Rathi Mahendran

Subjective quality of life in first episode schizophrenia spectrum disorders with comorbid depression

Previous studies have reported high prevalence rates of depressive symptoms or syndromes in subjects with first episode psychosis, but data are lacking on the quality of life (QOL) in these subjects. This cross-sectional study seeks to compare the subjective QOL of these individuals with and without a comorbid depressive syndrome at baseline. Using the Structured Clinical Interview to Diagnose DSM IV-Axis I Disorders, the Scale to Assess Unawareness of Mental Disorders (SUMD), Positive and Negative Syndrome Scale (PANSS), Hamilton Rating Scale for Depression (HAM-D), and the World Health Organization Quality of Life-Bref Scale (WHOQOL-BREF), we evaluated 66 consecutive subjects with first episode schizophrenia spectrum disorders (schizophrenia, schizoaffective and schizophreniform disorders) in our Early Psychosis Intervention Program. We found that subjects with a comorbid depressive syndrome had greater awareness of their mental illness, its social consequences and treatment efficacy, but poorer overall QOL, especially in the physical, psychological health, social relationships and environmental domains. The poorer QOL in subjects with a comorbid depressive syndrome may be explained by the greater degree of insight in these patients and their attributing their troubles to poor health, unsatisfactory social support and negative environment. Alternative explanations are also possible, providing possible foci for psychological support and intervention.

Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor

BACKGROUND Genetic factors have been implicated in the pathophysiology of the movement disorder tardive dyskinesia, which may involve dopamine-serotonin interaction. Case-control association studies have identified the T102C polymorphism of the 5-HT2A receptor gene as being associated with schizophrenia and responsiveness to clozapine. In this study, we examine the association of this polymorphism in the 5-HT2A receptor gene as a risk factor for developing schizophrenia and tardive dyskinesia from prolonged treatment with neuroleptics. METHODS Ninety-seven healthy control subjects with no history of mental illness and 221 schizophrenic patients (87 with tardive dyskinesia, 134 without) were genotyped by PCR-RFLP. RESULTS Comparison between cases and control subjects revealed no significant association between the C allele and schizophrenia. There was significant difference in allele frequency (p = .044, OR = 1.54 95% CI = 1.02-2.33) between patients who developed tardive dyskinesia and those who did not. Significant difference remains even after adjusting for age and neuroleptic dosage (p = .041) with the odds ratio at 1.64 (95% CI = 1.02-2.62). CONCLUSIONS A genetic variant of the 5-HT2A receptor may be associated with neuroleptic-induced tardive dyskinesia in schizophrenia. Further studies are needed to replicate the finding. The role of 5-HT2A receptor in the etiology of tardive dyskinesia or treatment-resistant schizophrenia should be further investigated.

Genetic analysis of the thermolabile methylenetetrahydrofolate reductase variant in schizophrenia and mood disorders.

Objective An elevated homocysteine level has been reported for patients with schizophrenia and depression. We investigated the frequency of the common C667 T variant of the enzyme methylenetetrahydrofolate reductase in controls and patients of Chinese descent. Methods Controls with no history of mental disorder and patients diagnosed with schizophrenia, bipolar and unipolar disorders were recruited. Genomic DNA from all were genotyped for the C667 T polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Results There was no significant difference in genotype distributions or allele frequencies between controls and any of the diagnostic groups, although the frequency of the T allele was higher for all diagnostic groups and for both the male and female genders. When data was analyzed with the minor T allele as dominant, there was an excess of the T-containing genotypes in each of the patient groups compared with controls. For the difference between controls and all cases combined it almost reached statistical significance (P=0.077), with an odds ratio of 1.46 (95% confidence interval, 0.96–2.22). Conclusions Although there was no significant association as measured by the P value, the odds ratio and confidence interval provided some evidence of increased risk for individuals with the T-containing genotypes. A minor role for this polymorphism in the pathogenesis of schizophrenia and depression could not be ruled out and would warrant further investigation.

