07/04/2025
Journal of Case Reports and Reviews in Medicine Research Article Open Access Full Text Article
The Fundamental Role of Oxytocin in The Treatment of Human Depression: Efficacy of Oxytocin in Depressant Patients Less Responsive to The Standard Anti-Depressive Therapies
Paolo Lissoni1, Giusy Messina*2, Diego Ceppodomo*3, Franco Rovelli4, Alejandra Monzon5, Giuseppe Di Fede6
1,4-6Institute of Biological Medicine, Milan, Italy.
2-3*International Institute of PNEI, Milan, Italy.
*Correspondence:
Giusy Messina, International Institute of PNEI, Milan, Italy. Email:
Received: January 01, 2025; Accepted: February 26, 2025; Published: March 07, 2025
How to cite this article: Lissoni P, Messina G, Ceppodomo D, Rovelli F, Monzon A, Di Fede G. The Fundamental Role of Oxytocin in The Treatment of Human Depression: Efficacy of Oxytocin in Depressant Patients Less Responsive to The Standard Anti-Depressive Therapies. J Case Rep Rev Med. 2025;1(1);1-4.
Abstract
The recent advances in Psycho-neuroendocrinology have suggested that depression-related serotonin deficiency is the simple consequence of an enhanced activity of the indole-2,3-dioxygenase (IDO), which transforms tryptophan into kynurenine instead of serotonin. Moreover, kynurenine, in addition to its neurotoxic action, has been proven to play an immunosuppressive activity by activating the regulatory T lymphocytes (T reg). IDO expression is stimulated by IL-17, whose brain production has appeared to be under a regulatory control played by ACE-ACE2 brain system. An enhanced expression of ACE with respect to ACE2 allows an enhance production of angiotensin II (Ang II) instead of angiotensin 1-7 (Ang 1-7). Ang II stimulates IL-17 secretion from glial cells, and IL-17 promotes glial cell release of other inflammatory cytokines, including IL-1beta and IL-6, which finally may activate the pituitary-adrenal axis, with a following enhanced cortisol secretion. On the contrary, Ang 1-7 has appeared to inhibit both IDO expression and IL-17 secretion, with a consequent anti-neuroinflammatory activity. In addition, recent studies have suggested a concomitant depression-related deficiency of oxytocin, which has been proven to play a fundamental role in the regulation of the affective and social relationships. Finally, pineal and endocannabinoid deficiencies have been also observed in depression. On these bases, a preliminary study was performed with oxytocin, the pineal hormones melatonin (MLT) during the night and 5-methoxytryptamine (5-MTT) during the day, low-dose Ang 1-7, and the non-psychotic cannabinol agent, cannabidiol (CBD) in depressant patients less responsive to the standard serotonin therapy. The study included 30 consecutive patients with diagnosis of depression according to Hamilton’s score (HS) (severe grade: 12; moderate grade: 10; low grade: 8), who were less responsive to the classical antidepressant therapy with selective serotonin re-uptake inhibitors (SSRIs). A relatively rapid improvement of mood was achieved within the first moth of therapy in 26/30 (85%), with a complete normalization of HS in 5/30 (20%) patients. No therapy-related toxicity occurred. On the contrary, most patients referred a relief of anxiety and an improvement in the quality of sleep. Moreover, the results were compared to those observed in a historical control group of 20 depressant patients less responsive to SSRIs, who received MAO inhibitors as a second-line therapy. A clear benefit with a decline in HS greater than 30% was achieved in only 5/20 (25%) patients. Then, the results were significantly lower with respect to those found in patients treated with the neuroendocrine regimen. This preliminary study would suggest the possibility to treat the human depression in a new manner other than the classical serotonin therapy, consisting of the exogenous correction of the main possible depression-related neuroendocrine deficiencies involving the pineal function, the cannabinoid system activity, oxytocin secretion, and ACE2-Ang 1-7 axis. Then, further studies by detecting MLT, oxytocin, Ang 1-7 and FAAH, will be required to establish which neuroendocrine deficiency may particularly occur in each single depressant patient.
Keywords: Angiotensin 1-7, Cannabinoids, Depression, IDO, Melatonin, Oxytocin
