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.

Neurocognitive subtypes of schizophrenia.

OBJECTIVE: To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. METHODS: Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. RESULTS: We identified four neurocognitive subtypes: 1) “Global cognitive deficit”, 2) “Memory and executive function deficit”, 3) “Memory and facial emotion recognition deficit,” and 4) “Without cognitive deficit.” In comparison with the subtype “without cognitive deficit,” we found that the “memory and executive function deficit subtype” and the “global cognitive deficit subtype” had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the “global cognitive deficit subtype” the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The “memory and facial recognition deficit subtype” had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). CONCLUSION: Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction.

Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence.

OBJECTIVE: To determine if the repeated occurrence of manic episodes in bipolar I disorder (BD-I) patients is associated with reduced cognitive performance, which could in turn imply a worsening in the disorder's evolution. METHOD: Cognitive performance in euthymic patients was assessed using attention, memory, and executive function tests on 24 BD-I patients who had experienced only 1 manic episode, on 27 BD-I patients with 2 manic episodes, on 47 BD-I patients with 3 or more manic episodes, and on 66 healthy control subjects. RESULTS: In BD-I patients, number of manic episodes was positively associated with poorer performance on neurocognitive tests, an association that was not accounted for by depression, disease chronicity, onset, or medication. Significant differences in attention and executive function were found between patients and controls and in those patients who had had just 1 manic episode compared to those who had 3 or more. CONCLUSION: The number of manic episodes predicted poor cognitive performance, suggesting that the recurrence of mania may have a long-term neuropsychological impact. Prospective follow-up studies need to be completed to explore this effect further as better treatment adherence may have a protective effect on neurocognitive function.

Evidence for a role of the NOS1AP (CAPON) gene in schizophrenia and its clinical dimensions: an association study in a South American population isolate.

BACKGROUND/AIMS: Recent studies have implicated a region on chromosome 1q21-23, including the NOS1AP gene, in susceptibility to schizophrenia. However, replication studies have been inconsistent, a fact that could partly relate to the marked psychopathological heterogeneity of schizophrenia. The aim of this study is to evaluate association of polymorphisms in the NOS1AP gene region to schizophrenia, in patients from a South American population isolate, and to assess if these variants are associated with specific clinical dimensions of the disorder. METHODS: We genotyped 24 densely spaced SNPs in the NOS1AP gene region in a schizophrenia trio sample. The transmission disequilibrium test (TDT) was applied to single marker and haplotype data. Association to clinical dimensions (identified by factor analysis) was evaluated using a quantitative transmission disequilibrium test (QTDT). RESULTS: We found significant association between eight SNPs in the NOS1AP gene region to schizophrenia (minimum p value = 0.004). The QTDT analysis of clinical dimensions revealed an association to a dimension consisting mainly of negative symptoms (minimum p value 0.001). CONCLUSIONS: Our findings are consistent with a role for NOS1AP in susceptibility to schizophrenia, especially for the 'negative syndrome' of the disorder.

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.

Genetics of schizophrenia: A consensus paper of the WFSBP Task Force on Genetics.

OBJECTIVES: Schizophrenia is a severe psychiatric disease affecting about 1% of the general population. The relative contribution of genetic factors has been estimated to be up to 80%. The mode of inheritance is complex, non-Mendelian, and in most cases involving the combined action of large numbers of genes. METHODS: This review summarises recent efforts to identify genetic variants associated with schizophrenia detected, e.g., through genome-wide association studies, studies on copy-number variants or next-generation sequencing. RESULTS: A large, new body of evidence on genetics of schizophrenia has accumulated over recent years. Many new robustly associated genetic loci have been detected. Furthermore, there is consensus that at least a dozen microdeletions and microduplications contribute to the disease. Genetic overlap between schizophrenia, other psychiatric disorders, and neurodevelopmental syndromes raised new questions regarding the current classification of psychiatric and neurodevelopmental diseases. CONCLUSIONS: Future studies will address especially the functional characterisation of genetic variants. This will hopefully open the doors to our understanding of the pathophysiology of schizophrenia and other related diseases. Complementary, integrated systems biology approaches to genomics, transcriptomics, proteomics and metabolomics may also play crucial roles in enabling a precision medicine approach to the treatment of individual patients.

Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response.

Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under- or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in antidepressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-α receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

[Isonymy analysis between 2 populations in northwestern Colombia]. / Análisis de isonimia entre poblaciones del noroeste de Colombia.

INTRODUCTION: Surname frequency (isonymy) is used as a marker of paternal lineage and is used to characterize human population structure. Principles of isonymy were used to determine the genetic structure, migration rates, ancestry relations and origins of populations. This analysis was applied to two historically related local populations which currently are considered to be genetically isolated. OBJECTIVE: The genetic relationships and influence zones of the Aranzazu and Marinilla populations were assessed by means of surname frequency analysis. MATERIALS AND METHODS: Data originated from database with the title "System of Identification of Beneficiaries of the Social Programs" database or Sisben. Population parameters such as a priori kinship (phi(ii)), population homogeneity with B and C estimators, and Cavalli-Sforza's genetic distance were calculated for (a) three towns of Marinilla and its influence zone and (b) Aranzazu. The Rionegro population served as an external, comparison population. RESULTS: The Aranzazu and Marinilla populations showed the higher homogeneity (B value between 0.25 and 0.5) in contrast with Rionegro (B = 0.159), as well as greater a priori kinship values (4), between 0.003 and 0.010). The lowest distances were found between Marinilla and Aranzazu. CONCLUSIONS: Aranzazu is a population with characteristics similar to those of Marinilla and its influence zone. The close similarity of genetic characteristics for these populations is due probably to a founder effect. Furthermore, the genetic similarity predicts that genetic diseases will have the same etiology in both populations and provides optimum conditions for gene mapping studies.

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.

Lithium treatment effects on the neuropsychological functioning of patients with bipolar I disorder.

OBJECTIVE: To determine if medication plays a major role in cognitive impairment in bipolar disorder and if regular treatment with lithium influences the cognitive performance of a group of euthymic patients with bipolar I disorder. METHOD: Cognitive performance was assessed using neuropsychological tests of attention, memory, and executive function on 60 subjects: 20 euthymic bipolar I patients with no medication intake, 20 euthymic bipolar I patients who were following regular treatment with lithium carbonate monotherapy, and a third group of 20 control healthy subjects. The subjects were evaluated from January 2005 to October 2006. Patients were diagnosed using DSM-IV criteria for bipolar disorder. RESULTS: Compared to the healthy group, bipolar I patients had significantly lower performance on episodic verbal and visual-verbal memory regardless of their medication status. No significant cognitive performance differences were found between the two groups of patients with bipolar disorder, suggesting that lithium therapy had no deleterious effects on cognition. CONCLUSION: Patients with bipolar I disorder have verbal memory deficits that are not explained by medication or by lithium monotherapy, but by the condition itself.

Sensibilidad en el Reconocimiento de Emociones Faciales Como Endofenotipo de Esquizofrenia / Sensitivity in the Recognition of Facial Emotions as an Endophenotype for Schizophrenia / Sensibilidade no Reconhecimento de Emoções Faciais Como Endofenótipo de Esquizofrenia

Los endofenotipos son rasgos presentes antes de la aparición de un trastorno y podrían ser útiles para identificar genes de susceptibilidad. Se determinó si personas con esquizofrenia y sus familiares de primer grado no afectados tenían un desempeño menor que los controles en la Tarea de Multitransformación de Expresión Emocional, que mide reconocimiento de emociones faciales. Las personas con esquizofrenia y sus familiares mostraron menor sensibilidad o requirieron más intensidad para identificar emociones que los controles. La exactitud para identificar emociones fue similar entre familiares y controles, pero menor en aquellos con esquizofrenia. Esto sugiere que la sensibilidad para el reconocimiento de emociones faciales es un endofenotipo de la esquizofrenia.

Endophentoypes are the traits present before the appearance of a disorder and could be useful to identify susceptibility genes. The purpose of this study was to determine whether persons suffering from schizophrenia and their immediate relatives performed less well than controls in the Emotional Expression Multi-transformation Task, which measures recognition of facial expressions. Persons with schizophrenia and their relatives showed less sensitivity than controls or required greater intensity to identify emotions than controls did. Accuracy in the identification of emotions was similar in relatives and controls, but lower in individuals with schizophrenia. This suggests that sensitivity in the recognition of facial emotions is an endophenotype for schizophrenia.

