Kang Sim

Publications (72)262.96 Total impact

• Article: The association between rare large duplication of 16p11.2 and schizophrenia in the Singaporean Chinese population.

  Xuebin Zheng, Jin-Xin Bei, Haiyan Xu, Jimmy Lee, Siow-Ann Chong, Kang Sim, Herty Liany, Tai E Shyong, Tian Liu, Jia Nee Foo, Ishak D Irwan, Yik-Ying Teo, Jianjun Liu
  Biological Psychiatry 03/2013; · 8.28 Impact Factor
• Article: Tracking cerebral white matter changes across the lifespan: insights from diffusion tensor imaging studies.

  Qian Jun Yap, Irvin Teh, Paolo Fusar-Poli, Min Yi Sum, Carissa Kuswanto, Kang Sim
  [show abstract] [hide abstract]
  ABSTRACT: Delineating the normal development of brain white matter (WM) over the human lifespan is crucial to improved understanding of underlying WM pathology in neuropsychiatric and neurological conditions. We review the extant literature concerning diffusion tensor imaging studies of brain WM development in healthy individuals available until October 2012, summarise trends of normal development of human brain WM and suggest possible future research directions. Temporally, brain WM maturation follows a curvilinear pattern with an increase in fractional anisotropy (FA) from newborn to adolescence, decelerating in adulthood till a plateau around mid-adulthood, and a more rapid decrease of FA from old age onwards. Spatially, brain WM tracts develop from central to peripheral regions, with evidence of anterior-to-posterior maturation in commissural and projection fibres. The corpus callosum and fornix develop first and decline earlier, whilst fronto-temporal WM tracts like cingulum and uncinate fasciculus have protracted maturation and decline later. Prefrontal WM is most vulnerable with greater age-related FA reduction compared with posterior WM. Future large scale studies adopting longitudinal design will better clarify human brain WM changes over time.
  Acta Neurovegetativa 01/2013; · 2.73 Impact Factor
• Article: Validated five-factor model of Positive and Negative Syndrome Scale for schizophrenia in Chinese population.

  Jundong Jiang, Kang Sim, Jimmy Lee
  [show abstract] [hide abstract]
  ABSTRACT: The Positive and Negative Syndrome Scale (PANSS) is the most widely used instrument to assess the severity of symptoms of schizophrenia. Most studies have showed that PANSS measures five dimensions of symptomatology of schizophrenia. However, few studies have ever investigated the structure of PANSS in Chinese schizophrenia population. We recruited two large independent study samples including 903 and 942 Chinese schizophrenia patients and examined the underlying structure of PANSS. By building a confirmatory factor analysis (CFA) model based on the factor loadings of the exploratory factor analysis (EFA) and by testing the CFA model in an independent validation sample, we found that PANSS scores consisted of five factors, which were positive factor, negative factor, excitement factor, depression factor, and cognitive factor. The items loaded on these factors were similar to the consensus items published in previous studies except for PANSS items P2 conceptual disorganization, P5 grandiosity, N5 abstract thinking, and G11 poor attention. This difference might be due to the influence of culture on clinical presentation of schizophrenia. By elucidating the structure, symptoms of Chinese schizophrenia patients could possibly be deconstructed and investigated in future studies.
  Biological Psychiatry 11/2012; · 8.28 Impact Factor
• Article: Common Use of Antipsychotic Polypharmacy in Older Asian Patients With Schizophrenia (2001-2009).

  Yu-Tao Xiang, Faith Dickerson, Julie Kreyenbuhl, Gabor S Ungvari, Chuan-Yue Wang, Tian-Mei Si, Edwin H M Lee, Yan-Ling He, Helen F K Chiu, Shu-Yu Yang, [......], Ee-Heok Kua, Senta Fujii, Kang Sim, Michael K H Yong, Jitendra K Trivedi, Eun-Kee Chung, Pichet Udomratn, Kok-Yoon Chee, Norman Sartorius, Naotaka Shinfuku
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE: The aim of this study was to survey the use of antipsychotic polypharmacy (APP) in older Asian patients with schizophrenia and examine its demographic and clinical correlates. METHODS: Information on hospitalized patients with schizophrenia aged 55 or older was extracted from the database of the Research on Asian Psychotropic Prescription Patterns study. Data on 1439 patients in 6 Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, and Taiwan were analyzed. Sociodemographic and clinical characteristics and antipsychotic prescriptions were recorded using a standardized protocol and data collection procedure. RESULTS: The frequency of APP prescription was 51.6% in the pooled sample with wide intercountry variations. Multiple logistic regression analysis of the whole sample showed that patients on APP had higher antipsychotic doses and also were more likely to receive first-generation antipsychotics. CONCLUSIONS: Use of APP was common in older Asian patients with schizophrenia. Given the limited evidence supporting its efficacy, the potentially severe side effects and high costs, APP should be used with caution in this population. The reasons for and outcomes of the use of APP in this patient population merit further exploration.
  Journal of clinical psychopharmacology 11/2012; · 5.09 Impact Factor
• Source

  Available from: Edimansyah Abdin

  Dataset: Safety and efficacy of long-acting injectable risperidone in patients with sz

  Swapna Verma, Mythily Subramaniam, Edimansyah Abdin, Kang Sim, Alex Su, Nelson Lee, Siow Ann Chong
• Article: Evidence-based options for treatment-resistant adult bipolar disorder patients.

  Shi Hui Poon, Kang Sim, Min Yi Sum, Carissa Nadia Kuswanto, Ross J Baldessarini
  [show abstract] [hide abstract]
  ABSTRACT: Many patients diagnosed with bipolar disorder (BD) respond incompletely or unsatisfactorily to available treatments. Given the potentially devastating nature of this prevalent disorder, there is a pressing need to improve clinical care of such patients. We performed a literature review of the research findings related to treatment-resistant BD reported through February 2012. Therapeutic trials for treatment-resistant bipolar mania are uncommon, and provide few promising leads other than the use of clozapine. Far more pressing challenges are the depressive-dysthymic-dysphoric-mixed phases of BD and long-term prophylaxis. Therapeutic trials for treatment-resistant bipolar depression have assessed anticonvulsants, modern antipsychotics, glutamate [N-methyl-D-aspartate (NMDA)] antagonists, dopamine agonists, calcium-channel blockers, and thyroid hormones, as well as behavioral therapy, sleep deprivation, light therapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation, and deep brain stimulation-all of which are promising but limited in effectiveness. Several innovative pharmacological treatments (an anticholinesterase, a glutamine antagonist, a calcium-channel blocker, triiodothyronine, olanzapine and topiramate), ECT, and cognitive-behavior therapy have some support for long-term treatment of resistant BD patients, but most of trials of these treatments have been methodologically limited. Most studies identified were small, involved supplementation of typically complex ongoing treatments, varied in controls, randomization, and blinding, usually involved brief follow-up, and lacked replication. Clearer criteria for defining and predicting treatment resistance in BD are needed, as well as improved trial design with better controls, assessment of specific clinical subgroups, and longer follow-up.
  Bipolar Disorders 09/2012; 14(6):573-84. · 5.29 Impact Factor
• Article: Use of first- and second-generation antipsychotic medications in older patients with schizophrenia in Asia (2001-2009).

