The role of CRHR1 genotype and hypothalamic-pituitary-adrenal axis dysfunction in depression after aneurysm rupture

Dr. Carroll’s work will focus on understanding the development of depression after aneurysmal subarachnoid hemorrhage (aSAH). From her successful proposal:Aneurysmal subarachnoid hemorrhage (aSAH) is associated with an incidence of new onset depression of 30-40%. Research into depression after critical illness and ischemic stroke implicates dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis as potentially contributing to the increased risk. My goal is to investigate the role of HPA axis dysregulation in the development of depression after aneurysmal subarachnoid hemorrhage (aSAH). I hypothesize that specific single-nucleotide polymorphisms (SNP) of corticotropin-releasing hormone receptor 1 (CRHR1), a G protein-coupled receptor in the limbic system and anterior pituitary, are associated with loss of negative feedback of the HPA axis and that this effect is modified by delayed cerebral ischemia. Second, I hypothesize that CRHR1 SNPs modify the risk of developing depression after aSAH.

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SNS Neurosurgeon-Scientist Training Program (NSTP)