Ahmad Hatim

Association of brain-derived neurotrophic factor Val66Met)genetic polymorphism with methamphetamine dependence in a Malaysian population.

Methamphetamine is a highly addictive psychostimulant that has surged in popularity worldwide in the last decade. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is widely expressed in the adult mammalian brain and plays an important role in the long-term survival, differentiation, and outgrowth of neurons. Previous studies suggested that the BDNF gene may be involved in the mechanisms underlying substance dependence. This study investigated the association of the BDNF gene Val66Met polymorphism with methamphetamine dependence and with psychosis in a Malaysian population with different ethnicities. The BDNF Val66Met polymorphism was genotyped by PCR-RFLP in 186 male methamphetamine-dependent subjects and in 154 male controls of four different ethnicities, namely, Malay, Chinese, Kadazan-Dusun, and Bajau. Our results showed that the distribution of the BDNF Val66Met genotype in Chinese subjects with methamphetamine dependence (OR=2.6, p=0.015) and methamphetamine psychosis (OR=0.2, p = 0.034) were significant compared with controls. The frequency of the 66Val allele in methamphetamine-dependent subjects was higher than that in the control group, suggesting that the 66Val carriers are more susceptible to methamphetamine dependence. However, 66Val allele frequency in other ethnicities was not significantly different from the controls. The results of the study also showed that in the Chinese methamphetamine-dependent subjects, there was a difference in allele frequency when comparing those who developed psychosis and those who did not. Our findings suggest that the BDNF Val66Met polymorphism may contribute to methamphetamine dependence and psychosis in the Chinese population but not in other Malaysian ethnicities.

Association of FTO, LEPR and MTHFR gene polymorphisms with metabolic syndrome in schizophrenia patients receiving antipsychotics

AIM The occurrence of metabolic syndrome (MS) in schizophrenia patients receiving long-term antipsychotics (APs) contributes to their high mortality rate. We aimed to determine whether genetic polymorphisms of identified candidate genes are associated with MS in our study population. MATERIALS & METHODS We recruited 206 schizophrenia patients receiving AP treatment for at least a year. Cross-sectional measurements of weight, height, blood pressure, waist and hip circumference, and other lipid profiles were recorded. Patient DNA was genotyped for 16 candidate gene polymorphisms. RESULTS Of these patients, 59.7% were found to have MS while 40.3% did not. All metabolic parameters were significantly different between the two groups. Only three of the 16 polymorphisms studied showed significant association with MS; rs9939609 of the FTO gene confers risk for MS (odds ratio [OR]: 1.73, 95% CI: 1.07-2.78, p = 0.026), while rs1137101 of the LEPR gene (OR: 0.47, 95% CI: 0.28-0.80, p = 0.005) and rs1801133 of the MTHFR gene (OR: 0.59, 95% CI: 0.35-0.99, p = 0.049) are protective against MS. CONCLUSION Polymorphisms of the FTO, LEPR and MTHFR genes may play a role in MS in Malaysian schizophrenia patients receiving long-term treatment with APs.

Clinical features of depression in Asia: Results of a large prospective, cross-sectional study

The objective of this study was to investigate the clinical features of depression in Asian patients.

Association of a functional FAAH polymorphism with methamphetamine-induced symptoms and dependence in a Malaysian population

AIM FAAH is a membrane enzyme that terminates the activity of a large class of endogenous signaling lipids. Recent studies suggest that the FAAH Pro129Thr polymorphism is a common mutation in the FAAH gene that is significantly associated with drug-addictive traits. This study investigated the association of the Pro129Thr polymorphism of the FAAH gene with methamphetamine dependence, methamphetamine-induced psychosis, manic episodes and panic disorder in a Malaysian population. MATERIALS & METHODS This polymorphism was genotyped in 232 male methamphetamine-dependent subjects and in 241 male controls of four different ethnicities: Malay, Chinese, Kadazan-Dusun and Bajau. Intergroup statistical analyses were performed by using the χ(2)-square test and Fishers exact test, where necessary. In cases of multiple comparisons, the Bonferroni correction was performed. RESULTS Our results indicated that the FAAH Pro129Thr polymorphism showed a significant association with risk of methamphetamine dependence in the pooled subjects (odds ratio [OR]: 2.017; p < 0.001) and in the Malay (OR: 2.829; p < 0.001) and Chinese (OR: 3.685; p < 0.001) groups. We also found an association of this polymorphism with episodes of methamphetamine-induced mania in the Malay group (OR: 2.836; p = 0.035). However, there was no association between this polymorphism and age of onset of drug use or the occurrence of methamphetamine-induced psychosis or of panic disorder. CONCLUSION Our findings suggest that the FAAH Pro129Thr polymorphism may contribute to methamphetamine dependence in the Malay and Chinese ethnic groups.

Association of ADRA2A and MTHFR gene polymorphisms with weight loss following antipsychotic switching to aripiprazole or ziprasidone

Various genetic polymorphisms have been reported to be associated with antipsychotic‐induced weight gain. In this study, we aimed to determine whether risk polymorphisms in 12 candidate genes are associated with reduction in body mass index (BMI) of patients following switching of antipsychotics to aripiprazole or ziprasidone.

