Paralimbic and medial prefrontal cortical involvement in neuroendocrine responses to traumatic stimuli.
OBJECTIVE
Hypothalamic-pituitary-adrenal axis activity and cortisol release are consequences of central stress system activation, but they may also influence cognitive and emotional processes within the brain. Despite the importance of central stress response systems, little is known about the specific brain circuits through which psychosocial stimuli activate the hypothalamic-pituitary-adrenal axis and through which cortisol feedback modulates central processing. The authors used [(15)O]H(2)O positron emission tomography (PET) on subjects with posttraumatic stress disorder (PTSD) to study these circuits.


METHODS
Participants were combat-PTSD patients, combat-exposed healthy comparison subjects, and noncombat-exposed healthy comparison subjects. Participants were scanned using [(15)O]H(2)O PET while they experienced a series of emotional-induction conditions, which included aversive pictures and autobiographic narratives. Blood samples were obtained 2 minutes before and 5 minutes after each activation scan in order to measure the subjects' plasma adrenocorticotropic hormone and cortisol levels.


RESULTS
In voxel-wise analyses, the authors found that adrenocorticotropic hormone responses were covaried with regional cerebral blood flow (rCBF) in the dorsal medial prefrontal cortex, rostral anterior cingulate cortex, and right insula, with some differences between PTSD patients and comparison subjects. Prestimulus cortisol levels covaried with rCBF responses in the rostral anterior cingulate cortex. In combat-PTSD patients only, prestimulus cortisol levels covaried with rCBF in the subgenual anterior cingulate cortex.


CONCLUSIONS
These findings provide evidence of cortical involvement in hypothalamic-pituitary-adrenal responses to psychological stimuli, specifically implicating the insula, dorsal medial prefrontal cortex, and rostral anterior cingulate cortex. These findings also show, for the first time, that cortisol may modulate activity in specific brain areas such as the rostral and subgenual anterior cingulate cortices. Differential patterns of covariation between combat veterans with and without PTSD potentially implicate the dorsal medial prefrontal cortex and subgenual anterior cingulate cortex as areas of dysregulation in PTSD.
Liberzon
Israel
I
Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, USA. liberzon@umich.edu
King
Anthony P
AP
Britton
Jennifer C
JC
Phan
K Luan
KL
Abelson
James L
JL
Taylor
Stephan F
SF
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation / Q000502:physiology; D003130:Combat Disorders / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology; D004644:Emotions / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D006179:Gyrus Cinguli; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000000981:diagnostic imaging / Q000503:physiopathology; D008016:Life Change Events; D008032:Limbic System / Q000098:blood supply* / Q000000981:diagnostic imaging; D008279:Magnetic Resonance Imaging; D010104:Oxygen Radioisotopes; D010913:Pituitary-Adrenal System / Q000000981:diagnostic imaging / Q000503:physiopathology; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data; D017397:Prefrontal Cortex / Q000098:blood supply / Q000000981:diagnostic imaging; D012039:Regional Blood Flow / Q000502:physiology; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D014728:Veterans; D014867:Water
D010104:Oxygen Radioisotopes; D014867:Water; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone