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Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety.

R M Birn¹, A J Shackman², J A Oler³

¹1] Department of Medical Physics, University of Wisconsin, Madison, WI, USA [2] Department of Psychiatry, University of Wisconsin, Madison, WI, USA [3] HealthEmotions Research Institute, Wisconsin Psychiatric Institute and Clinics, University of Wisconsin, Madison, WI, USA [4] Lane Neuroimaging Laboratory, University of Wisconsin, Madison, WI, USA [5] Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, USA.

Molecular Psychiatry

|May 28, 2014

Summary

Extreme anxious temperament (AT) in children and monkeys is linked to reduced brain connectivity. Lowered functional connectivity between the prefrontal cortex and the amygdala may increase anxiety risk.

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Area of Science:

Neuroscience
Psychiatry
Comparative Psychology

Background:

Extreme anxious temperament (AT) is a biological predisposition increasing risk for anxiety, depression, and substance abuse.
The central nucleus of the amygdala is a key brain region implicated in AT, with its connectivity to other areas crucial for anxiety regulation.
The functional architecture of the prefrontal-amygdala network in anxiety remains poorly understood.

Purpose of the Study:

To identify evolutionarily conserved patterns of functional connectivity associated with early-life anxiety in primates.
To investigate the relationship between prefrontal-amygdala connectivity and anxiety levels in young monkeys and children.

Main Methods:

Functional magnetic resonance imaging (fMRI) was used in anesthetized young monkeys and resting children with anxiety disorders.
18-fluorodeoxyglucose positron emission tomography (PET) imaging was employed to assess brain metabolism.
Anxiety was assessed using behavioral measures outside of scanning sessions.

Main Results:

Reduced functional connectivity between the dorsolateral prefrontal cortex and the central nucleus of the amygdala was associated with higher anxiety levels across species and awareness states.
Elevated metabolism in the central nucleus of the amygdala statistically mediated the link between prefrontal-amygdalar connectivity and anxiety.
An evolutionarily conserved pattern of functional connectivity relevant to early-life anxiety was identified.

Conclusions:

The findings reveal a specific brain network pattern underlying extreme early-life anxiety.
Reduced prefrontal-amygdala connectivity and altered amygdala metabolism are key factors in anxiety development.
This research provides a foundation for developing novel interventions for pediatric anxiety disorders.