Siow Ann Chong

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.

Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia.

Objectives: This study aimed to establish the prevalence of diabetes mellitus (DM) and impaired glucose tolerance in patients with schizophrenia and to elucidate some of the factors associated with hyperglycemia. Methods: We studied a sample of 194 patients with schizophrenia. We determined fasting blood glucose and insulin levels at the start of the testing period; patients were given an oral glucose tolerance test after an overnight fast. Results: The overall prevalence of diabetes and impaired glucose tolerance in these patients was 16.0% and 30.9%, respectively. These rates were higher than those reported in the general population. Patients with disordered glucose homeostasis were significantly older (P = 0.005, Kruskal–Wallis test). There was no significant effect of sex or ethnicity on diabetes. Conclusions: Our findings suggest that patients with schizophrenia are more vulnerable to developing DM. We caution clinicians to be mindful of the increased risk and to be vigilant for such a development.

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.

Augmentation Strategies in Clozapine-Resistant Schizophrenia

Abstract.The introduction of antipsychotics in the 1950s revolutionised the treatment of schizophrenia, but it soon became apparent that a substantial number of patients demonstrated a suboptimal response to these antipsychotics. Clozapine proved to be beneficial in patients whose symptoms were treatment resistant, but it too had limitations, with as many as 40–70% of those treated with clozapine demonstrating inadequate response to this drug as well. The availability of other ‘atypical’ antipsychotics offers options, but clozapine appears to remain the most effective option in treatment-resistant schizophrenia. This, of course, raises the question of what to do when clozapine is only partially effective.To address the issue of treatment in patients who have demonstrated a suboptimal response to clozapine, efforts have focused on a variety of augmentation strategies, including numerous medications and electroconvulsive therapy. The current body of evidence consists largely of data from smaller open trials and case series/reports, although data from a limited number of controlled studies are now available. Not surprisingly, the evidence drawn from the former is more supportive of augmentation strategies, although the controlled trials are not without positive findings.The available information is certainly not so overwhelming as to endorse any single augmentation approach. Indeed, it argues for more controlled data and cautions us regarding the cost-benefit ratio in adopting this strategy. Over and above the added adverse effects of another treatment, there is evidence to indicate that actual clinical worsening can occur.Without compelling evidence, clinicians must resort to guiding principles. The potential benefits of augmentation cannot be ruled out, but it should be approached with caution and in a systematic fashion. Factors compromising clozapine response should first be ruled out, and any augmentation trials should be guided by existing evidence and a treatment plan that incorporates a clear understanding of target symptoms. A means of evaluating outcome effectively needs to be in place, and the trial should be circumscribed to prevent needless polypharmacy. A priori, an endpoint needs to be established and the trial discontinued unless results firmly support added benefits.

Symptomatic and functional remission in patients with first-episode psychosis.

Verma S, Subramaniam M, Abdin E, Poon LY, Chong SA. Symptomatic and functional remission in patients with first‐episode psychosis.

Determinants of Duration of Untreated Psychosis and the Pathway to Care in Singapore

Introduction: Delays in providing effective treatment for a patient with psychosis has significant negative effects on the outcome. This includes more hospitalizations, longer periods of inpatient care, slower and less complete recovery, and more frequent relapses. In this study, we established the Duration of Psychosis (DUP) in a sample of patients with first-episode psychosis and examined the pathways to care. Methods: The sample comprised patients presenting with first-episode psychosis to the psychiatric services of the Institute of Mental Health, Singapore, from January to December 2000. The association between the DUP and demographic, clinical and social variables was examined. Results: The DUP ranged from 0.1 to 336 months. The mean DUP was 32.6 (SD 1/4 59.8) months, with a median of 12 months. Twenty four percent of the patients had sought consultation with a traditional healer prior to consulting a psychiatrist. The DUP of this group of patients was not significantly different from those who sought help elsewhere. Conclusions: The DUP of our patients was longer than that reported in studies done in the West. The attitudes and beliefs of family in the Asian society are likely to be crucial in the pathways to care.

Screening for Depressive Symptoms: Validation of the Center for Epidemiologic Studies Depression Scale (CES-D) in a Multiethnic Group of Patients With Diabetes in Singapore

OBJECTIVE—We determined the reliability and validity of the Center for Epidemiologic Studies Depression Scale (CES-D) against the DSM-IV–based diagnostic inventory, Schedule for Clinical Assessment in Neuropsychiatry (SCAN), in a multiethnic sample of adult subjects with diabetes attending a diabetes center in Singapore. RESEARCH DESIGN AND METHODS—A total of 522 subjects (74.7% Chinese, 11.1% Malay, and 14.2% Indian) completed culturally adapted versions of the CES-D; 291 subjects were administered the SCAN inventory. RESULTS—The CES-D (cutoff score 16) showed high negative predictive values of more than 90% in all three ethnic groups. The prevalence of depressive symptoms (CES-D) and depression (SCAN) was significantly different between the Chinese and Indian subjects (CES-D 27.4 vs. 43.2%, P = 0.006); (SCAN 15.0 vs. 31.1%, P = 0.01). CONCLUSIONS—The CES-D proved to be a reliable instrument for identifying patients with depressive symptoms in the multiethnic setting of this study.

Reducing the duration of untreated psychosis and changing help-seeking behaviour in Singapore

AimThis study was conducted to examine the impact of early detection strategies of an early psychosis intervention programme on the duration of untreated psychosis (DUP) and the pattern of help-seeking behaviour.MethodPatients with first-episode psychosis were compared before and after the initiation of a programme of public education and networking with primary health care providers. These two groups were compared on the DUP and the change in the pattern of help-seeking.ResultsThe DUP was significantly reduced from a median of 12 to median of 4 months (p=0.002, Mann–Whitney U-test). There was an increase in the proportion of self and family referrals, and a fall in the proportion of police referrals.ConclusionAwareness campaigns which target multiple groups and use various modes of communication are effective in influencing the DUP and patterns of help-seeking.

Polymorphisms of dopamine receptors and tardive dyskinesia among Chinese patients with schizophrenia

The putative role of dopamine in the pathophysiology of tardive dyskinesia (TD) makes the genes coding for dopamine receptors the appropriate candidates for study. We investigate the association of the polymorphism of the Ser311Cys and Ser9Gly of the dopamine D2 (DRD2) and D3 receptor (DRD3) genes respectively with TD in Chinese patients with schizophrenia. In a case‐control study, 117 Chinese patients with TD were compared to 200 patients without TD. Patients were diagnosed to have schizophrenia according to DSM‐IV criteria. Dyskinesia was assessed by the Abnormal Involuntary Movement Scale (AIMS), whereas extrapyramidal side‐effects (EPSE) were assessed by the Simpson‐Angus Rating Scale. Genotype groups were comparable in age, gender, duration of illness, daily neuroleptic and benzodiazepine dose as well as the mean scores for EPSE. We failed to find an association between the polymorphism of the DRD2 gene with TD but found an increased risk of developing TD among those with D3 serine/serine genotype. Our results did not indicate that the D2 genotype has a role in the pathophysiology of TD in Chinese patients with schizophrenia. The association of TD with the serine/serine genotype of the DRD3 may be an epiphenomenon of patients with a subtype of schizophrenia who had more exposure to neuroleptics.

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.