Os endofenótipos são traços presentes antes do surgimento de um transtorno e poderiam ser úteis para identificar genes de suscetibilidade. Determinou-se se pessoas com esquizofrenia e seus familiares de primeiro grau não afetados tinham um desempenho menor que os controles na Tarefa de Multitransformação de Expressão Emocional, que mede reconhecimento de emoções faciais. As pessoas com esquizofrenia e seus familiares mostraram menor sensibilidade ou requereram mais intensidade para identificar emoções que os controles. A exatidão para identificar emoções foi similar entre familiares e controles, mas menor naqueles com esquizofrenia. Isso sugere que a sensibilidade para o reconhecimento de emoções faciais é um endofenótipo da esquizofrenia.

Subtipos neurocognitivos de esquizofrenia / Neurocognitive Subtypes of Schizophrenia

Objetivo. Identificar empíricamente subtipos neurocognitivos de esquizofrenia y establecer la asociación de estos con características clínicas. Métodos. Se aplicaron pruebas de atención sostenida, función ejecutiva, reconocimiento facial de emociones, memoria verbal y de trabajo a 253 sujetos con esquizofrenia. A partir de los resultados de estas pruebas se identificaron los subtipos mediante análisis de clases latentes. Posteriormente, se evaluó la asociación de cada subtipo con características clínicas. Resultados. Se identificaron cuatro subtipos: 1) déficit cognitivo global, 2) déficit de memoria y función ejecutiva, 3) déficit de memoria y reconocimiento de emociones y 4) sin déficit cognitivo. Al comparar con el subtipo sin déficit cognitivo, se observó que tanto el de déficit de memoria y función ejecutiva como el de déficit cognitivo global tenían mayor frecuencia individuos de sexo masculino, desempleados, con deterioro grave y adherentes al tratamiento. Sin embargo, en el subtipo con déficit cognitivo global la diferencia fue más alta y presentaron una frecuencia más baja de antecedentes de episodios depresivos (OR 0,39; IC95%: 0,16 a 0,97). El subtipo de déficit de memoria y reconocimiento emocional tenía más sujetos con deterioro grave (OR 5,52; IC95%: 1,89 a 16,14) y desempleo (OR 2,43; IC95%: 1,06 a 5,55), pero menos con antecedentes de episodios depresivos (OR 0,21; IC95%: 0,07 a 0,66). Conclusión. Los resultados muestran cuatro subtipos neurocognitivos de esquizofrenia con un posible espectro de severidad, asociándose en un extremo con mayor disfunción, y en el otro con mayor psicopatología afectiva y menor adherencia al tratamiento

Objective. To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. Methods. Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. Results. We identified four neurocognitive subtypes: 1) 'Global cognitive deficit', 2) 'Memory and executive function deficit', 3) 'Memory and facial emotion recognition deficit,' and 4) 'Without cognitive deficit.' In comparison with the subtype 'without cognitive deficit,' we found that the 'memory and executive function deficit subtype' and the 'global cognitive deficit subtype' had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the 'global cognitive deficit subtype' the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The 'memory and facial recognition deficit subtype' had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). Conclusion. Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction

Análisis de isonimia entre poblaciones del noroeste de Colombia / Isonymy analysis between 2 populations in northwestern Colombia

Introducción. La utilización de la frecuencia de apellidos como marcadores de linajes paternos ha permitido caracterizar poblaciones. Los principios de isonimia se han empleado para determinar el grado de estructuración genética, las tasas de migraciones y las relaciones de ancestría y origen entre poblaciones. Este análisis se aplicó a dos poblaciones históricamente relacionadas y consideradas como aislados genéticos. Objetivo. Evaluar las relaciones genéticas y de origen entre Aranzazu y Marinilla y su zona de influencia por medio de análisis de frecuencia de apellidos. Materiales y métodos. A partir de la base de datos del Sistema de Identificación de Beneficiarios de los Programas Sociales, Sisbén, se calcularon los parámetros poblacionales de coeficiente de parentesco (ii), la homogeneidad poblacional con los estimadores B (porcentaje de la población que comparte los siete apellidos más frecuentes) y C (15 apellidos más frecuentes) y la distancia genética de Cavalli-Sforza en tres poblaciones del núcleo fundador de Marinilla y Rionegro como población externa. Resultados. Marinilla y Aranzazu, al igual que las poblaciones de Marinilla y su zona de influencia, mostraron los mayores valores de homogeneidad (valores B entre 0,25 y 0,5) comparados con Rionegro (B = 0,159) y también mayores valores de parentesco intrapoblacional (valores ii entre 0,0034 y 0,01). Las menores distancias se encontraron entre Marinilla y Aranzazu.Conclusiones. Aranzazu es una población con características similares a las de Marinilla y su zona de influencia y debido al efecto fundador, estas poblaciones pueden presentar características genéticas similares. Por lo tanto, las enfermedades genéticas, principalmente las de herencia compleja, podrían tener la misma etiología genética en ambas poblaciones, lo que garantizaría las condiciones óptimas para estudios de cartografía genética.

