Genome-wide search for schizophrenia susceptibility loci: The NIMH genetics initiative and millennium consortium

Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:275–281, 1998. © 1998 Wiley-Liss, Inc.     

Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms

Data from the Vietnam Era Twin (VET) Registry were analyzed to explore the degree to which the same genetic and environmental factors contribute to childhood conduct disorder symptoms and to alcohol and marijuana dependence symptoms. Data on conduct disorder and alcohol and marijuana dependence were obtained from administration of the Diagnostic Interview Schedule to 1,856 monozygotic and 1,479 dizygotic male-male twin pair members of the VET Registry. Multivariate genetic models were compared to determine the genetic and environmental influences common and or specific to all three phenotypes. A full model that allowed for common genetic and environmental influences to all three phenotypes gave a good fit to the data, but the best fitting reduced model did not allow for a genetic influence on conduct disorder symptoms. Under the best fitting reduced model, genes explained 44.7% of the variance in risk for alcohol dependence symptoms. The genetic liability for symptoms of marijuana dependence was due to a 36.3% specific contribution and a 7.6% contribution from genes common with alcohol dependence symptoms. Family environmental contributions common to all three phenotypes explained 46.7%, 11.9%, and 21.3% of variance in risk for symptoms of conduct disorder, alcohol dependence, and marijuana dependence, respectively. Common family environmental factors contribute to risk of conduct disorder symptoms and alcohol and marijuana dependence symptoms. Common genetic influences contribute to risk of symptoms of alcohol dependence and marijuana dependence. While our findings suggest genes do not contribute to co-morbid conduct disorder symptoms, comparisons with other twin studies suggest that the role of genes in risk for conduct disorder remains uncertain. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:391–397, 1999. © 1999 Wiley-Liss, Inc.     

上海市综合性医院腹泻患者中溶组织内阿米巴感染现状调查

目的 了解综合性医院腹泻患者溶组织内阿米巴感染现状,为防治工作提供科学依据。方法 选择上海市3所综合性医院肠道门诊,采集门诊腹泻患者新鲜粪便和血清,分别采用生理盐水涂片法和碘液染色法、免疫层析法、ELISA法进行检测,以了解腹泻患者溶组织内阿米巴感染状况,并对感染者特征进行分析。结果 检测腹泻患者粪便样本 1 015份, 检出溶组织内阿米巴原虫病原学阳性36份, 总阳性率为3.55%。3所医院腹泻患者病原学阳性率间差异无统计学意义（P > 0.05）,溶组织内阿米巴阳性者性别、年龄、职业和文化程度分布差异均无统计学意义（P均 > 0.05）,脓血便中溶组织内阿米巴阳性率显著高于稀便和水样便（P均 < 0.01）。7-9月为发病高峰。88.90%的阳性者有腹痛,75.00%和22.23%的阳性者粪便查见白细胞和红细胞。试剂条法检测溶组织内阿米巴粪抗原阳性率为8.18%（83/1 015）,ELISA 法检测溶组织内阿米巴IgG抗体阳性率为7.12%（48/675）。结论 夏秋季是溶组织内阿米巴感染高发季节,应加强监测;脓血便中溶组织内阿米巴检出阳性率较高,联合应用多种检测手段能提高检出率。     

Emotional management and 5-HT2A receptor gene variance in patients with schizophrenia

Individuals with schizophrenia exhibit impaired social cognitive functions, particularly emotion management. Emotion management may be partially regulated by the serotoninergic system; the −1438 A/G polymorphism in the promoter region of the 5-HT2A gene can modulate 5-HT2A activity and is linked to certain emotional traits and anger- and aggression-related behaviors. The current study aimed to investigate whether this 5-HT2A genetic variance is associated with social cognitive function, particularly the management of emotions. One hundred and fifteen patients with chronic schizophrenia were stabilized with an optimal-dose of antipsychotic treatment. All were genotyped for the −1438 A/G polymorphism and assessed with symptom rating scales, neurocognitive instruments, and the “Managing Emotions” section of Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Multiple regression showed that patients with the A/G genotype performed better than those with G/G in managing emotion (p = 0.018) but did not differ from those with the A/A genotype. Regarding the two subtasks of the Managing Emotions section, the A/G heterozygotes also performed better than the G/G homozygotes in the emotion management (p = 0.026) and emotional relations (p = 0.027) subtasks. The results suggest that variability in the 5-HT2A gene may influence emotion management in patients with schizophrenia.     

