Association of haplotypes spanning PDZ-GEF2, LOC728637 and ACSL6 with schizophrenia in Han Chinese

Background: Schizophrenia is a complex genetic disorder caused by multiple genetic and environmental factors. Several lines of linkage and association studies have repeatedly suggested that the chromosome 5q22-33 region is implicated in the aetiology of s

Analysis of mitochondrial DNA variants in Japanese patients with schizophrenia

To test the hypothesis that mitochondrial DNA (mtDNA) variants contribute to the susceptibility to schizophrenia, we sequenced the entire mtDNAs from 93 Japanese schizophrenic patients. Three non-synonymous homoplasmic variants in subunit six of the ATP s

Explorative study on the expression of neuregulin-1 gene in peripheral blood of schizophrenia

Neuregulin-1 (Nrg-1)(1) gene has been considered as a schizophrenia susceptibility gene. In order to observe the association of Nrg-1 gene with schizophrenia, the study was designed to investigate the effect of anti-psychotic treatment on the Nrg-1 mRNA e

Schizophrenia patients and their healthy siblings share disruption of white matter integrity in the left prefrontal cortex and the hippocampus but not the anterior cingulate cortex

Healthy siblings of schizophrenia patients have an almost 9-fold higher risk for developing the illness than the general population. Disruption of white matter (WM) integrity as indicated by reduced fractional anisotropy (FA) derived from diffusion tensor

精神分裂症易感基因GULP1与中国人群大脑容量的相关性研究

精神分裂症是一种复杂的精神疾病,全世界约有1%的人患有这种疾病.以往的研究发现精神分裂症患者的脑容量比正常人小,且一些精神分裂症易感的DNA序列多态性也同时与脑的结构异常有关,这与精神分裂症的神经发育假说是吻合的.最近研究发现人的GULP1基因的两个SNP(rs2004888和rs4522565)与精神分裂症显著相关.为了研究这两个精神分裂症易感的SNP是否也符合神绎发育假说,我们检测了791个正常人的这两个SNP的基因型并测量它们的脑容量,相关性分析发现这两个SNP和脑容量无关,说明GULP1的精神分裂症易感性存在更加复杂的机制.

Effect of adrenalectomy and corticosterone replacement on prepulse inhibition and locomotor activity in mice

1 Stress is a risk factor in psychiatric illnesses such as schizophrenia. The aim of the present study was to investigate the effect of different circulating levels of the adrenal steroid corticosterone (CORT) on locomotor hyperactivity and prepulse inhibition of acoustic startle, two behavioural animal models of aspects of schizophrenia. 2 Male C57BL/6J mice (n = 10 per group) were anaesthetised with isoflurane and sham-operated or adrenalectomised (ADX). ADX mice were implanted with 50 mg pellets consisting of 100% cholesterol, or 2, 10 or 50 mg of CORT mixed with cholesterol. CORT pellet implantation dose dependently increased plasma CORT levels 3 weeks after surgery. Starting 1 week after surgery, mice were tested for prepulse inhibition after injection of saline or 5 mg kg(-1) of haloperidol. 3 In intact mice and in mice implanted with 10 mg of CORT, haloperidol treatment significantly increased prepulse inhibition (average values from 38 - 42 to 52%). Similar results were observed when testing the mice for amphetamine-induced locomotor hyperactivity (5 mg kg(-1)). In contrast, there was no significant effect of haloperidol in mice implanted either with cholesterol or 2 or 50 mg of CORT. 4 These results in behavioural animal models of schizophrenia suggest an important role of the stress hormone CORT in modulating dopaminergic activity in this illness.

Interaction of corticosterone and nicotine in regulation of prepulse inhibition in mice

The aim of the present Study was to investigate if different levels of circulating corticosterone (CORT) modulate the effect of nicotine on prepulse inhibition (PPI), a measure of sensorimotor gating that is disrupted in schizophrenia and other mental illnesses. Four groups of mice were investigated: sham-operated, adrenalectomized (ADX) and implanted with a cholesterol pellet, ADX and implanted with a 10 mg CORT pellet, or ADX and 50 mg, of CORT. Different CORT levels or doses of nicotine did not significantly affect startle responses. Baseline PPI was significantly reduced in mice implanted with the highest dose of CORT. In ADX mice implanted with cholesterol, nicotine treatment influenced PPI depending on the prepulse intensity. In ADX mice implanted with 50 mg of CORT, treatment with 10 mg/kg of nicotine caused a significant increase in PPI at all prepulse intensities. Binding studies showed that corticosterone treatment had significantly affected nicotinic acetylcholine receptor (nAChR) density in the mouse brain. Treatment with 50 mg CORT decreased I-125-epibatidine binding in the globus pallidus and I-125-alpha-bungarotoxin binding in the claustrum. These results suggest a possible interaction of corticosterone and nicotine at the level of the alpha4- and alpha7-type nAChR in the regulation of PPI. In situations of high circulating levels of corticosterone, nicotine may be beneficial to restore disruption of PPI. (C) 2004 Elsevier Ltd. All rights reserved.

