Chi-Fa Hung

Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study

Background Obesity has been shown to be associated with depression and it has been suggested that higher body mass index (BMI) increases the risk of depression and other common mental disorders. However, the causal relationship remains unclear and Mendelian randomisation, a form of instrumental variable analysis, has recently been employed to attempt to resolve this issue. Aims To investigate whether higher BMI increases the risk of major depression. Method Two instrumental variable analyses were conducted to test the causal relationship between obesity and major depression in RADIANT, a large case-control study of major depression. We used a single nucleotide polymorphism (SNP) in FTO and a genetic risk score (GRS) based on 32 SNPs with well-established associations with BMI. Results Linear regression analysis, as expected, showed that individuals carrying more risk alleles of FTO or having higher score of GRS had a higher BMI. Probit regression suggested that higher BMI is associated with increased risk of major depression. However, our two instrumental variable analyses did not support a causal relationship between higher BMI and major depression (FTO genotype: coefficient –0.03, 95% CI –0.18 to 0.13, P = 0.73; GRS: coefficient –0.02, 95% CI –0.11 to 0.07, P = 0.62). Conclusions Our instrumental variable analyses did not support a causal relationship between higher BMI and major depression. The positive associations of higher BMI with major depression in probit regression analyses might be explained by reverse causality and/or residual confounding.

Monoamine oxidase A gene polymorphism and suicide: An association study and meta-analysis

BACKGROUND Abnormalities in brain monoamine transmission have been implicated in the pathogenesis of suicidal behavior. Studies examining the association between monoamine oxidase A (MAOA)-uVNTR polymorphism and suicide revealed inconsistent findings. This study aims to evaluate the possible association between the MAOA-uVNTR polymorphism and suicidal behaviors by examining our own subjects and conducting a meta-analytic review. METHODS 373 unrelated psychiatric patients (including 160 suicide attempters and 213 non-suicide attempters) were genotyped for the MAOA-uVNTR polymorphism. A meta-analysis was then performed by pooling data from seven case-control association studies by random effects model. RESULTS Our results indicate that there is no association between the MAOA-uVNTR polymorphism and suicide attempts in both genders. It also reveals that there is no association with violent suicide attempts. In the meta-analysis, there is no association between the polymorphism and suicidal behaviors. Also, there is no difference in the allelic distribution between psychiatric patients with and without suicidal behaviors. Limitations Our study was constrained by the insufficient information about environmental risk factors of suicide. CONCLUSIONS Our study is the first one to use meta-analysis in exploring the role of the MAOA-uVNTR polymorphism in suicidal behavior in psychiatric patients. No significant association was found in our study, suggesting MAOA-uVNTR polymorphism is unlikely to contribute significantly to suicide behavior. Further studies investigating the gene-environment interaction or focusing on the genetic risk factors of endophenotypes of suicidal behaviors are warranted.

A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder

BackgroundObesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD.MethodsLinear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case–control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity.ResultsIn the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P <0.001) but explained only a modest amount of variance. Adding ‘traditional’ risk factors to GRS significantly improved the predictive ability with the area under the curve (AUC) in the ROC analysis, increasing from 0.58 to 0.66 (95% CI, 0.62–0.68; χ2 = 27.68; P <0.0001). Although there was no formal evidence of interaction between depression status and GRS, there was further improvement in AUC in the ROC analysis when depression status was added to the model (AUC = 0.71; 95% CI, 0.68–0.73; χ2 = 28.64; P <0.0001). We further found that the GRS accounted for more variance of BMI in depressed patients than in healthy controls. Again, GRS discriminated obesity better in depressed patients compared to healthy controls. We later replicated these analyses in two independent samples (GSK-Munich and PsyCoLaus) and found similar results.ConclusionsA GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity.

