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Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):9118-22. doi: 10.1073/pnas.1508593112. Epub 2015 Jul 6.

Intergenerational neural mediators of early-life anxious temperament.

Author information

1
HealthEmotions Research Institute, Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719; Waisman Center, University of Wisconsin-Madison, Madison, WI 53705; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719; asfox@wisc.edu nkalin@wisc.edu.
2
HealthEmotions Research Institute, Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719;
3
Department of Psychology, University of Maryland, College Park, MD 20742;
4
HealthEmotions Research Institute, Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719;
5
Department of Genetics, Baylor College of Medicine, Houston, TX 77030;
6
Department of Psychiatry, Yale School of Medicine, New Haven, CT 06519;
7
Waisman Center, University of Wisconsin-Madison, Madison, WI 53705;
8
Waisman Center, University of Wisconsin-Madison, Madison, WI 53705; Department of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705;
9
HealthEmotions Research Institute, Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719; Waisman Center, University of Wisconsin-Madison, Madison, WI 53705; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719; Department of Psychology, University of Wisconsin-Madison, Madison, WI 53706;
10
Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78245.
11
HealthEmotions Research Institute, Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719; Waisman Center, University of Wisconsin-Madison, Madison, WI 53705; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719; Department of Psychology, University of Wisconsin-Madison, Madison, WI 53706; asfox@wisc.edu nkalin@wisc.edu.

Abstract

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.

KEYWORDS:

anxiety; brain volume; heritability; positron emission tomography; primate

PMID:
26150480
PMCID:
PMC4517228
DOI:
10.1073/pnas.1508593112
[Indexed for MEDLINE]
Free PMC Article

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