NMDA受体NR1亚单位基因与精神分裂症的连锁分析

目的 了解N-甲基-D-天冬氨酸(NMDA)受体NR1亚单位基因与精神分裂症的连锁关系.方法 选取NR1亚单位基因所在区域的2个微卫星标记D9s1838和D9s1826,对94个符合美国精神障碍诊断与统计手册第4版精神分裂症诊断标准(DSM-Ⅳ)的中国汉族精神分裂症受累同胞对及家系成员共376个个体作基因分型,其中男性194名,女性182名.采用美国国立精神卫生研究所(NIMH)制订的《遗传研究诊断问卷》(DIGS),对家系成员躯体和精神状况进行评定;采用NIMH制订的《遗传研究家族问卷》(FIGS)了解家系结构.选用GENEHUNTER 2.1软件对分型资料进行非参数连锁分析.结果 两点、多点非参数分析最大LOD值均位于D9s1826,分别为1.70(P=0.050),2.08(P=0.015),两者均大于验证性连锁阈值1.2.结论 NR1基因区域微卫星标记与精神分裂症存在验证性连锁关系,提示NR1基因可能为精神分裂症的易感基因之一.

精神分裂症患者及其未患病一级亲属的面孔情绪知觉研究

Schizophrenia is a heritable disorder. However, molecular genetics and related research area have not unmasked the nature and mechanisms of this disorder. Therefore, many researchers begin to explore the pathology mechanism from other approaches. High-risk study is one of the promising approaches. In this study, we mainly focused on facial emotion perception in schizophrenia and their non-psychotic first-degree relatives, and attempted to explore whether facial emotion perception is the potential biological marker of schizophrenia. This dissertation comprises 4 studies. In the first study, we conducted a meta-analysis on behavioral data of facial emotion perception in schizophrenia. Our findings showed that patients demonstrated general deficits in both facial emotion perception and facial processing tasks. In the second study, sixty-nine patients with schizophrenia and 56 of their first-degree relatives (33 parents and 23 siblings), and 92 healthy controls (67 younger and 25 older healthy controls) completed a set of facial emotion perception tasks. The results validated that patients with schizophrenia displayed general deficits in facial emotion perception. Study two also demonstrated that siblings of patients performed equally well compared to the corresponding younger healthy controls in all the facial emotion perception tasks, while the parents of patients behaved significantly worse than the corresponding older healthy controls in the composite index of facial emotion perception tasks. The results suggest that relatives of patients display more severely declining in facial emotion perception with the increasing of age. In the third study, we used an automated voxel-wise technique, activation likelihood estimation (ALE) to provide an objective, quantitative evaluation of facial emotion processing in schizophrenia. Our findings demonstrated a marked under-recruitment of the amygdala, accompanied by a substantial limitation in activation in schizophrenia throughout a ventral temporal-basal ganglia-prefrontal cortex ‘social-brain’ system may be central to the difficulties patients experience when processing facial emotion. In the last study, we did an fMRI study about facial emotion perception in 12 patients with schizophrenia, 12 non-psychotic siblings of patients and 12 healthy controls. The results suggest that siblings of patients demonstrate abnormal activation in a variety of brain areas, including prefrontal gyrus, insula, parahippocampal gyrus and superior temporal gyrus. Taken together, the current findings suggest facial emotion perception may be a potential biological marker of schizophrenia.

中文MMPI与MMPI－2效度量表及临床量表的比较研究

This study is aimed at examining the degree of the basic scales (validity scales and clinical scales) between The Chinese MMPI and MMPI-2. Four samples (include schizophrenia, affective disorder, neuroses and normal subjects) of 236 subjects completed MMPI/MMPI-2 Combined Questionnaires in groups. The concordance rate for total code types was 90.1%. For 1-point, 2-point, 3-point and elevated code types, they were separately 81.6%, 65.8%, 49.2%, 64%. Only 56.8% of men compared to 73.8% of the women showed concordance in 2-ponit code types between MMPI and MMPI-2. And 58% of normal subjects compared to 48% of the schizophrenia subjects showed concordance in 3-point code types. Of the 236 cases, 156 (66.1%) had code types that were "well-defined" (1-, 2- or 3-point). 1-point, 2-point, 3-point well-defined code types respectively were 38.6%, 29.7%, 21.6%. For 2-point code types which were well-defined, the concordances was 84.3%, 82.8%, 85.7% (all the cases, men, women), higher than 64.4%, 56.8%, 72.9% when they were free-defined. 96.4% of subjects with incongruent 2-point code types had one of the scales in their MMPI code types with MMPI-2 code types. When deference caused by the use of uniform T-scores and new norms in MMPI-2 were found, the differences typically in code types congruence were not very great. Comparison of mean scores for the validity and clinical scales, 7 raw scores and 12 T-scores showed significant difference for MMPI versus MMPI-2 (Form). In spite of significant mean differences, correlational analyses show correlations above 0.92 for the raw scores and T-scores for each gender. All these results showed the good consistence between MMPI and MMPI-2 in basic scales, and showed MMPI-2 should be studied deeply.