Adolescent alcohol use is a risk factor for adult alcohol and drug dependence: evidence from a twin design

BACKGROUND: Early alcohol use is associated with abuse and dependence of licit and illicit substances later in life. The role of genetic and environmental factors in this association is not conclusive. METHOD: In 1992, data on substance use, abuse/dependence and psychiatric disorders were collected from 8169 male twin members of the Vietnam Era Twin Registry. The interview obtained age of onset of regular drinking (one drink/month for 6 or more months). Regression analyses of twin pairs discordant for early alcohol use tested whether the association between early drinking (before age 17) and adult substance use and abuse/dependence remained after controlling for genetic factors, family environment and covariates. Twin models tested for common genetic and/or environmental influences on early drinking and adult alcohol dependence and ever use and abuse/dependence on marijuana and other drugs. RESULTS: Co-twin analyses suggested the association between early regular alcohol use and adult alcohol dependence, marijuana and other drug use, and marijuana and other drug abuse/dependence could not be entirely explained by common genetic and shared family environmental factors. Genetic contributions to early regular drinking were significantly correlated with those on use of marijuana (rA=0.59), use of other drugs (rA=0.64), alcohol dependence (rA=0.54) and abuse/dependence of marijuana and other drugs (rA=0.63 and 0.66). Small but significant unique environmental correlations (rE range 0.11-0.22) indicated that familial factors could not entirely explain the association between early alcohol use and later substance use, abuse and dependence. CONCLUSIONS: Early regular drinking is associated with later alcohol dependence and use, abuse/dependence on drugs. The association is not entirely explained by genetic or shared family environmental factors. This suggests unique environmental factors contribute to transitions from early regular alcohol drinking to use, abuse and dependence on alcohol and other substances.     

More severe sustained attention deficits in nonpsychotic siblings of multiplex schizophrenia families than in those of simplex ones

Sustained attention deficits measured by the Continuous Performance Test (CPT) have been proposed as an endophenotype of schizophrenia. However, little is known about whether sustained attention deficits in first-degree relatives of schizophrenic patients are associated with familial loading for schizophrenia. We examined 107 parents and 84 siblings of simplex schizophrenia families as well as 72 parents and 56 siblings of multiplex schizophrenia families, all nonpsychotic, using the Diagnostic Interview for Genetic Studies and two sessions of the CPT (undegraded and degraded). The effect of perceptual load was assessed using the residual of the regression of the degraded score on the undegraded one. Statistical models that can adjust for familial correlations were used to compare the CPT performance of relatives between the two types of families. Siblings from multiplex families exhibited worse performance on the degraded CPT and less proficiency in processing the perceptual load than those from simplex families. No such difference was observed for the parents on either CPT version. We concluded that sustained attention along with perceptual load processing is more impaired in the siblings of schizophrenic patients with high familial loading and that this finding might be useful for future genetic dissection of schizophrenia.     

Binge-eating disorder as a distinct familial phenotype in obese individuals

CONTEXT: Binge-eating disorder (BED)-a syndrome that only recently has attracted scientific attention-is often seen in obese individuals, especially those with severe obesity. However, it remains unclear whether BED represents an etiologically distinct behavioral phenotype of obesity or simply a nonspecific eating pattern sometimes seen in obese individuals. OBJECTIVE: To test whether BED aggregates in families independently of obesity, and if so, whether familial factors for BED also independently increase the risk of obesity. DESIGN, PATIENTS, AND SETTING: Blinded family interview study of overweight or obese probands with (n = 150) and without (n = 150) BED, and their first-degree relatives (n = 888) in a community setting evaluated between October 2002 and July 2004. MAIN OUTCOME MEASURES: Lifetime diagnosis of BED; current and highest lifetime body mass index (calculated as the weight in kilograms divided by the square of the height in meters). RESULTS: Binge-eating disorder aggregated strongly in families independently of obesity (odds ratio, 2.2; 95% confidence interval, 1.4-3.6; P<.001). Furthermore, relatives of probands with BED displayed a markedly higher prevalence of severe obesity in adulthood (body mass index >/=40) than relatives of probands without BED even when controlling for proband body mass index (odds ratio, 2.5; 95% confidence interval, 1.4-4.4; P = .002). CONCLUSIONS: Binge-eating disorder is a familial disorder caused in part by factors distinct from other familial factors for obesity. Furthermore, these BED-specific familial factors may independently increase the risk of obesity, especially severe obesity. It follows that targeted interventions capable of preventing or treating traits influenced by these BED-specific familial factors could reduce the public health burden of obesity.     

Intellectual decline in schizophrenia: evidence from a prospective birth cohort 28 year follow-up study

It is well established that IQ is lower among persons with schizophrenia than in the general population. However, it remains unclear if there is deterioration beyond a premorbid deficit. In order to assess the question of IQ deterioration, we assessed persons pre- and-post psychosis, comparing those who developed schizophrenia with those who did not. Twenty six patients with schizophrenia and 59 normal controls, evaluated at age 7 in the prospective, longitudinal, National Collaborative Perinatal Project (NCPP), were re-tested approximately 28 years later. We assessed change in an estimate of IQ based on the Vocabulary and Block Design tests from the Wechsler intelligence scales. Persons who later developed schizophrenia were significantly impaired on IQ compared to controls at age 7, especially on measures of attention. At age 35, persons with schizophrenia demonstrated significant impairment and deterioration on both IQ sub-tests compared to controls. Because impairment occurs by early childhood and subsequent deterioration occurs at an unknown period, designs with more frequent assessment of IQ through the premorbid, prodromal and early phases of illness are required to identify the key period of decline. Future research on this sample will evaluate the prospective roles of family history and perinatal complications on cognition, and assess the specificity of these findings.