Hai-Gwo Hwu

Taipei Medical University, T’ai-pei, Taipei, Taiwan

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Publications (116)403.97 Total impact

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    ABSTRACT: The neurocognitive functioning of patients with schizophrenia is likely to decline at the early stage of the illness. More evidence is needed to determine whether deficits in certain domains of neurocognition precede the onset of illness and can predict the onset of psychosis. Subjects were recruited from the SOPRES study in Taiwan. A neuropsychological battery including the continuous performance test, Wisconsin Card Sorting Test, Wechsler Adult Intelligence Scale-Third Edition, Trail Making Tests, Mandarin version of the Verbal Fluency Test, and Wechsler Memory Scale-Third Edition, was applied at baseline and 1-year follow-up. Neurocognitive profiles derived from these tests were categorized into 9 domains for comparisons among subjects with different levels of clinical severity. A total of 324 participants, including 49 with first episode psychosis (FEP), 53 with ultra-high risk (UHR), 42 with intermediate risk (IR), 43 with marginal risk (MR), and 137 normal controls completed a baseline assessment and 71% of the participants completed a 1-year follow-up assessment. The profiles of the UHR and IR groups were identical at baseline. Those who converted to FEP later on (UHR+) showed relatively poorer performance than non-converters (UHR-) at baseline. At follow-up the performance of UHR+ was compatible to that of FEP, while UHR- generally improved. By including subjects with early putative pre-psychotic states, our study clarifies some inconsistencies about the timing and stability of changes in neurocognitive functioning that occur at the start of psychosis; it also raises questions regarding the feasibility of using neurocognitive deficits to predict the risks of transition to psychosis. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 03/2015; DOI:10.1016/j.schres.2015.03.006 · 4.43 Impact Factor
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    ABSTRACT: To compare the efficacy and safety profile between intramuscular (IM) olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation. This was a prospective, randomized, open-label study. Acutely agitated patients with schizophrenia or schizoaffective disorder (n = 67) were randomized to receive 10 mg IM olanzapine (n = 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n = 30). Agitation was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after the first injection. Safety was assessed using the Simpson-Angus Scale and Barnes Akathisia Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated. The PANSS-EC scores decreased significantly at 2 hours after the first injection in both groups (olanzapine: -10.2, p < 0.001; haloperidol + lorazepam: -9.9, p < 0.001). Haloperidol plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no significant differences in PANSS-EC or ACES scores between the two groups within 2 hours following the first injection. The frequencies of adverse events and changes in Clinical Global Impression-Severity, Simpson-Angus Scale, and Barnes Akathisia Rating Scale scores from baseline to 24 hours showed no significant differences between the groups. The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate to severe agitation (ClinialTrials.gov identifier number NCT00797277). Copyright © 2015. Published by Elsevier B.V.
    Journal of the Formosan Medical Association 03/2015; DOI:10.1016/j.jfma.2015.01.018 · 1.70 Impact Factor
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    ABSTRACT: The USA Food and Drug Administration (FDA) issued warnings regarding the use of antipsychotics in patients with dementia in 2003 and 2005. We aimed to study the dose and duration of antipsychotic treatment in dementia, and to examine whether physicians' prescription behaviors changed after the FDA warnings. Medical charts of outpatients who had Alzheimer's disease, vascular dementia, or mixed dementia were reviewed. Patients must have achieved a clinically stable state for at least 4 weeks after receiving antipsychotic treatment for agitation or psychosis. Demographics, clinical correlates, and duration of antipsychotic treatment were compared among different antipsychotic groups. Because the quetiapine group had the largest sample size, the optimal dose and duration of quetiapine treatment were compared among three time periods (before 2003, 2003-2005, after 2005). Stable state was achieved in 215 patients (80 had Alzheimer's disease, 117 vascular dementia, and 18 mixed dementia). Most patients (177) took quetiapine, 25 took risperidone, and 13 took sulpiride. The whole sample had a long total duration of antipsychotic treatment (median 525 days, mean 707 days). The median dose and total duration of antipsychotic treatment were 1.0mg/day and 238 days for risperidone, 100mg/day and 390 days for sulpiride, and 25mg/day and 611 days for quetiapine, respectively. The optimal dose and total duration of quetiapine treatment decreased significantly after FDA warning in 2005, although the duration remained long. The optimal doses of antipsychotics were not higher than those of western reports, but the total duration of antipsychotic treatment was quite long. Although our study suggests the prescription dosage and duration of antipsychotic treatment decreased significantly after FDA warning in 2005, the duration of treatment was still long. Given the serious safety concerns, more effort should be made to avoid unnecessary and prolonged prescription. Copyright © 2012. Published by Elsevier B.V.
