Increased release of cortisol and ACTH have also been observed in patients with mood disorder. These, in turn, increase sensitization and vulnerability to mood disorders. High levels of cortisol would induce cell dysfunction or reorganization of dendrites in neurons in the long run, ultimately leading to significant neuroanatomical changes. 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. The activity of the hypothalamic-pituitary-adrenal (HPA) axis can be modulated by gonadal hormones. Presently, the relationship between gonadal hormones and mood episodes is unclear, and some studies have suggested that it may be related to mood episodes. Testosterone has been found to participate in the pathological process of BD and has anxiolytic and antidepressant effects in humans and animals, which are known to benefit negative emotions. Progestogens have significant, though indirect, effects by converting into neuroactive molecules, such as estrogens and testosterone. Estradiol is involved in a wide range of brain functions, including neurodevelopment, neuroplasticity, and anti-inflammatory effects, which have implications for emotions. Women with BD are more vulnerable to suffering from depression and an increased risk of affective dysregulation during periods of hormonal fluctuation. The widespread effects of gonadal hormones in the brain and pathophysiology of affective disorders, have become increasingly evident in recent decades. Therefore, to enrich the existing evidence, more and broader potential biomarkers need to be explored. Circulating blood-derived markers related to pathophysiologic processes of BD have been reported to differ among mood episodes, but none have been translated into clinical tests for traits or episodes of BD. Several studies have linked BD with sex hormone fluctuations, stress and inflammatory response. However, the etiology of BD is complex and not fully understood. The disorder results in significant functional impairment and high mortality, imposing a heavy social and economic burden on individuals, families, and countries at large. Globally, over 1% of the population is affected by BD. Our findings not only provide mood episode-related biological markers, but also better support for targeted intervention in BD treatments.īipolar disorder (BD) is a chronic recurrent disorder characterized by mood swings, involving episodes of mania, hypomania, and alternating depression. The biological signatures of mood episodes in BD patients may be sex- and age-specific. 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. 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. 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. 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. A receiver operating characteristic (ROC) curve was used to analyze the discriminatory potential of the biomarkers for mood episodes. 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). All patients were in acute state of mood episodes and need hospitalization. MethodsĪ total of 8332 BD patients (n = 2679 depressive episode n = 5653 manic episode) were included. 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. 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. Bipolar disorder (BD) is characterized by intensive mood fluctuations.
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