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Neuropsychopharmacology. 2015 Aug;40(9):2278-85. doi: 10.1038/npp.2015.77. Epub 2015 Mar 17.

Neural Correlates of the Cortisol Awakening Response in Humans.

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Central Institute for Mental Health, University of Heidelberg/Medical Faculty Mannheim, J5, Mannheim, Germany.


The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (voxel-based morphometry) magnetic resonance imaging. Across subjects, a smaller CAR was associated with reduced grey matter volume and increased stress-related brain activity in the perigenual ACC, a region which inhibits HPA axis activity during stress that is implicated in risk mechanisms and pathophysiology of stress-related mental diseases. Moreover, functional connectivity between the perigenual ACC and the hypothalamus, the primary controller of HPA axis activity, was associated with the CAR. Our findings provide support for a role of the perigenual ACC in regulating the CAR in humans and may aid future research on the pathophysiology of stress-related illnesses, such as depression, and environmental risk for illnesses such as schizophrenia.

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