Bioclimatic thermal stress indices and their relationships with andrological characteristics in hair rams.

This study evaluated relationships among reproductive parameters and the bioclimatic indices: temperature and humidity index (THI), equivalent temperature index (ETI), black globe temperature and humidity index (BGTHI), and thermal comfort index (TCI), during the first 45 days of spermatogenesis (SP-45) and during the 15 days of sperm transit through the epididymis (STP-15) that preceded the reproductive assessments (ReA). Such information is useful in determining the optimal breeding season in Northeast Brazil. Santa Inês rams (n = 25) underwent two ReA in three periods of the year (D-P = dry; R-P = rainy and RD-P = rainy/dry transition), and the bioclimatic indices were calculated at the corresponding SP-45 and STP-15 timepoints prior to each ReA. Sperm kinetic parameters in D-P were depressed compared to R-P and RD-P (P < 0.05). The index values had an antagonistic relationship with most parameters and regression analysis demonstrated that the BGTHI and the TCI had a negative association with the progressive motility, curvilinear, straight line, and average path velocities, and a positive association with slow sperm in the ejaculate in SP-45 and STP-15 phases (P < 0.01). Semen quality kinetics is affected throughout the year by the environment and it is apparent that it is impaired in D-P and better in R-P and RD-P seasons. The BGTHI and TCI measured in the sperm production phase classified the environment most coherently and presented better association with the behavior of sperm kinetics.

Genome-wide mapping of brain phenotypes in extended pedigrees with strong genetic loading for bipolar disorder.

Bipolar disorder is a highly heritable illness, associated with alterations of brain structure. As such, identification of genes influencing inter-individual differences in brain morphology may help elucidate the underlying pathophysiology of bipolar disorder (BP). To identify quantitative trait loci (QTL) that contribute to phenotypic variance of brain structure, structural neuroimages were acquired from family members (n = 527) of extended pedigrees heavily loaded for bipolar disorder ascertained from genetically isolated populations in Latin America. Genome-wide linkage and association analysis were conducted on the subset of heritable brain traits that showed significant evidence of association with bipolar disorder (n = 24) to map QTL influencing regional measures of brain volume and cortical thickness. Two chromosomal regions showed significant evidence of linkage; a QTL on chromosome 1p influencing corpus callosum volume and a region on chromosome 7p linked to cortical volume. Association analysis within the two QTLs identified three SNPs correlated with the brain measures.

Genetic analysis of activity, brain and behavioral associations in extended families with heavy genetic loading for bipolar disorder.

BACKGROUND: Disturbed sleep and activity are prominent features of bipolar disorder type I (BP-I). However, the relationship of sleep and activity characteristics to brain structure and behavior in euthymic BP-I patients and their non-BP-I relatives is unknown. Additionally, underlying genetic relationships between these traits have not been investigated. METHODS: Relationships between sleep and activity phenotypes, assessed using actigraphy, with structural neuroimaging (brain) and cognitive and temperament (behavior) phenotypes were investigated in 558 euthymic individuals from multi-generational pedigrees including at least one member with BP-I. Genetic correlations between actigraphy-brain and actigraphy-behavior associations were assessed, and bivariate linkage analysis was conducted for trait pairs with evidence of shared genetic influences. RESULTS: More physical activity and longer awake time were significantly associated with increased brain volumes and cortical thickness, better performance on neurocognitive measures of long-term memory and executive function, and less extreme scores on measures of temperament (impulsivity, cyclothymia). These associations did not differ between BP-I patients and their non-BP-I relatives. For nine activity-brain or activity-behavior pairs there was evidence for shared genetic influence (genetic correlations); of these pairs, a suggestive bivariate quantitative trait locus on chromosome 7 for wake duration and verbal working memory was identified. CONCLUSIONS: Our findings indicate that increased physical activity and more adequate sleep are associated with increased brain size, better cognitive function and more stable temperament in BP-I patients and their non-BP-I relatives. Additionally, we found evidence for pleiotropy of several actigraphy-behavior and actigraphy-brain phenotypes, suggesting a shared genetic basis for these traits.

