COVID-19 and long-term impact on symptoms and Health-Related Quality of Life in Costa Rica: the RESPIRA cohort study.

BACKGROUND: Evidence continues to accumulate regarding the potential long-term health consequences of COVID-19 in the population. To distinguish between COVID-19-related symptoms and health limitations from those caused by other conditions, it is essential to compare cases with community controls using prospective data ensuring case-control status. The RESPIRA study addresses this need by investigating the lasting impact of COVID-19 on Health-related Quality of Life (HRQoL) and symptomatology in a population-based cohort in Costa Rica, thereby providing a robust framework for controlling HRQoL and symptoms. METHODS: The study comprised 641 PCR-confirmed, unvaccinated cases of COVID-19 and 947 matched population-based controls. Infection was confirmed using antibody tests on enrollment serum samples and symptoms were monitored monthly for 6 months post-enrolment. Administered at the 6-month visit (occurring between 6- and 2-months post-diagnosis for cases and 6 months after enrollment for controls), HRQoL and Self-Perceived Health Change were assessed using the SF-36, while brain fog, using three items from the Mental Health Inventory (MHI). Regression models were utilized to analyze SF-36, MHI scores, and Self-Perceived Health Change, adjusted for case/control status, severity (mild case, moderate case, hospitalized) and additional independent variables. Sensitivity analyses confirmed the robustness of the findings. RESULTS: Cases showed significantly higher prevalences of joint pain, chest tightness, and skin manifestations, that stabilized at higher frequencies from the fourth month post-diagnosis onwards (2.0%, 1.2%, and 0.8% respectively) compared to controls (0.9%, 0.4%, 0.2% respectively). Cases also exhibited significantly lower HRQoL than controls across all dimensions in the fully adjusted model, with a 12.4 percentage-point difference [95%CI: 9.4-14.6], in self-reported health compared to one year prior. Cases reported 8.0% [95%CI: 4.2, 11.5] more physical limitations, 7.3% [95%CI: 3.5, 10.5] increased lack of vitality, and 6.0% [95%CI: 2.4, 9.0] more brain fog compared to controls with similar characteristics. Undiagnosed cases detected with antibody tests among controls had HRQoL comparable to antibody negative controls. Differences were more pronounced in individuals with moderate or severe disease and among women. CONCLUSIONS: PCR-confirmed unvaccinated cases experienced prolonged HRQoL reductions 6 months to 2 years after diagnosis, this was particularly the case in severe cases and among women. Mildly symptomatic cases showed no significant long-term sequelae.

Systematic exploration of a decade of publications on psychiatric genetics in Latin America.

Psychiatric disorders have a great impact in terms of mortality, morbidity, and disability across the lifespan. Considerable effort has been devoted to understanding their complex and heterogeneous genetic architecture, including diverse ancestry populations. Our aim was to review the psychiatric genetics research published with Latin American populations from 2010 to 2019, and classify it according to country of origin, type of analysis, source of funding, and other variables. We found that most publications came from Brazil, Mexico, and Colombia. Also, local funds are generally not large enough for genome-wide studies in Latin America, with the exception of Brazil and Mexico; larger studies are often done in collaboration with international partners, mostly funded by US agencies. In most of the larger studies, the participants are individuals of Latin American ancestry living in the United States, which limits the potential for exploring the complex gene-environment interaction. Family studies, traditionally strong in Latin America, represent about 30% of the total research publications. Scarce local resources for research in Latin America have probably been an important limitation for conducting bigger and more complex studies, contributing to the reduced representation of these populations in global psychiatric genetics studies. Increasing diversity must be a goal to improve generalizability and applicability in clinical settings.

Identity-by-descent analysis of a large Tourette's syndrome pedigree from Costa Rica implicates genes involved in neuronal development and signal transduction.

