Publications (17)128.11 Total impact
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Article: Effective connectivity of AKT1-mediated dopaminergic working memory networks and pharmacogenetics of anti-dopaminergic treatment.
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ABSTRACT: Working memory is a limited capacity system that integrates and manipulates information across brief periods of time, engaging a network of prefrontal, parietal and subcortical brain regions. Genetic control of these heritable brain processes have been suggested by functional genetic variations influencing dopamine signalling, which affect prefrontal activity during complex working memory tasks. However, less is known about genetic control over component working memory cortical-subcortical networks in humans, and the pharmacogenetic implications of dopamine-related genes on cognition in patients receiving anti-dopaminergic drugs. Here, we examined predictions from basic models of dopaminergic signalling in cortical and cortical-subcortical circuitries implicated in dissociable working memory maintenance and manipulation processes. We also examined pharmacogenetic effects on cognition in the context of anti-dopaminergic drug therapy. Using dynamic causal models of functional magnetic resonance imaging in normal subjects (n = 46), we identified differentiated effects of functional polymorphisms in COMT, DRD2 and AKT1 genes on prefrontal-parietal and prefrontal-striatal circuits engaged during maintenance and manipulation, respectively. Cortical synaptic dopamine monitored by the COMT Val158Met polymorphism influenced prefrontal control of both parietal processing in working memory maintenance and striatal processing in working memory manipulation. DRD2 and AKT1 polymorphisms implicated in DRD2 signalling influenced only the prefrontal-striatal network associated with manipulation. In the context of anti-psychotic drugs, the DRD2 and AKT1 polymorphisms altered dose-response effects of anti-psychotic drugs on cognition in schizophrenia (n = 111). Thus, we suggest that genetic modulation of DRD2-AKT1-related prefrontal-subcortical circuits could at least in part influence cognitive dysfunction in psychosis and its treatment.Brain 04/2012; 135(Pt 5):1436-45. · 9.46 Impact Factor -
Article: Investigation of anatomical thalamo-cortical connectivity and FMRI activation in schizophrenia.
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ABSTRACT: The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age- and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 09/2011; 37(2):499-507. · 6.99 Impact Factor -
Article: Interactive effects of DAOA (G72) and catechol-O-methyltransferase on neurophysiology in prefrontal cortex.
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ABSTRACT: Accumulating evidence indicates that genetic polymorphisms of D-amino acid oxidase activator (DAOA) (M24; rs1421292; T-allele) and catechol-O-methyltransferase (COMT) (Val¹⁵⁸Met; rs4680) likely enhance susceptibility to schizophrenia. Previously, clinical association between DAOA M24 (T-allele) and a functionally inefficient 3-marker COMT haplotype (that included COMT Val¹⁵⁸Met) uncovered epistatic effects on risk for schizophrenia. Therefore, we projected that healthy control subjects with risk genotypes for both DAOA M24 (T/T) and COMT Val¹⁵⁸Met (Val/Val) would produce prefrontal inefficiency, a critical physiological marker of the dorsolateral prefrontal cortex (DLPFC) in schizophrenic patients influenced by both familial and heritable factors. With 3T blood oxygen level dependent functional magnetic resonance imaging data, we analyzed in SPM5 the proposed interaction of DAOA and COMT in 82 healthy volunteers performing an N-back executive working memory paradigm (2-back > 0-back). As predicted, we detected a functional gene x gene interaction between DAOA and COMT in the DLPFC. The neuroimaging findings here of inefficient information processing in the prefrontal cortex seem to echo prior statistical epistasis between risk alleles for DAOA and COMT, albeit within a small sample. These in vivo results suggest that deleterious genotypes for DAOA and COMT might contribute to the pathophysiology of schizophrenia, perhaps through combined glutamatergic and dopaminergic dysregulation.Biological psychiatry 01/2011; 69(10):1006-8. · 8.93 Impact Factor -
Article: Biological validation of increased schizophrenia risk with NRG1, ERBB4, and AKT1 epistasis via functional neuroimaging in healthy controls.
