title: Intergenerational neural mediators of early-life anxious temperament.
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.
authors.affiliation: 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.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Fox
authors.affiliation: HealthEmotions Research Institute, Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719; Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719;
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Oler
authors.affiliation: Department of Psychology, University of Maryland, College Park, MD 20742;
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Shackman
authors.affiliation: HealthEmotions Research Institute, Department of Psychiatry, University of Wisconsin-Madison, Madison, WI 53719;
authors.forename: Steven E
authors.initials: SE
authors.lastname: Shelton
authors.affiliation: Department of Genetics, Baylor College of Medicine, Houston, TX 77030;
authors.forename: Muthuswamy
authors.initials: M
authors.lastname: Raveendran
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT 06519;
authors.forename: D Reese
authors.initials: DR
authors.lastname: McKay
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, WI 53705;
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Converse
authors.affiliation: Waisman Center, University of Wisconsin-Madison, Madison, WI 53705; Department of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705;
authors.forename: Andrew
authors.initials: A
authors.lastname: Alexander
authors.affiliation: 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;
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Davidson
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX 78245.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Department of Genetics, Baylor College of Medicine, Houston, TX 77030;
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Rogers
authors.affiliation: 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.
authors.forename: Ned H
authors.initials: NH
authors.lastname: Kalin
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D005191:Family Characteristics; D040582:Inheritance Patterns; D008253:Macaca mulatta; D009474:Neurons / Q000502:physiology*; D013694:Temperament
keywords: anxiety; brain volume; heritability; positron emission tomography; primate