Fine-mapping scan of bipolar disorder susceptibility loci in Latino pedigrees.

We previously identified bipolar disorder (BD) susceptibility loci on 8q24, 14q32, and 2q12-14 in a genome-wide nonparametric linkage screen in a Latino cohort. We now perform a fine mapping analysis using a dense map of additional SNPs to identify BD susceptibility genes within these regions. One thousand nine hundred and thirty-eight individuals with Latino ancestry (880 individuals with BD Type I or Schizoaffective, Bipolar Type) from 416 Latino pedigrees from the United States, Mexico, Costa Rica, and Guatemala were genotyped with 3,074 SNPs to provide dense coverage of the 8q24 (11.

Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort.

Objectives: Recent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD.

Identification of circadian gene variants in bipolar disorder in Latino populations.

Background: Variations in circadian genes can impact biological rhythms. Given the rhythm disturbances that characterize bipolar disorder (BD), genes encoding components of molecular clocks are good candidate genes for the illness.

Methods: A family based association analysis of circadian gene single nucleotide polymorphisms (SNPs) and BD was conducted in Latino pedigrees.

A genome-wide linkage scan of bipolar disorder in Latino families identifies susceptibility loci at 8q24 and 14q32.

A genome-wide nonparametric linkage screen was performed to localize Bipolar Disorder (BP) susceptibility loci in a sample of 3757 individuals of Latino ancestry. The sample included 963 individuals with BP phenotype (704 relative pairs) from 686 families recruited from the US, Mexico, Costa Rica, and Guatemala. Non-parametric analyses were performed over a 5 cM grid with an average genetic coverage of 0.

A survey of perceived barriers and attitudes toward mental health care among OEF/OIF veterans at VA outpatient mental health clinics.

Objective: In an effort to improve our understanding of perceived treatment barriers among veterans of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF) relative to other era veterans, the current study examined veteran attitudes and beliefs about mental health treatment and treatment-seeking, and perceived patient and institution-level logistical barriers to care.

Method: A survey was conducted among 434 Combat veterans seeking care in nine Veterans Affairs mental health care outpatient clinics.

Results: When compared to Vietnam and Gulf War veterans, OEF/OIF veterans were significantly more likely to endorse negative treatment attitudes as possible barriers to care.

Suggestive evidence for association between L-type voltage-gated calcium channel (CACNA1C) gene haplotypes and bipolar disorder in Latinos: a family-based association study.

Objectives:   Through recent genome-wide association studies (GWASs), several groups have reported significant association between variants in the calcium channel, voltage-dependent, L-type, alpha 1C subunit (CACNA1C) and bipolar disorder (BP) in European and European-American cohorts. We performed a family-based association study to determine whether CACNA1C is associated with BP in the Latino population.

Methods:   This study included 913 individuals from 215 Latino pedigrees recruited from the USA, Mexico, Guatemala, and Costa Rica.

Can medication management coordinators help improve continuity of care after psychiatric hospitalization?

Objective: This demonstration project examined whether medication management coordinators enhanced continuity of care from inpatient facilities to an outpatient public mental health clinic.

Methods: From 2004 to 2008, patients (N=325) hospitalized with schizophrenia or schizoaffective or bipolar disorder enrolled in a medication management program before discharge or at their first clinic appointment. Medication management coordinators supplemented existing clinic practices by identifying recently hospitalized patients, providing inpatient and outpatient prescribing clinicians with patients' complete medication history, meeting with patients for six months postdischarge to assess clinical status and provide medication education, and advocating guideline-concordant prescribing.

A case control study of the implementation of change model versus passive dissemination of practice guidelines for compliance in monitoring for metabolic syndrome.

We developed an intervention to improve compliance with guidelines for monitoring metabolic syndrome and compared compliance prior to intervention and three times post-intervention at three community mental health clinics in Texas. One test clinic received intervention and two other clinics served as controls. Fifty random charts were reviewed from each clinic for three specific, 1-2 weeks periods over the course of 18 months.

Barriers to, and strategies for, starting a long acting injection clinic in a community mental health center.

As many as 50% of patients with schizophrenia do not take oral antipsychotic medications as prescribed, yet long acting injections are rarely utilized. Community agencies that serve this population are often over-burdened and poorly funded. There are negative attitudes on the part of both physicians and consumers about injections.

Factors in second-generation antipsychotic switching patterns in a national sample of older veterans with schizophrenia.

Objective: A 2004 consensus statement by the American Psychiatric Association and other groups noted that metabolic side effects of second-generation antipsychotics require monitoring. To reduce risk, prescribers may consider factors differentially associated with development of metabolic abnormalities, such as age, gender, and race-ethnicity. As part of a study of older patients with schizophrenia (50-102 years), this study evaluated factors associated with antipsychotic switches and switches that incurred a greater or lesser metabolic risk.

Public-academic partnerships: tools for mental health agencies to evaluate research protocols.

Research involving community mental health center clients, resources, or both can affect clinical care, administrative processes, and costs. To help agencies identify and quantify these effects, a stakeholder group examined and discussed a range of protocols and then developed questionnaires and rating scales for agency use. The purpose of these materials is to make explicit the risks, costs, and benefits of a research protocol so an agency can make informed decisions about protocol approval and implementation.

Substance use disorder comorbidity with schizophrenia in families of Mexican and Central American ancestry.

