Biomarkers and treatments for mood disorders encompassing the neurosteroid and endocannabinoid systems. (10th January 2023)

• Record Type: Journal Article
• Authors: Pinna, Graziano
• 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: 2023-01-10
• Subjects: allopregnanolone -- GABA‐A receptors -- mood disorders -- N‐palmitoyl ethanolamide -- PPAR‐alpha; Neuroendocrinology -- Periodicals; 616.4
• DOI: 10.1111/jne.13226
• Languages: English
• ISSNs: 0953-8194

Abstract

Abstract: Mood disorders, including major depressive disorder, postpartum depression, post‐traumatic stress disorder and suicidality are highly prevalent, associated with a significant economic burden, and remain poorly diagnosed and poorly treated psychiatric conditions. In part, this may result from the lack of biomarkers that can guide precision medicine with individualized treatments for millions of individuals who suffer these debilitating conditions worldwide. While several biomarker candidates have been proposed for mood disorders, none has been implemented in clinical practice and the treatment still relies in the prescription of selective serotonin reuptake inhibitors that shows mixed efficacy and significant side effects. Both neurosteroid biosynthesis and the endocannabinoid system have recently provided evidence for pharmacological targets to improve mood symptoms and the neuroactive steroid allopregnanolone has recently been approved by the USA Food and Drug Administration for the treatment of post‐partum depression. Clinical studies also show efficacy for the management of major depression and more studies are being conducted to study efficacy in post‐traumatic stress disorder. Likewise, the endocannabinoid‐like modulator, N ‐palmioyl ethanolamide (PEA) has shown efficacy in the treatment of major depression and bipolar disorder. While these new agents are coming forward in the field of neuropsychopharmacology as a new generation of fast‐acting antidepressants, the hypothesis of whether their deficits underlying mood disorders could constitute valid predictive biomarkers to facilitate diagnosis and treatment of these conditions is under consideration. Abstract : Allopregnanolone (Allo) and pregnanolone (PA) biosynthesis is altered in mood disorders in a manner that inversely correlates with symptom severity. It is widely recognized that Allo and its equipotent GABAergic isomer, PA pharmacological effects are mediated by the activation of extrasynaptic GABAA receptors mainly expressing α4βδ subunits. Allo neurophysiological role includes fine‐tuning the strength of GABAA receptors, which is believed to constitute the main mechanism by which Allo regulates emotional behavior. Whether fluctuations in neuroactive steroid biosynthesis (levels and neurosteroidogenic enzyme expression/function), changes in GABAA receptor subunit expression as well as altered production of endocannabinoid‐like modulators (e.g., PEA), which have been recently linked to neurosteroidogenesis and affective instability, represent suitable biomarkers for mood disorders is promising but deserves further investigation.