  Yu-Tao Xiang, Julie Kreyenbuhl, Faith B Dickerson, Gabor S Ungvari, Chuan-Yue Wang, Tian-Mei Si, Edwin H Lee, Yan-Ling He, Helen F Chiu, Shu-Yu Yang, [......], Ee-Heok Kua, Senta Fujii, Kang Sim, Michael K Yong, Jitendra K Trivedi, Eun-Kee Chung, Pichet Udomratn, Kok-Yoon Chee, Norman Sartorius, Naotaka Shinfuku
  [show abstract] [hide abstract]
  ABSTRACT: Objective:This study examined the prescribing patterns of several first- (FGAs) and second-generation antipsychotic (SGAs) medications administered to older Asian patients with schizophrenia during the period between 2001 and 2009.Method:Information on hospitalized patients with schizophrenia aged 65 or older was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001-2009). There were no older patients in Thailand, therefore data on 467 patients in eight Asian countries and territories including China, Hong Kong SAR, India, Japan, Korea, Malaysia, Singapore, and Taiwan were analysed. Cross-sectional socio-demographic data, clinical characteristics and antipsychotic prescriptions were assessed using a standardized protocol and data collection procedure.Results:Of the 467 patients, 192 patients (41.1%) received FGAs only, 166 (35.5%) received SGAs only and 109 (23.3%) received a combination of FGAs and SGAs. Of the FGAs, haloperidol was the most commonly used (31.3%; mean 9.4 ± 6.7 mg/day), followed by chlorpromazine (15.4%; mean 126.4 ± 156.4 mg/day) and sulpiride (6.6%; mean 375.0 ± 287.0 mg/day). Of the SGAs, risperidone was the most commonly used (31.5%; mean 4.5 ± 2.7 mg/day), followed by olanzapine (13.1%; mean 13.6 ± 6.5 mg/day), quetiapine (7.3%; mean 325.0 ± 237.3 mg/day) and aripiprazole (1.9%; mean 17.6 ± 7.7 mg/day).Conclusions:FGAs and higher doses of certain SGAs (risperidone, olanzapine and quetiapine) were still commonly dispensed to older Asian patients with schizophrenia. Considering older patients' reduced tolerability of potentially severe side effects associated with FGAs and higher doses of certain SGAs, continuing education and training addressing the rational use of antipsychotics in this population is clearly needed.
  Australian and New Zealand Journal of Psychiatry 07/2012; · 2.93 Impact Factor
• Article: Common use of anticholinergic medications in older patients with schizophrenia: findings of the Research on Asian Psychotropic Prescription Pattern (REAP) study, 2001-2009.

  Yu-Tao Xiang, Faith Dickerson, Julie Kreyenbuhl, Gabor S Ungvari, Chuan-Yue Wang, Tian-Mei Si, Edwin H M Lee, Helen F K Chiu, Kelly Y C Lai, Yan-Ling He, [......], Ee-Heok Kua, Senta Fujii, Kang Sim, Michael K H Yong, Jitendra K Trivedi, Eun-Kee Chung, Pichet Udomratn, Kok-Yoon Chee, Norman Sartorius, Naotaka Shinfuku
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE: This study surveyed the use of anticholinergic medications (ACMs) in older Asian patients with schizophrenia and examined its demographic and clinical correlates. METHOD: A total of 1452 hospitalized patients with schizophrenia aged 55 years or older in nine Asian countries and territories were surveyed between 2001 and 2009. The cross-sectional data of patients' socio-demographic and clinical characteristics and the prescriptions of antipsychotic drugs and ACM were recorded using a standardized protocol and data collection procedure. RESULTS: The frequency of ACM prescription was 64.6% in the pooled sample, with 72.4%, 61.9%, and 59.5% in 2001, 2004, and 2009, respectively. Multiple logistic regression analysis of the whole sample revealed that patients on ACM had a higher dose of antipsychotic medications, and were more likely to have extrapyramidal side effects and receive first-generation antipsychotic medications. CONCLUSIONS: Anticholinergic medications were frequently used in older Asian patients with schizophrenia. Considering the potential side effects of ACM, the rationale for their widespread use in this patient population should be revisited. Copyright © 2012 John Wiley & Sons, Ltd.
  International Journal of Geriatric Psychiatry 05/2012; · 2.42 Impact Factor
• Article: Antipsychotic treatment in older schizophrenia patients with extrapyramidal side effects in Asia (2001 - 2009).

