Subgenual prefrontal cortex activity predicts individual differences in hypothalamic-pituitary-adrenal activity across different contexts.
BACKGROUND
Hypothalamic-pituitary-adrenal (HPA) system activation is adaptive in response to stress, and HPA dysregulation occurs in stress-related psychopathology. It is important to understand the mechanisms that modulate HPA output, yet few studies have addressed the neural circuitry associated with HPA regulation in primates and humans. Using high-resolution F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in rhesus monkeys, we assessed the relation between individual differences in brain activity and HPA function across multiple contexts that varied in stressfulness.


METHODS
Using a logical AND conjunctions analysis, we assessed cortisol and brain metabolic activity with FDG-PET in 35 adolescent rhesus monkeys exposed to two threat and two home-cage conditions. To test the robustness of our findings, we used similar methods in an archival data set. In this data set, brain metabolic activity and cortisol were assessed in 17 adolescent male rhesus monkeys that were exposed to three stress-related contexts.


RESULTS
Results from the two studies revealed that subgenual prefrontal cortex (PFC) metabolism (Brodmann's area 25/24) consistently predicted individual differences in plasma cortisol concentrations regardless of the context in which brain activity and cortisol were assessed.


CONCLUSIONS
These findings suggest that activation in subgenual PFC may be related to HPA output across a variety of contexts (including familiar settings and novel or threatening situations). Individuals prone to elevated subgenual PFC activity across multiple contexts may be individuals who consistently show heightened cortisol and may be at risk for stress-related HPA dysregulation.
Jahn
Allison L
AL
Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA.
Fox
Andrew S
AS
Abercrombie
Heather C
HC
Shelton
Steven E
SE
Oakes
Terrence R
TR
Davidson
Richard J
RJ
Kalin
Ned H
NH
D000818:Animals; D001921:Brain / Q000378:metabolism; D001931:Brain Mapping; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007118:Immunoassay / Q000379:methods; D007206:Individuality; D016015:Logistic Models; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D010913:Pituitary-Adrenal System / Q000000981:diagnostic imaging / Q000503:physiopathology*; D049268:Positron-Emission Tomography / Q000379:methods; D011237:Predictive Value of Tests; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011336:Probability; D012934:Social Isolation / Q000523:psychology; D013315:Stress, Psychological / Q000000981:diagnostic imaging / Q000473:pathology*
D019788:Fluorodeoxyglucose F18; D006854:Hydrocortisone