Neuroendocrine Stress System in Bipolar Disorder

Juruena, Mário F.; Cleare, Anthony J.; Young, Allan H.

doi:10.1007/7854_2020_184

Cited by 7 publications

(3 citation statements)

References 102 publications

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“…Cortisol and ACTH are important biological indicators of a dysfunctional HPA axis and have been included as routine clinical test items to evaluate the status of the axis. High levels of cortisol would induce cell dysfunction or reorganization of dendrites in neurons in the long run, ultimately leading to significant neuroanatomical changes [ 13 ]. These, in turn, increase sensitization and vulnerability to mood disorders [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study

Lyu

Zhao

et al. 2023

BMC Psychiatry

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Background Bipolar disorder (BD) is characterized by intensive mood fluctuations. While hormones imbalance plays important role in the mood swings, it is unknown whether peripheral hormones profiles could differentiate the manic and depressive mood episodes in BD. In this study, we investigated the changes of various hormones and inflammatory markers across distinct mood episodes of BD in a large clinical study to provide mood episode-specific peripheral biomarkers for BD. Methods A total of 8332 BD patients (n = 2679 depressive episode; n = 5653 manic episode) were included. All patients were in acute state of mood episodes and need hospitalization. A panel of blood tests were performed for levels of sex hormones (serum levels of testosterone, estradiol, and progesterone), stress hormones (adrenocorticotropic hormone and cortisol), and an inflammation marker (C-reactive protein, CRP). A receiver operating characteristic (ROC) curve was used to analyze the discriminatory potential of the biomarkers for mood episodes. Results In overall comparison between mood episodes, the BD patients expressed higher levels of testosterone, estradiol, progesterone, and CRP (P < 0.001) and lower adrenocorticotropic hormone (ACTH) level (P < 0.001) during manic episode. The episode-specific changes of testosterone, ACTH, and CRP levels remained between the two groups (P < 0.001) after correction for the confounding factors including age, sex, BMI, occupation, marital status, tobacco use, alcohol consumption, psychotic symptoms, and age at onset. Furthermore, we found a sex- and age-specific impact of combined biomarkers in mood episodes in male BD patients aged ≥ 45 years (AUC = 0.70, 95% CI, 0.634–0.747), not in females. Conclusions While both hormone and inflammatory change is independently associated with mood episodes, we found that the combination of sex hormones, stress hormones and CRP could be more effective to differentiate the manic and depressive episode. The biological signatures of mood episodes in BD patients may be sex- and age-specific. Our findings not only provide mood episode-related biological markers, but also better support for targeted intervention in BD treatments.

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Section: Introductionmentioning

confidence: 99%

Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study

Lyu

Zhao

et al. 2023

BMC Psychiatry

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“…Many psychiatric disturbances including bipolar disorder are deeply affected by the activity of the HPA axis, and at the same time, they also have a reciprocal effect on this neuroendocrine system (Trinetti et al., 2021 ). Based on growing evidence, an important part of the underlying psychopathology of bipolar disorder may be seen in persistent malfunction in the expression and role of mineralocorticoid and glucocorticoid receptors in the hippocampus, which mediates the effects of glucocorticoids in the form of negative feedback binding and is in a clear connection with the impact of stressful life events on the HPA axis (Juruena et al., 2021 ). Chronic stress mediated by the HPA axis—the subsequent increase in ACTH serum levels—may be related to the pathophysiology of bipolar disorder and especially manic symptoms (direct relationship between ACTH levels and manic symptoms) (Zhang et al., 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of spironolactone as adjunctive therapy to sodium valproate in bipolar‐I disorder: A double‐blind, randomized, placebo‐controlled clinical trial

