GPCR-mediated calcium and cAMP signaling determines psychosocial stress susceptibility and resiliency

概要

Major depressive disorder (MDD) is a highly prevalent disorder,
and its core symptoms include depressed mood, loss of interest or
pleasure, suicidal thoughts, and lack of hope or motivation (1).
Genetic epidemiological studies estimated the heritability of
MDD at 37%, which is relatively low compared to that of schizophrenia and bipolar disorder (2), suggesting that factors other
than genetic factors also contribute to the risk of depression.
While genetic factors are important, stressful life events are also
known to be associated with the etiology of this complex psychiatric
disorder (3–5). Therefore, the current working hypothesis for the
etiology of depression is that highly complex genetic (G) differences
and environmental (E) factors work together (GxE interaction) to
determine resilience and susceptibility to MDD (5–7).
Organisms must overcome adverse stressful experiences to
survive, and the brain is the central organ that reacts and adapts
to psychosocial stress. Successful adaptation to chronic stress is a
dynamic process that is dependent on the attributes of the stress exposure, such as severity, modality, and duration (8, 9). Stress “habituation” is presumed to be an important adaptive response to
repeated challenges that allows an organism to a homeostatic
state, promoting stress resilience. However, when stress exposure
becomes chronic and severe for an individual, the stress response
becomes maladaptive and results in detrimental effects, leading to
pathological conditions (8–11). ...

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