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Infant inhibited temperament in primates predicts adult behavior, is heritable, and is associated with

Andrew S Fox1,2, Ronald A Harris3, Laura Del Rosso4

  • 1Department of Psychology, University of California, Davis, CA, USA. dfox@ucdavis.edu.

Molecular Psychiatry
|May 26, 2021
PubMed

Insights

Infant inhibited temperament (IT) in monkeys predicts adult anxiety-related behaviors and is partially heritable. Genetic analysis identified a potential gene near CTNNA2 linked to this inherited risk for stress-related disorders.

Area of Science:

  • Behavioral Neuroscience
  • Genetics
  • Psychopathology

Background:

  • Anxious or inhibited temperament (IT) in infancy is a significant predictor of stress-related psychopathology in adulthood.
  • Temperament, including IT, can be observed in nonhuman primates during infancy when exposed to novel stimuli, mirroring human development.
  • Understanding the genetic and behavioral underpinnings of IT is crucial for identifying risks for anxiety and depressive disorders.

Purpose of the Study:

  • To investigate the predictive validity of infant inhibited temperament (IT) on adult behavior in rhesus monkeys.
  • To determine the heritability of infant IT using a large, multi-generational family pedigree.
  • To identify genetic variations associated with IT through whole-genome sequencing.

Main Methods:

  • Study 1: Assessed infant IT in over 600 monkeys and tracked adult behavior, specifically treat refusal towards human experimenters.
  • Study 2: Analyzed infant IT in over 4000 monkeys from a multi-generational pedigree to assess heritability.
  • Study 3: Performed whole-genome sequencing on 106 monkeys to identify single-nucleotide variations (SNVs) associated with IT.

Main Results:

  • Infant IT significantly predicted adult behavior, with inhibited infants being more likely to refuse treats as adults.
  • Infant IT demonstrated partial heritability and reflected a co-inherited substrate across multiple latent variables.
  • A genome-wide significant SNV near CTNNA2 was identified, and genes implicated in human neuroticism and depression showed lower p-values.

Conclusions:

  • The rhesus monkey model of infant inhibited temperament is a valuable tool for studying inherited risk factors for anxiety and depressive disorders.
  • IT has predictive validity for adult behavioral phenotypes related to stress and anxiety.
  • Genetic factors contribute to IT, with specific genes and variations potentially linked to psychopathology risk.

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