We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 a-Nacetyl-neuraminide a-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with Pvalues of 4.87 Â 10 À7 (rs2709736) and 6.05 Â 10 À6 (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P = 9.74 Â 10 À6 ) and in CACNB2 (Calcium channel, voltage-dependent, b-2 subunit) gene (rs11013860, P = 5.15 Â 10 À5 ), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P = 6.55 Â 10 À5 and P = 1.48 Â 10 À5 , respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of D-amino acids by blocking their metabolism. Sodium benzoate is a D-amino acid oxidase inhibitor.OBJECTIVE To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia. DESIGN, SETTING, AND PARTICIPANTSA randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer.INTERVENTIONS Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo. MAIN OUTCOMES AND MEASURESThe primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment.RESULTS Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects. CONCLUSIONS AND RELEVANCEBenzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT 00960219

This purpose of this study was to investigate the relationship between quality of life and psychiatric impairment in a Taiwanese community located near the epicenter of the 1999 earthquake, as assessed four to six months after the natural catastrophe. Trained assistants interviewed the 4223 respondents using the disaster-related psychological screening test (DRPST), an instrument specifically designed and validated by senior psychiatrists for assessment of psychiatric impairment after natural catastrophe. Additionally, the 36-Item Short-Form Health Survey (SF-36) was used to evaluate quality of life. The collected results were analyzed using Windows SPSS 10.0 software. Psychiatric impairment rated moderate to severe was assessed for 1448 (34.3%) of the responding residents. The 4223 respondents were divided into 4 psychiatric-impairment groups based on DPRST score: healthy (n = 952); mild impairment (n = 1823); moderate impairment (n = 1126); and, severe impairment (n = 322). The four groups were compared for a number of salient factors, including gender, age, current marital status and psychiatric-impairment score, to determine impact on quality of life. Respondents assessed as psychiatrically impaired tended to be older, female, divorced/widowed, and less educated, and they were more likely to have experienced major familial financial loss as an immediate consequence of the earthquake. Further, the greater the severity of the psychiatric impairment, the lower the scores for quality of life, for both the physical and mental aspects of this important general indicator.

Patients not even minimally improved by week 2 of antipsychotic treatment are unlikely to respond later and may benefit from a treatment change.

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