A case of left atrial compression secondary to angioedema.

Angioedema due to angiotensin-converting enzyme (ACE) inhibitors is an uncommon, but deadly adverse reaction with an overall incidence of 0.1%-0.2%. Rapid accumulation of interstitial fluid and vasodilation classically involves the mucus membranes of the mouth and face but has the ability to affect other areas. We describe a case of angioedema secondary to ACE inhibitor that affected the esophagus causing left atrial compression and hemodynamic compromise.

Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder.

Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes.

Modulation of exercise-induced muscular damage and hyperalgesia by different 630 nm doses of light-emitting diode therapy (LEDT) in rats.

We compared the acute effects of different doses of 630 nm light-emitting diode therapy (LEDT) on skeletal muscle inflammation and hyperalgesia in rats submitted to exercise-induced muscle damage (EIMD). Wistar rats were divided into five experimental groups (n = 5-8/group): sedentary control (CON); exercise + passive recovery (PR); and exercise + LEDT (1.2 J/cm2, 1.8 J; 4.2 J/cm2, 6.3 J; 10.0 J/cm2, 15 J). After 100 min of swimming, the rats in the LEDT groups were exposed to phototherapy on the triceps surae muscle. For mechanical hyperalgesia evaluation, paw withdrawal threshold was assessed before and 24 h after swimming. Immediately after hyperalgesia tests, blood samples were collected to analyze creatine kinase (CK) activity and the soleus muscle was removed for histological and tumor necrosis factor (TNF)-α immunohistological analyses. In all LEDT groups, plasma CK activity was reduced to levels similar to those measured in the CON group. Paw withdrawal threshold decreased in the PR group (- 11.9 ± 1.9 g) when compared to the CON group (2.2 ± 1.5 g; p < 0.01) and it was attenuated in the group LEDT 4.2 J/cm2 (- 3.3 ± 2.4 g, p < 0.05). Less leukocyte infiltration and edema and fewer necrotic areas were found in histological sections of soleus muscle in LEDT (4.2 J/cm2) and LEDT (10.0 J/cm2) groups compared to the PR group. Also, LEDT (4.2 J/cm2) and LEDT (10.0 J/cm2) groups showed less immunostaining for TNF-α in macrophages or areas with necrosis of muscle fibers compared to the PR group. LEDT (4.2 J/cm2, 6.3 J)-reduced muscle inflammation and nociception in animals submitted to EIMD.

Reconstructing Native American population history.

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning.

Association between different soy lecithin-based extenders and freezing rates in ram semen cryopreservation.

The aim of the study was to evaluate the effect of the association between glycine-milk (GM) based extenders made with different concentrations of soy lecithin (SL) and freezing rates (FR) on semen quality after thawing. Pooled semen from rams (n = 12) were diluted in GM extenders with 20% egg yolk (EY-20%) or with different concentrations of SL: 0.5% (SL-0.5%), 1.0% (SL-1.0%), and 2.0% (SL-2.0%). The diluted semen (150 ×106 spermatozoa/0.25 mL) was frozen at three FR of - 10, - 20, and - 60 °C/min, and subsequently thawed and analyzed. Results revealed that EY-20% and SL-2.0% had better kinetic parameters, and showed higher proportions of viable, non-apoptotic, plasma-membrane-intact spermatozoa (A-/PI-) and non-capacitated spermatozoa (F), and had lower acrosome-reacted spermatozoa (AR) in the EY-20% and satisfactory values for SL-2.0% compared to SL-0.5% and SL-1.0% (P < 0.05). The FR at - 20 and - 60 °C/min maintained higher A-/PI- and viable spermatozoa compared to - 10 °C/min. The combination EY-20% and - 60 °C/min showed the highest A-/PI- and F (P < 0.05) and the lowest AR, and it did not differ from the combinations EY-20% at - 20 °C/min and SL-2.0% at - 20 °C/min (P > 0.05). In conclusion, the combination EY-20% and - 60 °C/min, showed the best cryoprotective effects on ram spermatozoa. Changes in spermatozoa after thawing were related to the use of the type of extender, the amounts of the same compound in the extender, and the freezing rates to which they were subjected.