Clinical and sociodemographic correlates of suicidality in patients with major depressive disorder from six Asian countries

BackgroundEast Asian countries have high suicide rates. However, little is known about clinical and sociodemographic factors associated with suicidality in Asian populations. The aim of this study was to evaluate the factors associated with suicidality in patients with major depressive disorder (MDD) from six Asian countries.MethodsThe study cohort consisted of 547 outpatients with MDD. Patients presented to study sites in China (n = 114), South Korea (n = 101), Malaysia (n = 90), Singapore (n = 40), Thailand (n = 103), and Taiwan (n = 99). All patients completed the Mini-International Neuropsychiatric Interview (MINI), the Montgomery–Asberg Depression Rating Scale (MADRS), the Global Severity Index(SCL-90R), the Fatigue Severity Scale, the 36-item short-form health survey, the Sheehan Disability Scale, and the Multidimensional Scale of Perceived Social Support (MSPSS). Patients were classified as showing high suicidality if they scored ≥6 on the MINI suicidality module. Multivariate logistic regression analysis was used to examine sociodemographic and clinical factors related to high suicidality.ResultsOne hundred and twenty-five patients were classed as high suicidality. Unemployed status (adjusted odds ratio [OR] 2.43, p < 0.01), MADRS score (adjusted OR 1.08), p < 0.001, and GSI (SCL-90R) score (adjusted OR 1.06, p < 0.01) were positively related to high suicidality. Hindu (adjusted OR 0.09, p < 0.05) or Muslim (adjusted OR 0.21, p < 0.001) religion and MSPSS score (adjusted OR 0.82, p < 0.05) were protective against high suicidality.ConclusionsA variety of sociodemographic and clinical factors were associated with high suicidality in Asian patients with MDD. These factors may facilitate the identification of MDD patients at risk of suicide.

Recommendations for the optimal care of patients with recent‐onset psychosis in the Asia‐Pacific region

Providing optimal care to patients with recent‐onset psychosis can improve outcomes and reduce relapse. However, there is a lack of consistency of the implementation of guidelines for such patients across the Asia‐Pacific region. We determined a pragmatic set of recommendations for use on a day‐to‐day basis to help provide optimal care at this crucial stage of illness. The recommendations were developed over a series of meetings by an international faculty of 15 experts from the Asia‐Pacific region, Europe, and South Africa. A structured search of the PubMed database was conducted. This was further developed based on the facultys clinical experience and knowledge of the literature into 10 key aspects of optimal care for patients during the first five years of a diagnosis of a psychotic disorder, with particular relevance to the Asia‐Pacific region. Several common principles emerged: adherence to antipsychotic medications is crucial; substance abuse, psychiatric and medical comorbidities should be addressed; psychosocial interventions play a pivotal role; and family members can play a vital role in overall patient care. By following these recommendations, clinicians may improve outcomes for patients with recent‐onset psychosis.

Stressful life events preceding the onset of depression in Asian patients with major depressive disorder

Background: Previous studies have identified the significant role of stressful life events in the onset of depressive episodes. However, there is a paucity of cross-national studies on stressful life events that precede depression. Aims: We aimed to compare types of stressful life events associated with the onset of depressive episodes in patients with major depressive disorder (MDD) in five Asian countries. Method: A total of 507 outpatients with MDD were recruited in China (n = 114), South Korea (n = 101), Malaysia (n = 90), Thailand (n = 103) and Taiwan (n = 99). All patients were assessed with the Mini-International Neuropsychiatric Interview and the List of Threatening Experiences. The prevalence of each type of stressful life events was calculated and compared between each country. Results: The type of stressful life event that preceded the onset of a depressive episode differed between patients in China and Taiwan and those in South Korea, Malaysia and Thailand. Patients in China and Taiwan were less likely to report interpersonal relationship problems and occupational/financial problems than patients in South Korea, Malaysia and Thailand. Conclusion: Understanding the nature and basis of culturally determined susceptibilities to specific stressful life events is critical for establishing a policy of depression prevention and providing effective counseling services for depressed patients.

Is Early-onset in Major Depression a Predictor of Specific Clinical Features with More Impaired Social Function?

Background:Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods:In total, 547 out-patients aged 18–65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results:Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ⩽ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions:EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment.

Genetic polymorphism in DTNBP1 gene is associated with methamphetamine-induced panic disorder.

Objective:The dysbindin-1 (dystrobrevin-binding protein-1 [DTNBP-1]) gene has repeatedly been shown to be associated with psychotic disorder across diverse populations. In this study, we attempted to investigate the association of the rs3213207 (P1635) genetic polymorphism of the DTNBP1 gene with methamphetamine dependence and with methamphetamine-induced psychosis, manic episodes, and panic disorder in a male Malaysian population. Methods:This polymorphism was genotyped in 233 male methamphetamine-dependent subjects and in 301 male controls of the following 4 different ethnicities: Malay, Chinese, Kadazan-Dusun, and Bajau. Intergroup statistical analyses were performed by using the &khgr;2 test and the Fisher exact test where necessary. In cases of multiple comparisons, the Bonferroni correction was performed. Results:Our results indicated that the DTNBP1 rs3213207 polymorphism did not show any significant association with risk of methamphetamine dependence, either in the pooled subjects or after stratification into the 4 different ethnic groups (P > 0.05). Furthermore, we did not find any association of this polymorphism with methamphetamine-induced psychosis and episodes of methamphetamine-induced mania. However, there was a strong association between this polymorphism and the occurrence of methamphetamine-induced panic disorder in the pooled subjects (odds ratio [OR] = 6.739, P < 0.001) and in the Malay (OR = 11.93, P = 0.022) and Kadazan-Dusun (OR = 115.0, P < 0.001) groups. Conclusions:Our findings suggest that the DTNBP1 rs3213207 polymorphism may contribute to methamphetamine-induced panic disorder in the pooled Malaysian male population, especially in the Malay and Kadazan-Dusun ethnic groups. However, no association was found with methamphetamine dependence, methamphetamine-induced psychosis, or methamphetamine-induced mania.