. Other clinical and socio-demographic variables were recorded to rule out possible confounding effects. Patients homozygous for the Leu allele of the rs6675281 SNP had a significant (p?<?0.05) descend in CT over the 3-years period, while those carrying the Phe allele presented an increase in CT. When combining the two SNPs we found a synergic effect on CT progression, presenting those patients homozygous for Leu607 +Ser704 a more pronounced cortical thinning. In conclusion, DISC1 gene variations may modulate the longitudinal changes in cortical thickness in patients suffering from a first episode of non-affective psychosis.     

A novel SNP in <Emphasis Type="Italic">COMT</Emphasis> is associated with alcohol dependence but not opiate or nicotine dependence: a case control study

Background

It is well established that COMT is a strong candidate gene for substance use disorder and schizophrenia. Recently we identified two SNPs in COMT (rs4680 and rs165774) that are associated with schizophrenia in an Australian cohort. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. Association of both rs4680 and rs165774 with substance dependence, a common comorbidity of schizophrenia has not been investigated.

Methods

To determine whether COMT is important in substance dependence, rs165774 and rs4680 were genotyped and haplotyped in patients with nicotine, alcohol and opiate dependence.

Results

The rs165774 SNP was associated with alcohol dependence. However, it was not associated with nicotine or opiate dependence. Individuals with alcohol dependence were more than twice as likely to carry the GG or AG genotypes compared to the AA genotype, indicating a dominant mode of inheritance. The rs4680 SNP showed a weak association with alcohol dependence at the allele level that did not reach significance at the genotype level but it was not associated with nicotine or opiate dependence. Analysis of rs165774/rs4680 haplotypes also revealed association with alcohol dependence with the G/G haplotype being almost 1.5 times more common in alcohol-dependent cases.

Conclusions

Our study provides further support for the importance of the COMT in alcohol dependence in addition to schizophrenia. It is possible that the rs165774 SNP, in combination with rs4680, results in a common molecular variant of COMT that contributes to schizophrenia and alcohol dependence susceptibility. This is potentially important for future studies of comorbidity. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

     

Investigating SAPAP3 variants in the etiology of obsessive-compulsive disorder and trichotillomania in the South African white population

Background

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric disorder characterized by repeated obsessions and compulsions. Trichotillomania (TTM), a psychiatric disorder characterized by repetitive hairpulling, is presently classified as an impulse control disorder, but has also been viewed as an obsessive-compulsive spectrum disorder. Both conditions are complex disorders, with evidence from family and twin studies indicating that their etiology includes a genetic component. Results from a recent knockout animal model suggest that SAP90/PSD95-associated protein 3 (SAPAP3) may be involved in the pathophysiology of both disorders.

Methods

Seven polymorphic variants distributed across the gene encoding SAPAP3 were genotyped in South African white OCD (n = 172), TTM (n = 45), and control (n = 153) subjects. Single-locus and haplotype analyses were conducted to determine association between genetic variants and subjects with OCD, TTM, and controls.

Results

Although single-locus analysis revealed a significant association between rs11583978 in SAPAP3 and TTM, this association was nonsignificant after correction for multiple testing. In the OCD group, a significant association was observed between earlier age at onset and the A-T-A-T (rs11583978-rs7541937-rs6662980-rs4652867) haplotype compared with the C-G-G-G haplotype.

Conclusions

This study generated preliminary evidence to link SAPAP3 variants to the development of earlier onset OCD. Future studies should concentrate on locating the susceptibility variant(s) by focusing on functional polymorphisms within SAPAP3.     

Association study in the 5q31-32 linkage region for schizophrenia using pooled DNA genotyping

Background

Several linkage studies suggest that chromosome 5q31-32 might contain risk loci for schizophrenia (SZ). We wanted to identify susceptibility genes for schizophrenia within this region.

Methods

We saturated the interval between markers D5S666 and D5S436 with 90 polymorphic microsatellite markers and genotyped two sets of DNA pools consisting of 300 SZ patients of Bulgarian origin and their 600 parents. Positive associations were followed-up with SNP genotyping.

Results

Nominally significant evidence for association (p < 0.05) was found for seven markers (D5S0023i, IL9, RH60252, 5Q3133_33, D5S2017, D5S1481, D5S0711i) which were then individually genotyped in the trios. The predicted associations were confirmed for two of the markers: D5S2017, localised in the SPRY4-FGF1 locus (p = 0.004) and IL9, localized within the IL9 gene (p = 0.014). Fine mapping was performed using single nucleotide polymorphisms (SNPs) around D5S2017 and IL9. In each region four SNPs were chosen and individually genotyped in our full sample of 615 SZ trios. Two SNPs showed significant evidence for association: rs7715300 (p = 0.001) and rs6897690 (p = 0.032). Rs7715300 is localised between the TGFBI and SMAD5 genes and rs6897690 is within the SPRY4 gene.

