A viewpoint on aldosterone and BMI related brain morphology in relation to treatment outcome in patients with major depression. (20th December 2022)

• Record Type: Journal Article
• Authors: Murck, Harald; Lehr, Lisa; Jezova, Daniela
• Other Names: Panzica GianCarlo guestEditor.; Melcangi Roberto C. guestEditor.
• Is Part Of: Journal of neuroendocrinology. Volume 35:Number 2(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: aldosterone -- autonomic nervous system -- choroid plexus -- lateral ventricle volume -- major depression; Neuroendocrinology -- Periodicals; 616.4
• DOI: 10.1111/jne.13219
• Languages: English
• ISSNs: 0953-8194

Abstract

Abstract: An abundance of knowledge has been collected describing the involvement of neuroendocrine parameters in major depression. The hypothalamic–pituitary–adrenocortical (HPA) axis regulating cortisol release has been extensively studied; however, attempts to target the HPA axis pharmacologically to treat major depression have failed. This review focuses on the importance of the adrenocortical stress hormone aldosterone, which is released by adrenocorticotropic hormone and angiotensin, and the mineralocorticoid receptor (MR) in depression. Depressed patients, in particular those with atypical depression, have signs of central hyperactivation of the aldosterone sensitive MR, potentially as a consequence of a reactive aldosterone release induced by low blood pressure and as a result of low sensitivity of peripheral MR. This is reflected in reduced heart rate variability, increased salt appetite and sleep changes in this group of patients. In addition, enlarged brain ventricles, compressed corpus callosum and changes of the choroid plexus are associated with increased aldosterone (in relation to cortisol). Furthermore, subjects with these features often show obesity. These characteristics are related to a worse antidepressant treatment outcome. Alterations in choroid plexus function as a consequence of increased aldosterone levels, autonomic dysregulation, metabolic changes and/or inflammation may be involved. The characterization of this regulatory system is in its early days but may identify new targets for therapeutic interventions. Abstract : Aldosterone (ALDO) is released by stress through the HPA‐axis and the renin‐angiotensin aldosterone system, which is activated by sympathetic influences. ALDO changes the activity of the nucleus of the solitary tract (NTS). The NTS projects (indirectly) to prefrontal cortical areas involved in behavior and emotian regulation; it also connects to the sympathetic nervous system (SNS). ALDO may act directly at the choroid plexus and lead to ventricular volume increase and consequently white matter compression. The SNS (via the superior cervical ganglion) provides and additional path for choroid plexus regulation and brain perfusion changes. The choroid plexus also releases inflammatory mediators, which act synergistically with aldosterone.