    Journal of the Formosan Medical Association 02/2015; 114(2). DOI:10.1016/j.jfma.2012.09.002 · 1.70 Impact Factor
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    ABSTRACT: The mirror neuron system (MNS) may be implicated in schizophrenia. This study investigated MNS structures, including the pars opercularis (Pop), the supramarginal gyrus (SMg), the third branch of the superior longitudinal fasciculus, and callosal fibers interconnecting bilateral Pop (CC-Pop) and SMg (CC-SMg), and clarified their relationships with positive and negative symptoms of schizophrenia. Participants comprised 32 schizophrenia patients and 32 matched controls who received T1-weighted structural magnetic resonance imaging (MRI, T1WI) and diffusion spectrum imaging (DSI). The cortical measures were computed from the T1WI data. Tract integrity was assessed using a tractography-based analysis of the generalized fractional anisotropy (GFA) derived from the DSI data. Pearson׳s correlations and multiple linear regression analysis were used to investigate the associations between MNS structures and positive and negative symptom scores of schizophrenia. Cortical thickness in bilateral Pop and SMg were significantly thinner and mean GFA of CC-Pop was significantly decreased in patients. Negative symptoms were significantly correlated with left SMg volume, and positive symptoms were significantly correlated with right SMg thickness. Multiple linear regression analysis showed left SMg volume to be the strongest contributor to the negative symptoms. The association between left SMg volume and negative symptoms may reflect the degree of social cognition impairment in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research Neuroimaging 01/2015; DOI:10.1016/j.pscychresns.2015.01.010 · 2.83 Impact Factor
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    ABSTRACT: Orexin A and B, a pair of hypothalamic neuropeptides also named hypocretin 1 and 2, play a role in the regulation of arousal, appetite, reward, attention, and cognition. Animal studies showed that antipsychotics can activate orexin neurons in a manner correlated with their weight gain liability. However, little is known about the role of orexin in patients with schizophrenia. This study aimed to investigate the correlation of plasma orexin level with clinical symptom profile, neurocognitive functioning and weight gain liability of the antipsychotics taken in patients with schizophrenia. We measured plasma levels of orexin A in 127 patients with schizophrenia and 34 healthy controls by radioimmunoassay. In patients, we assessed clinical symptoms on the Positive and Negative Syndrome Scale and executive function by the Wisconsin Card Sorting test (WCST), and examined their associations with plasma orexin A level. Patients with schizophrenia had a significantly higher mean orexin A level than healthy controls (60.7±37.9 vs. 38.8±15.5pg/ml). Patients were divided into two subgroups based on their orexin A levels that were distributed in two clusters divided by 80pg/ml. Patients in the high-orexin subgroup had significantly fewer negative and disorganized symptoms, and tended to have fewer perseverative errors, more failure to maintain set yet comparable category achieved on the WCST than the normal-orexin subgroup. There was no significant difference in orexin A levels among patients taking antipsychotics with different weight gain liabilities. Higher level of orexin A seems to be related to favorable clinical symptom profiles of schizophrenia, but the causal relationship needs further clarification. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Psychoneuroendocrinology 12/2014; 53C:1-9. DOI:10.1016/j.psyneuen.2014.12.012 · 5.59 Impact Factor
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    ABSTRACT: The study explored associations between mismatch negativity and N-methyl-d-aspartic acid receptor subunit genes, GRIN1, GRIN2B and GRIN3B in healthy subjects and schizophrenia. Nineteen single-nucleotide polymorphisms were genotyped in 138 schizophrenia patients and 103 healthy subjects. Rs2240158 of GRIN3B was significantly associated with mismatch negativity in healthy subjects.
