Sharmilla Kanagasundram

Genetic association of LMAN2L gene in schizophrenia and bipolar disorder and its interaction with ANK3 gene polymorphism

Recent studies have shown that bipolar disorder (BPD) and schizophrenia (SZ) share some common genetic risk factors. This study aimed to examine the association between candidate single nucleotide polymorphisms (SNPs) identified from genome-wide association studies (GWAS) and risk of BPD and SZ. A total of 715 patients (244 BPD and 471 SZ) and 593 controls were genotyped using the Sequenom MassARRAY platform. We showed a positive association between LMAN2L (rs6746896) and risk of both BPD and SZ in a pooled population (P-value=0.001 and 0.009, respectively). Following stratification by ethnicity, variants of the ANK3 gene (rs1938516 and rs10994336) were found to be associated with BPD in Malays (P-value=0.001 and 0.006, respectively). Furthermore, an association exists between another variant of LMAN2L (rs2271893) and SZ in the Malay and Indian ethnic groups (P-value=0.003 and 0.002, respectively). Gene-gene interaction analysis revealed a significant interaction between the ANK3 and LMAN2L genes (empirical P=0.0107). Significant differences were shown between patients and controls for two haplotype frequencies of LMAN2L: GA (P=0.015 and P=0.010, for BPD and SZ, respectively) and GG (P=0.013 for BPD). Our study showed a significant association between LMAN2L and risk of both BPD and SZ.

Nonsynonymous polymorphisms of the PDLIM5 gene association with the occurrence of both bipolar disorder and schizophrenia.

Two single nucleotide polymorphisms of PDLIM5, rs7690296 and rs11097431, were genotyped using Mass-Array SNP genotyping by Sequenom technology in 244 bipolar disorder patients, 471 schizophrenia patients, and 601 control individuals who were Malay, Chinese, and Indian ethnic groups in the Malaysian population. A significant association was observed in allele frequency between the rs7690296 polymorphism and bipolar disorder in the Indian ethnic group [P=0.02, adjusted odds ratio (OR) 0.058, 95% confidence interval (CI) 0.36–0.93]. A significant association was also observed between the rs7690296 polymorphism and schizophrenia under the recessive model for both Malay (P=0.02, adjusted OR 1.86, 95% CI 1.12–3.10) and Indian (P=0.02, adjusted OR 1.92, 95% CI 1.10–3.37) ethnic groups. However, no association was detected between the rs11097431 polymorphism either with bipolar disorder or with schizophrenia. Therefore, it can be deduced that the nonsynonymous rs7690296 polymorphism could play an important role in the pathophysiology of both bipolar disorder and schizophrenia.

Peripheral PDLIM5 expression in bipolar disorder and the effect of olanzapine administration

BackgroundOne of the genes suggested to play an important role in the pathophysiology of bipolar disorder (BPD) is PDLIM5, which encodes LIM domain protein. Our main objective was to examine the effect of olanzapine treatment on PDLIM5 mRNA expression in the peripheral blood leukocytes of BPD patients.MethodsWe measured the expression of PDLIM5 mRNA from 16 patients with BPD Type I after 0, 4, and 8 weeks of treatment with olanzapine using quantitative real-time PCR. The Young Mania Rating Scale was used to evaluate the severity of manic symptoms in BPD patients. We also compared PDLIM5 mRNA expression in treatment-naïve BPD patients with that in healthy control subjects.ResultsNo significant difference was found in PDLIM5 mRNA expression between patients before olanzapine treatment and following 4 and 8 weeks of treatment (p>0.05). Although we observed a significant reduction in the severity of manic symptoms in all BPD patients (p<0.05), the effectiveness of the medication did not significantly correlate with the expression of PDLIM5 mRNA (p>0.05). Interestingly, PDLIM5 mRNA expression differed significantly between treatment-naïve BPD patients and healthy control subjects (p=0.002).ConclusionPDLIM5 mRNA expression did not appear to be a reflection of the efficacy of olanzapine in reducing the manic symptoms of BPD. The significant difference in expression of PDLIM5 mRNA in the peripheral blood leukocytes of treatment-naïve BPD patients versus that of healthy control subjects, however, suggests that it may be a good biological marker for BPD.

