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.

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.

Aproximación a una neurobiologia de las psicoterapias / The Neurobiology of Psychotherapy

Introducción: A pesar de la efectividad de diversas psicoterapias, poco se sabe sobre sus mecanismos de acción, específicamente en la esfera neurobiológica. Desde Sigmund Freud hasta Erick Kandel, han existido varios intentos por estudiar los correlatos neurales de las intervenciones psicoterapéuticas. Hasta ahora se concibe como un proceso de aprendizaje de nuevas formas de percibir el mundo, por lo que involucra estructuras encefálicas relacionadas con la memoria, la función ejecutiva, la percepción de sí mismo y la regulación emocional. Las pruebas electroquímicas y las neuroimágenes son métodos de aproximación al funcionamiento neuronal que pueden ayudar a entender mejor la relación psicoterapia-cerebro. Método: Se revisan algunos estudios que demuestran una relación empírica entre diferentes técnicas psicoterapéuticas y un cambio observable en pruebas de laboratorio o neuroimágenes en pacientes con algunos trastornos psiquiátricos. Resultados y conclusión: Pese a las limitaciones de los estudios, como muestras pequeñas y la heterogeneidad en la metodología, ahora es más evidente que la psicoterapia funciona con un mecanismo biológico, expresado en cambios neurofuncionales. Ello aporta sólidos argumentos al debate permanente en filosofía de la mente sobre la dicotomía mente-cerebro que demuestran una implausibilidad ontológica de esta dicotomía y que permiten a la psicología y a la psiquiatría enriquecerse del desarrollo de las neurociencias básicas.

Introduction: Despite the recognized effectiveness of diverse psychotherapies, very little is known about their action mechanisms specifically from a neurobiological point of view. Since Sigmund Freud to Eric Kandel, there have been several attempts to study the neural correlates of psychotherapeutic interventions. So far they have been conceived as a learning process of new ways to perceive the world, since they involve encephalic structures related to memory, executive function, self-perception, and emotional regulation. Neuroimaging and electro-chemical testing are methods of approaching neuronal functioning that could help to better understand the relationship between psychotherapy and the brain. Method: A contextual framework is proposed in this article in order to review some of the studies that demonstrate an empiric relation between different psychotherapeutic techniques and an observable change in laboratory parameters or neuroimaging findings in patients with some psychiatric disorders. Results and Conclusions: Despite the limitations of the studies such as small sample sizes and heterogeneous methodology, there is now far more clear evidence that psychotherapy works with a cerebral mechanism expressed in neurofunctional changes that provide solid arguments to the permanent debate in Philosophy of Mind about the mind-brain dichotomy, showing the ontological implausibility of this dichotomy, and the need for different epistemological levels that will allow Psychology and Psychiatry to benefit from the development of the neurosciences.

Terapia cognitivo-conductual en esquizofrenia: una revisión narrativa de la literatura / Cognitive Behavioral Therapy In Schizophrenia: A Narrative Review of Literature

Introducción: La esquizofrenia es un trastorno grave e incapacitante. Aunque el tratamiento farmacológico ha sido efectivo, hasta 60% de los pacientes muestran una respuesta insuficiente. Desde el inicio de las terapias psicológicas ha existido interés en el uso de estas intervenciones en pacientes con psicosis. Objetivo: Revisar los aspectos más importantes de la terapia cognitivo conductual (TCC) en el tratamiento de pacientes con esquizofrenia y los datos más relevantes que sustentan su utilidad en este trastorno. Desarrollo: El psicoanálisis, la terapia conductual, la terapia de apoyo y las intervenciones familiares fueron las únicas intervenciones psicológicas durante largo tiempo. Se llegó al consenso de que el psicoanálisis no está indicado en estos pacientes. Las terapias conductuales más ortodoxas hicieron aportes importantes, pero han estado dirigidas a compensar el déficit comportamental. La terapia de familia ha demostrado efectos positivos en resultados clínicos importantes, como recurrencias psicóticas, rehospitalización y cooperación con el tratamiento. La TCC ha sido implementada para compensar algunos déficits y, principalmente, para complementar los tratamientos farmacológicos, así como para tratar síntomas positivos, emocionales y negativos. Conclusiones: Varios estudios controlados y metaanálisis han demostrado que la TCC es útil para reducir los síntomas positivos y tratar las alteraciones emocionales; también ha tenido impacto en los síntomas negativos.

Introduction: Schizophrenia is a severe and disabling disorder. Although pharmacological treatment has been effective for this condition, up to 60% of patients show an insufficient response. Since the beginnings of psychological therapies, there has been an interest in these interventions in psychotic patients. Objectives: This paper reviews the most important aspects of CBT in the treatment of patients with schizophrenia and the most relevant data supporting its usefulness in this severe disorder. Development: Psychoanalysis, behavioral therapy, supportive therapy and family interventions were the only available psychotherapies for a long time. Consensus was reached in that psychoanalysis is not indicated in patients with schizophrenia. Orthodox behavioral therapy made valuable contributions, but was mostly aimed at compensating behavioral deficits. Family therapy has shown positive effects in important clinical outcomes like psychotic relapse, rehospitalization and medication compliance. Cognitive behavioral therapy (CBT) has been introduced not only for helping to compensate certain deficits of schizophrenia, but also to complement medication in the treatment of positive, emotional and negative symptoms. Conclusions: Several controlled studies and metanalysis have shown that CBT is useful in reducing positive symptoms, for treating emotional disorders, and has had some impact on negative symptoms.

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...