    04/2014; 218(3). DOI:10.1016/j.psychres.2014.04.032
  • Chen-Chung Liu, Mau-Sun Hua, Hai-Gwo Hwu
    Schizophrenia Research 04/2014; 153:S158. DOI:10.1016/S0920-9964(14)70468-2 · 4.43 Impact Factor
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    ABSTRACT: To test whether gender and parental factors moderate the relationships between symptoms of eating disorder (ED) and other psychiatric symptoms. A total of 5,015 new entrants completed several questionnaires and 541individuals with ED symptoms were identified by the Adult Self-Report Inventory-4 that assessed a wide range of Diagnostic and Statistical Manual of Mental Disorders Fourth Edition psychopathology. The participants also reported on their parents' attitude toward them before their ages of 16. ED symptoms, female gender, less parental care, and more parental protection were associated with more severe co-occurring psychiatric symptoms. Gender and parental factors also demonstrated differential moderating effects on the relationships between ED and co-occurring psychiatric symptoms. Parenting counseling may be individualized to young adults with ED symptoms and different co-occurring psychiatric symptoms.
    Journal of Clinical Psychology 03/2014; 70(3):224-237. DOI:10.1002/jclp.22014 · 2.12 Impact Factor
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    ABSTRACT: A dysfunction in working memory (WM) is a core cognitive impairment in schizophrenia that involves the cortical-subcortical-cerebellar network. We propose that in addition to other often-referred markers, the signal reduction in the network during verbal working memory (VWM) is a stable and intrinsic indicator of illness. We presented a Sternberg VWM task to 46 patients with schizophrenia and 46 healthy controls matched on performance accuracy during functional magnetic resonance imaging (fMRI). Reduced activation was demonstrated in the thalamus, cerebellar vermis, pons and the triangular part of the inferior frontal gyrus (IFG) in the patient group. We also found a "failure of deactivation" in the default mode network (DMN) in patients as represented by a low versus high load VWM. In addition, a reduced left lateralization in the triangular and opercular parts of the IFG was observed in the patient group replicating previous "failure of lateralization" findings in schizophrenia. A comparison of long (10 to 19years) and short (3 to 9years) durations of illness (DoIs) demonstrated that the DoI was only associated with the activation changes in the middle frontal gyrus and lateral temporal cortex but not with the IFG-subcortico-cerebellar regions observed. These alterations were consistent with the cognitive dysmetria described in the cortical-subcortical-cerebellar network in schizophrenia. In conclusion, the combination of reduced activation in the cortical-subcortical-cerebellar network during VWM in particular, reduced deactivation in the DMN and reduced lateralization in the IFG is thought to be stable neuroimaging signatures of schizophrenia.
    Schizophrenia Research 11/2013; 151(1-3). DOI:10.1016/j.schres.2013.10.028 · 4.43 Impact Factor
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    ABSTRACT: A standard measure to assess and predict violence is important for psychiatric services. No prospective study has examined the history of violence and heterogeneity of violence in predicting specific types of violence among inpatient with schizophrenia. This study aimed to prospectively examine the accuracy of prediction of types of violence using the Chinese modified version of Violence Scale (VS-CM) among inpatients with schizophrenia based on their past history of violence and the real occurrence of violence during hospitalization. A prospective cohort study design. A total of 107 adult patients with schizophrenia spectrum disorders, consecutively admitted to an acute psychiatric ward of a university hospital in Taiwan, were recruited. In addition to data about demographics and clinical illness, count records of the history of violence within one month prior to admission by interview and the actual occurrence of violence during the whole course of hospitalization by participant observation were collected using the VS-CM. Multivariate logistic analysis and area under the Receiver Operating Characteristic curve (AUC) analysis were applied to examine the predictive ability of the VS-CM. A patient's history of violence assessed by the VS-CM predicted the actual occurrence of violence during hospitalization with the Odds Ratio of 17.5 (p=0.001). The predictive accuracy of the VS-CM had high sensitivity (97.0%), moderate positive predictive value (71.4%), and high negative predictive value (87.5%); however, the specificity was relatively low (35.0%). The AUC was 79.5% using the total scale of the VS-CM and 70.7-74.5% using the subscales in predicting corresponding types of violence. The VS-CM is a valid and reliable measure of potential violence. It can be applied to assess and predict specific types of violence among inpatient with schizophrenia.