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ABSTRACT: NRG1 is a schizophrenia candidate gene and plays an important role in brain development and neural function. Schizophrenia is a complex disorder, with etiology likely due to epistasis. To examine epistasis between NRG1 and selected N-methyl-d-aspartate-glutamate pathway partners implicated in its effects, including ERBB4, AKT1, DLG4, NOS1, and NOS1AP. Schizophrenia case-control sample analyzed using machine learning algorithms and logistic regression with follow-up using neuroimaging on an independent sample of healthy controls. A referred sample of schizophrenic patients (n = 296) meeting DSM-IV criteria for schizophrenia spectrum disorder and a volunteer sample of controls for case-control comparison (n = 365) and a separate volunteer sample of controls for neuroimaging (n = 172). Epistatic association between single-nucleotide polymorphisms (SNPs) and case-control status; epistatic association between SNPs and the blood oxygen level-dependent physiological response during working memory measured by functional magnetic resonance imaging. We observed interaction between NRG1 5' and 3' SNPs rs4560751 and rs3802160 (likelihood ratio test P = .00020) and schizophrenia, which was validated using functional magnetic resonance imaging of working memory in healthy controls; carriers of risk-associated genotypes showed inefficient processing in the dorsolateral prefrontal cortex (P = .015, familywise error corrected). We observed epistasis between NRG1 (rs10503929; Thr286/289/294Met) and its receptor ERBB4 (rs1026882; likelihood ratio test P = .035); a 3-way interaction with these 2 SNPs and AKT1 (rs2494734) was also observed (odds ratio, 27.13; 95% confidence interval, 3.30-223.03; likelihood ratio test P = .042). These same 2- and 3-way interactions were further biologically validated via functional magnetic resonance imaging: healthy individuals carrying risk genotypes for NRG1 and ERBB4, or these 2 together with AKT1, were disproportionately less efficient in dorsolateral prefrontal cortex processing. Lower-level interactions were not observed between NRG1 /ERBB4 and AKT1 in association or neuroimaging, consistent with biological evidence that NRG1 × ERBB4 interaction modulates downstream AKT1 signaling. Our data suggest complex epistatic effects implicating an NRG1 molecular pathway in cognitive brain function and the pathogenesis of schizophrenia.Archives of general psychiatry 10/2010; 67(10):991-1001. · 12.26 Impact Factor -
Article: Prefrontal cognitive systems in schizophrenia: towards human genetic brain mechanisms.
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ABSTRACT: Schizophrenia has complex genetic heritability. It is also genetically heterogeneous. To the extent that genes are associated with symptom constellations in schizophrenia, they do so by affecting the development and function of neural systems that mediate the expression of such diverse behavioral, cognitive and perceptual phenomena. The genetic mechanisms of human brain dysfunction remain to be well understood. "Imaging genetics" is an emerging field that attempts to integrate the basic biology of putative disease mechanisms with physiological correlates from the live human brain. Here, we review recent imaging genetics work on prefrontal brain systems associated with working memory and executive function - heritable traits relevant to schizophrenia. Starting with genetic variation in dopaminergic systems (e.g., COMT), we examined the modulation of prefrontal brain networks during active cognitive processing; there is also evidence that variation in the expression of dopamine-related downstream intra-cellular signaling molecules (e.g., AKT1) are implicated. Moreover, these genetic variants evidence epistasis on neuroimaging measures, lending further support to the conceptualization that non-additive combinations of multiple genes modulate active human cognitive brain mechanisms. The imaging genetics platform therefore could extend understanding of genetic mechanisms of human cognitive brain processes relevant to neuropsychiatric disease.Cognitive Neuropsychiatry 08/2009; 14(4-5):277-98. -
Article: Catechol-O-methyltransferase valine(158)methionine polymorphism modulates brain networks underlying working memory across adulthood.
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ABSTRACT: Cognitive abilities decline with age with large individual variability. Genetic variations have been suggested to be an important source for some of this heterogeneity. Among these variations, those related to the dopaminergic system, particularly the valine(158)methionine polymorphism in catechol-O-methyltransferase (COMTval(158)met), have been implicated in modulating age-related changes in executive function. We studied 75 subjects (age 21-90 years) using functional neuroimaging while they performed a low-level working memory (WM) task to explore the effects of aging, of the COMTval(158)met polymorphism, and their interactions on the physiological patterns of interconnected cortical activity engaged by WM. Our results show that val homozygotes and older subjects showed increased activity in dorsolateral prefrontal cortex (DLPFC) and decreased activity in ventrolateral prefrontal cortex (VLPFC) relative to met homozygotes and younger subjects, respectively. Interestingly, there were also independent effects of the COMTval(158)met polymorphism and age on the strength of connectivity between brain regions within the left prefrontal-parietal network; val homozygotes and older subjects showed greater connectivity between the DLPFC and other brain regions within the network and met homozygotes showed greater connectivity between the VLPFC and other brain regions within the network. Furthermore, the greater functional connectivity strength of DLPFC in val homozygotes relative to met homozygotes was much more pronounced in older adults Our findings suggest that the COMTval(158)met polymorphism modulates both the activity and functional connectivity of brain regions within WM networks and most importantly that this effect is exaggerated with increasing age, contributing to the variability in age-related decline in executive cognition.Biological psychiatry 07/2009; 66(6):540-8. · 8.93 Impact Factor -
Article: Cognitive dysfunction in schizophrenia: a perspective from the clinic to genetic brain mechanisms.
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ABSTRACT: Schizophrenia is a brain disease with differing symptomatic presentations, outcomes, and complex genetic mechanisms. A selection of recent work integrating clinical observations, human brain imaging and genetics will be reviewed. While the mechanics of brain dysfunction in schizophrenia remains to be well understood, the emerging evidence suggests that a number of interacting genetic mechanisms in dopaminergic and glutamatergic systems affect fundamental disease-related cognitive brain processes and may do so early in disease neurodevelopment. The availability of new imaging and genetic technologies, and institutional support for research in the translational neurosciences, extends the hope that increased understanding of these brain processes could yield meaningful clinical applications.Annals of the Academy of Medicine, Singapore 06/2009; 38(5):420-5. · 1.25 Impact Factor -
Article: Age-related alterations in simple declarative memory and the effect of negative stimulus valence.
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ABSTRACT: Healthy aging has been shown to modulate the neural circuitry underlying simple declarative memory; however, the functional impact of negative stimulus valence on these changes has not been fully investigated. Using BOLD fMRI, we explored the effects of aging on behavioral performance, neural activity, and functional coupling during the encoding and retrieval of novel aversive and neutral scenes. Behaviorally, there was a main effect of valence with better recognition performance for aversive greater than neutral stimuli in both age groups. There was also a main effect of age with better recognition performance in younger participants compared to older participants. At the imaging level, there was a main effect of valence with increased activity in the medial-temporal lobe (amygdala and hippocampus) during both encoding and retrieval of aversive relative to neutral stimuli. There was also a main effect of age with older participants showing decreased engagement of medial-temporal lobe structures and increased engagement of prefrontal structures during both encoding and retrieval sessions. Interestingly, older participants presented with relatively decreased amygdalar-hippocampal coupling and increased amygdalar-prefrontal coupling when compared to younger participants. Furthermore, older participants showed increased activation in prefrontal cortices and decreased activation in the amygdala when contrasting the retrieval of aversive and neutral scenes. These results suggest that although normal aging is associated with a decline in declarative memory with alterations in the neural activity and connectivity of brain regions underlying simple declarative memory, memory for aversive stimuli is relatively better preserved than for neutral stimuli, possibly through greater compensatory prefrontal cortical activity.Journal of Cognitive Neuroscience 10/2008; 21(10):1920-33. · 5.18 Impact Factor -
Article: Age-related alterations in default mode network: impact on working memory performance.
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ABSTRACT: The default mode network (DMN) is a set of functionally connected brain regions which shows deactivation (task-induced deactivation, TID) during a cognitive task. Evidence shows an age-related decline in task-load-related modulation of the activity within the DMN during cognitive tasks. However, the effect of age on the functional coupling within the DMN and their relation to cognitive performance has hitherto been unexplored. Using functional magnetic resonance imaging, we investigated functional connectivity within the DMN in older and younger subjects during a working memory task with increasing task load. Older adults showed decreased connectivity and ability to suppress low frequency oscillations of the DMN. Additionally, the strength of the functional coupling of posterior cingulate (pCC) with medial prefrontal cortex (PFC) correlated positively with performance and was lower in older adults. pCC was also negatively coupled with task-related regions, namely the dorsolateral PFC and cingulate regions. Our results show that in addition to changes in canonical task-related brain regions, normal aging is also associated with alterations in the activity and connectivity of brain regions within the DMN. These changes may be a reflection of a deficit in cognitive control associated with advancing age that results in deficient resource allocation to the task at hand.Neurobiology of aging 08/2008; 31(5):839-52. · 5.94 Impact Factor -
Article: Genetic variation in AKT1 is linked to dopamine-associated prefrontal cortical structure and function in humans.
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ABSTRACT: AKT1-dependent molecular pathways control diverse aspects of cellular development and adaptation, including interactions with neuronal dopaminergic signaling. If AKT1 has an impact on dopaminergic signaling, then genetic variation in AKT1 would be associated with brain phenotypes related to cortical dopaminergic function. Here, we provide evidence that a coding variation in AKT1 that affects protein expression in human B lymphoblasts influenced several brain measures related to dopaminergic function. Cognitive performance linked to frontostriatal circuitry, prefrontal physiology during executive function, and frontostriatal gray-matter volume on MRI were altered in subjects with the AKT1 variation. Moreover, on neuroimaging measures with a main effect of the AKT1 genotype, there was significant epistasis with a functional polymorphism (Val158Met) in catechol-O-methyltransferase [COMT], a gene that indexes cortical synaptic dopamine. This genetic interaction was consistent with the putative role of AKT1 in dopaminergic signaling. Supportive of an earlier tentative association of AKT1 with schizophrenia, we also found that this AKT1 variant was associated with risk for schizophrenia. These data implicate AKT1 in modulating human prefrontal-striatal structure and function and suggest that the mechanism of this effect may be coupled to dopaminergic signaling and relevant to the expression of psychosis.Journal of Clinical Investigation 07/2008; 118(6):2200-8. · 15.39 Impact Factor -
Article: Catechol-O-methyltransferase Val158Met modulation of prefrontal-parietal-striatal brain systems during arithmetic and temporal transformations in working memory.
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ABSTRACT: Working memory (WM) is critically mediated by dopaminergic tuning of signal-to-noise in cortical neural assemblies. However, little is known about the distributed neuronal networks impacted by dopaminergic modulation in the component processes of WM. Here, we used the genotype of the Val158Met polymorphism in catechol-O-methyltransferase (COMT) as an index of relative cortical dopamine bioavailability and tuning efficiency, to examine the spatial and subprocess specificity by which dopaminergic modulation occurs within the prefrontal-parietal-striatal network during WM, thus empirically showing that dopamine plays key roles in updating and stabilizing new information at the neural systems level. In an event-related fMRI task dissociating component numerical WM subprocesses, baseline numerical size comparison engaged ventrolateral prefrontal cortical activation that correlated with COMT Val-allele load (COMT Val>Met), while performing arithmetic transformations further engaged this genotype effect in dorsolateral prefrontal cortex (DLPFC), as well as in parietal and striatal regions. Critically, additional temporal integration of information in WM disproportionately engaged greater COMT Val>Met effects only at DLPFC. COMT Val>Met effects were also observed in DLPFC during encoding of new information into WM, but not at its subsequent retrieval. Thus, temporal updating operations, but less so the retrieval of already encoded representations, engaged relatively specific dopaminergic tuning at the DLPFC. Manipulating and rapidly updating representations were sensitive to dopaminergic modulation of neural signaling in a larger prefrontal-parietal-striatal network. These findings add to the integration of dopaminergic signaling in basic cortical assemblies with their roles in specific human brain networks during the orchestration of information processing in WM.Journal of Neuroscience 12/2007; 27(49):13393-401. · 7.11 Impact Factor -
Article: Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia.
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ABSTRACT: Cognitive deficits are critical determinants of schizophrenia morbidity. In this review, we offer a mechanistic perspective regarding schizophrenia-related changes observed in prefrontal cortical networks engaged in working memory. A body of earlier work converges on aberrations in putative macrocircuit stability and functional efficiency as the underlying pathophysiology of the cognitive deficits in schizophrenia. In parsing the dysfunctional prefrontal cortical dynamics of schizophrenia, recent functional magnetic resonance imaging and electoencephalography works suggest that in the context of reduced capacity for executive aspects of working memory, patients engage a larger network of cortical regions consistent with an interplay between reduced signal-to-noise components and the recruitment of compensatory networks. The genetic programming underlying these systems-level cortical interactions has been examined under the lens of certain schizophrenia susceptibility genes, especially catechol-o-methyltransferase (COMT) and GRM3. Variation in COMT, which presumably impacts on cortical dopamine signaling, translates into variable neural strategies for working memory and altering patterns of intracortical functional correlations. GRM3, which impacts on synaptic glutamate, interacts with COMT and exaggerates the genetic dissection of cortical processing strategies. These findings reveal novel insights into the modulation and parcellation of working memory processing in cortical assemblies and provide a mechanistic link between susceptibility genes and cortical pathophysiology related to schizophrenia.Cerebral Cortex 10/2007; 17 Suppl 1:i171-81. · 6.54 Impact Factor -
Article: Epistasis between catechol-O-methyltransferase and type II metabotropic glutamate receptor 3 genes on working memory brain function.
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ABSTRACT: Dopaminergic and glutamatergic systems are critical components responsible for prefrontal signal-to-noise tuning in working memory. Recent functional MRI (fMRI) studies of genetic variation in these systems in catechol-O-methyltransferase (COMT) and in metabotropic glutamate receptor mgluR3 (GRM3), respectively, suggest that these genes influence prefrontal physiological signal-to-noise in humans. Here, using fMRI, we extend these individual gene findings to examine the combined effects of COMT and GRM3 on dissociable components of the frontoparietal working memory network. We observed an apparent epistatic interaction of these two genes on the engagement of prefrontal cortex during working memory. Specifically, the GRM3 genotype putatively associated with suboptimal glutamatergic signaling was significantly associated with inefficient prefrontal engagement and altered prefrontal-parietal coupling on the background of COMT Val-homozygous genotype. Conversely, COMT Met-homozygous background mediated against the effect of GRM3 genotype. These findings extend putative brain dopaminergic and glutamatergic relationships indexed by COMT and GRM3 to a systems-level interaction in human cortical circuits implicated in working memory dysfunction such as in schizophrenia.Proceedings of the National Academy of Sciences 08/2007; 104(30):12536-41. · 9.68 Impact Factor -
Article: Dysfunctional prefrontal regional specialization and compensation in schizophrenia.
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ABSTRACT: It has been suggested that in healthy persons higher-order cognitive processing engaged by incremental working memory load hierarchically employs more dorsal than ventral prefrontal resources in healthy individuals. Given that working memory performance is impaired in schizophrenia, especially at higher executive loads, the authors investigated how this prefrontal functional organization might be altered in disease, independent of performance deficits. Using N-back working memory functional magnetic resonance imaging (fMRI) data, the authors studied 15 patients with schizophrenia and 26 healthy comparison subjects. Subgroups based on median performance accuracy at 2-back were analyzed; high performers included eight schizophrenia patients and 14 comparison subjects, and low performers included seven patients and 12 comparison subjects. High-performing but not low-performing comparison subjects responded to incremental working memory executive load with disproportionately greater dorsal but not ventral prefrontal cortex activation, which also predicted performance accuracy. In the high- and low-performing patient groups, incremental working memory load caused a disproportionate increase in ventral but not dorsal prefrontal cortex activation relative to the respective comparison group, which also correlated with accuracy. Functional connectivity between the ventral prefrontal cortex and posterior parietal cortex was relatively greater in patients, whereas comparison subjects had greater functional connectivity between the dorsal prefrontal cortex and posterior parietal cortex. The hierarchical organization of the prefrontal cortex may be compromised in schizophrenia, resulting in loss of functional specialization and integration at the dorsal prefrontal cortex and in compensatory activation from the ventral prefrontal cortex, which may ultimately affect working memory and executive cognition.American Journal of Psychiatry 12/2006; 163(11):1969-77. · 12.54 Impact Factor -
Article: fMRI study of maintenance and manipulation processes within working memory in first-episode schizophrenia.