Tourette Syndrome (TS) is a heritable, early-onset neuropsychiatric disorder that typically begins in early childhood. Identifying rare genetic variants that make a significant contribution to risk in affected families may provide important insights into the molecular aetiology of this complex and heterogeneous syndrome. Here we present a whole-genome sequencing (WGS) analysis from the 11-generation pedigree (>500 individuals) of a densely affected Costa Rican family which shares ancestry from six founder pairs. By conducting an identity-by-descent (IBD) analysis using WGS data from 19 individuals from the extended pedigree we have identified putative risk haplotypes that were not seen in controls, and can be linked with four of the six founder pairs. Rare coding and non-coding variants present on the haplotypes and only seen in haplotype carriers show an enrichment in pathways such as regulation of locomotion and signal transduction, suggesting common mechanisms by which the haplotype-specific variants may be contributing to TS-risk in this pedigree. In particular we have identified a rare deleterious missense variation in RAPGEF1 on a chromosome 9 haplotype and two ultra-rare deleterious intronic variants in ERBB4 and IKZF2 on the same chromosome 2 haplotype. All three genes play a role in neurodevelopment. This study, using WGS data in a pedigree-based approach, shows the importance of investigating both coding and non-coding variants to identify genes that may contribute to disease risk. Together, the genes and variants identified on the IBD haplotypes represent biologically relevant targets for investigation in other pedigree and population-based TS data.

Attitudes of Costa Rican individuals towards donation of personal genetic data for research.

Aim: We explore attitudes from the public in Costa Rica regarding willingness to donate DNA data for research. Materials & methods: A total of 224 Costa Rican individuals answered the anonymous online survey 'Your DNA, Your Say'. It covers attitudes toward DNA and medical data donation, trust in research professionals and concerns about consequences of reidentification. Results & conclusion: Most individuals (89%) are willing to donate their information for research purposes. When confronted with different potential uses of their data, participants are significantly less likely to donate data to for-profit researchers (34% willingness to donate). The most frequently cited concerns regarding donation of genetic data relate to possible discrimination by health/life insurance companies and employers. For the participants in the survey, the most trusted professionals are their own medical doctor and nonprofit researchers from their country. This is the first study regarding attitudes toward genetic data donation in Costa Rica.

Un cuarto de siglo de investigación genética en los trastornos neuropsiquiátricos en Costa Rica

El estudio de la base genética de los trastornos neuropsiquiátricos se inició en Costa Rica hace más de 25 años. En este tiempo se han realizado investigaciones enfocadas en diferentes trastornos: esquizofrenia, trastorno bipolar, demencia de Alzheimer, trastorno obsesivo compulsivo, trastorno obsesivo compulsivo, trastorno por déficit de atención y síndrome de Tourette. Los estudios realizados han tenido una amplia variación en lo que se refiere a diseño (ligamiento/asociación), muestra utilizada (familias/parejas de hermanos afectados/tríos), cobertura genómica (estudios con genes candidatos/tamizajes de todo el genoma) y definición del fenotipo (categoría diagnóstica/clasificación sindrómica/endofenotipo). Presentamos un resumen de los principales hallazgos genómicos obtenidos en estos estudios multidisciplinarios y discutimos la importancia, lecciones y retos de la investigación genética en trastornos psiquiátricos complejos.

In Costa Rica, the study of the genetic basis of neuropsychiatric disorders started more than 25 years ago. During this time, different research efforts have focused on several disorders: schizophrenia, bipolar disorder, Alzheimer's disease, obsessive-compulsive disorder, attention deficit/hyperactivity disorder, and Tourette syndrome. The studies have had a wide scope regarding design (linkage/association), sample used (families/sib pairs/trios), genome coverage (candidate gene studies/genome-wide scans), and phenotype definition (diagnostic category/syndromic classification/endophenotype). Here we present a summary of the main genomic findings of these multidisciplinary studies, and discuss the importance, lessons, and challenges of genetic research of complex psychiatric disorders.

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 (11.5 cM), 14q32 (7.5 cM), and 2q12-14 (6.5 cM) chromosomal loci. Single-marker association tests in the presence of linkage were performed using the LAMP software. The top linkage peak (rs7834818; LOD = 5.08, p = 3.30E - 5) and associated single marker (rs2280915, p = 2.70E - 12) were located within FBXO32 on 8q24. On chromosome 2, the top linkage peak (rs6750326; LOD = 5.06, p = 3.50E - 5) and associated single marker (rs11887088, p = 2.90E - 6) were located in intragenic regions near ACTR3 and DPP10. None of the additional markers in the region around chromosome 14q32 met significance levels for linkage or association. We identified six SNPs on 2q12-q14 and one SNP in FBXO32 on 8q24 that were significantly associated with BD in this Latino cohort.