    International journal of nursing studies 07/2013; 51(2). DOI:10.1016/j.ijnurstu.2013.06.002 · 1.91 Impact Factor
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    ABSTRACT: Patients with schizophrenia perform significantly worse on emotion recognition tasks than healthy participants across several sensory modalities. Emotion recognition abilities are correlated with the severity of clinical symptoms, particularly negative symptoms. However, the relationships between specific deficits of emotion recognition across sensory modalities and the presentation of psychotic symptoms remain unclear. The current study aims to explore how emotion recognition ability across modalities and neurocognitive function correlate with clusters of psychotic symptoms in patients with schizophrenia. 111 participants who met the DSM-IV diagnostic criteria for schizophrenia and 70 healthy participants performed on a dual-modality emotion recognition task, the Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW), and selected subscales of WAIS-III. Of all, 92 patients received neurocognitive evaluations, including CPT and WCST. These patients also received the PANSS for clinical evaluation of symptomatology. The emotion recognition ability of patients with schizophrenia was significantly worse than healthy participants in both facial and vocal modalities, particularly fearful emotion. An inverse correlation was noted between PANSS total score and recognition accuracy for happy emotion. The difficulty of happy emotion recognition and earlier age of onset, together with the perseveration error in WCST predicted total PANSS score. Furthermore, accuracy of happy emotion and the age of onset were the only two significant predictors of delusion/hallucination. All the associations with happy emotion recognition primarily concerned happy prosody. Deficits in emotional processing in specific categories, i.e. in happy emotion, together with deficit in executive function, may reflect dysfunction of brain systems underlying severity of psychotic symptoms, in particular the positive dimension.
    PLoS ONE 06/2013; 8(6):e66571. DOI:10.1371/journal.pone.0066571 · 3.53 Impact Factor
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    ABSTRACT: Disruption of disrupted-in-schizophrenia 1 (DISC1), a candidate susceptibility gene for schizophrenia, was first identified in a large Scottish family in which many members suffered from various psychiatric disorders, including schizophrenia. To model the Scottish DISC1 truncation, we established a Disc1 mutant mouse line in which the 129S6/SvEv 25-bp deletion variant was transferred into the C57BL/6J strain by backcrossing. A battery of behavioral tasks was conducted to evaluate the basic behaviors and cognitive function of these mice. In heterozygote and homozygote Disc1 mutant (Het and Homo) mice, behavioral impairments were noted in working memory test which is thought to be mediated by the function of the medial prefrontal cortex (mPFC). The properties of mPFC neurons were characterized in both morphological and physiological aspects. The dendritic diameters were decreased in layer II/III mPFC pyramidal neurons of Het and Homo mice, whereas a significant reduction in spine density was observed in Homo mice. Neuronal excitability was declined in layer II/III mPFC pyramidal neurons of Het and Homo mice, yet increased transmitter release was identified in Homo mice. Thus, the structural and functional alterations of the mPFC in Het and Homo mice might account for their cognitive impairment. Since most of the gene knockout mice are generated from 129 substrain-derived embryonic stem cells, potential Disc1 deficiency should be considered.
    Brain Structure and Function 05/2013; DOI:10.1007/s00429-013-0577-8 · 7.84 Impact Factor
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    ABSTRACT: This study assessed facial emotion recognition abilities in subjects with paranoid and non-paranoid schizophrenia (NPS) using signal detection theory. We explore the differential deficits in facial emotion recognition in 44 paranoid patients with schizophrenia (PS) and 30 non-paranoid patients with schizophrenia (NPS), compared to 80 healthy controls. We used morphed faces with different intensities of emotion and computed the sensitivity index (d') of each emotion. The results showed that performance differed between the schizophrenia and healthy controls groups in the recognition of both negative and positive affects. The PS group performed worse than the healthy controls group but better than the NPS group in overall performance. Performance differed between the NPS and healthy controls groups in the recognition of all basic emotions and neutral faces; between the PS and healthy controls groups in the recognition of angry faces; and between the PS and NPS groups in the recognition of happiness, anger, sadness, disgust, and neutral affects. The facial emotion recognition impairment in schizophrenia may reflect a generalized deficit rather than a negative-emotion specific deficit. The PS group performed worse than the control group, but better than the NPS group in facial expression recognition, with differential deficits between PS and NPS patients.