  Yu-Tao Xiang, Julie Kreyenbuhl, Faith B Dickerson, Gabor S Ungvari, Chuanâ Yue Wang, Tian-Mei Si, Edwin H M Lee, Helen F K Chiu, Kelly Y C Lai, Yan-Ling He, [......], Eeâ Heok Kua, Senta Fujii, Kang Sim, Michael K H Yong, Jitendra K Trivedi, Eunâ Kee Chung, Pichet Udomratn, Kok-Yoon Chee, Norman Sartorius, Naotaka Shinfuku
  [show abstract] [hide abstract]
  ABSTRACT: This study surveyed the prescribing patterns of antipsychotic medications in Asian older schizophrenia patients with extrapyramidal side effects (EPS) during the period between 2001 and 2009. Information on 848 hospitalized patients with schizophrenia aged 60 or older was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001 - 2009). Data from those patients with reported EPS from 8 Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, Taiwan, India and Malaysia were analyzed. The cross-sectional data of sociodemographic and clinical characteristics and antipsychotic prescriptions were collected using a standardized protocol and data collection procedure. Of the 309/848 (36%) patients suffering from EPS, 210 patients (210/309; 68.0%) received at least one type of first generation antipsychotic (FGA), and 99 (99/309; 32.0%) received second generation antipsychotics (SGAs) only. Of SGAs prescribed in patients with EPS, risperidone was the most commonly used (100/309; 32.4%) followed by olanzapine (33/309; 10.7%) and quetiapine (25/309; 8.1%). FGAs were frequently used in Asian older schizophrenia patients with EPS. Considering the potential adverse effects of FGAs on existing EPS, the reasons for the frequent use of FGAs need to be urgently identified.
  International journal of clinical pharmacology and therapeutics 04/2012; 50(7):500-4. · 1.18 Impact Factor
• Article: Diffusion tensor imaging findings of white matter changes in first episode schizophrenia: a systematic review.

  Carissa Nadia Kuswanto, Irvin Teh, Tih-Shih Lee, Kang Sim
  [show abstract] [hide abstract]
  ABSTRACT: Earlier structural magnetic resonance imaging in schizophrenia have noted smaller white matter volumes in diverse brain regions and recent diffusion tensor imaging (DTI) studies have allowed better elucidation of changes in brain white matter integrity within the illness. As white matter abnormalities have been reported to occur early in the course of schizophrenia, we systematically review extant DTI studies of anomalies of white matter integrity in first episode schizophrenia (FES) up till October 2011. Overall, disruptions of white matter integrity were found in the cortical, subcortical brain regions and white matter associative and commissural tracts, suggesting that changes of cortical-subcortical white matter integrity were found at an early stage of the disorder. These changes in white matter integrity were correlated with specific cognitive deficits (verbal and spatial working memory) as well as psychopathology (positive more than negative symptoms) in patients with FES. The correlation of these white matter integrity changes with cognitive and phenomenological factors may shed light on neurobiological substrates underlying these clinical manifestations. Future studies need to validate these findings in larger samples of subjects and in different populations as well as chart the progress of these cerebral white matter changes over time so as to better appreciate their trajectory with illness course, treatment and chronicity.
  Clinical Psychopharmacology and Neuroscience 04/2012; 10(1):13-24.
• Article: Genome-wide supported psychosis risk variant in ZNF804A gene and impact on cortico-limbic WM integrity in schizophrenia.

  Carissa Nadia Kuswanto, Puay-San Woon, Xue Bin Zheng, Anqi Qiu, Yih-Yian Sitoh, Yiong Huak Chan, Jianjun Liu, Hywel Williams, Wei Yi Ong, Kang Sim
  [show abstract] [hide abstract]
  ABSTRACT: Genome-wide association, case association genetic and meta-analytic studies have highlighted ZNF804A as a robust genome-wide supported susceptibility gene for schizophrenia (SCZ). In view of the possible involvement of ZNF804A gene in early neurodevelopment and cellular processes including oligodendrocyte proliferation and differentiation, we examined the effect of ZNF804A on brain WM (WM) integrity in patients with SCZ. Based on extant data in healthy controls (HC), we hypothesized that ZNF804A risk variant rs1344706 is associated with lower fractional anisotropy (FA) in brain regions within cortico-limbic circuits, namely frontal, parietal, medial temporal lobes, and cingulate gyri in SCZ. A total of 200 Chinese participants (125 patients with DSM-IV diagnosis of SCZ and 75 controls) were genotyped using blood samples, a subset of 153 participants (89 patients with DSM-IV diagnosis of SCZ and 64 controls) underwent structural magnetic resonance imaging and diffusion tensor imaging (DTI). There are significant effects of diagnosis (left cingulate gyrus: Adjusted F(1,149)  = 9.36, P = 0.003) and diagnosis-genotype interactions (left parietal lobe: Adjusted F(1,147)  = 7.39, P = 0.007; right parietal lobe: Adjusted F(1,147)  = 6.95, P = 0.009; right medial temporal lobe: Adjusted F(1,147)  = 8.79, P = 0.004; left cingulate gyrus: Adjusted F(1,147)  = 8.02, P = 0.005). Specifically, we found that patients with SCZ who are risk T homozygotes have lower FA in bilateral parietal lobes, and left cingulate gyrus compared with G carriers. Compared with risk T homozygotes in HC, patients with SCZ who are risk T homozygotes have decreased FA in bilateral parietal lobes, and left cingulate gyrus as well as right medial temporal lobe. Our findings suggest that ZNF804A risk variant influence WM integrity involving cortico-limbic brain regions in SCZ and highlight the importance of investigating the impact of genome-wide supported risk factors on intermediate phenotypes with potential to shed light on the neurobiology of SCZ.
  American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2012; 159B(3):255-62. · 3.70 Impact Factor
• Article: Prescribing patterns of low doses of antipsychotic medications in older Asian patients with schizophrenia, 2001-2009.

  Yu-Tao Xiang, Faith Dickerson, Julie Kreyenbuhl, Gabor S Ungvari, Chuan-Yue Wang, Tian-Mei Si, Edwin H M Lee, Yan-Ling He, Helen F K Chiu, Kelly Y C Lai, [......], Ee-Heok Kua, Senta Fujii, Kang Sim, Michael K H Yong, Jitendra K Trivedi, Eun-Kee Chung, Pichet Udomratn, Kok-Yoon Chee, Norman Sartorius, Chay-Hoon Tan
  [show abstract] [hide abstract]
  ABSTRACT: This study examined the use of low doses of antipsychotic medications (300 mg/day CPZeq or less) in older Asian patients with schizophrenia and its demographic and clinical correlates. Information on hospitalized patients with schizophrenia, aged 55 years or older, was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) study (2001-2009). Data on 1,452 patients in eight Asian countries and territories including China, Hong Kong, Japan, Korea, Singapore, Taiwan, India, and Malaysia were analyzed. Sociodemographic and clinical characteristics and antipsychotic prescriptions were recorded using a standardized protocol and data collection procedure. The prescription frequency for low doses of antipsychotic medications was 40.9% in the pooled sample. Multiple logistic regression analysis of the whole sample showed that patients on low doses of antipsychotic medications were more likely to be female, have an older age, a shorter length of illness, and less positive symptoms. Of patients in the six countries and territories that participated in all the surveys between 2001 and 2009, those in Japan were less likely to receive low doses of antipsychotics. Low doses of antipsychotic medications were only applied in less than half of older Asian patients with schizophrenia.
  International Psychogeriatrics 02/2012; 24(6):1002-8. · 2.24 Impact Factor
• Article: Arcuate fasciculus abnormalities and their relationship with psychotic symptoms in schizophrenia.

