Intergenerational neural mediators of early-life anxious temperament

Andrew S. Fox, Jonathan A. Oler, Alexander J. Shackman, Steven E. Shelton, Muthuswamy Raveendran, D. Reese McKay, Alexander K. Converse, Andrew Alexander, Richard J. Davidson, John Blangero, Jeffrey Rogers, Ned H. Kalin

    Research output: Contribution to journalArticlepeer-review

    61 Scopus citations


    Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology cosegregate as they fall through the family tree, we can identify the brain systems that underlie the parent-to-child transmission of psychopathology. Although research has identified genes and neural circuits that contribute to the risk of developing anxiety and depression, the specific neural systems that mediate the inborn risk for these debilitating disorders remain unknown. In a sample of 592 young rhesus monkeys that are part of an extended multigenerational pedigree, we demonstrate that metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression. Importantly, although brain volume is highly heritable early in life, it is brain metabolism - not brain structure - that is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.

    Original languageEnglish (US)
    Pages (from-to)9118-9122
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number29
    StatePublished - Jul 21 2015


    • Anxiety
    • Brain volume
    • Heritability
    • Positron emission tomography
    • Primate

    ASJC Scopus subject areas

    • General


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