    04/2013; DOI:10.1016/j.psychres.2013.03.026
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    ABSTRACT: To study the outcome of a group of patients with schizophrenia receiving community home care case management programs by delineating the relationship among their psychopathology, rehospitalization rates and health-related quality of life (HRQoL). This is a cross-sectional study on HRQoL, functioning and associating factors and a retrospectivehistorical control study by comparing the frequency and duration of rehospitalization in a sample of 60 patients with schizophrenia under nonintensive case management (non-ICM) in Taiwan. All participants were assessed on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) for psychopathology, on EuroQoL-5D (EQ-5D) and EQ visual analogue (EQ-VAS) for HRQoL, andGlobal Assessment of Functioning (GAF) for socio-occupational dysfunction. Other clinical characteristics are also gathered. Patients with schizophrenia treated with non-ICM had a significant reduction in admission frequency (-0.10 ± 0.36 times per year, p = 0.042) and length of inpatient stay (-27.8 ± 78.0 days per year, p = 0.008). Better EQ-5D and EQ-VAS are significantly associated with lower general psychopathology score, while better EQ-VAS is significantly associated with older age and higher negative symptoms subscale score. GAF is negatively associated with higher positive symptoms and negative symptoms subscale scores, while positively correlated with a greater reduction in number and frequency of admission. Non-ICM can help to decrease rehospitalization of home care patients. HRQoL and functioning can be assessed by the three perspectives we used, and each measure was correlated to different dimensions of patient psychopathology. It will be better if we include baseline and post-intervention PANSS scores, HRQoL and functioning as outcome indicators.
    Journal of the Formosan Medical Association 04/2013; 112(4):208-15. DOI:10.1016/j.jfma.2012.01.018 · 1.70 Impact Factor
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    ABSTRACT: Schizophrenia is a highly heritable disease with a polygenic mode of inheritance. Many studies have contributed to our understanding of the genetic underpinnings of schizophrenia, but little is known about how interactions among genes affect the risk of schizophrenia. This study aimed to assess the associations and interactions among genes that confer vulnerability to schizophrenia and to examine the moderating effect of neuropsychological impairment. We analyzed 99 SNPs from 10 candidate genes in 1,512 subject samples. The permutation-based single-locus, multi-locus association tests, and a gene-based multifactorial dimension reduction procedure were used to examine genetic associations and interactions to schizophrenia. We found that no single SNP was significantly associated with schizophrenia. However, a risk haplotype, namely A-T-C of the SNP triplet rsDAO7-rsDAO8-rsDAO13 of the DAO gene, was strongly associated with schizophrenia. Interaction analyses identified multiple between-gene and within-gene interactions. Between-gene interactions including DAO*DISC1 , DAO*NRG1 and DAO*RASD2 and a within-gene interaction for CACNG2 were found among schizophrenia subjects with severe sustained attention deficits, suggesting a modifying effect of impaired neuropsychological functioning. Other interactions such as the within-gene interaction of DAO and the between-gene interaction of DAO and PTK2B were consistently identified regardless of stratification by neuropsychological dysfunction. Importantly, except for the within-gene interaction of CACNG2, all of the identified risk haplotypes and interactions involved SNPs from DAO. These results suggest that DAO, which is involved in the N-methyl-d-aspartate receptor regulation, signaling and glutamate metabolism, is the master gene of the genetic associations and interactions underlying schizophrenia. Besides, the interaction between DAO and RASD2 has provided an insight in integrating the glutamate and dopamine hypotheses of schizophrenia.
    PLoS ONE 03/2013; 8(3):e60099. DOI:10.1371/journal.pone.0060099 · 3.53 Impact Factor
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    ABSTRACT: Low frequency oscillations are essential in cognitive function impairment in schizophrenia. While functional connectivity can reveal the synchronization between distant brain regions, the regional abnormalities in task-independent baseline brain activity are less clear, especially in specific frequency bands. Here, we used a regional homogeneity (ReHo) method combined with resting-state functional magnetic resonance imaging to investigate low frequency spontaneous neural activity in the three different frequency bands (slow-5∶0.01-0.027 Hz; slow-4∶0.027-0.08 Hz; and typical band: 0.01-0.08 Hz) in 69 patients with schizophrenia and 62 healthy controls. Compared with controls, schizophrenia patients exhibited decreased ReHo in the precentral gyrus, middle occipital gyrus, and posterior insula, whereas increased ReHo in the medial prefrontal cortex and anterior insula. Significant differences in ReHo between the two bands were found in fusiform gyrus and superior frontal gyrus (slow-4> slow-5), and in basal ganglia, parahippocampus, and dorsal middle prefrontal gyrus (slow-5> slow-4). Importantly, we identified significant interaction between frequency bands and groups in the inferior occipital gyrus and caudate body. This study demonstrates that ReHo changes in schizophrenia are widespread and frequency dependent.