  Muhammad Farid Abdul-Rahman, Anqi Qiu, Puay San Woon, Carissa Kuswanto, Simon L Collinson, Kang Sim
  [show abstract] [hide abstract]
  ABSTRACT: Disruption of fronto-temporal connections involving the arcuate fasciculus (AF) may underlie language processing anomalies and psychotic features such as auditory hallucinations in schizophrenia. No study to date has specifically investigated abnormalities of white matter integrity at particular loci along the AF as well as its regional lateralization in schizophrenia. We examined white matter changes (fractional anisotropy (FA), axial diffusivity (AD), asymmetry indices) along the whole extent of the AF and their relationship with psychotic symptoms in 32 males with schizophrenia and 44 healthy males. Large deformation diffeomorphic metric mapping and Fiber Assignment Continuous Tracking were employed to characterize FA and AD along the geometric curve of the AF. Our results showed that patients with schizophrenia had lower FA in the frontal aspects of the left AF compared with healthy controls. Greater left FA and AD lateralization in the temporal segment of AF were associated with more severe positive psychotic symptoms such as delusions and hallucinations in patients with schizophrenia. Disruption of white matter integrity of the left frontal AF and accentuation of normal left greater than right asymmetry of FA/AD in the temporal AF further support the notion of aberrant fronto-temporal connectivity in schizophrenia. AF pathology can affect corollary discharge of neural signals from frontal speech/motor initiation areas to suppress activity of auditory cortex that may influence psychotic phenomena such as auditory hallucinations and facilitate elaboration of delusional content.
  PLoS ONE 01/2012; 7(1):e29315. · 4.09 Impact Factor
• Article: Delayed neuropsychiatric sequelae and recovery following carbon monoxide poisoning.

  Jegan Yogaratnam, Jayaraman Hariram, Dawn S F Lee, Soo Piang Chua, Jieun Kim, Somnath Sengupta, Kang Sim
  Annals of the Academy of Medicine, Singapore 11/2011; 40(11):516-7. · 1.25 Impact Factor
• Article: ARVCF genetic influences on neurocognitive and neuroanatomical intermediate phenotypes in Chinese patients with schizophrenia.

  Kang Sim, Wai-Yen Chan, Puay-San Woon, Hui-Qi Low, Linda Lim, Guo-Liang Yang, Jimmy Lee, Siow Ann Chong, Yih-Yian Sitoh, Yiong Huak Chan, Jianjun Liu, Ene Choo Tan, Hywel Williams, Wieslaw Lucjan Nowinski
  [show abstract] [hide abstract]
  ABSTRACT: There are notable similarities between velocardiofacial syndrome and schizophrenia in terms of neurocognitive deficits and brain structural abnormalities. These similarities have supported the role of the armadillo repeat gene deleted in velocardiofacial syndrome (ARVCF) as a susceptibility gene in schizophrenia. This study investigated the relationships between haplotypes of the ARVCF gene and specific intermediate phenotypes in schizophrenia. We hypothesized that ARVCF gene haplotypes influence caudate nucleus volume, fractional anisotropy, and neurocognitive functioning in schizophrenia. Between May 2006 and November 2009, 200 Chinese participants (125 patients with DSM-IV diagnosis of schizophrenia and 75 controls) were genotyped using blood samples, and a subset of 166 participants (99 patients with DSM-IV diagnosis of schizophrenia and 67 controls) underwent structural magnetic resonance imaging, diffusion tensor imaging, and completed neuropsychological testing. The haplotype T-G-A-T-T-G-G-C-T-G-T (ARVCF-Hap1) was significantly associated with fractional anisotropy of the caudate nucleus and executive functioning in patients. Specifically, patients with more copies of ARVCF-Hap1 have lower white matter integrity in caudate nucleus (P = .0008) and greater perseverative errors (P = .00003) on the Wisconsin Card Sorting Test. A trend of lower caudate volume (P = .015) in patients with more copies of ARVCF-Hap1 was also observed. These findings are consistent with known ARVCF gene effects on neurodevelopment in terms of cellular arrangement, migration, and intracellular signaling involving the striatum and may involve interactions with other brain networks such as prefrontal cortex, and they underscore the importance of imaging-genetic studies to elucidate the genetic influences underlying intermediate phenotypes in complex neurobehavioral disorders.
  The Journal of Clinical Psychiatry 10/2011; 73(3):320-6. · 5.80 Impact Factor
• Article: Adjunctive mood stabilizer treatment for hospitalized schizophrenia patients: Asia psychotropic prescription study (2001–2008)