Introduction. Surname frequency (isonymy) is used as a marker of paternal lineage and is used to characterize human population structure. Principles of isonymy were used to determine the genetic structure, migration rates, ancestry relations and origins of populations. This analysis was applied to two historically related local populations which currently are considered to be genetically isolated. Objective. The genetic relationships and influence zones of the Aranzazu and Marinilla populations were assessed by means of surname frequency analysis. Materials and methods. Data originated from database with the title “System of Identification of Beneficiaries of the Social Programs” database or Sisben. Population parameters such as a priori kinship (fii), population homogeneity with B and C estimators, and Cavalli-Sforza’s genetic distance were calculated for (a) three towns of Marinilla and its influence zone and (b) Aranzazu. The Rionegro population served as an external, comparison population. Results. The Aranzazu and Marinilla populations showed the higher homogeneity (B value between 0.25 and 0.5) in contrast with Rionegro (B = 0.159), as well as greater a priori kinship values (fii between 0.003 and 0.010). The lowest distances were found between Marinilla and Aranzazu. Conclusions. Aranzazu is a population with characteristics similar to those of Marinilla and its influence zone. The close similarity of genetic characteristics for these populations is due probably to a founder effect. Furthermore, the genetic similarity predicts that genetic diseases will have the same etiology in both populations and provides optimum conditions for gene mapping studies.

El uso de endofenotipos en el estudio del componente genÚtico de la esquizofrenia / The use of endophenotypes in the study of the genetic component in squizophrenia

Se revisa el concepto de endofenotipo, desde su origen histórico hasta su concepción actual. Ademßs, se hace una aproximación a la metodologÝa utilizada para la detección y validación de un endofenotipo, y se analizan las ventajas que ofrecen Ústos en el estudio del componente genÚtico de las enfermedades psiquiatricas, especificamente en la esquizofrenia.

Esquizofrenia y Neurodesarrollo / Schizophrenia and neurodevelopment

La hipótesis del neurodesarrollo con respecto al origen de la esquizofrenia postula que ésta es producto de una alteración cerebral primaria, resultante de un defecto estructural que ocurre temprano en la vida. Este defecto interactúa con eventos del desarrollo del sistema nervioso central y produce deficiencias que, junto con precipitantes ambientales, llevan a las manifestaciones clínicas de la esquizofrenia. Esta hipótesis ha tenido gran aceptación y ha sido la base de múltiples estudios de genética molecular en los últimos años. En este artículo se revisan los estudios médicos que apoyan dicha hipótesis y aquellos que la controvierten, al mostrar hallazgos de procesos neurodegenerativos dentro del trastorno...

Acción neurobiológica de los antipsicóticos / Neurobiologic action of antipsychotics

Antes de la década de los 50, basados en los efectos alucinógenos del L.S.D., se atribuía a sustancia psicomiméticas serotoninérgicas endógenas los síntomas delirante-alucinatorios de las psicosis, especialmente de la esquizofrenia. En los años 50 se descubren los efectos neurolépticos (sedantes, antipsicóticos y motores) de la clorpromazina (Delay y Deniker, 1952) y del haloperidol (Janssen, 1957) y se sostiene la hipótesis serotoninérgica, paradójicamente por el perfil antidopaminérgico de ambos fármacos

