Health-related conditions and depression in elderly mexican american and non-Hispanic white residents of a United States-Mexico border county: moderating effects of educational attainment.

We investigated the prevalence of "high" levels of depressive symptomatology and 13 health-related medical conditions in elderly Mexican American (MA) and non-Hispanic white (NHW) residents of El Paso County, Texas. We analyzed the extent to which depressive symptoms in this population are associated with these conditions. Elderly MA residents possessed a higher prevalence of current depression, a relatively unique health-related condition profile, and were more likely to experience a set of conditions that impede participation in daily life-conditions that we found to be strongly associated with high depressive symptomatology in the elderly. After adjusting for educational attainment, using multiple regression analyses, depression was not associated with ethnicity and only six of the health related conditions showed significant differences between MA and NHW subjects. We believe these results provide an important insight into the mechanism of health-related conditions and depressive symptomatology in a large sample of elderly MAs; and how conditions typically attributed to MA ethnicity may in actuality be an artifact of socioeconomic status variables such as educational-attainment.

Social and clinical comparison between schizophrenia and bipolar disorder type I with psychosis in Costa Rica.

INTRODUCTION: Schizophrenia (SC) and bipolar disorder (BP) are two of the most severe and incapacitating mental disorders. It has been questioned whether these two conditions designate distinct illnesses with different etiologies or whether they represent different ends of a clinical spectrum with a common etiology. MATERIALS AND METHODS: This study compares social and clinical characteristics of 84 SC and 84 BP subjects from the Costa Rican Central Valley (CRCV) using information from the DIGS, FIGS and psychiatric records. Each of these subjects had a best estimate lifetime consensus diagnosis of either bipolar type I or SC. RESULTS: Subjects with SC differed from subjects with BP in social adjustment measures like marital and employment status, and number of children. Both groups were very similar in years of education, age of onset of their illness, history of other psychiatric co-morbidities, and treatment received. DISCUSSION: The high percentage of psychosis in the BP group (97.6%) may largely explain the similarities found between groups in their clinical characteristics. CONCLUSION: The differences in social and functional decline support the original dichotomy described by Kraepelin based on chronicity and periodicity between these two psychotic disorders.

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. In a corollary gene expression study, one of these genes, malic enzyme 2 (ME2), showed levels of gene expression 5.6-fold lower in anterior cingulate tissue from post-mortem bipolar brains. Subsequent analysis of individual SNPs in strong linkage disequilibrium with the ME2 gene revealed one SNP and one haplotype associated with the phenotype of psychosis in the CVCR sample. ME2 interacts directly with the malate shuttle system, which has been shown to be altered in schizophrenia and bipolar disorder, and has roles in neuronal synthesis of glutamate and gamma-amino butyric acid. The present study suggests that genetic variation in or near the ME2 gene is associated with both psychotic and manic disorders, including schizophrenia and bipolar disorder.

Linkage disequilibrium analyses in the Costa Rican population suggests discrete gene loci for schizophrenia at 8p23.1 and 8q13.3.

Linkage studies using multiplex families have repeatedly implicated chromosome 8 as involved in schizophrenia etiology. The reported areas of linkage, however, span a wide chromosomal region. The present study used the founder population of the Central Valley of Costa Rica and phenotyping strategies alternative to DSM-IV classifications in attempts to further delimitate the areas on chromosome 8 that may harbor schizophrenia susceptibility genes. A linkage disequilibrium screen of chromosome 8 was performed using family trios of individuals with a history of psychosis. Four discrete regions showing evidence of association (nominal P values less than 0.05) to the phenotype of schizophrenia were identified: 8p23.1, 8p21.3, 8q13.3 and 8q24.3. The region of 8p23.1 precisely overlaps a region showing strong evidence of linkage disequilibrium for severe bipolar disorder in Costa Rica. The same chromosomal regions were identified when the broader phenotype definition of all individuals with functional psychosis was used for analyses. Stratification of the psychotic sample by history of mania suggests that the 8q13.3 locus may be preferentially associated with non-manic psychosis. These results may be helpful in targeting specific areas to be analyzed in association-based or linkage disequilibrium-based studies, for researchers who have found evidence of linkage to schizophrenia on chromosome 8 within their previous studies.

Evidence of genetic overlap of schizophrenia and bipolar disorder: linkage disequilibrium analysis of chromosome 18 in the Costa Rican population.

