Genome-wide copy number variation-, validation- and screening study implicates a new copy number polymorphism associated with suicide attempts in major depressive disorder.

BACKGROUND: The genetic basis of suicide attempts (SA) remains unclear. Especially the role of copy number variations (CNVs) remains to be elucidated. The present study aimed to identify susceptibility variants associated with SA among Chinese with major depressive disorder (MDD), covering both CNVs and single-nucleotide polymorphisms (SNPs). METHODS: We conducted a genome-wide association study (GWAS) on MDD patients with and without SA and top results were tested in a replication study. A genome-wide CNV study was also performed. Subsequently, a validation assay using qRT-PCR technology was performed to confirm any associated CNVs and then applied to the entire cohort to examine the association. RESULTS: Although GWAS did not identify any SNPs reaching genome-wide significance, we identified TPH2 as the top susceptibility gene (p-value = 2.75e-05) in gene-based analysis, which is a strong biological candidate for its role in the serotonergic system. As for CNV analysis, we found that the global rate of CNV was higher in SA than that in non-SA subjects (p-value = 0.023). Genome-wide CNV study revealed an SA-associated CNV region that achieved genome-wide significance (corrected p-value = 0.014). The associated CNV was successfully validated with a more rigorous qRT-PCR assay and identified to be a common variant in this cohort. Its deletion rate was higher in SA subjects [OR = 2.05 (1.02-4.12), adjusted p-value = 0.045]. Based on the GTEx database, genetic variants that probed this CNV were significantly associated with the expression level of ZNF33B in two brain regions (p-value < 4.2e-05). In stratified analysis, the CNV showed a significant effect [OR = 2.58 (1.06-6.27), p-value = 0.039] in those with high neuroticism but not in those with average or low neuroticism. CONCLUSIONS: We identified a new common CNV likely involved in the etiology of SA. This finding sheds light on an important role of common CNVs in the pathophysiology of SA, suggesting a new promising avenue for investigating its genetic architecture.

High incidence of hepatocellular carcinoma and cirrhotic complications in patients with psychiatric illness: a territory-wide cohort study.

BACKGROUND: Because of high-risk behaviours, sedentary lifestyle and side effects of medications, psychiatric patients are at risk of viral hepatitis, alcohol-related liver disease and non-alcoholic fatty liver disease. We aimed to study the incidence of hepatocellular carcinoma (HCC) and cirrhotic complications in psychiatric patients. METHODS: We identified consecutive adult patients in all public hospitals and clinics in Hong Kong with psychiatric diagnoses between year 2003 and 2007 using the Clinical Data Analysis and Reporting System, which represents in-patient and out-patient data of approximately 80% of the 7.4-million local population. The patients were followed for liver-related events (HCC and cirrhotic complications) and deaths until December 2017. Age- and sex-standardized incidence ratio (SIR) of HCC in psychiatric patients to the general population was estimated by Poisson model. RESULTS: We included 105,763 psychiatric patients without prior liver-related events in the final analysis. During a median (interquartile range) follow-up of 12.4 (11.0-13.7) years, 1461 (1.4%) patients developed liver-related events; 472 (0.4%) patients developed HCC. Compared with the general population, psychiatric patients had increased incidence of HCC (SIR 1.42, 95% confidence interval [CI] 1.28-1.57, P < 0.001). The SIR was highest in patients with drug-induced (SIR 3.18, 95% CI 2.41-4.11, P < 0.001) and alcohol-induced mental disorders (SIR 2.98, 95% CI 2.30-3.81, P < 0.001), but was also increased in patients with psychotic disorders (SIR 1.39, 95% CI 1.16-1.65, P < 0.001) and mood disorders (SIR 1.16, 95% CI 1.00-1.34, P = 0.047). Liver disease was the fifth most common cause of death in this population, accounting for 595 of 10,614 (5.6%) deaths. Importantly, 569 (38.9%) patients were not known to have liver diseases at the time of liver-related events. The median age at HCC diagnosis (61 [range 26-83] years) was older and the median overall survival (8.0 [95% CI 5.0-10.9] months) after HCC diagnosis was shorter in this cohort of psychiatric patients than other reports from Hong Kong. CONCLUSIONS: HCC, cirrhotic complications, and liver-related deaths are common in psychiatric patients, but liver diseases are often undiagnosed. More efforts are needed to identify liver diseases in the psychiatric population so that treatments and screening for HCC and varices can be provided to patients in need.

Associations of Homer Scaffolding Protein 1 gene and psychological correlates with suicide attempts in Chinese: A pilot study of multifactorial risk model.

BACKGROUND: Suicide is a fatal outcome for subjects with mental ill-health. Genetic factors and psychological correlates are believed to contribute to the risk of suicide attempts (SA), whereas both factors are reported to exert a small effect. This study therefore tried to investigate if combination of the two aspects can enhance the explanation of variance in SA. METHODS: A common variant rs7713917 in HOMER1 gene was genotyped for 333 Chinese psychiatric patients with or without SA. Multifactorial risk models comprised of this variant and psychological correlates were identified by logistic regression analysis (LRA) and Multifactor Dimensionality Reduction (MDR) method separately, and then evaluated for their performance by biostatistical methods. RESULTS: An association of A-carrier genotypes in rs7713917 with an increased risk of SA was observed (OR = 1.79, 95% CI = 1.08-2.98). Although with a medium effect size, this variant alone could only explain 1.9% variance of SA. Interestingly, this study was the first time to show that the association of the rs7713917 and SA was significantly mediated by the NEO conscientiousness (NEOC) dimension (p-value = 0.002), with a greater genetic effect observed in subjects with a low NEO-C level (OR = 2.89, 95% CI = 1.16-7.18) but not in subjects with an average or high level. Upon the LRA method, the multifactorial risk model constituted of the two interacted factors and their interaction effect could explain up to 17.0% variance, which was almost 9-fold higher than the one explained by the rs7713917 alone. Furthermore, this model owned a higher effectiveness than the three models identified by the MDR method (p-value < 0.0007). CONCLUSIONS: The present study identified an effective multifactorial risk model, in which the combination of the HOMER1 variant and the NEO-C dimension could enhance explanation of the variance of SA in Chinese. This pilot study may provide a novel avenue to investigate the pathogenesis of SA in psychiatric patients.