    PLoS ONE 03/2013; 8(3):e57516. DOI:10.1371/journal.pone.0057516 · 3.53 Impact Factor
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    ABSTRACT: Endophenotypes in schizophrenia research is a contemporary approach to studying this heterogeneous mental illness, and several candidate neurophysiological markers (e.g. P50 sensory gating) and neuropsychological tests (e.g. Continuous Performance Test (CPT) and Wisconsin Card Sorting Test (WCST)) have been proposed. However, the clinical utility of a single marker appears to be limited. In the present study, we aimed to construct a diagnostic model incorporating P50 sensory gating with other neuropsychological tests in order to improve the clinical utility. We recruited clinically stable outpatients meeting DSM-IV criteria of schizophrenia and age- and gender-matched healthy controls. Participants underwent P50 sensory gating experimental sessions and batteries of neuropsychological tests, including CPT, WCST and Wechsler Adult Intelligence Scale Third Edition (WAIS-III). A total of 106 schizophrenia patients and 74 healthy controls were enrolled. Compared with healthy controls, the patient group had significantly a larger S2 amplitude, and thus poorer P50 gating ratio (gating ratio = S2/S1). In addition, schizophrenia patients had a poorer performance on neuropsychological tests. We then developed a diagnostic model by using multivariable logistic regression analysis to differentiate patients from healthy controls. The final model included the following covariates: abnormal P50 gating (defined as P50 gating ratio >0.4), three subscales derived from the WAIS-III (Arithmetic, Block Design, and Performance IQ), sensitivity index from CPT and smoking status. This model had an adequate accuracy (concordant percentage = 90.4%; -statistic = 0.904; Hosmer-Lemeshow Goodness-of-Fit Test, = 0.64>0.05). To the best of our knowledge, this is the largest study to date using P50 sensory gating in subjects of Chinese ethnicity and the first to use P50 sensory gating along with other neuropsychological tests to develop a diagnostic model for schizophrenia. Further research to validate the predictive accuracy of this model by applying it on other samples is warranted.
    PLoS ONE 02/2013; 8(2):e57197. DOI:10.1371/journal.pone.0057197 · 3.53 Impact Factor
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    ABSTRACT: Previous studies have reported significant associations between schizophrenia and the dopamine receptor D2 gene (DRD2) variants. The relationships between DRD2 and clinical phenotypes are of particular interest because DRD2 has been shown to associate with treatment response and prefrontal dopamine transmission. Glatt et al. reported significant associations between schizophrenia and DRD2 variants (two single-nucleotide polymorphisms (SNPs) rs1079727 and rs2283265, and two haplotypes, block 3 (rs1079727(A)-rs2440390(C)-rs2283265(G)) and block 4 (rs1801028(G)-rs1110977(A)-rs1124492(C)-rs2734841 (T))) in 2408 Han Chinese individuals in Taiwan. To further investigate the relationships between the SNPs/haplotypes of DRD2 and clinical symptoms and neuropsychological function, we compared the quantitative phenotypes in patients with risk alleles/haplotypes and those without. The results showed that the A allele of rs1079727, G allele of rs2283265, A allele of rs1124492 and the risk haplotype (A-C-G) of block 3 were associated with more severe negative symptoms. With regard to neuropsychological performance, the risk haplotype (G-A-C-T) of block 4 was associated with poorer performance in the sustained attention task. Our results imply that the genetic variants of DRD2 might not only have a role in susceptibility to schizophrenia, but also influence the phenotypes of negative symptoms and sustained attention in schizophrenia. This association warrants further validation.Journal of Human Genetics advance online publication, 31 January 2013; doi:10.1038/jhg.2012.157.
