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October 23, 2011

Depressed due to stress? Blame your genes...

Everyone experiences stress on a daily basis, whether it be due to misplaced car keys or the impending doom of taking Intro to Neuroscience quizzes online, knowing that Teamviewer will crash at least 3 times. There are many ways to deal with everyday stress; some combat the stressor head on, and others try finding ways around it. Us college students seem to combat the never-ending stress during the week with shots (usually one too many) on weekend nights. Most of us can find ways to effectively relieve this everyday stress and continue on our merry ways, ready for the next stressor that rears its ugly head. But for some, stress can cause a detour from this merry path, instead leading to a path of anhedonia, a defining symptom of depression characterized by an inability to find pleasure in activities once found pleasurable. So why can most people cope with stress, while others seem to fall apart at the seams? Ryan Bogdan and his affiliates may have found a simple answer as to why some follow this crippling detour.

Before I go any further, let me give some background into the neurobiology of stress response. Corticotropin-releasing hormone (CRH) is a hormone released by the paraventricular nucleus of the hypothalamus in response to stressful stimuli. CRH binds to the corticotropin-releasing hormone type 1 receptor (CRHR1) to exert its critical role in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, a complex neuronal network responsible for a wide variety of processes, including mood and reactions to stress. Got all that? Good.

Recently discovered is a genetic variation in the DNA encoding CRHR1, coined the CRHR1 A allele, that contains a single point mutation. This small mutation has big consequences, most notably an attenuated response to positive feedback in the ventral striatal region under stress. So what the hell does this all mean? Simply put, it means that the A allele of this receptor have disrupts processing rewarding stimuli under stress. When an individual cannot process something as rewarding, such as activities and hobbies that they used to find pleasurable (anhedonia), the inevitable result is clinical depression.

Ryan Bogdan used this information collected on the A allele to design a study focused on reward learning, an important behavioral aspect of anhedonia. In this study, control subjects and subjects homozygous for the A allele were subjected to two separate tasks involving reward; one task was stress-free, the other under the stressful possibility of electric shock should one fail the task. Under the stress condition, subjects homozygous for the A allele performed far more poorly than the control subjects, confirming that this genetic mutation produced stress-induced behavioral deficits in reward learning. Surprisingly, these same A allele subjects performed better than control under the no-stress condition.

This unfortunate genotype sheds more light on the high cormobidity between stress, anxiety, and depression. However, it could also possibly lead to effective treatments for families carrying this A allele. Stress sucks for everyone, but for certain individuals, it sucks way, way worse. Keep this in mind while studying for your next midterm, and remember, the weekend (and shots) are coming soon.
Posted by      Kevin K. at 11:27 PM MDT


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