The long-standing concept that schizophrenia (SC) and bipolar disorder (BP) represent two distinct illnesses has been recently challenged by findings of overlap of genetic susceptibility loci for these two diseases. We report here the results of a linkage disequilibrium (LD) analysis of chromosome 18 utilizing subjects with SC from the Central Valley of Costa Rica. Evidence of association (P < 0.05) was obtained in three chromosomal regions: 18p11.31 (D18S63), 18q12.3 (D18S474), and 18q22.3-qter (D18S1161, D18S70), all of which overlap or are in close proximity with loci previously shown to be in LD with BP, type I in this population. Since both the SC and bipolar samples contained cases with a history of mania and almost all cases of SC and BP had a history of psychosis, we performed an alternative phenotyping strategy to determine whether presence or absence of mania, in the context of psychosis, would yield distinct linkage patterns along chromosome 18. To address this issue, a cohort of psychotic patients (including a range of DSMIV diagnoses) was divided into two groups based on the presence or absence of mania. Regions that showed association with SC showed segregation of association when the sample was stratified by history of mania. Our results are compared with previous genetic studies of susceptibility to SC or BP, in Costa Rica as well as in other populations. This study illustrates the importance of detailed phenotype analysis in the search for susceptibility genes influencing complex psychiatric disorders in isolated populations and suggests that subdivision of psychoses by presence or absence of past mania syndromes may be useful to define genetic subtypes of chronic psychotic illness.

Genetic studies of neuropsychiatric disorders in Costa Rica: a model for the use of isolated populations.

The importance of genetics in understanding the etiology of mental illness has become increasingly clear in recent years, as more evidence has mounted that almost all neuropsychiatric disorders have a genetic component. It has also become clear, however, that these disorders are etiologically complex, and multiple genetic and environmental factors contribute to their makeup. So far, traditional linkage mapping studies have not definitively identified specific disease genes for neuropsychiatric disorders, although some potential candidates have been identified via these methods (e.g. the dysbindin gene in schizophrenia; Straub et al., 2002; Schwab et al., 2003). For this reason, alternative approaches are being attempted, including studies in genetically isolated populations. Because isolated populations have a high degree of genetic homogeneity, their use may simplify the process of identifying disease genes in disorders where multiple genes may play a role. Several areas of Latin America contain genetically isolated populations that are well suited for the study of neuropsychiatric disorders. Genetic studies of several major psychiatric illnesses, including bipolar disorder, major depression, schizophrenia, Tourette Syndrome, alcohol dependence, attention deficit hyperactivity disorder, and obsessive-compulsive disorder, are currently underway in these regions. In this paper we highlight the studies currently being conducted by our groups in the Central Valley of Costa Rica to illustrate the potential advantages of this population for genetic studies.

Comorbidity of bipolar disorder and substance abuse in Costa Rica: pedigree- and population-based studies.

BACKGROUND: The purpose of this study was to determine the prevalence of substance use disorders (substance abuse or substance dependence: SA/SD) in a large sample of Bipolar Type I (BPI) patients drawn from the Costa Rican population and to describe the effects of SA/SD on the course of their bipolar disorder. METHOD: 110 subjects from two high-risk (for BPI) Costa Rican pedigrees and 205 unrelated Costa Rican BPI subjects were assessed using structured interviews and a best estimate process. Chi(2) and survival analyses were performed to assess the effect of gender on comorbidity risk, and the effect of comorbidity on the clinical course of BPI. RESULTS: SA/SD (primarily alcohol dependence) occurred in 17% of the BPI patients from the population sample and 35% of the BPI patients from the pedigree sample. Comorbid SA/SD was strongly associated with gender chi(2) = 16.84, P = 0.00004). In comorbid subjects, alcohol dependence tended to predate the first manic episode (chi(2) = 6.54, P < 0.025). History of SA/SD did not significantly alter the prevalence of psychosis or age of onset of mania in BPI subjects. CONCLUSIONS: These results suggest that SA/SD comorbidity rates are lower in this type of population than in BPI patient populations in the US. Gender is a strong predictor of comorbidity prevalence in BPI patients from this population. Although SA/SD may be a risk factor for precipitating BPI in those at risk, in this population comorbid BPI subjects do not have a different onset or course of BPI in comparison to BPI patients without comorbidity.

Genomewide linkage disequilibrium mapping of severe bipolar disorder in a population isolate.

Genomewide association studies may offer the best promise for genetic mapping of complex traits. Such studies in outbred populations require very densely spaced single-nucleotide polymorphisms. In recently founded population isolates, however, extensive linkage disequilibrium (LD) may make these studies feasible with currently available sets of short tandem repeat markers, spaced at intervals as large as a few centimorgans. We report the results of a genomewide association study of severe bipolar disorder (BP-I), using patients from the isolated population of the central valley of Costa Rica. We observed LD with BP-I on several chromosomes; the most striking results were in proximal 8p, a region that has previously shown linkage to schizophrenia. This region could be important for severe psychiatric disorders, rather than for a specific phenotype.