RESUMO
La mayoría de los trastornos psiquiátricos tienen una heredabilidad de moderada a alta, con diferentes arquitecturas genéticas. Aunque la investigación genética en psiquiatría ha tenido un avance progresivo, sus hallazgos, interpretación e impacto en la psiquiatría clínica resultan desconocidos para la mayoría de los profesionales de salud mental. En este artículo se abordan conceptos clave sobre genética para el entendimiento de algunas entidades clínicas, con énfasis en la nomenclatura genética y los tipos de mutaciones. Particularmente, se plantea el rol de la herencia en los inicios de la investigación genética en psiquiatría, los diseños de estudio más utilizados y sus principales objetivos. Por otro lado, se revisan algunas bases de datos genéticas y genómicas que pueden ser de utilidad para la práctica clínica. Entre ellas destacan , ClinVar, Ensembl y . Finalmente, se plantea una viñeta clínica en donde es posible aplicar algunas de las herramientas de la medicina genómica. Debido a que la evidencia en genética psiquiátrica se basa en estudios realizados en poblaciones con origen ancestral europeo o norteamericano, es de suma relevancia desarrollar estudios locales para incrementar el conocimiento y la aplicación de la medicina genómica sobre poblaciones subrepresentadas.
Most psychiatric disorders are moderate to highly heritable, often with different genetic architectures. Although genetic research in psychiatry has progressed, its findings, interpretation, and impact on clinical psychiatry are unknown to most mental healthcare professionals. This article addresses key genetic concepts to understand some clinical entities, emphasizing genetic terminology and types of mutations. Particularly, we describe the role of heritability in the early days of psychiatry genetic research, the most used study designs, and their main objectives. On the other hand, we review some genetic and genomic databases useful for clinical practice. These include Online Mendelian Inheritance in Man, ClinVar, Ensembl, and The Single Nucleotide Polymorphism Database. Finally, a clinical vignette is presented in which we can apply genomic medicine tools. Since the evidence in psychiatric genetics is based on studies carried out in European or North American ancestral populations, we must develop local studies to increase the knowledge and application of genomic medicine on underrepresented populations.
RESUMO
Inicialmente la catatonía fue un componente clínico de algunas formas de esquizofrenia, pero la evidencia básica y epidemiológica demuestra su vinculación con múltiples cuadros somáticos y psiquiátricos. Se describen y analizan conceptos clínicos, etiológicos, fisiopatológicos y terapéuticos actuales respecto a la catatonía. Se realizó una revisión narrativa amplia de artículos publicados en MEDLINE/PubMed. El diagnóstico es clínico y puede apoyarse en exámenes complementarios, pero existen instrumentos psicométricos con distinto énfasis clínico. Los subtipos más validados son el inhibido y el excitado. Se asocia mayormente a patologías somáticas, neurológicas, afectivas, psicóticas y del espectro autista. En su fisiopatología se han estudiado factores genéticos relacionados con los oligodendrocitos. Algunos hallazgos señalan un desbalance en la neurotransmisión y densidad de receptores de GABA y dopamina, hecho concordante con su función en las vías motoras y la respuesta terapéutica con benzodiacepinas. Asimismo, se ha analizado la actividad glutamatérgica, desde el modelo fisiopatológico de la encefalitis autoinmune. Las vías córtico-corticales y córtico-subcorticales tendrían un rol central, incluyendo estructuras como las cortezas orbitofrontal y temporal, núcleos basales y tronco encefálico, involucradas en la toma de decisiones, regulación emocional, almacenamiento, planificación y elaboración motora. Las principales líneas terapéuticas son las benzodiacepinas y la terapia electroconvulsiva. Otras intervenciones estudiadas son el zolpidem, antipsicóticos, estabilizadores del ánimo, moduladores glutamatérgicos y estimulación magnética transcraneal. Los nuevos hallazgos neurobiológicos discuten los preceptos nosológicos y terapéuticos, renovando el ciclo en la conceptualización de la catatonía. Se destaca el componente afectivo del síndrome psicomotor y el rol de las intervenciones que apunten a su modulación.