Conclusion

Our screening of 5q31-32 implicates three potential candidate genes for SZ: SMAD5, TGFBI and SPRY4.

     

Comparing algorithms for deriving psychosis diagnoses from longitudinal administrative clinical records

Purpose

Registers derived from administrative datasets are valuable tools in psychosis research, but diagnostic accuracy can be problematic. We sought to compare the relative performance of four methods for assigning a single diagnosis from longitudinal administrative clinical records when compared with reference diagnoses.

Methods

Diagnoses recorded in inpatient and community mental health records were compared to research diagnoses of psychotic disorders obtained from semi-structured clinical interviews for 289 persons. Diagnoses were derived from administrative datasets using four algorithms; ‘At least one’ diagnosis, ‘Last’ or most recent diagnosis, ‘Modal’ or most frequently occurring diagnosis, and ‘Hierarchy’ in which a diagnostic hierarchy was applied. Agreements between algorithm-based and reference diagnoses for overall presence/absence of psychosis and for specific diagnoses of schizophrenia, schizoaffective disorder, and affective psychosis were examined using estimated prevalence rates, overall agreement, ROC analysis, and kappa statistics.

Results

For the presence/absence of psychosis, the most sensitive and least specific algorithm (‘At least one’ diagnosis) performed best. For schizophrenia, ‘Modal’ and ‘Last’ diagnoses had greatest agreement with reference diagnosis. For affective psychosis, ‘Hierarchy’ diagnosis performed best. Agreement between clinical and reference diagnoses was no better than chance for diagnoses of schizoaffective disorder. Overall agreement between administrative and reference diagnoses was modest, but may have been limited by the use of participants who had been screened for likely psychosis prior to assessment.

Conclusion

The choice of algorithm for extracting a psychosis diagnosis from administrative datasets may have a substantial impact on the accuracy of the diagnoses derived. An ‘Any diagnosis’ algorithm provides a sensitive measure for the presence of any psychosis, while ‘Last diagnosis’ is more accurate for specific diagnosis of schizophrenia and a hierarchical diagnosis is more accurate for affective psychosis.     

No genetic association between NCAM1 gene polymorphisms and schizophrenia in the Chinese population

Background

The neural cell adhesion molecule 1(NCAM1, aliases NCAM and CD56) is a cell-surface molecule which makes homophilic adhesion between neural cells involved in cell migration, axon outgrowth and synaptic plasticity. Recent studies reported that NCAM1 might act as a candidate schizophrenia susceptibility gene.

Method

We genotyped five SNPs (rs1943620, rs1836796, rs1821693, rs686050, rs584427) within the NCAM1 gene and conducted a case-control study in 288 schizophrenic patients and 288 healthy subjects in the Chinese Han population. We compared allele and genotype frequencies and haplotype distributions between cases and controls.

Result

No significant differences in allele and genotype frequencies were found for each single SNP between schizophrenic patients and healthy subjects. Moreover, there were no significant differences in haplotype distributions between cases and controls (global χ² = 1.318, P = 0.725, df = 3).

Conclusion

Our study suggests that the five SNPs within NCAM1 gene we studied may not play a major role in the schizophrenia susceptibility in the Chinese Han population.     

Reliability and validity of the life functioning assessment inventory (L-FAI) for patients with psychosis

Purpose

Functioning level is one of the major indicators of recovery in schizophrenia. It is important that the assessment of functioning is performed accurately. However, functioning evaluation is difficult due to the absence of specific anchor points in the widely used functioning assessment scales. We aimed to validate a new functioning scale, the life functioning assessment inventory (L-FAI), which assesses the functioning outcome of patients with psychosis in a more objective, and comprehensive manner. L-FAI assesses four life domains including work, social relationships, leisure, and homemaking. Specific and concrete anchor points are set in each of these domains.

Methods

The reliability and validity of L-FAI were assessed in 32 patients with psychosis. Opinions towards the scale were also obtained from experienced mental health professionals and members of a local advocacy group.

Results

Good inter-rater reliability (Cohen’s kappa 0.67–0.97) and test–retest reliability (Cohen’s kappa 0.67–0.86) were found. The scale has also been found to have good concurrent validity, correlating well with social and occupational functioning assessment scale (SOFAS) and role functioning scale (RFS) (Spearman’s r 0.53–0.89). The scale was associated solely with negative symptoms (Spearman’s r ?0.48) but not with positive symptoms.