IVF in Costa Rica.

For 16 years, Costa Rica was the only country in the world that banned IVF, after it had been successfully conducted from 1995 to 2000. It also has been the only country that banned IVF based on the argument that it protects the embryo. After years of conflict, the prohibition has finally been lifted and the first baby girl was born in March 2017. This paper recounts the judicial and legal struggles Costa Rica faced in order to reestablished its IVF program.

Neuropsychological Test Performance in Cognitively Normal Spanish-speaking Nonagenarians with Little Education.

To find associations of age, sex, and education with neuropsychological test performance in cognitively normal Spanish-speaking Costa Rican nonagenarians with little education; to provide norms; and to compare their performance with similar Puerto Ricans. For 95 Costa Ricans (90-102 years old, 0-6 years of education), multiple regression assessed associations with demographics of performance on six neuropsychological tests. Analyses of covariance compared them with 23 Puerto Ricans (90-99 years old). Younger age and being female-but not education-were associated with better performance on some neuropsychological tests, in particular episodic memory. The Puerto Ricans performed better on learning and memory tasks. In cognitively intact Spanish-speaking nonagenarians with little or no education, education did not affect test performance. Additional studies of the effect of education on cognitive performance are warranted in other samples with extremely low education or old age. National differences in performance highlight the importance of group-specific norms.

Call for a change in research funding priorities: the example of mental health in Costa Rica / Solicitud de un cambio en las prioridades de financiamiento de la investigación: el ejemplo de la salud mental en Costa Rica

The World Health Organization (WHO) Mental Health Action Plan 2013-2020 urges its Member States to strengthen leadership in mental health, ensure mental and social health interventions in community-based settings, promote mental health and strengthen information systems, and increase evidence and research for mental health. Although Costa Rica has strongly invested in public health and successfully reduced the burden of nutritional and infectious diseases, its transitional epidemiological pattern, population growth, and immigration from unstable neighboring countries has shifted the burden to chronic disorders. Although policies for chronic disorders have been in place for several decades, mental disorders have not been included. Recently, as the Ministry of Health of Costa Rica developed a Mental Health Policy for 2013-2020, it became evident that the country needs epidemiological data to prioritize evidence-based intervention areas. This article stresses the importance of conducting local epidemiological studies on mental health, and calls for changes in research funding priorities by public and private national and international funding agencies in order to follow the WHO Mental Health Action Plan.

El Plan de Acción sobre Salud Mental 2013-2020 de la Organización Mundial de la Salud (OMS) insta a sus Estados Miembros a que fortalezcan el liderazgo en el ámbito de la salud mental, garanticen las intervenciones de salud mental y asistencia social en los entornos comunitarios, promuevan la salud mental y fortalezcan los sistemas de información, e incrementen los datos científicos y las investigaciones sobre salud mental. Aunque Costa Rica ha invertido mucho en salud pública y ha reducido con éxito la carga de enfermedades nutricionales e infecciosas, su modelo epidemiológico transitorio, el crecimiento de la población y la inmigración desde países vecinos inestables han desplazado la carga de morbilidad hacia los trastornos crónicos. Aunque existen políticas en vigor dirigidas a los trastornos crónicos desde hace varios decenios, no se ha incluido en ellas a los trastornos mentales. Recientemente, cuando el Ministerio de Salud de Costa Rica elaboró una Política Nacional de Salud Mental para el periodo del 2013 al 2020, se hizo evidente que el país necesita datos epidemiológicos para priorizar las áreas de intervención con base en pruebas científicas. Este artículo subraya la importancia de llevar a cabo estudios epidemiológicos de ámbito local sobre salud mental, y solicita cambios en las prioridades de financiamiento de la investigación por parte de los organismos de financiamiento públicos y privados, nacionales e internacionales, con objeto de cumplir con lo que establece el Plan de Acción sobre Salud Mental de la OMS.

Association of apolipoprotein E-e4 and dementia declines with age.

