Gabriel Montoya

An association study of bipolar mood disorder (type I) with the 5-HTTLPR serotonin transporter polymorphism in a human population isolate from Colombia.

The short variant of a functional length polymorphism in the promoter region of the serotonin transporter has been associated with several behavioural and psychiatric traits, including bipolar mood disorder. The same short allele has also been implicated as a modifier of the bipolar phenotype. Here we evaluate the etiologic/modifier role of this polymorphism in a case (N=103) / control (N=112) sample for bipolar mood disorder (type I) collected from an isolated South American population. We did not detect an association between bipolar disorder and the 5-HTT promoter polymorphism in this sample. However, an excess of the short allele was seen in younger cases and in cases with psychotic symptoms. When combined with data from the literature, the increased frequency of the short allele in patients with psychotic symptoms was statistically significant.

Multisystem Component Phenotypes of Bipolar Disorder for Genetic Investigations of Extended Pedigrees

IMPORTANCE Genetic factors contribute to risk for bipolar disorder (BP), but its pathogenesis remains poorly understood. A focus on measuring multisystem quantitative traits that may be components of BP psychopathology may enable genetic dissection of this complex disorder, and investigation of extended pedigrees from genetically isolated populations may facilitate the detection of specific genetic variants that affect BP as well as its component phenotypes. OBJECTIVE To identify quantitative neurocognitive, temperament-related, and neuroanatomical phenotypes that appear heritable and associated with severe BP (bipolar I disorder [BP-I]) and therefore suitable for genetic linkage and association studies aimed at identifying variants contributing to BP-I risk. DESIGN, SETTING, AND PARTICIPANTS Multigenerational pedigree study in 2 closely related, genetically isolated populations: the Central Valley of Costa Rica and Antioquia, Colombia. A total of 738 individuals, all from Central Valley of Costa Rica and Antioquia pedigrees, participated; among them, 181 have BP-I. MAIN OUTCOMES AND MEASURES Familial aggregation (heritability) and association with BP-I of 169 quantitative neurocognitive, temperament, magnetic resonance imaging, and diffusion tensor imaging phenotypes. RESULTS Of 169 phenotypes investigated, 126 (75%) were significantly heritable and 53 (31%) were associated with BP-I. About one-quarter of the phenotypes, including measures from each phenotype domain, were both heritable and associated with BP-I. Neuroimaging phenotypes, particularly cortical thickness in prefrontal and temporal regions as well as volume and microstructural integrity of the corpus callosum, represented the most promising candidate traits for genetic mapping related to BP based on strong heritability and association with disease. Analyses of phenotypic and genetic covariation identified substantial correlations among the traits, at least some of which share a common underlying genetic architecture. CONCLUSIONS AND RELEVANCE To our knowledge, this is the most extensive investigation of BP-relevant component phenotypes to date. Our results identify brain and behavioral quantitative traits that appear to be genetically influenced and show a pattern of BP-I association within families that is consistent with expectations from case-control studies. Together, these phenotypes provide a basis for identifying loci contributing to BP-I risk and for genetic dissection of the disorder.

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

Significance Characterizing the abnormalities in sleep and activity that are associated with bipolar disorder (BP) and identifying their causation are key milestones in unraveling the biological underpinnings of this severe and highly prevalent disorder. We have conducted the first systematic evaluation of sleep and activity phenotypes in pedigrees that include multiple BP-affected members. By delineating specific sleep and activity measures that are significantly heritable in these families, and those whose variation correlated with the BP status of their members, and by determining the chromosomal position of loci contributing to many of these traits, we have taken the first step toward discovery of causative genetic variants. These variants, in turn, could provide clues to new approaches for both preventing and treating BP. 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.

Exploring epistasis in candidate genes for antisocial personality disorder

Objective To identify and characterize high-order gene-to-gene interactions in antisocial personality disorder (ASPD). Methods Participants for case–control study were selected from the inmate male population in Bellavista prison from Medellin. The study included 310 individuals with ASPD and 200 with no ASPD. Diagnoses were made according to a best-estimate procedure based on a semistructured interview (diagnostic interview for genetic studies 3.0). We genotyped some single-nucleotide polymorphisms in candidate genes with main serotonin pathway effects. The gene–gene interaction was examined using the multifactor dimensionality reduction method version 2.0.&agr;. We assessed model sizes of 2 and 3 loci and counted the number of replicates that contained the causal loci in the final best model that was identified using 10-fold cross validation. Results We find epistatic interaction with catechol-O-methyl transferase (COMT), tryptophan hydroxylase, and 5-HTR2A (serotonin receptor) with ASPD. This data supports an important role of polymorphism in serotonin receptors and low enzyme activity of COMT for susceptibility to ASPD. Conclusion This study suggests that gene interactions between genetic variants in COMT, 5-HTR2A and tryptophan hydroxylase gene would be associated with ASPD and influence the dopamine rewards pathways and modulate serotonin levels in ASPD.

Características de los suicidios de áreas rurales y urbanas de Antioquia, Colombia

Resumen Objetivo Determinar si existen diferencias entre areas rurales y urbanas de Antioquia en las caracteristicas asociadas con el suicidio. Metodo Se compararon 79 sujetos provenientes de areas rurales y 75 de areas urbanas de Antioquia. Se hizo autopsia psicologica y se calcularon razones de prevalencia (RP) (frecuencia de la caracteristica en zona rural/frecuencia de la caracteristica en zona urbana). Resultados Las caracteristicas asociadas de manera independiente con provenir de area rural y urbana fueron: “momento del suicidio durante la noche” (RP = 0,65; IC 95%: 0,48–0,89) y “vivir solo” (RP = 0,40; IC 95%: 0,17–0,98), que fueron mas frecuentes en zona urbana, y “envenenamiento con pesticidas”, que ocurrio mas en zona rural (RP = 1,80; IC 95%: 1,39–2,34). Conclusiones Los individuos suicidas provenientes de zonas rurales y urbanas tenian caracteristicas diferentes. Ello puede tener implicaciones para el diseno de las estrategias de prevencion del suicidio en cada una de las zonas. Se requieren otros estudios para determinar los factores de riesgo propios de cada area.