Conclusions

L-FAI is suited for both clinical and research purposes in evaluating functioning level in patients with psychosis. More research is needed to replicate the current study with a larger sample size.     

Childhood sexual trauma, cannabis use and psychosis: statistically controlling for pre-trauma psychosis and psychopathology

Purpose

Recurring evidence seems to suggest that sexual trauma in childhood may moderate associations between cannabis consumption and psychosis. It has also been suggested, however, that poor childhood mental health may explain linkages between these phenomena.

Methods

The current study, using data from the National Comorbidity Survey-Replication (N = 2,355), sought to revaluate the stability of the childhood trauma–cannabis interaction while statistically controlling for pre-trauma psychotic experiences and psychopathology in childhood.

Results

Psychotic experiences that occurred before childhood sexual trauma significantly influenced adult psychosis symptomatology (psychosis pre-rape B = 0.10; psychosis pre-sexual assault B = 0.23). Social phobia (B = 0.07) also conferred risk for adult psychosis. Pre-trauma childhood psychopathology, however, did not account for the interaction between childhood sexual trauma and cannabis consumption in a multivariate model. Childhood experiences of rape (B = 0.15) and an interaction between cannabis use and childhood sexual assault (B = 0.05) independently contributed to adult psychosis. Cannabis use conferred no independent risk.

Conclusions

With specific regard to research methodology, the current findings offer further justification for the inclusion of childhood sexual trauma in analyses investigating associations between cannabis use and psychosis.     

Possible association between Interleukin-1beta gene and schizophrenia in a Japanese population

Background

Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism.

Methods

We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software.

Results

We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values.

Conclusions

Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.     

Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from Malaysia

Objective

Even though the role of the DICS1 gene as a risk factor for schizophrenia is still unclear, there is substantial evidence from functional and cell biology studies that supports the connection of the gene with schizophrenia. The studies associating the DISC1 gene with schizophrenia in Asian populations are limited to East-Asian populations. Our study examined several DISC1 markers of schizophrenia that were identified in the Caucasian and East-Asian populations in Malaysia and assessed the role of rs2509382, which is located at 11q14.3, the mutual translocation region of the famous DISC1 translocation [t (1; 11) (p42.1; q14.3)].

Methods

We genotyped eleven single-neucleotide polymorphism (SNPs) within or related to DISC1 (rs821597, rs821616, rs4658971, rs1538979, rs843979, rs2812385, rs1407599, rs4658890, and rs2509382) using the PCR-RFLP methods.

Results

In all, there were 575 participants (225 schizophrenic patients and 350 healthy controls) of either Malay or Chinese ethnicity. The case-control analyses found two SNPs that were associated with schizophrenia [rs4658971 (p=0.030; OR=1.43 (1.35-1.99) and rs1538979-(p=0.036; OR=1.35 (1.02-1.80)] and rs2509382-susceptibility among the males schizophrenics [p=0.0082; OR=2.16 (1.22-3.81)]. This is similar to the meta-analysis findings for the Caucasian populations.

Conclusion

The study supports the notion that the DISC1 gene is a marker of schizophrenia susceptibility and that rs2509382 in the mutual DISC1 translocation region is a susceptibility marker for schizophrenia among males in Malaysia. However, the finding of the study is limited due to possible genetic stratification and the small sample size.     

The need for culture sensitive diagnostic procedures

Objective

We examine the procedural validity of a standardized instrument for the diagnosis of psychotic disorders in Morocco.

Method

Twenty-nine patients from Casablanca, Morocco, with a psychotic or mood disorder were examined using the Comprehensive Assessment of Symptoms and History (CASH) an adapted version using cultural formulation to make the instrument more culturally sensitive (CASH-CS). Chance corrected agreement was calculated between diagnoses based on these two versions of CASH and independent clinical diagnoses according to local psychiatrists.

Results

Agreement for traditional CASH versus clinical diagnosis and for CASH versus CASH-CS was low (kappa = ?0.19; SD 0.16 and kappa = 0.21; SD 0.16, respectively). De CASH-CS, showed good agreement with clinical diagnosis (kappa = 0.79; SD 0.11).

Conclusion

Standardized instruments for the assessment of psychosis such as the CASH may be liable to cultural misinterpretations. This may be relevant to the interpretation of the high incidence rates of schizophrenia among immigrants.

Significant outcomes

Agreement between a culturally naïve version of a standardized diagnostic instrument for the assessment of psychosis and clinical diagnosis by Moroccan psychiatrists is poor. Adding additional probes and decision rules based on cultural formulation improves agreement with clinical diagnosis significantly.

Limitations

The study was conducted in a small sample. Both versions of CASH were administered by the same interviewer in a single interview session.