OBJECTIVE: To study the association of dementia with apolipoprotein E-e4 (APOE-e4) and its interaction with age in a nonagenarian Costa Rican group (N-sample) and a general elderly contrast group (GE-sample). METHODS: In both case-control studies, participants were cognitively intact or diagnosed with dementia. The N-sample (N = 112) was at least age 90 years; the GE-sample (N = 98) was at least age 65 years. RESULTS: Dementia and APOE-e4 were not significantly associated in the N-sample, but were in the GE-sample. There was a significant interaction of age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively dividing the N-sample at the median (age 93 years) showed a group interaction: APOE-e4 was more associated with dementia in the younger N-sample than in the older N-sample, where six of seven APOE-e4 carriers were cognitively intact. CONCLUSIONS: The results support the reduction in association of APOE-e4 with dementia in extreme old age, consistent with a survivor effect model for successful cognitive aging.

Call for a change in research funding priorities: the example of mental health in Costa Rica.

The World Health Organization (WHO) Mental Health Action Plan 2013-2020 urges its Member States to strengthen leadership in mental health, ensure mental and social health interventions in community-based settings, promote mental health and strengthen information systems, and increase evidence and research for mental health. Although Costa Rica has strongly invested in public health and successfully reduced the burden of nutritional and infectious diseases, its transitional epidemiological pattern, population growth, and immigration from unstable neighboring countries has shifted the burden to chronic disorders. Although policies for chronic disorders have been in place for several decades, mental disorders have not been included. Recently, as the Ministry of Health of Costa Rica developed a Mental Health Policy for 2013-2020, it became evident that the country needs epidemiological data to prioritize evidence-based intervention areas. This article stresses the importance of conducting local epidemiological studies on mental health, and calls for changes in research funding priorities by public and private national and international funding agencies in order to follow the WHO Mental Health Action Plan.

Foro sobre salud mental 2011, conclusiones y pasos futuros / Mental health panel 2011, conclusions and future steps

Antecedentes: la salud es un proceso social que tiene como fin el bienestar físico y mental del individuo a través de todas las etapas de su vida. A pesar de numerosos esfuerzos, en Costa Rica, el abordaje en salud mental se ha basado principalmente en la atención de la enfermedad y muy poco en la prevención. Se resumen las conclusiones sobre el Foro de Salud Mental. Métodos: foro de discusión sobre salud mental con la participación de prestadores de servicios, investigadores, los que definen las políticas a nivel gubernamental y los usuarios. Resultados: participación de 148 representantes de distintas instituciones y organizaciones. Se resalta la ausencia de indicadores salutogénicos y escasa medición del impacto en las acciones de prevención y promoción. Existe inconformidad con la calidad y acceso a la atención. Se documenta un único programa de rehabilitación psicosocial con pocos recursos intermedios. Discusión: el proceso de consulta y discusión incluye a usuarios quienes, con los otros autores, identifican necesidades y proponen posibles soluciones en salud mental. Dificultad para la implementación de un plan de acción concreto constituye la principal limitante en promoción, atención y rehabilitación...

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. The Illumina GoldenGate Genotyping Assay was used to genotype 58 single-nucleotide polymorphisms (SNPs) that spanned a 602.9-kb region encompassing the CACNA1C gene including two SNPs (rs7297582 and rs1006737) previously shown to associate with BP. Individual SNP and haplotype association analyses were performed using Family-Based Association Test (version 2.0.3) and Haploview (version 4.2) software. RESULTS: An eight-locus haplotype block that included these two markers showed significant association with BP (global marker permuted p = 0.0018) in the Latino population. For individual SNPs, this sample had insufficient power (10%) to detect associations with SNPs with minor effect (odds ratio = 1.15). CONCLUSIONS: Although we were not able to replicate findings of association between individual CACNA1C SNPs rs7297582 and rs1006737 and BP, we were able to replicate the GWAS signal reported for CACNA1C through a haplotype analysis that encompassed these previously reported significant SNPs. These results provide additional evidence that CACNA1C is associated with BP and provides the first evidence that variations in this gene might play a role in the pathogenesis of this disorder in the Latino population.

Ancestry informative markers clarify the regional admixture variation in the Costa Rican population.