No association between the Catechol-O-Methyltransferase (COMT) val158met polymorphism and cognitive improvement following cognitive remediation therapy (CRT) in schizophrenia

Cognitive deficits are rate limiters on recovery in schizophrenia that respond poorly to pharmacotherapy. Cognitive remediation therapy (CRT), a novel psychological therapy, has produced promising outcomes for cognition. However, little is known about the biological mechanisms that might underlie individual differences in CRT response. Catechol-O-Methyltransferase (COMT) is associated specifically with prefrontal cognition. The COMT Val158Met polymorphism is known to have a functional effect on the rate of dopamine degradation, which may be related to cognitive treatment response. This study aimed to determine whether COMT genotype influences cognitive improvement following CRT in schizophrenia. Participants with schizophrenia were recruited from three randomised controlled trials of CRT compared to treatment as usual, and one CRT treatment only trial, each providing 40 CRT sessions. Eighty-seven participants (40%) agreed to participate in the genetic study, and provided DNA for COMT genotyping. Cognitive function and psychopathology were assessed at baseline, post-treatment and 3-6-month follow-up. People with the COMT Val/Met genotype performed more poorly on categories achieved at baseline on the Wisconsin Card Sorting Test (WCST) than those homozygous for the Val or Met allele. Cognitive function improved with CRT but there was no association between this cognitive improvement and COMT genotype, either in the CRT group or in the total sample. The COMT val158Met polymorphism does not appear to be a clinically useful biomarker of cognitive improvement following CRT in schizophrenia. A complex set of factors may influence cognitive change, however, such that the COMT genotype might still have a subtle effect on response to CRT or similar interventions.

Anxiety and depression in patients with head and neck cancer: 6-month follow-up study.

Objective We aimed to assess psychiatric morbidities of patients with head and neck cancer (HNC) in a prospective study at pretreatment, and 3 and 6 months after treatment, and to compare their health-related quality of life (HRQL) between those with and without depressive disorders (depression). Materials and methods Patients with newly diagnosed HNC from a tertiary hospital were recruited into the study. They were assessed for psychiatric morbidities using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Their HRQL was simultaneously evaluated using the quality of life questionnaire of the European Organisation for Research and Treatment of Cancer with a specific module for head and neck cancer; and depressed and nondepressed HNC patients were compared by using the generalized mixed-effect model for repeated measurements. Results A total of 106 patients were recruited into this study. High rates of anxiety were found at pretreatment, but steadily declined over time (from 27.3% to 6.4%, and later 3.3%). A skew pattern of depression was observed, with prevalence rates from 8.5% at pretreatment to 24.5% and 14% at 3 and 6 months, respectively, after treatment. We found that loss of sense (P=0.001), loss of speech (P<0.001), low libido (P=0.001), dry mouth (P<0.001), and weight loss (P=0.001) were related to depression over time. The depressed patients had a higher consumption of painkillers (P=0.001) and nutrition supplements (P<0.001). The results showed that depression was predicted by sticky saliva (P<0.001) and trouble with social contact (P<0.001) at 3 months, and trouble with social eating (P<0.001) at 6 months. Conclusion Patients with HNC experienced different changes in anxiety and depression in the first 6 months of treatment. Dysfunction in salivation, problems with eating, and problems with social contacts were major risk factors for depression.

Age-associated decrease in global DNA methylation in patients with major depression

Background Evidence has supported a role of DNA methylation in the pathophysiology of mood disorders. The purpose of the current study is to examine 5-methylcytosine (5-mc) and 5-hydroxymethylcytosine (5-hmc) levels in patients with major depressive disorder (MDD) at different disease states. Methods Forty-nine patients with MDD and 25 healthy control subjects were included. The severity in the disease was assessed by using the 17-item Hamilton Rating Scale of Depression (HAM-D) (HAM-D ≥19 for severe MDD and HAM-D ≤7 for remitted MDD). The 5-mc and 5-hmc levels in leukocyte DNA were measured using an enzyme-linked immunosorbent assay-based method. Results We found a significant decrease in 5-hmc and trends of decreasing 5-mc levels in patients with severe MDD compared to healthy controls (P=0.059 for 5-mc and P=0.013 for 5-hmc). The decrease in the level exists only in the older age group (P=0.035 for 5-mc and P=0.002 for 5-hmc) but not in the younger age group (P=0.077 for 5-mc and P=0.620 for 5-hmc). In addition, the 5-mc level was found to be inversely correlated with disease severity (P=0.011). Conclusion Our results support a decrease in global DNA methylation associated with age in patients with severe depression. Further studies are needed to clarify the role of the methylation level as a disease marker of depression and whether antidepressant treatment changes the methylation profiles.