    Journal of Human Genetics 01/2013; DOI:10.1038/jhg.2012.157 · 2.53 Impact Factor
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    ABSTRACT: Thought disorder is a core symptom of schizophrenia. However, the underlying mechanism is not well understood. Functional MRI (fMRI) was used to examine the neural mechanism of thought disorder in 20 patients with schizophrenia and 20 healthy controls during semantic judgments. Two indexes of disorganized thought were further used to evaluate individual differences in thought disturbance in the patients. Compared with the controls, the patients showed greater activation in left inferior frontal gyrus (BA45) and reduced activation in the left caudate nucleus for meaning-related pairs. Moreover, in patients, effective connectivity from Dynamic Causal Modeling showed that the modulatory effect from the caudate nucleus to the inferior frontal gyrus was weaker than that in controls, indicating a disrupted cortical-subcortical language loop for semantic processing in patients. Finally, increasing scores of disorganized thought were correlated with greater activation in the inferior frontal gyrus and weaker connection strength from the caudate nucleus to the inferior frontal gyrus. Patients with more severe disorganized symptoms might receive less efficient regulation from the caudate nucleus, resulting in increased demands for the inferior frontal gyrus to retrieve or select semantic knowledge in the cortical-subcortical circuit.
    Neuroreport 01/2013; 24(3). DOI:10.1097/WNR.0b013e32835df562 · 1.40 Impact Factor
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    ABSTRACT: The copy number variation (CNV) is a type of genetic variation in the genome. It is measured based on signal intensity measures and can be assessed repeatedly to reduce the uncertainty in PCR-based typing. Studies have shown that CNVs may lead to phenotypic variation and modification of disease expression. Various challenges exist, however, in the exploration of CNV-disease association. Here we construct latent variables to infer the discrete CNV values and to estimate the probability of mutations. In addition, we propose to pool rare variants to increase the statistical power and we conduct family studies to mitigate the computational burden in determining the composition of CNVs on each chromosome. To explore in a stochastic sense the association between the collapsing CNV variants and disease status, we utilize a Bayesian hierarchical model incorporating the mutation parameters. This model assigns integers in a probabilistic sense to the quantitatively measured copy numbers, and is able to test simultaneously the association for all variants of interest in a regression framework. This integrative model can account for the uncertainty in copy number assignment and differentiate if the variation was de novo or inherited on the basis of posterior probabilities. For family studies, this model can accommodate the dependence within family members and among repeated CNV data. Moreover, the Mendelian rule can be assumed under this model and yet the genetic variation, including de novo and inherited variation, can still be included and quantified directly for each individual. Finally, simulation studies show that this model has high true positive and low false positive rates in the detection of de novo mutation.
    Frontiers in Genetics 01/2013; 4:185. DOI:10.3389/fgene.2013.00185

Publication Stats

1k Citations
403.97 Total Impact Points


  • 2010–2014
    • Taipei Medical University
      T’ai-pei, Taipei, Taiwan
    • University of Toyama
      Тояма, Toyama, Japan
  • 1996–2014
    • National Taiwan University
      • • College of Medicine
      • • Department of Psychology
      • • Graduate Institute of Epidemiology and Preventive Medicine
      T’ai-pei, Taipei, Taiwan
  • 1997–2013
    • National Taiwan University Hospital
      • Department of Psychiatry
      T’ai-pei, Taipei, Taiwan
  • 2012
    • National Taiwan Normal University
      • Department of Health Promotion and Health Education
      T’ai-pei, Taipei, Taiwan
  • 2011–2012
    • National Cheng Kung University
      • Institute of Clinical Medicine
      Tainan, Taiwan, Taiwan
    • Chi-Mei Medical Center
      臺南市, Taiwan, Taiwan
    • Chang Jung Christian University
      臺南市, Taiwan, Taiwan
  • 2009
    • National Health Research Institutes
      • Institute of Population Health Sciences
      Miao-li-chieh, Taiwan, Taiwan
  • 2006
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2002
    • Cathay General Hospital
      T’ai-pei, Taipei, Taiwan
  • 2001
    • Aalborg University
      Ålborg, North Denmark, Denmark