Catatonia was initially a clinical presentation of certain types of schizophrenia, but basic and epidemiological evidence has demonstrated its association with multiple somatic and psychiatric conditions. We describe and discuss current clinical, etiological, pathophysiological, and therapeutic concepts regarding catatonia. We conducted a broad narrative review of articles published in MEDLINE/PubMed. The diagnosis is clinical and can be supported by additional tests, but there are psychometric instruments with different clinical focus. The most validated subtypes are inhibited and excited catatonia. It is mostly associated with somatic, neurological, affective, psychotic, and autistic spectrum disorders. Genetic factors related to oligodendrocytes have been studied in its pathophysiology. Some findings point to an imbalance in neurotransmission and density of GABA and dopamine receptors, consistent with their function in motor pathways and therapeutic response with benzodiazepines. Likewise, glutamatergic activity has been analyzed from the pathophysiological model of autoimmune encephalitis. The cortico-cortical and cortico-subcortical pathways would have a central role, including structures such as the orbitofrontal and temporal cortex, basal nuclei, and brainstem, involved in decision-making, emotion regulation, storage, planning, and motor processing. The main therapeutic lines are benzodiazepines and electroconvulsive therapy. Other interventions studied are zolpidem, antipsychotics, mood stabilizers, glutamatergic modulators, and transcranial magnetic stimulation. New neurobiological findings challenge nosological and therapeutic precepts, renewing the cycle in the conceptualization of catatonia. We highlight the affective component of the psychomotor syndrome and the role of interventions aimed at its modulation.
RESUMO
The mechanisms of action (MA) of electroconvulsive therapy (ECT) in affective disorders are poorly understood. We synthesized and discussed the evidence provided by primary studies and systematic reviews in humans. There are differences in the methylation of candidate genes involved in the response to ECT. Functioning of the hippocampal serotonin receptor 5-HT1B is associated with the response in patients with major depressive disorder (PMDD), while the striatal dopamine transporter would participate in the response of PMDD and in patients with bipolar disorders (BD). The only neurotrophic factor associated with ECT response was vascular endothelial growth factor. In BD, some oxidative stress metabolites had a clinical correlation, while tryptophan metabolism showed a clinical association in BD and PMDD. Furthermore, in PMDD, some neurodegeneration markers were implicated in the MA of ECT. There were no other biological dimensions associated with BD. In PMDD, multiple inflammatory mediators were associated with the clinical response (natural killer cells, tumor necrosis and growth factors, and interleukins 1, 4, 6, 10,1β). Likewise, some structures and circuits consistently involved at the morphological and functional level are the default mode network, cognitive control networks, frontal, temporal, cingulate, occipital and temporal cortices, frontal, temporal, precentral, fusiform and left angular gyri, hippocampus, thalamus and amygdala. Investigations are mostly focused on PMDD, are observational, and their samples limited, but they show relatively consistent results with clinical significance.
RESUMO
Background: A history of child abuse is common and has a significant impact in the clinical course of patients diagnosed with bipolar disorders (BD). Aims: To assess the frequency of child abuse experiences in patients BD type I and to evaluate its association with clinical course and cognitive functioning variables. Material and Methods: 117 patients with BD aged 45 ± 14 years (66% women) answered the Childhood Trauma Questionnaire (CTQ). The clinical course (illness onset, history of suicide attempts and number of hospitalizations) was obtained from medical records. Cognitive functioning was evaluated through social and non-social cognition tasks. Results: 64% of participants reported some type of child abuse. This variable was associated with an early onset of the disease (Odds ratio (OR) = 3.3; p < 0.02), increased risk of suicide attempts (OR = 2.4; p < 0.04) and specific disturbances in social cognitive tasks. Conclusions: Our study supports evidence of a common history of child abuse in patients with BD. Although child abuse predicts a worse clinical course, major clinical practice guidelines, as well as research designs, do not highlight this evidence.