  Kang Sim, Kian Hui Yong, Yiong Huak Chan, Phern-Chern Tor, Yu-Tao Xiang, Chuan-Yue Wang, Edwin Ho Ming Lee, Senta Fujii, Shu-yu Yang, Mian-Yoon Chong, Gabor S. Ungvari, Ee Heok Kua, Chay Hoon Tan
  [show abstract] [hide abstract]
  ABSTRACT: Recent studies indicate relatively high international rates of adjunctive psychotropic medication, including mood stabilizers, for patients with schizophrenia. Since such treatments are little studied in Asia, we examined the frequency of mood-stabilizer use and its clinical correlates among hospitalized Asian patients diagnosed with schizophrenia in 2001–2008. We evaluated usage rates of mood stabilizers with antipsychotic drugs, and associated factors, for in-patients diagnosed with DSM-IV schizophrenia in 2001, 2004 and 2008 in nine Asian regions: China, Hong Kong, India, Korea, Japan, Malaysia, Taiwan, Thailand, and Singapore. Overall, mood stabilizers were given to 20.4% (n=1377/6761) of hospitalized schizophrenia patients, with increased usage over time. Mood-stabilizer use was significantly and independently associated in multivariate logistic modeling with: aggressive behaviour, disorganized speech, year sampled (2008 vs. earlier), multiple hospitalizations, less negative symptoms, younger age, with regional variation (Japan, Hong Kong, Singapore>Taiwan or China). Co-prescription of adjunctive mood stabilizers with antipsychotics for hospitalized Asian schizophrenia patients increased over the past decade, and was associated with specific clinical characteristics. This practice parallels findings in other countries and illustrates ongoing tension between evidence-based practice vs. individualized, empirical treatment of psychotic disorders.
  The International Journal of Neuropsychopharmacology 09/2011; 14(09):1157 - 1164. · 4.58 Impact Factor
• Article: Genome wide association studies (GWAS) and copy number variation (CNV) studies of the major psychoses: what have we learnt?

  Kok Wei Lee, Puay San Woon, Yik Ying Teo, Kang Sim
  [show abstract] [hide abstract]
  ABSTRACT: Schizophrenia (SZ) and bipolar disorder (BPD) have high heritabilities and are clinically and genetically complex. Genome wide association studies (GWAS) and studies of copy number variations (CNV) in SZ and BPD have allowed probing of their underlying genetic risks. In this systematic review, we assess extant genetic signals from published GWAS and CNV studies of SZ and BPD up till March 2011. Risk genes associated with SZ at genome wide significance level (p value<7.2 × 10(-8)) include zinc finger binding protein 804A (ZNF804A), major histocompatibility (MHC) region on chromosome 6, neurogranin (NRGN) and transcription factor 4 (TCF4). Risk genes associated with BPD include ankyrin 3, node of Ranvier (ANK3), calcium channel, voltage dependent, L type, alpha 1C subunit (CACNA1C), diacylglycerol kinase eta (DGKH), gene locus on chromosome 16p12, and polybromo-1 (PBRM1) and very recently neurocan gene (NCAN). Possible common genes underlying psychosis include ZNF804A, CACNA1C, NRGN and PBRM1. The CNV studies suggest that whilst CNVs are found in both SZ and BPD, the large deletions and duplications are more likely found in SZ rather than BPD. The validation of any genetic signal is likely confounded by genetic and phenotypic heterogeneities which are influenced by epistatic, epigenetic and gene-environment interactions. There is a pressing need to better integrate the multiple research platforms including systems biology computational models, genomics, cross disorder phenotyping studies, transcriptomics, proteomics, metabolomics, neuroimaging and clinical correlations in order to get us closer to a more enlightened understanding of the genetic and biological basis underlying these potentially crippling conditions.
  Neuroscience & Biobehavioral Reviews 09/2011; 36(1):556-71. · 8.65 Impact Factor
• Article: Clozapine use in schizophrenia: findings of the Research on Asia Psychotropic Prescription (REAP) studies from 2001 to 2009.

