Infant inhibited temperament in primates predicts adult behavior, is heritable, and is associated with anxiety-relevant genetic variation.

TitleInfant inhibited temperament in primates predicts adult behavior, is heritable, and is associated with anxiety-relevant genetic variation.
Publication TypeJournal Article
Year of Publication2021
AuthorsFox, AS, Harris, RA, Del Rosso, L, Raveendran, M, Kamboj, S, Kinnally, EL, Capitanio, JP, Rogers, J
JournalMol Psychiatry
Date Published2021 Nov
KeywordsAnimals, Anxiety, Anxiety Disorders, Genetic Variation, Macaca mulatta, Temperament

An anxious or inhibited temperament (IT) early in life is a major risk factor for the later development of stress-related psychopathology. Starting in infancy, nonhuman primates, like humans, begin to reveal their temperament when exposed to novel situations. Here, in Study 1 we demonstrate this infant IT predicts adult behavior. Specifically, in over 600 monkeys, we found that individuals scored as inhibited during infancy were more likely to refuse treats offered by potentially-threatening human experimenters as adults. In Study 2, using a sample of over 4000 monkeys from a large multi-generational family pedigree, we demonstrate that infant IT is partially heritable. The data revealed infant IT to reflect a co-inherited substrate that manifests across multiple latent variables. Finally, in Study 3 we performed whole-genome sequencing in 106 monkeys to identify IT-associated single-nucleotide variations (SNVs). Results demonstrated a genome-wide significant SNV near CTNNA2, suggesting a molecular target worthy of additional investigation. Moreover, we observed lower p values in genes implicated in human association studies of neuroticism and depression. Together, these data demonstrate the utility of our model of infant inhibited temperament in the rhesus monkey to facilitate discovery of genes that are relevant to the long-term inherited risk to develop anxiety and depressive disorders.

Alternate JournalMol Psychiatry
PubMed ID34035480
PubMed Central IDPMC8613309
Grant ListR01 MH121735 / MH / NIMH NIH HHS / United States
P51 OD011107 / OD / NIH HHS / United States
R24 OD010962 / OD / NIH HHS / United States
R24 OD011173 / OD / NIH HHS / United States

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