Abstract
Background
Anxious temperament (AT) is an early-life heritable trait that predisposes individuals
to develop anxiety and depressive disorders. Our previous work in preadolescent children
suggests alterations in the uncinate fasciculus (UF), the white matter tract that
connects prefrontal with limbic regions, in boys with anxiety disorders. Here, using
a nonhuman primate model of AT, we tested whether this sexually dimorphic finding
is evolutionarily conserved and examined the extent to which heritable and environmental
influences contribute to UF microstructure.
Methods
Diffusion tensor images were collected in 581 young rhesus monkeys (1.89 ± 0.77 years
old; 43.9% female). Using tract-based analyses, we assessed the relationship among
AT, UF microstructure (as measured with fractional anisotropy), and sex. Heritability
of tract microstructure was determined using oligogenic linkage analysis of this large
multigenerational pedigree.
Results
We predicted and found a negative relation between AT and UF fractional anisotropy
in male but not female monkeys (AT × sex; p = .032, 1-tailed). Additionally, heritability analyses revealed that variation in
UF fractional anisotropy was largely due to nonheritable factors (h2 = 0.185, p = .077).
Conclusions
These results demonstrate a cross-species, male-specific relation between UF microstructure
and anxiety and provide a potential substrate for anxiety-related prefrontal-limbic
dysregulation. The heritability analyses point to the importance of environmental
influences on UF microstructure, which could be important in mediating the nonheritable
components of pathological anxiety. These findings have the potential to guide new
treatment strategies for childhood anxiety disorders and further support the use of
nonhuman primates as a translational model to discover mechanisms underlying the development
of anxiety.
Keywords
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Article info
Publication history
Published online: July 31, 2019
Accepted:
July 23,
2019
Received in revised form:
July 6,
2019
Received:
January 17,
2019
Identification
Copyright
© 2019 Society of Biological Psychiatry.
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- The Uncinate Fasciculus in Anxiety Disorders: A Potential Treatment Target?Biological PsychiatryVol. 86Issue 12
- PreviewAnxiety disorders, the most prevalent class of pediatric mental disorders, are viewed as conditions of abnormal threat processing. The circuitry engaged by threats in a range of mammalian species encompasses the amygdala and its connections to the ventral prefrontal cortex, insula, and hippocampus. Thus, this circuitry can be targeted in translational research. Cross-species translational research is crucial for psychiatry given the inaccessibility of the human brain to many research techniques.
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