Zandifar,

Badrfam,

Gholamian

et al. 2023

Brain and Behavior

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IntroductionTreatment of mood and cognitive symptoms of patients with bipolar disorder is associated with many complications and is generally not associated with therapeutic satisfaction. In this clinical trial, we evaluated the effectiveness of spironolactone in controlling mood and cognitive symptoms, sleep quality, appetite, and body mass index in patients with bipolar disorder in manic episodes.MethodsSixty inpatients with bipolar disorder in manic episodes were treated with spironolactone/placebo in an 8‐week randomized, double‐blind, placebo‐controlled clinical trial. They were evaluated using the Young Mania Rating Scale (YMRS), mini‐mental state examination (MMSE), Pittsburgh sleep quality index, Simplified Nutritional Appetite Questionnaire, and body mass index in weeks 1, 4, and 8.ResultsFor cognitive impairment (MMSE), there were significant interaction effects of group and time at week 8 (B = −1.60, SE = 0.69, t = −2.33, p = .021) such that individuals in the spironolactone group experienced more improvement in their cognitive performance. For manic symptoms (YMRS), there were no significant interaction effects of group and time at week 8 (B = −2.53, SE = 1.46, t = −1.73, p = .085).ConclusionsConsidering the promising findings in this clinical trial, further study of spironolactone as adjunctive therapy in bipolar disorder in manic episodes with larger sample sizes, multicenter settings, and longer follow‐ups are recommended.

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“… 78 Excessive HPA axis activity is also a feature of bipolar disorder, 79 with more robust hyperactivity observed in patients with severe manic symptoms 80 or a history of suicidal behavior. 81 In schizophrenia, changes in hair cortisol concentration are negatively associated with delusion severity, and evidence supports the use of measures of HPA axis activity as biomarkers for associated brain tissue loss. 82 , 83 A dysregulated HPA axis response to stress is associated with anorexia and bulimia nervosa and is exacerbated by the added experience of childhood trauma.…”

Section: Hpa Axis Impairment In Depression Neuropsychiatric Disorders...mentioning

confidence: 95%

Targeting the Arginine Vasopressin V1b Receptor System and Stress Response in Depression and Other Neuropsychiatric Disorders

Kanes¹,

Dennie²,

Perera³

2023

NDT

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A healthy stress response is critical for good mental and overall health and promotes neuronal growth and adaptation, but the intricately balanced biological mechanisms that facilitate a stress response can also result in predisposition to disease when that equilibrium is disrupted. The hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine system plays a critical role in the body’s response and adaptation to stress, and vasopressinergic regulation of the HPA axis is critical to maintaining system responsiveness during chronic stress. However, exposure to repeated or excessive physical or emotional stress or trauma can shift the body’s stress response equilibrium to a “new normal” underpinned by enduring changes in HPA axis function. Exposure to early life stress due to adverse childhood experiences can also lead to lasting neurobiological changes, including in HPA axis function. HPA axis impairment in patients with depression is considered among the most reliable findings in biological psychiatry, and chronic stress has been shown to play a major role in the pathogenesis and onset of depression and other neuropsychiatric disorders. Modulating HPA axis activity, for example via targeted antagonism of the vasopressin V 1b receptor, is a promising approach for patients with depression and other neuropsychiatric disorders associated with HPA axis impairment. Despite favorable preclinical indications in animal models, demonstration of clinical efficacy for the treatment of depressive disorders by targeting HPA axis dysfunction has been challenging, possibly due to the heterogeneity and syndromal nature of depressive disorders. Measures of HPA axis function, such as elevated cortisol levels, may be useful biomarkers for identifying patients who may benefit from treatments that modulate HPA axis activity. Utilizing clinical biomarkers to identify subsets of patients with impaired HPA axis function who may benefit is a promising next step in fine-tuning HPA axis activity via targeted antagonism of the V 1b receptor.

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Neuroendocrine Stress System in Bipolar Disorder

Cited by 7 publications

References 102 publications

Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study

Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study

Efficacy of spironolactone as adjunctive therapy to sodium valproate in bipolar‐I disorder: A double‐blind, randomized, placebo‐controlled clinical trial

Targeting the Arginine Vasopressin V1b Receptor System and Stress Response in Depression and Other Neuropsychiatric Disorders

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