The genetic structure of Costa Rica's population is complex, both by region and by individual, due to the admixture process that started during the 15th century and historical events thereafter. Previous studies have been done mostly on Amerindian populations and the Central Valley inhabitants using various microsatellites and mitochondrial DNA markers. Here, we study for the first time a random sample from all regions of the country with ancestry informative markers (AIMs) to address the individual and regional admixture proportions. A sample of 160 male individuals was screened for 78 AIMs customized in a GoldenGate platform from Illumina. We observed that this small set of AIMs has the same power of hundreds of microsatellites and thousands of single-nucleotide polymorphisms to evaluate admixture, with the benefit of reducing genotyping costs. This type of investigation is necessary to explore new genetic markers useful for forensic and genetic investigation. Our data showed a mean admixture proportion of 49.2% European (EUR), 37.8% Native American (NAM), and 12.9% African (AFR), with a disproportionate admixture composition by region. In addition, when Chinese (CHB) was included as a fourth component, the proportions changed to 45.6% EUR, 33.5% NAM, 11.7% AFR, and 9.2% CHB. The admixture trend is consistent among all regions (EUR > NAM > AFR), and individual admixture estimates vary broadly in each region. Though we did not find stratification in Costa Rica's population, gene admixture should be evaluated in future genetic studies of Costa Rica, especially for the Caribbean region, as it contains the largest proportion of African ancestry (30.9%).

Heritability of cognitive functions in families of successful cognitive aging probands from the Central Valley of Costa Rica.

We sought to identify cognitive phenotypes for family/genetic studies of successful cognitive aging (SCA; maintaining intact cognitive functioning while living to late old age). We administered a battery of neuropsychological tests to nondemented nonagenarians (n = 65; mean age = 93.4 ± 3.0) and their offspring (n = 188; mean age = 66.4 ± 5.0) from the Central Valley of Costa Rica. After covarying for age, gender, and years of education, as necessary, heritability was calculated for cognitive functions at three pre-defined levels of complexity: specific neuropsychological functions (e.g., delayed recall, sequencing), three higher level cognitive domains (memory, executive functions, attention), and an overall neuropsychological summary. The highest heritability was for delayed recall (h² = 0.74, se = 0.14, p < 0.0001) but significant heritabilities involving memory were also observed for immediate recall (h² = 0.50), memory as a cognitive domain (h² = 0.53), and the overall neuropsychological summary (h² = 0.42). Heritabilities for sequencing (h² = 0.42), fluency (h² = 0.39), abstraction (h² = 0.36), and the executive functions cognitive domain (h² = 0.35) were also significant. In contrast, the attention domain and memory recognition were not significantly heritable in these families. Among the heritable specific cognitive functions, a strong pleiotropic effect (i.e., evidence that these may be influenced by the same gene or set of genes) for delayed and immediate recall was identified (bivariate statistic = 0.934, p < 0.0001) and more modest but significant effects were found for four additional bivariate relationships. The results support the heritability of good cognitive function in old age and the utilization of several levels of phenotypes, and they suggest that several measures involving memory may be especially useful for family/genetic studies of SCA.

Mitochondrial polymorphisms associated with differential longevity do not impact lifetime-reproductive success.

OBJECTIVE: To determine if individuals who carry mitochondrial markers which have been previously shown to affect longevity also have differential lifetime reproductive success (LRS). METHODS: We extracted the mtDNA from living subjects residing in Atenas, Costa Rica. Since mtDNA does not recombine, and its probability of mutation is low, we assume that all maternal ancestors of the living subjects have the same mtDNA. We reconstructed the maternal genealogy of the living subjects, so that we have information on the LRS and longevity of the maternal ancestors of the living subjects. We compared the LRS of women who carried the 5178A marker in haplogroup D (associated with decreased longevity) and who carried the 150T polymorphism (associated with increased longevity) with the LRS of controls born in the same half century time period from 1750 to 1939. RESULTS: We found that the LRS of neither group of women with a longevity-associated polymorphism (LAP) differed from the LRS of controls, even if these women differed significantly from the controls in their longevity. CONCLUSIONS: Although LAPS significantly affect longevity, such differential longevity does not result in differential lifetime reproductive success. From an evolutionary perspective, these longevity-associated polymorphisms do not affect the carriers' Darwinian fitness.

