The serotonin transporter 5-HTTPR polymorphism is associated with current and lifetime depression in persons with chronic psychotic disorders.

OBJECTIVE: Variation in the serotonin transporter gene (SLC6A4) promoter region has been shown to influence depression in persons who have been exposed to a number of stressful life events. METHOD: We evaluated whether genetic variation in 5-HTTLPR, influences current depression, lifetime history of depression and quantitative measures of depression in persons with chronic psychotic disorders. This is an association study of a genetic variant with quantitative and categorical definitions of depression conducted in the southwest US, Mexico and Costa Rica. We analyzed 260 subjects with a history of psychosis, from a sample of 129 families. RESULTS: We found that persons carrying at least one short allele had a statistically significant increased lifetime risk for depressive syndromes (P < 0.02, odds ratio 2.18, 95% CI 1.10-4.20). CONCLUSION: The 'ss' or 'sl' genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of psychotic individuals to develop major depression during the course of their illness.

TGFB-induced factor (TGIF): a candidate gene for psychosis on chromosome 18p.

Schizophrenia (SC) and bipolar disorder (BP) share many clinical features, among them psychosis. We previously identified a putative gene locus for psychosis on chromosome 18p in a sample from the Central Valley of Costa Rica (CVCR) population. The present study replicated the association to a specific allele of microsatellite marker D18S63 on 18p11.3, using a newly collected sample from the CVCR. A combined analysis of both samples, plus additional subjects, showed that this specific allele on D18S63, which lies within an intron on the TGFB-induced factor (TGIF) gene, is strongly associated (P-value=0.0005) with psychosis. Eleven additional SNP markers, spanning five genes in the region, were analyzed in the combined sample from the CVCR. Only the four SNPs within the TGIF gene were in strong linkage disequilibrium with D18S63 (D'=1.00). A specific haplotype for all five markers within the TGIF gene showed evidence of association (P-value=0.011) to psychosis. A second, distinct haplotype, containing a newly identified nonsynonymous polymorphism in exon 5 of the TGIF gene, showed a nonsignificant trend towards association to psychosis (P-value=0.077). TGIF is involved in neurodevelopment, neuron survival and controls the expression of dopamine receptors. Altogether, our results point to the possible involvement of TGIF in the pathophysiology of psychotic disorders in the CVCR population.

A genome-wide scan for schizophrenia and psychosis susceptibility loci in families of Mexican and Central American ancestry.

Schizophrenia is a complex psychiatric disorder, likely to be caused in part by multiple genes. In this study, linkage analyses were performed to identify chromosomal regions most likely to be associated with schizophrenia and psychosis in multiplex families of Mexican and Central American origin. Four hundred and fifty-nine individuals from 99 families, containing at least two siblings with hospital diagnoses of schizophrenia or schizoaffective disorder, were genotyped. Four hundred and four microsatellite markers were genotyped for all individuals and multipoint non-parametric linkage analyses were performed using broad (any psychosis) and narrow (schizophrenia and schizoaffective disorder) models. Under the broad model, three chromosomal regions (1pter-p36, 5q35, and 18p11) exhibited evidence of linkage with non-parametric lod (NPL) scores greater than 2.7 (equivalent to empirical P values of less than 0.001) with the peak multipoint NPL = 3.42 (empirical P value = 0.00003), meeting genomewide evidence for significant linkage in the 1pter-p36 region. Under the narrow model, the same three loci showed (non-significant) evidence of linkage. These linkage findings (1pter-p36, 18p11, and 5q35) highlight where genes for psychosis and schizophrenia are most likely to be found in persons of Mexican and Central American ancestry, and correspond to recent linkages of schizophrenia or psychosis in other populations which were formed in part from emigrants from the Spanish empire of the 15th and 16th centuries.

Association analyses of the neuregulin 1 gene with schizophrenia and manic psychosis in a Hispanic population.

OBJECTIVE: This study used the population of the Central Valley of Costa Rica (CVCR) and phenotyping strategies alternative to DSMIV classifications to investigate the association of neuregulin 1 with schizophrenia. METHOD: Using 134 family trios with a history of psychosis, we genotyped six of the seven markers originally identified to be associated with schizophrenia in Iceland. RESULTS: The neuregulin Icelandic haplotype was not associated with schizophrenia in the CVCR population. However, a novel haplotype was found to be overrepresented in subjects with functional psychosis (global P-value > 0.05). Stratification of the sample by history of mania suggests that this haplotype may be preferentially over-transmitted to persons with a history of manic psychosis. CONCLUSION: These results suggest that the neuregulin 1 gene is unlikely to play a major role in predisposing to schizophrenia in the CVCR. Further studies in the CVCR and other Latin American populations should be performed in order to corroborate these findings.