An inter-ethnic comparison study of clozapine dosage, clinical response and plasma levels

The present study investigated clozapine dosage, plasma clozapine and metabolite levels, clinical and side-effect profiles in Asian versus Caucasian patients with chronic schizophrenia who were on stable maintenance treatment. Twenty Asian patients from Singapore and 20 Caucasian patients from Australia were systematically evaluated with the following rating scales: Positive and Negative Syndrome Scale for Schizophrenia, drug attitude scale (DAI-10), drug adverse reaction profile (Liverpool University Neuroleptic Side-effect Rating Scale), extrapyramidal side-effects scales (Abnormal Involuntary Movement Scale, Simpson and Angus Scale). Cigarette and caffeine consumption were recorded and steady-state plasma clozapine and metabolites levels were measured. Although Asian patients received a significantly lower mean clozapine dose (176 mg/day) than the Caucasian group (433 mg/day, P<0.001), plasma clozapine levels were similar between the groups. As a result, Asian patients had more than twice the effective clozapine concentration to dose ratio (P<0.001). The findings remained significant even after controlling for gender, body mass index, cigarette, alcohol and caffeine use. Conversely, the plasma metabolites (desmethylclozapine and clozapine N-oxide) to clozapine ratios were higher in the Caucasian patients (P<0.01). Compared to Caucasian patients, Asian patients appeared to have a lower dosage requirement for clinical efficacy. Hence, appropriate dose adjustment should be considered in Asian patients receiving maintenance clozapine therapy in clinical practice.

Psychiatric comorbidity in first episode psychosis: the Early Psychosis Intervention Program (EPIP) experience.

Objective: To determine the prevalence rates of psychiatric comorbidity in a hospitalized Asian patient group with first episode psychosis and examine its clinical correlates.

Physical comorbidity, insight, quality of life and global functioning in first episode schizophrenia: A 24-month, longitudinal outcome study

This prospective study sought to determine the clinical impact of physical comorbidity on patients with first episode schizophrenia (FES) and we tested the hypothesis that patients with physical comorbidity were associated with poorer clinical and functional outcomes. The severity of psychopathology, insight, social/occupational functioning and quality of life were evaluated using Positive And Negative Syndrome Scale (PANSS), Scale to assess Unawareness of Mental Disorder, Global Assessment of Functioning Scale (GAF), and World Health Organisation Quality of Life-Bref Scale (WHOQOL-Bref) respectively at baseline and at 6, 12, 18 and 24 months. Out of 142 patients, physical comorbidity was present in 21.8% (n=31) of the patients, and they were mainly related to the cardiovascular, respiratory and endocrine systems. Compared to baseline measurements, patients with physical comorbidity had greater awareness into the consequences of their psychiatric illness at 12 months, the need for treatment at 12 and 18 months, and better improvement of PANSS total and general psychopathology subscale scores at 24 months. FES patients with physical comorbidity also had less reduction in their WHOQOL-Bref scores in the physical health domain at 12 and 18 months and greater increase in the GAF scores at 18 and 24 months, indicating better subjective rating of quality of life and objective measure of their global functioning prospectively. Clinicians need to be aware of the substantial rates of physical comorbidity in FES patients which may not be necessarily associated with worse longitudinal outcomes and the findings should encourage even greater efforts at early identification and management of these physical conditions.

Tumor necrosis factor-α gene promoter polymorphisms in chronic schizophrenia

Abstract Background Alterations in cytokine levels in patients with schizophrenia have been documented. Polymorphisms in these cytokine genes are thus potential genetic markers for schizophrenia. The aim of this study was to investigate four biallelic polymorphisms in the tumor necrosis factor-α (TNFα) gene promoter in relation to susceptibility to schizophrenia. Methods Three hundred two patients and 152 control subjects were genotyped and frequencies of genotypes and alleles were compared for the −1031T/C, −863C/A, −857C/T, and −308G/A polymorphisms. Genotype and allele frequencies were compared between controls and patients. Results There were statistically significant differences in genotype distribution and allele frequencies for the −308 polymorphism ( p Conclusions The −308 polymorphism or another genetic variant in linkage disequilibrium with it could be a susceptibility factor for chronic schizophrenia.