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ABSTRACT: Working memory, a critical cognitive capacity that is affected in schizophrenia, can be divided into maintenance and manipulation processes. Previous behavioral research suggested that manipulation is more affected than maintenance in patients with chronic schizophrenia. In this study of first-episode schizophrenia patients, the authors evaluated the extent to which the two working memory processes are affected early in the course of schizophrenia. Study subjects were 11 first-episode schizophrenia patients and 11 matched healthy comparison subjects. Each group performed two verbal working memory tasks while undergoing functional magnetic resonance imaging. One task required maintenance of information; the other required manipulation of information in addition to maintenance. Under behaviorally matched conditions, both groups activated a predominantly left-sided frontal-parietal network. The manipulation plus maintenance task elicited activation of greater magnitude and spatial extent. With both tasks, patients showed less bilateral dorsolateral prefrontal cortex activation and greater ventrolateral prefrontal cortex activation, relative to the comparison subjects. A group-by-task interaction was observed for activation at the left dorsolateral and ventrolateral prefrontal cortex. The increase in activation when patients engaged in the manipulation plus maintenance task was disproportionately less in the dorsolateral prefrontal cortex and greater in the ventrolateral prefrontal cortex. These functional neuroanatomical findings add support to earlier suggestions that manipulation of information is selectively more affected than maintenance of information in persons with schizophrenia. They also suggest the presence of interacting regions of dysfunctional and compensatory prefrontal responses in the dorsolateral and ventrolateral prefrontal cortex, respectively, that are more prominent when information is manipulated. This disrupted prefrontal network is present relatively early in the course of schizophrenia.American Journal of Psychiatry 11/2005; 162(10):1849-58. · 12.54 Impact Factor -
Article: A community study of the health-related quality of life of schizophrenia and general practice outpatients in Singapore.
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ABSTRACT: Health-related quality of life (HRQOL) is an important outcome indicator of healthcare that has been little studied in East Asia, where, culturally, there is greater family interdependence than in the West. We aimed to study the HRQOL of schizophrenia outpatients compared to general practice outpatients, and to examine determinants of schizophrenia HRQOL in our community. The HRQOL of 94 schizophrenia and 90 general practice outpatients was assessed using the COOP/WONCA chart. Clinical status, demographics, medication dosages, extrapyramidal side-effects, and frequency of personal, family and social functioning were assessed using standardized questionnaires. Some 90% of schizophrenia outpatients still lived with their immediate families, and the majority were single, unemployed, and rarely engaged in social activities. They had poorer satisfaction with overall HRQOL compared to general practice outpatients. Using stepwise linear regression analysis, poorer schizophrenia overall HRQOL was predicted by dissatisfaction with and poorer participation in family relationships, dissatisfaction with emotional well-being and male gender [R(2) = 0.40, p = 0.040; F(4, 5.1) = 14.3, p < 0.001]. Strained family relationships appeared to be an important contributor to poorer schizophrenia HRQOL in our East Asian community. This could possibly be related to the narrowing of social-occupational functioning and its burden on the family.Social Psychiatry and Psychiatric Epidemiology 02/2004; 39(2):106-12. · 2.70 Impact Factor -
Article: A community study of the health-related quality of life of schizophrenia and general practice outpatients in Singapore
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ABSTRACT: Background:Health-related quality of life (HRQOL) is an important outcome indicator of healthcare that has been little studied in East Asia, where, culturally, there is greater family interdependence than in the West. We aimed to study the HRQOL of schizophrenia outpatients compared to general practice outpatients, and to examine determinants of schizophrenia HRQOL in our community.Methods:The HRQOL of 94 schizophrenia and 90 general practice outpatients was assessed using the COOP/WONCA chart. Clinical status, demographics, medication dosages, extrapyramidal side-effects, and frequency of personal, family and social functioning were assessed using standardized questionnaires.Results:Some 90% of schizophrenia outpatients still lived with their immediate families, and the majority were single, unemployed, and rarely engaged in social activities. They had poorer satisfaction with overall HRQOL compared to general practice outpatients. Using stepwise linear regression analysis, poorer schizophrenia overall HRQOL was predicted by dissatisfaction with and poorer participation in family relationships, dissatisfaction with emotional well-being and male gender [R2 = 0.40, p = 0.040; F(4, 5.1) = 14.3, p < 0.001].Conclusions:Strained family relationships appeared to be an important contributor to poorer schizophrenia HRQOL in our East Asian community. This could possibly be related to the narrowing of social-occupational functioning and its burden on the family.Social Psychiatry and Psychiatric Epidemiology 01/2004; 39(2):106-112. · 2.70 Impact Factor
Top co-authors
Top Journals
Institutions
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2006–2012
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National Institute of Mental Health (NIMH)
- Clinical Brain Disorders Branch
Bethesda, MD, USA
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2007–2009
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National Institutes of Health
Bethesda, MD, USA
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2004–2005
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National University of Singapore
- Department of Psychological Medicine
Singapore, Singapore
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