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.α. 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.

Aspectos neurobiológicos de la psicopatía / Neurobiological aspects of psychopathy

La psicopatía es un constructo psiquiátrico caracterizado por un patrón permanente de déficit afectivo y una falta de respeto por los derechos de los demás y por las normas sociales. El término equivale al "trastorno de personalidad antisocial" DSM-IV-TR y al "Trastorno disocial de personalidad" de la Clasificación Internacional de Enfermedades (CIE-10). Los individuos afectados comienzan a presentar características psicopáticas desde la niñez, son propensos a involucrarse en conductas criminales pero no a resocializarse con los programas penitenciarios, y reinciden con más rapidez, crueldad y violencia que los criminales no psicópatas. La etiopatogenia parece basarse en la interacción compleja de factores biológicos y psicosociales. El objetivo del presente artículo es presentar una revisión actualizada de los aspectos neurobiológicos de la psicopatía entre los cuales se encuentran los obstétricos, neuroanatómicos, neuroquímicos y genéticos.

Psychopathy is a psychiatric construct characterized by a permanent pattern of affective deficit, and a lack of respect for the rights of other people and the social norms. The term is equivalent to the "Antisocial personality disorder" of the DSMIV-TR, and to the "Dissocial personality disorder" of the CIE-10. Since childhood, the affected individuals begin to display psychopathic characteristics and they have tendency to become involved in criminal behaviors but not to resocialice themselves with penitentiary programs; they reoffend more rapidly, with more cruelty and violence than non-psychopathic criminals. Etiopathogenesis of psychopathy is based on the complex interaction of biological and psychosocial factors. The objective of the present article is to provide an updated review about the neurobiological aspects of psychopathy among them the obstetric, neuroanatomical, neurochemical and genetic