The natural history of dementia

This review summarizes studies on the natural history of dementia with a focus on Alzheimers disease and vascular dementia. Understanding the course of dementia is important not only for patients, caregivers, and health professionals, but also for health policy‐makers, who have to plan for national resources needed in the management of an increasing number of dementia cases. From the available published data, the life expectancy of elderly people with dementia is shorter than that of non‐demented elderly. Reports on survival after a diagnosis of dementia vary from 3 to 12 years. The wide variation is partly due to the diagnostic criteria used in the studies and the sites where they were conducted (i.e. hospitals, clinics, or homes). There is an apparent difference in survival between Alzheimers disease patients with onset of illness before 75 years and those after 75 years: the younger patients have a longer life expectancy. However, there are conflicting data on survival (in years) comparing male and female patients and comparing patients of different ethnicities. For vascular dementia, published papers on life expectancy vary between 3 to 5 years. Vascular dementia appears to have a poorer prognosis than Alzheimers disease. The stages of severity of dementia were compared in a follow‐up of a sample of Alzheimers disease patients in Singapore, and the mean duration of the mild phase (clinical dementia rating 1) was 5.6 years, the moderate phase (clinical dementia rating 2) was 3.5 years, and the severe phase (clinical dementia rating 3) was 3.2 years. At the various phases of the disease, the demand on health‐care services and economic cost are different.

Tardive dyskinesia among Chinese and Malay patients with schizophrenia.

The prevalence of tardive dyskinesia (TD) was studied with the Abnormal Involuntary Movements Scale in Chinese and Malay patients with schizophrenia who were hospitalized in a Singapore state psychiatric institute. We also studied the relationship of neuroleptic-induced extrapyramidal side effects to TD. By using established criteria, the rates of TD were 40.6% for Chinese and 29.0% for Malays, higher than previously reported for Chinese subjects. Older age and lower current neuroleptic dose were significantly associated with TD. Multivariate analysis, after controlling for other salient risk variables, did not show a significant difference in TD prevalence rates between the two races. We conclude that suggested differences in interethnic rates of TD among Chinese, Malays, and Westerners are unlikely to exist and that any variation in prevalence is more likely to be determined by differences in duration of exposure and dose levels of neuroleptic drugs.

Coexisting medical comorbidity and depression: multiplicative effects on health outcomes in older adults.

BACKGROUND Depression in the elderly is often associated with coexisting medical illnesses. We investigated the individual and combined impacts of depression and medical illnesses on disability and quality of life among community-living older persons. METHODS Cross-sectional and longitudinal analyses of data from 1,844 participants aged 55 and above of the Singapore Longitudinal Aging Study (SLAS-1). Baseline depressive symptoms (Geriatric Depressive Scale, GDS≥5) and chronic medical comorbidity (≥2) from self-reports were related to baseline and 2-year follow up instrumental and basic activities of daily living (IADL-BADL), and quality of life (Medical Outcomes Study 12-item Short Form (SF-12) physical component summary (PCS) and mental component summary (MCS) scores. RESULTS The prevalence of depressive symptoms was 11.4%. In main effect analyses of cross-sectional and longitudinal relationships, depression and medical comorbidity were individually associated with higher risk of IADL-BADL disability and lower PCS and MCS scores of quality of life, and only medical comorbidity was associated with increased risk of hospitalization. Significant interactive effects of depression and medical comorbidity were observed in longitudinal relationships with IADL-BADL disability (p = 0.03), PCS (p < 0.01), and MCS (p < 0.01) scores at follow up. The associations of medical comorbidity with increased odds of IADL-BADL disability and decreased SF-12 PCS and MCS scores were at least threefolds stronger among depressed than nondepressed individuals. CONCLUSION Medical comorbidities and depression exert additive and multiplicative effects on functional disability and quality of life. The adverse impact and potential treatment benefits of coexisting mental and physical conditions should be seriously considered in clinical practice.