Prevalence of Mental Illness among Homeless People in Hong Kong.

METHOLODOGY: This study examined the prevalence and correlates of mental illness in homeless people in Hong Kong and explored the barriers preventing their access to health care. Ninety-seven Cantonese-speaking Chinese who were homeless during the study period were selected at random from the records of the three organisations serving the homeless population. The response rate was 69%. Seventeen subjects could not give valid consent due to their poor mental state, so their responses were excluded from the data analysis. A psychiatrist administered the Structured Clinical Interview for DSM-IV Axis-I disorders (SCID-I) and the Mini -Mental State Examination. Consensus diagnoses for subjects who could not complete the SCID-I were established by three independent psychiatrists. FINDINGS: The point prevalence of mental illness was 56%. Seventy-one percent of the subjects had a lifetime history of mental illness, 30% had a mood disorder, 25% had an alcohol use disorder, 25% had a substance use disorder, 10% had a psychotic disorder, 10% had an anxiety disorder and 6% had dementia. Forty-one percent of the subjects with mental illness had undergone a previous psychiatric assessment. Only 13% of the subjects with mental illness were receiving psychiatric care at the time of interview. The prevalence of psychotic disorders, dementia and the rate of under treatment are hugely underestimated, as a significant proportion (18%) of the subjects initially selected were too ill to give consent to join the study. CONCLUSION: The low treatment rate and the presence of this severely ill and unreached group of homeless people reflect the fact that the current mode of service delivery is failing to support the most severely ill homeless individuals.

Mental morbidities and chronic fatigue in severe acute respiratory syndrome survivors: long-term follow-up.

BACKGROUND: Short-term follow-up studies of severe acute respiratory syndrome (SARS) survivors suggested that their physical conditions continuously improved in the first year but that their mental health did not. We investigated long-term psychiatric morbidities and chronic fatigue among SARS survivors. METHODS: All SARS survivors from the hospitals of a local region in Hong Kong were assessed by a constellation of psychometric questionnaires and a semistructured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) to determine the presence of psychiatric disorders and chronic fatigue problems. RESULTS: Of 369 SARS survivors, 233 (63.1%) participated in the study (mean period of time after SARS, 41.3 months). Over 40% of the respondents had active psychiatric illnesses, 40.3% reported a chronic fatigue problem, and 27.1% met the modified 1994 Centers for Disease Control and Prevention criteria for chronic fatigue syndrome. Logistic regression analysis suggested that being a health care worker at the time of SARS infection (odds ratio [OR], 3.24; 95% confidence interval [CI], 1.12- 9.39; P = .03), being unemployed at follow-up (OR, 4.71; 95% CI, 1.50-14.78; P = .008), having a perception of social stigmatization (OR, 3.03; 95% CI, 1.20-7.60; P = .02), and having applied to the SARS survivors' fund (OR, 2.92; 95% CI, 1.18-7.22; P = .02) were associated with an increased risk of psychiatric morbidities at follow-up, whereas application to the SARS survivors' fund (OR, 2.64; 95% CI, 1.07-6.51; P = .04) was associated with increased risk of chronic fatigue problems. CONCLUSIONS: Psychiatric morbidities and chronic fatigue persisted and continued to be clinically significant among the survivors at the 4-year follow-up. Optimization of the treatment of mental health morbidities by a multidisciplinary approach with a view for long-term rehabilitation, especially targeting psychiatric and fatigue problems and functional and occupational rehabilitation, would be needed.

High prevalence of hypokalemia in acute psychiatric inpatients.

BACKGROUND: Hypokalemia is an easily identifiable, clinically important but commonly neglected condition in psychiatric patients. This study intended to examine the prevalence of hypokalemia and its clinical correlates in acute psychiatric inpatients. METHOD: This retrospective study was conducted over a 6 month period in 2008. The case notes, computerized records and laboratory results of all patients who were consecutively admitted to the acute psychiatric wards in a University-affiliated regional psychiatric unit were studied. RESULT: Three hundred forty-seven patients out of 440 admissions were studied. Hypokalemia, as defined by serum potassium level of less than 3.5 mmol/L, was found in 20.5% of patients with a higher prevalence in psychotic patients (27.7%). The mean potassium level of psychotic patients was lower than that of the overall study population (3.72 vs. 3.81 mmol/L, P<.05). White cell counts among the hypokalemic patients were higher than those without hypokalemia (7.8 vs. 7.1 x 10(9)/L, P=.02). CONCLUSION: Hypokalemia was common among acute psychiatric inpatients. Both agitation and the use of antipsychotics were postulated to contribute to the high prevalence of hypokalemia among acutely ill psychiatric patients.