Aproximación bioética a las terapias reparativas. Tratamiento para el cambio de la orientación homosexual

Resumen es: La articulacion tematica entre bioetica y estudios de genero resulta evidente, ademas de vigente, en el analisis de las llamadas terapias reparativas par...

La ética del cuidado en el contexto de la salud sexual y reproductiva

Ethics of care is a theoretical and practical construct which highlights the essentially human and emotional bond between the health care professional and the patient. This essay emphasizes its application to the field of reproductive health and, mainly, to the dissemination and setting of the reproductive rights. Such strategy is oriented towards allowing a bioethics dialogue among health care professionals and whoever receives their care, since knowledge and information reciprocity generates empathy and humane treatment. The definition of sexual health, the Declaration of Sexual Rights and sexual ethics are considered integrated elements in the ethics of care for those looking for health care services in the Latin American context.La etica del cuidado es un constructo teorico y practico que busca resaltar la vinculacion esencialmente humana y emocional entre el profesional de la salud y el paciente. En este articulo se propone su instrumentacion en el campo de la salud sexual y, principalmente, en la difusion y establecimiento de los derechos sexuales. Dicha estrategia esta orientada a propiciar el dialogo bioetico entre los profesionales de la salud y las personas que reciben su cuidado, puesto que la reciprocidad de conocimientos e informacion genera empatia y trato humanizado. Se consideran la definicion de salud sexual, la declaracion de los Derechos Sexuales y la etica de la sexualidad como elementos que se integran finalmente en la etica del cuidado de las personas que acuden a los servicios de salud en el contexto latinoamericano

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 evaluate this hypothesis, we conducted genetic analyses in 26 Colombian (CO) and Costa Rican (CR) pedigrees ascertained for BP1, the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 856 individuals and high-coverage whole-genome sequencing of 454 individuals. Compared to their unaffected relatives, BP1 individuals had higher polygenic risk scores estimated from SNPs associated with BP discovered in independent genome-wide association studies, and also displayed a higher burden of rare deleterious single nucleotide variants (SNVs) and rare copy number variants (CNVs) in genes likely to be relevant to BP1. Parametric and non-parametric linkage analyses identified 15 BP1 linkage peaks, encompassing about 100 genes, although we observed no significant segregation pattern for any particular rare SNVs and CNVs. These results suggest that even in extended pedigrees, genetic risk for BP appears to derive mainly from small to moderate effect rare and common variants.

Understanding the Hidden Complexity of Latin American Population Isolates

Most population isolates examined to date were founded from a single ancestral population. Consequently, there is limited knowledge about the demographic history of admixed population isolates. Here we investigate genomic diversity of recently admixed population isolates from Costa Rica and Colombia and compare their diversity to a benchmark population isolate, the Finnish. These Latin American isolates originated during the 16th century from admixture between a few hundred European males and Amerindian females, with a limited contribution from African founders. We examine whole-genome sequence data from 449 individuals, ascertained as families to build mutigenerational pedigrees, with a mean sequencing depth of coverage of approximately 36×. We find that Latin American isolates have increased genetic diversity relative to the Finnish. However, there is an increase in the amount of identity by descent (IBD) segments in the Latin American isolates relative to the Finnish. The increase in IBD segments is likely a consequence of a very recent and severe population bottleneck during the founding of the admixed population isolates. Furthermore, the proportion of the genome that falls within a long run of homozygosity (ROH) in Costa Rican and Colombian individuals is significantly greater than that in the Finnish, suggesting more recent consanguinity in the Latin American isolates relative to that seen in the Finnish. Lastly, we find that recent consanguinity increased the number of deleterious variants found in the homozygous state, which is relevant if deleterious variants are recessive. Our study suggests that there is no single genetic signature of a population isolate.

Artifex spondet peritiam artis (El artesano responde de su arte)

who passed away in February 2016, pointed out the “incompossibility” of simultaneously and harmoniously honouring ioethics fits into psychiatric practice in an incisive – someimes uncomfortable – way, as a discourse and also as a ractice that fully brings together care and clinical research nder the aegis of protecting human dignity. Psychiatry tends o be discussed in terms of care in the therapeutic tradition, on he one hand, and unlimited monitoring of the findings from echnoscience, on the other. On this point, it is worth cauioning that the dialogue between psychiatry and bioethics is ramed within a dynamic of mutual questioning: from a deterinistic perspective, advances in technoscience question the apacity of humans to make truly autonomous decisions, it is ven feasible that the brain precedes a course of action before hat phenomenon becomes known to the conscious mind. In his problematic context, it is known that psychoactive drugs r procedures that act on the brain change the moral decisionaking structure, although so to do the disorders that they eek to correct or treat. As artisans of mental health, psychiatrists are at a crossoads of their art: on one side functionality that enables n individual’s multidimensional wellbeing must be restablished; on the other, any harm resulting from their ntervention must be prevented. This ethical conflict is in urn intercepted by the profound and pressing need to lisen to what the patient wants, to move in parallel with their utonomy. Whereupon it is possible that therapists may come o realise that, for example, not prescribing psychoactive rugs such as benzodiazepines is the best option they can hoose and the one that causes the least harm, even though heir decision may not always resonate emotionally with the atient or their family members. In addition, psychiatrists ust also be prepared to patiently overcome widespread antisychiatry sentiments about the nearly universal dependence