Objectives: The aims of this study were to estimate the frequency and course of substances use disorders in Latino patients with schizophrenia and to ascertain risk factors associated with substance use disorders in this population.

Method: We studied 518 subjects with schizophrenia recruited for a genetic study from the Southwest United States, Mexico, and Central America (Costa Rica and Guatemala). Subjects were assessed using structured interviews and a best estimate consensus process.

Neurocognitive endophenotypes for bipolar disorder identified in multiplex multigenerational families.

Context: Although genetic influences on bipolar disorder are well established, localization of genes that predispose to the illness has proven difficult. Given that genes predisposing to bipolar disorder may be transmitted without expression of the categorical clinical phenotype, a strategy for identifying risk genes is to identify and map quantitative intermediate phenotypes or endophenotypes.

Objective: To adjudicate neurocognitive endophenotypes for bipolar disorder.

APOE-epsilon3 and APOE-219G haplotypes increase the risk for schizophrenia in sibling pairs.

To investigate the role of the apolipoprotein E (APOE) gene in schizophrenia, the authors analyzed 60 families with this mental disorder. An association in the presence of linkage test (APL) and haplotypes analysis were undertaken using the APL v1.1 software.

Diagnosis of schizophrenia in latino populations: a comparison of direct interview and consensus based multi-source methods.

We determined the rates of agreement between diagnoses, using the Diagnostic Interview for Genetic Studies (DIGS) and diagnoses arrived at, using additional sources of information, to establish whether there are differences in agreement between direct interview diagnoses at US and non-US sites in comparison best estimate consensus process and to identify diagnoses that could increase diagnostic error when only the DIGS is used. DIGS diagnoses were compared with consensus diagnoses that used the same DIGS interview, plus Family Interview for Genetic Studies (FIGS) and review of medical records in 342 psychotic subjects. We found similar numbers of subjects diagnosed with schizophrenia (225 by direct interview, and 232 by consensus process).

Heritability of age of onset of psychosis in schizophrenia.

Schizophrenia is a genetically complex illness with heterogeneous clinical presentation, including variable age of onset. In this study, the heritability, or proportion of variation in age of onset of psychotic symptoms due to genetic factors, was estimated using a maximum likelihood method. The subjects were 717 members of families with more than one member affected with schizophrenia from Mexican and Central American populations.

A schizophrenia gene locus on chromosome 17q21 in a new set of families of Mexican and central american ancestry: evidence from the NIMH Genetics of schizophrenia in latino populations study.

Objective: The present study investigated a new set of families of Latin American ancestry in order to detect the location of genes predisposing to schizophrenia and related psychotic disorders.

Method: A genome-wide scan was performed for 175 newly recruited families with at least two siblings suffering from a psychotic disorder. Best-estimate consensus procedures were used to arrive at diagnoses, and nonparametric allele-sharing statistics were calculated to detect linkage.

Public-academic partnerships: research in community mental health settings: a practicum experience for researchers.

Applying research findings to community mental health practices is slowed by provider concerns that research participants often differ from community populations in duration of illness, comorbid conditions, and illness severity. Selecting participants from community settings makes research results demonstrably relevant, but researchers and community providers can be mistrustful of one another, feeling that the other has little understanding of their needs and work. This mistrust impedes patient referrals for research.

The epsin 4 gene is associated with psychotic disorders in families of Latin American origin.

This study attempted to replicate evidence for association of the Epsin 4 gene (which encodes enthoprotin, a protein involved in vesicular transport) to schizophrenia in a new sample of families segregating schizophrenia drawn from the Latin American population. 1,423 subjects (767 with a history of psychosis) from 337 Latino families were genotyped using three single nucleotide polymorphisms (SNPs) spanning the Epsin 4 gene. A family based association test was utilized to test for association of these SNPs to the phenotypes of psychosis and schizophrenia.

Methionine sulfoxide reductase: a novel schizophrenia candidate gene.

Methionine sulfoxide reductase (MSRA) is an antioxidant enzyme implicated in protection against oxidative stress and protein maintenance. We have previously reported the association of marker D8S542, located within the MSRA gene, with schizophrenia in the Central Valley of Costa Rica (CVCR). By performing fine mapping analysis, we have now identified a potential three-marker at risk haplotype within MSRA in the same CVCR sample, with a global P-value slightly above nominal significance (P = 0.

Cannabinoid receptor 1 gene (CNR1) and susceptibility to a quantitative phenotype for hebephrenic schizophrenia.

Functional alterations of components of the endogenous cannabinoid system, in particular of the cannabinoid receptor 1 protein (CB1), are hypothetical contributors to many of the symptoms seen in schizophrenia. Variants within the cannabinoid receptor 1 gene (CNR1) have been shown to be directly associated with the hebephrenic form of schizophrenia in a Japanese population. This finding, however, has yet to be replicated.

Malic enzyme 2 and susceptibility to psychosis and mania.

Previous studies have identified a putative gene locus for both schizophrenia and bipolar disorder in the chromosome 18q21 region. To identify candidate genes associated with these disorders we completed fine mapping analyses (using microsatellite markers) in 152 families from the Central Valley of Costa Rica (CVCR) (376 total subjects, 151 with a history of psychosis, 97 with a history of mania). Microsatellite analyses showed evidence of association at two contiguous markers, both located at the same genetic distance and spanning approximately 11 known genes.