Assessment of genetic ancestry and population substructure in Costa Rica by analysis of individuals with a familial history of mental disorder.

The population of Costa Rica has been considered valuable for locating susceptibility genes of complex disorders because of historical events and a gradual admixture process. We present an assessment of 426 unrelated individuals with a familial history of mental disorder and with ancestors born in the Central Valley, genotyped at 730 microsatellites to evaluate genetic diversity, ancestry, and substructure at the general and regional population levels using quantitative methods. Low population substructure was found. Estimated mean ancestry proportions were 54%, 32%, and 13% for European, Amerindian, and African components, respectively, with some regional variation. The F(ST) values obtained confirm the largest genetic similarity to Europeans. Subdivision of the Amerindians into individual populations revealed strong similarity to Chibchan groups. Analysis of the African ancestry showed high similarity to West and Central African populations. Gene ancestries from other African areas were also detected, probably resulting from ancestral admixture within Africa prior to colonial times. Our analyses show, in an ethnohistorical-genetic context, that gene flow and admixture are important components of Costa Rican population history. The results confirm the need to consider the particular regional genetic structure, the effects of genetic drift and the ancestry when designing and interpreting investigations of genetic traits in this population.

Association of serotonin transporter promoter gene polymorphism (5-HTTLPR) with depression in Costa Rican schizophrenic patients.

Depression and suicidal behavior are frequently observed in patients with schizophrenia. The serotonin transporter protein regulates serotonergic signaling at synapses and is encoded by a single gene (SLC6A4; Locus Link ID: 6532), located at 17q11.1-q12 with two polymorphic variants (the short and the long allele). The short allele of serotonin transporter gene has been associated with depression and suicidality in individuals who suffered negative life events and with depression in individuals with chronic psychosis.. Subjects were recruited from a genetic study of schizophrenia conducted in Costa Rica. The authors replicated their previous research, using a more narrow phenotype (only schizophrenic subjects) and a more ethnically homogenous sample (only Costa Rican schizophrenic individuals who were not included in the previous study). The authors hypothesized that subjects with at least one copy of the serotonin transporter promoter gene polymorphism (5-HTTLPR) "s" allele would have a greater history of lifetime depression and suicidability rate than those who had an "l/l" genotype. The authors analyzed 155 subjects with a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of schizophrenia (73% male, age at interview 38.3, SD = 11.23). The genotype distribution was "ss" 58 (37%), "sl" 69 (45%), and "ll" 28 (18%). In the secondary analysis, the authors explored association of the "s" allele with lifetime history of suicide behavior in 173 subjects (18 more subjects than primary analysis because schizophrenic individuals were included regardless of history of depression). The authors found that subjects carrying at least one short allele had a significant increased lifetime risk for depressive syndromes (chi(2) = 5.4, df = 1, P = 0.02; odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.15-6.3). No association was found for suicidal behavior in the same sample (chi(2) = 0.928, P = 0.629). In conclusion, the genotype at the 5-HTTLPR promoter polymorphic locus increases the risk of developing major depression but not suicidal behavior during the course of the schizophrenia in these patients. Due to the small sample size, these results should be followed by definitive replication.

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. Logistic regression, chi(2), t test, Fisher's exact test, and Yates' correction, as appropriate, were performed to assess the sociodemographic variables associated with dual diagnosis. We defined substance use disorder as either alcohol or substance abuse or dependence. RESULTS: Out of 518 patients with schizophrenia, 121 (23.4%) had substance use disorders. Comorbid substance use disorders were associated with male gender, residence in the United States, immigration of Mexican men to the United States, history of depressive syndrome or episode, and being unemployed. The most frequent substance use disorder was alcohol abuse/dependence, followed by marijuana abuse/dependence, and solvent abuse/dependence. CONCLUSION: This study provides data suggesting that depressive episode or syndrome, unemployment, male gender, and immigration of Mexican men to the United States were factors associated with substance use disorder comorbidity in schizophrenia. Binary logistic regression showed that country of residence was associated with substance use disorder in schizophrenic patients. The percentage of subjects with comorbid substance use disorders was higher in the Latinos living in the United States compared with subjects living in Central America and Mexico.