Hypothalamic-pituitary-adrenal Axis and Bipolar Disorder

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Glucocorticoids

Glucocorticoids are hormones that are end products of the HPA axis and are central to the stress response. During the acute stress response, glucocorticoids induce short-term adaptive changes such as mobilizing energy reserves. They are also involved in long-term adaptive changes such as shaping and regulating a number of physiologic processes including immune responsiveness and activation of the sympathetic nervous system Overproduction of glucocorticoids is generally linked to significant

Summary

There is robust evidence demonstrating abnormalities of the HPA axis in bipolar disorder. Hypercortisolism may be central to the pathogenesis of depressive symptoms and cognitive deficits, which may in turn result from neurocytotoxic effects of raised cortisol levels. Manic episodes may be preceded by increased ACTH and cortisol levels, leading to cognitive problems and functional impairments. Identification and effective treatment of mood and cognitive symptoms of mood disorders are clinical

Acknowledgments

The authors thank the Stanley Medical Research Institute for its generous support of their research programs.

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      There is evidence, however, that mediators of increased inflammation/immune dysfunction and oxidative stress as well as hypothalamic-pituitary-adrenal (HPA) axis alterations may result in brain structural abnormalities and reduced neuroplasticity affecting cognition (Grande et al., 2012; Van Rheenen et al., 2020). The effect of cortisol on cognition has been relatively understudied in BD despite various lines of evidence suggesting the presence of HPA axis abnormalities (such as hypercortisolemia and increased rates of non-suppression at HPA challenging tests) (Belvederi Murri et al., 2016; Daban et al., 2005; McQuade and Young, 2000; Watson et al., 2004). Moreover, cortisol has been related to neuroplastic alterations in the hippocampus, amygdala and prefrontal cortex (McEwen, 2004).

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