Amygdalar and hippocampal substrates of anxious temperament differ in their heritability

Jonathan A. Oler, Andrew S. Fox, Steven E. Shelton, Jeffrey Rogers, Thomas D. Dyer, Richard J. Davidson, Wendy Shelledy, Terrence R. Oakes, John Blangero, Ned H. Kalin

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli. Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression and comorbid substance abuse. Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we studied a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution 18 F-labelled deoxyglucose positron-emission tomography (FDG-PET) was selected as the imaging modality because it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited for assessing temperament- associated sustained brain responses. Here we demonstrate that the central nucleus region of the amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. We also show significant heritability of the AT phenotype by using quantitative genetic analysis. Additionally, using voxelwise analyses, we reveal significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT is not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differ from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk of developing anxiety and depression.

Original languageEnglish (US)
Pages (from-to)864-868
Number of pages5
JournalNature
Volume466
Issue number7308
DOIs
StatePublished - Aug 12 2010
Externally publishedYes

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Temperament
Brain
Amygdala
Phenotype
Haplorhini
Depression
Deoxyglucose
Pedigree
Anxiety Disorders
Macaca mulatta
Psychopathology
Positron-Emission Tomography
Primates
Substance-Related Disorders
Hippocampus
Anxiety

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Oler, J. A., Fox, A. S., Shelton, S. E., Rogers, J., Dyer, T. D., Davidson, R. J., ... Kalin, N. H. (2010). Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. Nature, 466(7308), 864-868. https://doi.org/10.1038/nature09282

Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. / Oler, Jonathan A.; Fox, Andrew S.; Shelton, Steven E.; Rogers, Jeffrey; Dyer, Thomas D.; Davidson, Richard J.; Shelledy, Wendy; Oakes, Terrence R.; Blangero, John; Kalin, Ned H.

In: Nature, Vol. 466, No. 7308, 12.08.2010, p. 864-868.

Research output: Contribution to journalArticle

Oler, JA, Fox, AS, Shelton, SE, Rogers, J, Dyer, TD, Davidson, RJ, Shelledy, W, Oakes, TR, Blangero, J & Kalin, NH 2010, 'Amygdalar and hippocampal substrates of anxious temperament differ in their heritability', Nature, vol. 466, no. 7308, pp. 864-868. https://doi.org/10.1038/nature09282
Oler JA, Fox AS, Shelton SE, Rogers J, Dyer TD, Davidson RJ et al. Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. Nature. 2010 Aug 12;466(7308):864-868. https://doi.org/10.1038/nature09282
Oler, Jonathan A. ; Fox, Andrew S. ; Shelton, Steven E. ; Rogers, Jeffrey ; Dyer, Thomas D. ; Davidson, Richard J. ; Shelledy, Wendy ; Oakes, Terrence R. ; Blangero, John ; Kalin, Ned H. / Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. In: Nature. 2010 ; Vol. 466, No. 7308. pp. 864-868.
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