  Yu-Tao Xiang, Chuan-Yue Wang, Tian-Mei Si, Edwin H M Lee, Yan-Ling He, Gabor S Ungvari, Helen F K Chiu, Naotaka Shinfuku, Shu-Yu Yang, Mian-Yoon Chong, [......], Kang Sim, Michael K H Yong, Jitendra K Trivedi, Eun-Kee Chung, Pichet Udomratn, Kok-Yoon Chee, Norman Sartorius, Lisa B Dixon, Julie A Kreyenbuhl, Chay-Hoon Tan
  [show abstract] [hide abstract]
  ABSTRACT: Optimizing treatment and outcomes for people with schizophrenia requires understanding of how evidence-based treatments are utilized. Clozapine is the most effective antipsychotic drug for treatment-refractory schizophrenia, but few studies have investigated trends and patterns of its use over time internationally. This study examined the prescription patterns of clozapine and its demographic and clinical correlates in Asia from 2001 to 2009. Clozapine prescriptions were collected in a sample of 6761 hospitalized schizophrenia patients in nine Asian countries and regions using a standardized protocol and data collection procedure. Overall, the proportion of patients receiving clozapine prescriptions was stable across the three surveys from 2001 to 2009, ranging from 14.5% to 15.9%. However, the rates and patterns observed within different regions and countries at each survey differed considerably. Clozapine use decreased significantly over time in China, while it increased in Korea and Singapore. Multiple logistic regression analysis revealed that patients taking clozapine were significantly younger, had a higher dose of antipsychotic drugs in chlorpromazine equivalents, were more likely to be female, had fewer extrapyramidal symptoms, and had more negative symptoms, admissions and weight gain in the past month than those not receiving clozapine. The variability in overall rates and changes in prescription rates over time in these samples suggest that factors other than psychopharmacological principles play an important role in determining the use of clozapine in schizophrenia in Asia.
  Australian and New Zealand Journal of Psychiatry 09/2011; 45(11):968-75. · 2.93 Impact Factor
• Article: MELAS associated pathological hyperemotionalism: a case report.

  Suet Bin Chai, Sandeep R K Naik, Kang Sim
  Annals of the Academy of Medicine, Singapore 09/2011; 40(9):418-9. · 1.25 Impact Factor
• Article: The low frequency of reported sexual dysfunction in Asian patients with schizophrenia (2001-2009): low occurrence or ignored side effect?

  Yu-Tao Xiang, Chuan-Yue Wang, Tian-Mei Si, Edwin H M Lee, Yan-Ling He, Gabor S Ungvari, Helen F K Chiu, Shu-Yu Yang, Mian-Yoon Chong, Chay-Hoon Tan, Ee-Heok Kua, Senta Fujii, Kang Sim, Michael K H Yong, Jitendra K Trivedi, Eun-Kee Chung, Pichet Udomratn, Kok-Yoon Chee, Norman Sartorius, Naotaka Shinfuku
  [show abstract] [hide abstract]
  ABSTRACT: The purpose of the study was to evaluate the frequency of reported sexual dysfunction (SD) in schizophrenia and its associations with sociodemographic and clinical variables in selected Asian countries. A total of 5877 schizophrenia patients in nine Asian countries and territories were examined between 2001 and 2009. The patients' sociodemographic and clinical characteristics, prescription of psychotropic drugs, and drug-induced side effects were recorded using a standardized protocol and data collection. SD was evaluated as "present" or "absent" according to the clinical judgment of experienced psychiatrists. The frequency of reported SD in the whole sample in women and men was 3.0%, 0.8%, and 4.6%, respectively, with variations across study sites. In the multivariate analyses, male sex, more second-generation antipsychotics, benzodiazepines, and antidepressants were independently associated with higher likelihood of reported SD, whereas negative symptoms had an inverse association with reported SD. The results of this study indicate that SD was seldom recorded as a side effect by Asian psychiatrists while treating patients with schizophrenia. It is unclear whether the low prevalence of reported SD compared with Western data is real or whether the results are being insufficiently recognized. Copyright © 2011 John Wiley & Sons, Ltd.
  Human Psychopharmacology Clinical and Experimental 07/2011; 26(4-5):352-7. · 2.48 Impact Factor