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. 2010;12(1):103-14.
doi: 10.31887/DCNS.2010.12.1/trkjennerud.

The genetic epidemiology of personality disorders

Affiliations

The genetic epidemiology of personality disorders

Ted Reichborn-Kjennerud. Dialogues Clin Neurosci. 2010.

Abstract

Genetic epidemiologic studies indicate that all ten personality disorders (PDs) classified on the DSM-IV axis II are modestly to moderately heritable. Shared environmental and nonadditive genetic factors are of minor or no importance. No sex differences have been identified, Multivariate studies suggest that the extensive comorbidity between the PDs can be explained by three common genetic and environmental risk factors. The genetic factors do not reflect the DSM-IV cluster structure, but rather: i) broad vulnerability to PD pathology or negative emotionality; ii) high impulsivity/low agreeableness; and iii) introversion. Common genetic and environmental liability factors contribute to comorbidity between pairs or clusters of axis I and axis II disorders. Molecular genetic studies of PDs, mostly candidate gene association studies, indicate that genes linked to neurotransmitter pathways, especially in the serotonergic and dopaminergic systems, are involved. Future studies, using newer methods like genome-wide association, might take advantage of the use of endophenotypes.

Los estudios de epidemiología genética señalan que los diez trastornos de personalidad (TP) clasificados en el eje II del DSM-IV tienen una herencia leve a moderada. Los factores ambientales compartidos y genéticos no aditivos son de importancia menor o carecen de ésta. No se han identificado diferencias por sexo. Los estudios multivariados sugieren que la amplia comorbilidad entre los TP se puede explicar por tres factores de riesgo ambientales y genéticos comunes. Los factores genéticos no reflejan la estructura de grupos del DSM-IV, pero sí: 1) la alta vulnerabilidad para la patología de los TP o para la emocionalidad negativa, 2) la alta impulsividad/baja afabilidad y 3) la introversión. Los factores de riesgo genéticos y ambientales comunes contribuyen a la comorbilidad entre parejas o grupos de trastornos de los ejes I y II. Los estudios de genética molecular de los TP, principalmente los estudios de asociación de genes candidatos, señalan que están involucrados los genes vinculados a los sistemas de neurotransmisión, principalmente serotoninérgicos y dopaminérgicos. Estudios a futuro, que utilicen métodos más nuevos como la asociación del genoma completo, pueden aprovechar el empleo de endofenotipos.

Des études d'épidémiologie génétique montrent que les 10 troubles de la personnalité (TP) classés sur l'axe II du DSM-IV sont légèrement à modérément transmissibles. Les facteurs génétiques non additifs et les facteurs environnementaux partagés sont de peu ou sans importance et il n'y a pas de différences selon le sexe. Des études multivariées suggèrent que trois facteurs de risque génétiques et environnementaux courants peuvent expliquer la comorbidité importante entre les TP. Les facteurs génétiques ne reflètent pas la structure en cluster du DSM-IV mais plutôt: 1) une grande vulnérabilité aux TP ou à une émotivité négative ; 2) une impulsivité importante/peu d'amabilité ; 3) une introversion. Des facteurs de susceptibilité génétiques et environnementaux communs participent à la comorbidité entre les paires ou les groupes des troubles de l'axe I et de l'axe II. Des études de génétique moléculaire des TP, pour la plupart des études d'association de gène candidat, montrent que sont impliqués les gènes liés aux voies des neurotransmetteurs, surtout dans les systèmes sérotoninergiques et dopaminergiques. Des études futures, utilisant la méthodologie de recherche d'associations sur génome entiers pourraient bénéficier de l'utilisation d' endophénotypes.

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Figures

Figure 1
Figure 1. Genetic parameter estimates from best fitting model for ten DSM-IV personality disorders. Path estimates are standardized regression coefficients, so they must be squared to equal the proportion of variance accounted for in the dependent variable. A stands for additive genetic effects. The subscripts C and S stand, respectively, for common factor and disorder-specific effects. The first, second and third genetic common factors are indicated by the subscripts C1' C2 and C3'. Paths with values ≥+0.28 (which account for ≥8% of phenotypic variance) are colored with the first, second, and third common factor indicated by, respectively, red, green, and blue and the disorder-specific factors by magenta. Paths not exceeding the + 0.28 cutoff are depicted in gray. From ref 52: Kendler KS, Aggen SH, Czajkowski N, et al. The structure of genetic and environmental risk factors for DSM-IV personality disorders a multivariate twin study. Arch Gen Psychiatry. 2008;65:1438-1446. Copyright © American Medical Association 2008

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