Evaluation of air pollution tolerance index and anticipated performance index of six plant species, in an urban tropical valley: Medellin, Colombia.

High atmospheric pollution levels in urban areas have become a global problem that threatens both human health and urban ecosystems. Trees that grow near areas with vehicular and industrial emissions can be highly affected, since they constitute the main barrier for emitted pollutants, with trees being either tolerant or sensitive to them. Different methodologies worldwide have been implemented to evaluate the tolerance and sensitivity of tree species to atmospheric pollutants. In this research, the air pollution tolerance index (APTI) and the anticipated performance index (API) are evaluated in order to determine both the degree of tolerance or sensitivity of trees to pollutants in the air and their performance in urban areas. To this end, six tree species found in four biomonitoring zones in the city of Medellín, Colombia, were selected: Mangifera indica, Tabebuia chrysantha-rosea, Erythrina fusca, Jacaranda mimosifolia, Fraxinus uhdei, and Spathodea campanulata. A total of 54 individual trees were evaluated by means of the APTI and API, and it was determined that the species with the highest tolerance (APTI≥16) and the best performance (81

Geographic patterns of genome admixture in Latin American Mestizos.

The large and diverse population of Latin America is potentially a powerful resource for elucidating the genetic basis of complex traits through admixture mapping. However, no genome-wide characterization of admixture across Latin America has yet been attempted. Here, we report an analysis of admixture in thirteen Mestizo populations (i.e. in regions of mainly European and Native settlement) from seven countries in Latin America based on data for 678 autosomal and 29 X-chromosome microsatellites. We found extensive variation in Native American and European ancestry (and generally low levels of African ancestry) among populations and individuals, and evidence that admixture across Latin America has often involved predominantly European men and both Native and African women. An admixture analysis allowing for Native American population subdivision revealed a differentiation of the Native American ancestry amongst Mestizos. This observation is consistent with the genetic structure of pre-Columbian populations and with admixture having involved Natives from the area where the Mestizo examined are located. Our findings agree with available information on the demographic history of Latin America and have a number of implications for the design of association studies in population from the region.

Contrasting patterns of nuclear and mtDNA diversity in Native American populations.

We report an integrated analysis of nuclear (autosomal, X- and Y-chromosome) short tandem repeat (STR) data and mtDNA D-loop sequences obtained in the same set of 22 Native populations from across the Americas. A north to south gradient of decreasing population diversity was observed, in agreement with a settlement of the Americas from the extreme northwest of the continent. This correlation is stronger with "least cost distances," which consider the coasts as facilitators of migration. Continent-wide estimates of population structure are highest for the Y-chromosome and lowest for the autosomes, consistent with the effective size of the different marker systems examined. Population differentiation is highest in East South America and lowest in Meso America and the Andean region. Regional analyses suggest a deviation from mutation-drift equilibrium consistent with population expansion in Meso America and the Andes and population contraction in Northwest and East South America. These data hint at an early divergence of Andean and non-Andean South Americans and at a contrasting demographic history for populations from these regions.

Compliance with a sepsis bundle and its effect on intensive care unit mortality in surgical septic shock patients.

