The complex genetics and biology of human temperament: a review of traditional concepts in relation to new molecular findings
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Cloninger, C. R., Cloninger, K. M., Zwir, I., & Keltikangas-Järvinen, L. (2019). The complex genetics and biology of human temperament: a review of traditional concepts in relation to new molecular findings. Translational psychiatry, 9(1), 1-21.
SponsorshipThis review was supported by the Anthropedia Foundation (C.R.C., K.M.C.), by grants from the NIH (5 R01 MH104414-02, 1 R41 HD097833-01) and the Spanish Ministerio de Ciencia y Tecnologia, para Proyectos de Investigacion Cientifica y Desarrollo Tecnologico (DPI2015-69585-R) (I.Z.), and the Young Finns Study (L.K.J.). The Young Finns Study has been financially supported by the Academy of Finland: grants 286284, 322098, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), 41071 (Skidi), and 308676; the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association and EU Horizon 2020 (grant 755320 for TAXINOMISIS); Tampere University Hospital Supporting Foundation.
Recent genome-wide association studies (GWAS) have shown that temperament is strongly influenced by more than 700 genes that modulate associative conditioning by molecular processes for synaptic plasticity and long-term learning and memory. The results were replicated in three independent samples despite variable cultures and environments. The identified genes were enriched in pathways activated by behavioral conditioning in animals, including the two major molecular pathways for response to extracellular stimuli, the Ras-MEK-ERK and the PI3K-AKTmTOR cascades. These pathways are activated by a wide variety of physiological and psychosocial stimuli that vary in positive and negative valence and in consequences for health and survival. Changes in these pathways are orchestrated to maintain cellular homeostasis despite changing conditions by modulating temperament and its circadian and seasonal rhythms. In this review we first consider traditional concepts of temperament in relation to the new genetic findings by examining the partial overlap of alternative measures of temperament. Then we propose a definition of temperament as the disposition of a person to learn how to behave, react emotionally, and form attachments automatically by associative conditioning. This definition provides necessary and sufficient criteria to distinguish temperament from other aspects of personality that become integrated with it across the life span. We describe the effects of specific stimuli on the molecular processes underlying temperament from functional, developmental, and evolutionary perspectives. Our new knowledge can improve communication among investigators, increase the power and efficacy of clinical trials, and improve the effectiveness of treatment of personality and its disorders.