Validation of the Chinese version of Brief Assessment of Cognition in Schizophrenia

Objective A test battery that measures cognitive function impairment in patients with schizophrenia, the Brief Assessment of Cognition in Schizophrenia (BACS), has been translated into various languages and validated. This study aimed to test the reliability and validity of the Chinese version of the BACS in a Chinese-speaking population. Methods All participants in this study (66 patients with schizophrenia [mean age: 41.2 years, 57.6% male] and 66 age- and sex-matched healthy controls) were from Taiwan and assessed using the BACS and the University of California, San Diego (UCSD) Performance-Based Skills Assessment, Brief Version (UPSA-B). Thirty-eight of the 66 patients with schizophrenia received a reassessment using the BACS. Results The BACS had good test–retest reliability, and all BACS subtests had statistically insignificant practice effects. Principal components analysis demonstrated that a one-factor solution best fits our dataset (60.9% of the variance). In both patients and controls, the BACS composite scores were positively correlated with all BACS subscales (P<0.001) and UPSA-B scales (P<0.001). Furthermore, all BACS subtests (verbal memory, working memory, motor speed, verbal fluency, attention and processing speed, and executive function) significantly differentiated patients with schizophrenia from healthy controls (P<0.001), and the BACS composite score had the best discriminative validity (P<0.001). Conclusion The Chinese version of the BACS exhibits satisfactory psychometric properties, including high test–retest reliability, high internal consistency, acceptable concurrent validity, and good discriminant validity. We suggest that the BACS is a reliable and practical tool for assessing cognitive function in patients with schizophrenia.

Repeated suicide attempts among suicidal cases: Outcome of one-year follow-up

To assess the mortality rates and risk factors involved in repeated suicide attempts.

Development and validation of the Assessment for Repeated Suicide

This study developed and validated a multidimensional measure, the Assessment for Repeated Suicide (ARS), to assess suicide risk and predict future suicidal attempts within psychiatric populations who have previously attempted suicide.

Increased serum levels of cysteine in patients with schizophrenia: A potential marker of cognitive function preservation

BACKGROUND Oxidative stress has been implicated in the psychopathology of schizophrenia. Cysteine, a semi-essential amino acid, is the precursor of the antioxidant glutathione. The aim of this study was to investigate the differences in serum levels of cysteine between patients with schizophrenia and healthy controls. The relationships between levels of cysteine, psychopathology and cognitive function were also explored. METHODS We recruited 65 patients with schizophrenia and 65 age- and gender-matched healthy controls. Blood samples were collected to determine the serum levels of cysteine and plasma levels of metabolic parameters. The cognitive function of participants was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). The psychopathology of schizophrenic patients was evaluated using the Positive and Negative Syndrome Scale. RESULTS Serum cysteine levels were significantly higher in schizophrenic patients than in controls (P<0.001). In patients with schizophrenia, serum levels of cysteine were positively correlated with cognitive function in terms of verbal memory (P=0.013), working memory (P=0.004), verbal fluency (P=0.027), attention and processing speed (P=0.025), executive function (P=0.024) and the composite score on the BACS (P=0.013). In healthy controls, no significant correlation was observed between cysteine level and cognitive function. CONCLUSIONS These findings suggest that oxidative stress may be involved in the pathogenesis of schizophrenia, and compensatory elevated levels of cysteine may serve as an indicator of cognition preservation. Further prospective studies are warranted to investigate the dynamic alterations in cysteine and the underlying pathophysiology of schizophrenia.