A comprehensive typology for the biopsychosociocultural evaluation of child-killing behavior.

The homicide of children by their parents has been reported across numerous cultural settings around the world and in many historical periods. A comprehensive and systematic understanding of parental child killing can be optimally obtained through a biopsychosociocultural approach. In this article we present the case of a woman who committed neonaticide. We illustrate the cultural formulation of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and recommend that this formulation has a central role in the evaluation of cultural factors of parents who kill their children.

Concurrent and predictive validity of the Allen Cognitive Levels Assessment.

The present study examined the concurrent and predictive validity of the Allen Cognitive Levels (ACL) Assessment in a sample of 110 medicated patients with schizophrenia who received the ACL at discharge from a state psychiatric facility. Subsamples within this group of patients had received an Activities of Daily Living assessment (n = 64) and a comprehensive neuropsychological test battery (n = 48) at discharge, or a battery of community follow-up measures (n = 30) 1-3.5 years following discharge as part of other investigations. Positive correlations were found between the ACL and concurrent measures of adaptive and cognitive function. With respect to cognitive variables, stepwise multiple regression analysis revealed that the majority of the variance in ACL scores was predicted by neuropsychological test scores assessing higher level cognitive processes, such as visual organization, manipulation of information in working memory, and ability to inhibit a response to a prepotent stimulus. Finally, results revealed positive relationships between the ACL obtained at discharge and community functioning at follow-up. The results of this study provide some evidence for the concurrent and predictive validity of the ACL for patients with schizophrenia and suggest that further study of this assessment tool would be important to pursue in future investigations.

Ethnicity and negative symptoms in patients with schizophrenia.

The purpose of this study was to assess ethnic differences in the negative symptom profile of 25 Anglo American and 26 Mexican American subjects with schizophrenia. Subjects were rated at the end of a 1-2-week medication washout period (time 1) and at discharge (time 2) with the Negative Symptoms Assessment (NSA), Brief Psychiatric Research Scale, (BPRS), the [Diagnostic and Statistical Manual of Mental Disorders (4th edition)] DSM-IV negative factor score and LAECA acculturation scale. Total NSA scores were significantly higher among Mexican Americans both at time 1 and time 2. Among the five subscales of the NSA, ethnic differences were significant only for the Cognition subscale at time 1. Results indicate no ethnic differences in core negative symptoms (alogia, avolition, flat affect), but do suggest that a cognition-related factor differs between Mexican American and Anglo American schizophrenic patients.

Poland sequence in two siblings suggesting an autosomal inheritance transmission.

We report on Poland sequence observed in two siblings (a girl and a boy) in the same family. This suggests an inheritance pattern consistent with an autosomal recessive or dominant trait transmission with reduced penetrance.

Schizophrenia among Hispanics: epidemiology, phenomenology, course, and outcome.

A number of studies point to the influence of culture and ethnicity on the presentation and course of schizophrenia. In general, a relatively powerful influence of environmental factors is identified. This article reviews the literature on schizophrenia among Hispanics in the United States and uses the results of this review as a basis for identifying directions for future study. Research is divided into three major areas: epidemiology, phenomenology, and illness course and outcome. Ethnic comparisons suggest similar prevalence rates of schizophrenia. However, differences in illness phenomenology between certain subgroups of Hispanics are also observed. Moreover, culture can affect various aspects of the illness process, including illness definition, help- seeking behavior, response to treatment, and post-treatment adjustment. Proposed guidelines to direct future research ventures include (1) better delineation of the sociocultural attributes of the group under study, (2) validation of assessment instruments across ethnic groups, (3) use of innovative approaches to assess incidence and prevalence, (4) incorporation of qualitative methodology, (5) use of illness behavior models to provide a conceptual framework to guide investigations, and (6) integration of cross-cultural and biological studies.

Suicidal indicators in schizophrenia.

The clinical and sociodemographic profile of suicidal and nonsuicidal schizophrenia patients was investigated in 801 patients with this diagnosis seen at a comprehensive psychiatric facility between 1983 and 1987. Suicidal patients tended to exhibit depression, aggressiveness, substance abuse and a severe and progressive impairment in adaptive functioning.