En busqueda de los genes bipolares / Looking for the bipolar genes

Objetivos: Caracterizar una muestra de familias y tríos de una población colombiana aislada para mapear loci involucrados en la vulnerabilidad al Transtorno Bipolar tipo I (TAB-I). Se evaluaron endofenotipos clínicos, neuropsicológicos y moleculares, para acortar el camino entre la identificación de genes y sus expressiones fenotípicas, y luego se realizaron estudios de ligamiento. Métodos: Se recolectaron tríos y genealogías utilizando las entrevistas FIGS-DIGS en miembros de familias y sus posibles afectados. El poder para detectar ligamiento (PDL) se estimó por simulación. Como endofenotipos clínicos comparamos casos de TAB-I con agregación familiar y controles sin agregación. Realizamos una evaluación neuropsicológica comparativa en casos eutímicos y controles sanos. Evaluamos el polimorfismo de longitud del gen del promotor del receptor de serotonina (5HTTLP) y la asociación con el TAB-I. Luego estudiamos el desequilibrio promedio en tríos y familias tamizando los cromosomas 12, 18 y 21.Resultados:Se identificaron 28 familias co TAB-I, asumiendo homogencidad genetica y la evidencia de mestizaje recientemente hallada por nosotros, las simulaciones mostraron PDL significativo de 100 por cento para un LOD-score menor 3. En la población con TAB-I familiar se encontró peor funcionamiento intercrítico, mayor gravedad en episodios depresivos, disfunción neuropsicológica en eutímia y posible evidencia de ligamiento al cromosoma 21 q 22.3. Conclusión : Tenemos un grupo significativo de familias y tríos pertenecientes a una población aislada con un poder para detectar ligamiento al Trastorno Anímico Bipolar. Las características de esta población y los hallazgos actuales en ella sugieren gran probabilidad de encontrar rasgos de expresión clínica y neuropsicológica y genes de susceptibilidad al TAB-I. En el barrido genómico que llevamos a cabo actualmente pretendemos profundizar estos hallazgos.

Efecto de la agregacion familiar en la caracterizacion clinica del trastorno afectivo bipolar tipo I en pacientes de poblacion antioqueña / Effects of family aggregation in bipolar disorder in Antioquiaïs people

El objetivo de este estudio es caracterizar clínicamente a los pacientes con trastorno afectivo bipolar I (TAB I), teniendo en cuenta la presencia de agregación familiar. Métodos: éste es un estudio observacional de corte transversal. Se extendieron genealogías de pacientes con TAB I, se identificaron familiares posibles afectados y psiquiatras que desconocían los antecedentes familiares de los sujetos realizaron una entrevista diagnóstica para estudios genéticos (DIOS) para confirmar el diagnóstico y recolectar información clínica. Se efectuó el análisis estadístico con el método de correspondencias múltiples. Resultados: se describen las características clínicas del TAB I en este grupo de pacientes. En el análisis de correspondencias se identificaron diversas agrupaciones sintomáticas. Se encontró asociación entre agregación familiar y mayor gravedad de los episodios depresivos junto con peor funcionamiento intercrítico. Conclusiones: (1) las características clínicas y agrupaciones sintomáticas encontradas son similares a las descritas en la literatura médica. (2) Los pacientes con agregación familiar parecen presentar un trastorno de mayor gravedad. (3) El análisis de correspondencias múltiples es una herramienta útil para estudios sobre fenomenología psiquiátrica

Características neuropsicológicas del trastorno bipolar I / Neuropsychological Characteristics of the Bipolar Disorder I

La neuropsicología es la disciplina que estudia la relación cerebro-mente-conducta por medio del analisis de la estructura y los procesos cerebrales que están en la base de las funciones psicológicas superiores como la conciencia, la atención, el aprendizaje, la memoria, el pensamiento, el lenguaje, la motivación y la afectividad. Las alteraciones neuropsicológicas en los pacientes con trastorno bipolar han sido poco evaluadas en comparación con otros trastornos psiquiatricos como la esquizofrenia. Sin embargo, se ha incrementado el interés por las implicaciones etiológicas, de tratamientos, de prevención y de pronóstico, como predictores de ajuste, competencia social y de calidad de vida en estos pacientes. En este artículo se pretende hacer una revisión de las investigaciones que se han realizado hasta la fecha, y que relacionan el trastorno bipolar con anormalidades neuropsicológicas. Se revisaron investigaciones realizadas en diferentes fases del trastorno, como manía, depresión o eutimia, así como estudios comparativos con pacientes esquizofrénicos, y además se discute la posible influencia de los psicofármacos...