Preliminary examination of microRNA expression profiling in bipolar disorder I patients during antipsychotic treatment

Although major progress has been achieved in research and development of antipsychotic medications for bipolar disorder (BPD), knowledge of the molecular mechanisms underlying this disorder and the action of atypical antipsychotics remains incomplete. The levels of microRNAs (miRNAs)—small non‐coding RNA molecules that regulate gene expression, including genes involved in neuronal function and plasticity—are frequently altered in psychiatric disorders. This study aimed to examine changes in miRNA expression in bipolar mania patients after treatment with asenapine and risperidone. Using a miRNA microarray, we analyzed miRNA expression in the blood of 10 bipolar mania patients following 12 weeks of treatment with asenapine or risperidone. Selected miRNAs were validated by using real‐time PCR. A total of 16 miRNAs were differentially expressed after treatment in the asenapine group, 14 of which were significantly upregulated and the other two significantly downregulated. However, all three differentially expressed miRNAs in the risperidone group were downregulated. MiRNA target gene prediction and gene ontology analysis revealed significant enrichment for pathways associated with immune system response and regulation of programmed cell death and transcription. Our results suggest that candidate miRNAs may be involved in the mechanism of action of both antipsychotics in bipolar mania.

Meningoencephalitis or clozapine withdrawal catatonia or both in a patient with schizophrenia

In large psychiatric hospitals, entire wards used to be designated for managing ‘catatonic patients’; however, this is now a footnote in history. In modern in-patient psychiatric practice, patients presenting with catatonic features invariably necessitates the uncovering of ‘organic’ aetiologies, though psychiatric (i.e. ‘non-organic’) conditions such as schizophrenia, bipolar or major depressive disorder or neurological conditions such as epilepsy may sometimes manifest with catatonic features also.

Core Symptoms of Major Depressive Disorder among Palliative Care Patients

A valid method to diagnose depression in palliative care has not been established. In this study, we aim to determine the prevalence of depression and the discriminant validity of the items of four sets of diagnostic criteria in palliative care. This is a cross-sectional study on 240 palliative care patients where the presence of depression was based on the Diagnostic and Statistical Manual of Mental Disorders, DSM–IV Criteria, Modified DSM–IV Criteria, Cavanaugh Criteria, and Endicott’s Criteria’s. Anxiety, depression, and distress were measured with Hospital Anxiety and Depression Scale and Distress Thermometer. The prevalence of depression among the palliative care patients was highest based on the Modified DSM–IV Criteria (23.3%), followed by the Endicott’s Criteria (13.8%), DSM–IV Criteria (9.2%), and Cavanaugh Criteria (5%). There were significant differences (p < 0.05) in the depressive symptoms showed by DSM–IV item 1 (dysphoric mood), item 2 (loss of interest or pleasure), and Endicott’s criteria item 8 (brooding, self-pity, or pessimism) among the palliative patients, even after adjustment for the anxiety symptoms and distress level. We found that dysphoric mood, loss of interest, and pessimism are the main features of depression in palliative patients. These symptoms should be given more attention in identifying depression in palliative care patients.

Risk and associated factors of female sexual orgasmic disorder in women with hypertension in Malaysia

The objective of this study was to examine the risk of female sexual orgasmic disorder among a group of women with hypertension in Malaysia. The associated factors were also examined.

Sexual Arousal Difficulties in Women Treated with Antidepressants: A Comparison between Escitalopram and Fluoxetine

Objective: To compare the risk of sexual arousal difficulties between two groups of depressed female patients in remission who were treated with either escitalopram or fluoxetine. Associated factors were also examined. Methods: This was a cross-sectional study involving 112 female patients attending the psychiatric clinic, University Kebangsaan Malaysia Medical Centre (UKMMC) with depressive disorders as assessed by using the Structured Clinical Interview for DSM-IV (SCID), who had been in remission for the previous 2 months as defined by a score of ⩽ 10 from an assessment using the Montgomery-Asberg Depression Rating Scale (MADRS) and were treated with either fluoxetine or escitalopram. Sexual arousal difficulties were assessed using the arousal subscale of Malay Version of the Female Sexual Function Index (MVFSFI). Results: The rate of sexual arousal difficulties was 41.1% for all subjects. Sexual arousal difficulties occurred in 50.0% of subjects treated with fluoxetine and 32.1% with escitalopram. However, this difference was not statistically significant (p = 0.055). Multivariate logistic regression analysis showed that higher dose of antidepressant (adjusted OR=4.08, 95 CI=1.70–9.81) was significantly associated with female sexual arousal difficulties. Conclusion: The risk of sexual arousal difficulties was higher in female patients who were treated with higher doses of either fluoxetine or escitalopram.