Hypothalamic-pituitary-adrenal Axis and Bipolar Disorder
Section snippets
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.
References (58)
- et al.
Interrelationships between the endocrine system and the neuropsychiatry
Int Rev Neurobiol
(1963) - et al.
The combined dexamethasone-CRH-test: a refined laboratory test for psychiatric disorder
J Psychiatry Res
(1994) - et al.
Pituitary-adrenal function in depressed patients: resistance to dexamethasone suppression
J Psychiatry Res
(1975) - et al.
Neuroendocrine aspects of hypercortisolism in major depression
Horm Behav
(2003) - et al.
Twenty-four-hour ACTH and cortisol pulsatility in depressed women
Neuropsychopharmacology
(2001) The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety
J Psychiatr Res
(1999)- et al.
Cortisol response in the combined dexamethasone/CRH test as predictor of relapse in patients with remitted depression: a prospective study
J Psychiatr Res
(2001) - et al.
Dexamethasone response, thyrotropin-releasing hormone stimulation, rapid eye movement latency and subtypes of depression
Biol Psychiatry
(1997) - et al.
Combined DEX/CRH test in acute and remitted manic patients, in acute depression and in normal controls
I. Biol Psychiatry
(1995) - et al.
The dexamethasone/corticotropin-releasing hormone test in depression in bipolar and unipolar affective illness
J Psychiatr Res
(1999)
Decreased pituitary volume in patients with bipolar disorder
Biol Psychiatry
High levels of cortisol among adolescent offspring of parents with bipolar disorder: a pilot study
Psychoneuroendocrinology
Antidepressant regulate glucocorticoids receptor messenger RNA concentrations in primary neuronal cultures
Mol Brain Res
Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain
Psychoneuroendocrinology
The effect of repeated combined treatment with nifedipine and antidepressant drugs or electroconvulsive shock on the hippocampal corticosteroid receptors in rats
Neuropharmacology
Lithium augmentation increases the ACTH and cortisol response in the combined DEX/RH test in unipolar major depression
Neuropsychopharmacology
Bipolar disorder: are repeated episodes associated with neuroanatomic and cognitive changes?
Biol Psychiatry
Hippocampal remodelling and damage by corticosteroids: implications for mood disorders
Neuropsychopharmacology
An open label trial of C-1073 (mifepristone) for psychotic major depression
Biol Psychiatry
A specific laboratory test for the diagnosis of melancholia: standardization, validation and clinical utility
Arch Gen Psychiatry
Elevated concentrations of CSF corticotrophin-releasing factor-like immunoreactivity in depressed patients
Science
ACTH levels after the dexamethasone suppression in depression
N Engl J Med
The role of corticotropin releasing factor in the pathophysiology of affective and anxiety disorders: laboratory and clinical studies
Ciba Found Symp
24h monitoring of cortisol and corticotropin secretion in psychotic and non-psychotic major depression
Arch Gen Psychiatry
Altered hypothalamic pituitary adrenocortical regulation in healthy subjects at high family risk for affective disorders
Neuroendocrinology
Psychiatric implications of basic and clinical studies with corticotropin-releasing factor
Am J Psychiatry
Manic-depressive illness
Prediction of depressive relapse in remitted bipolar patients using corticotropin-releasing hormone challenge test
Acta Psychiatr Scand
Dexamethasone suppression test and urinary MHPGX SO4 determination in depressive disorders
Biol Psychiatry
Cited by (220)
The effect of neuroendocrine abnormalities on the risk of psychiatric readmission after hospitalization for bipolar disorder: A retrospective study
2024, Progress in Neuro-Psychopharmacology and Biological PsychiatryInflammation, stress, and gut-brain axis as therapeutic targets in bipolar disorder
2022, Biomarkers in Bipolar DisordersDifferential association of cortisol with visual memory/learning and executive function in Bipolar Disorder
2022, Psychiatry ResearchCitation Excerpt :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).