Love in the Time of COVID: Psychiatric Outcomes Related to Oxytocin and the “Endocrine Organ”

The COVID-19 pandemic was an eye-opener for many medical disciplines. It highlighted viral exploitation of physiological cellular processes, including endocytosis and cellular senescence. These pathways play an essential role in cancer, neurodegenerative disorders, and schizophrenia (SCZ). Oxytocin, commonly called the “love hormone,” is produced in the posterior hypothalamus and is crucial for various physiological processes, including social intelligence, sexual activity, and metabolism. Many viruses, including SARS-CoV-2, have been shown to inhibit the release of oxytocin from intestinal epithelial cells, thus hastening gut barrier senescence. Premature molecular aging at this level enables microbial migration outside the intestinal lumen, triggering inflammation and immunogenicity. The gut microbial community is immunologically tolerated within the gastrointestinal tract but can activate host immunity upon translocation. Immune responses to displaced commensals and/or their components may contribute to neuroinflammation and gray matter volume reduction, a hallmark of severe mental illness. Oxytocin opposes microbial translocation into the systemic circulation through several mechanisms, including anti-inflammatory, tight junctions-upregulation, and suppression of senescence-associated secretory phenotype—the toxic secretome produced by senescent cells. <i>Limosilactobacillus reuterii,</i> a commensal microbe known for producing oxytocin, shows antiviral and anti-translocation effects, implying a beneficial role in schizophrenia. This condition has been linked to a dysfunctional gut barrier and increased microbial migration outside the intestinal lumen, suggesting that oxytocin replacement therapy could benefit patients with this mental illness. This review article summarizes the current understanding of oxytocin's role in schizophrenia and discusses natural and synthetic compounds that promote gut barrier homeostasis.