BACKGROUND: The Surviving Sepsis Campaign was launched in 2002, aiming at a 25% reduction in mortality in sepsis during a 5-year period. We hypothesized that the compliance with an adapted sepsis bundle would improve intensive care unit (ICU) survival in a cohort of surgical septic shock patients. METHODS: A retrospective, observational study was performed in surgical ICUs from two University hospitals. Seven quality indicators were considered to study the compliance with the sepsis bundle in 182 patients: (1) administration of antibiotics within 6 hours from diagnosis of septic shock, (2) initial effective antibiotic treatment, (3) adequate resuscitation within 6 hours after the diagnosis of septic shock, (4) administration of steroids, (5) use of activated protein C, (6) glucose control, and (7) protective ventilation. Univariate and multivariate logistic regression analyses were performed to make a predictive model to study the probability of survival according to the number of therapeutic guidelines fulfilled and to adjust for other predictive factors. RESULTS: Compliance with individual guidelines was considered adequate in more than 60% of the cases, except in the case of glucose control. For all quality indicators, ICU survival was higher in the bundle-compliant patients. Survival (61%) was associated with the fulfilment of increasing number of therapeutic guidelines (odds ratio, 1.64; 95% confidence interval, 1.28-2.1; p < 0.001). CONCLUSIONS: In surgical septic shock patients, the outcome was significantly related to the number of fulfilled therapeutic guidelines included in a sepsis bundle.

Genetic variation and population structure in native Americans.

We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians--signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas.

Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.

Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants.

Efficacy and safety of treatment of hyposecretory dry eye with platelet-rich plasma.

OBJECTIVE: To evaluate and compare the symptomatology and clinical findings in hyposecretory dry eye of the treatment with platelet-rich plasma (PRP) and artificial tears of sodium hyaluronate (SH). METHODS: Blind single-centre prospective comparative randomized study including 83 patients with hyposecretory dry eye and mean age of 64.0 years. Two groups were differentiated depending on the treatment applied: 44 patients treated with PRP (PRP group), and 39 patients treated with artificial tears of SH (SH group). Changes in Schimer test, tear osmolarity, corneal and conjunctival staining, tear film break-up time (TF-BUT), conjunctival hyperaemia, dry eye-related symptoms with the Ocular Surface Disease Index questionnaire, and caliciform cell density were evaluated during 30 days of treatment. RESULTS: Significantly larger reduction in symptomatology (p < 0.001), visual improvement (p < 0.001), reduction in hyperaemia (p < 0.001), and corneal and conjunctival staining (p < 0.001), increment of Schirmer test outcome (p ≤ 0.005), and reduction of osmolarity were found in the PRP group in both eyes compared to SH group at 15 and 30 days of treatment. Likewise, a significantly higher increment of caliciform cell density (p < 0.001) was found in the PRP group. Strong and statistically significant correlations were found in the PRP group of the change achieved in visual acuity, hyperaemia, osmolarity, and conjunctival and corneal staining with the baseline values of these variables (p < 0.001). CONCLUSION: PRP treatment in hyposecretory dry eye induces a more significant positive effect over symptomatology and different dry eye signs than SH, especially in moderate and severe cases.

Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance.

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.

Escoliosis idiopática del adolescente de bajo grado / Low grade adolescent idioaphic scoliosis

La escoliosis idiopática del adolescente (eia) es la forma de escoliosis más frecuente, afecta al 1 a 3% de los adolescentes. Su etiología aún no está totalmente definida siendo la causa genética la más probable. El objetivo principal del tratamiento es evitar la progresión de la curva y por ende prescindir del tratamiento quirúrgico. Tratamiento en curvas no severas dependerá de la madurez esquelética del paciente y de la magnitud de la curva, siendo la observación en curvas leves y el uso de corsé en las moderadas los tratamientos más aceptados.

Adolescent idiopathic scoliosis (ais) is the most frequent form of scoliosis, affecting 1 to 3% of adolescent. Its etiology is not yet fully defined, being the genetic factor the most important. The main objective of the treatment is to avoid the progression of the curve and therefore dispense with surgical treatment. Treatment in non-severe curves will depend of the skeletal maturity of the patient and the magnitude of the curve, being the observation in slight curves and the use of corset in the moderate ones the most accepted treatments.

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.