Inter-individual differences in neurobiology as vulnerability factors for affective disorders: Implications for psychopharmacology

Susceptibility to affective disorders is individually different, and determined both by genetic variance and life events that cause significant differences in the CNS structure and function between individual subjects. Therefore it is plausible that search for the inter-individual differences in endophenotypes that mediate the effects of causal factors, both genetic and environmental, will reveal the substrates for vulnerability, help to clarify pathogenetic mechanisms, and possibly aid in developing strategies to discover better, more personalized treatments. This review first examines comparatively a number of animal models of human affect and affect-related disorders that rely on persistent inter-individual differences, and then highlights some of the neurobiological findings in these models that are compatible with much of research in human behavioural and personality traits. Many behaviours occur in specific combinations in several models, but often remarkable dissociations are observed, providing a variety of constellations of traits. It is concluded that more systematic comparative experimentation on behaviour and neurobiology in different models is warranted to reveal possible “building blocks” of affect-related personality common in animals and humans. Looking into the perspectives in psychopharmacology the focus is placed on probable associations of inter-individual differences with brain structure and function, personality and coping strategies, and psychiatric vulnerability, highlighting some unexpected interactions between vulnerability endophenotypes, adverse life events, and behavioural traits. It is argued that further studies on inter-individual differences in affect and underlying neurobiology should include formal modeling of their epistatic, hierarchical and dynamic nature.