Helping oxytocin deliver: considerations in the development of oxytocin-based therapeutics for brain disorders

Abstract

Concerns regarding a drought in psychopharmacology have risen from many quarters. From one perspective, the wellspring of bedrock medications for anxiety disorders, depression, and schizophrenia was serendipitously discovered over 30 year ago, the swell of pharmaceutical investment in drug discovery has receded, and the pipeline's flow of medications with unique mechanisms of action (i.e., glutamatergic agents, CRF antagonists) has slowed to a trickle. Might oxytocin (OT)-based therapeutics be an oasis? Though a large basic science literature and a slowly increasing number of studies in human diseases support this hope, the bulk of extant OT studies in humans are single-dose studies on normals, and do not directly relate to improvements in human brain-based diseases. Instead, these studies have left us with a field pregnant with therapeutic possibilities, but barren of definitive treatments. In this clinically oriented review, we discuss the extant OT literature with an eye toward helping OT deliver on its promise as a therapeutic agent. To this end, we identify 10 key questions that we believe future OT research should address. From this overview, several conclusions are clear: (1) the OT system represents an extremely promising target for novel CNS drug development; (2) there is a pressing need for rigorous, randomized controlled clinical trials targeting actual patients; and (3) in order to inform the design and execution of these vital trials, we need further translational studies addressing the questions posed in this review. Looking forward, we extend a cautious hope that the next decade of OT research will birth OT-targeted treatments that can truly deliver on this system's therapeutic potential.

Effects of MDMA and Intranasal Oxytocin on Social and Emotional Processing

“…Interestingly, the finding that the lower oxytocin dose produced greater effects on subjective feelings of sociability is consistent with previous studies indicating that the effects of oxytocin are non-linear. It has been suggested that higher doses of oxytocin may block some if its effects because of increased binding with vasopressin receptors (for a review, see MacDonald and Feifel, 2013). Additionally, we found that oxytocin (40 IU) improved emotion recognition only in women.…”

An Oxytocin-Induced Facilitation of Neural and Emotional Responses to Social Touch Correlates Inversely with Autism Traits

“…In the light of evidence indicating lower-than-normal OXT levels in ASDs (Modal et al, 1998), the observed reduction in OXT effects with higher AQ scores in the present study may suggest an ASD-symptom load-dependent dose threshold for OXT to be effective in this population. To date, evidence for an OXT dose-response relationship is still lacking (Macdonald and Feifel, 2013); assuming a linear doseresponse relationship, an almost three-fold higher OXT dose would be required to reach similar effect sizes in our subjects with higher AQ scores (d ¼ 0.15) than in those with lower ones (d ¼ 0.42). For ASD patients, it may therefore be appropriate to adjust the individual OXT dose depending on the autistic symptom load.…”

Oxytocin reactivity during intergroup conflict in wild chimpanzees

“…We achieved this by using peripheral oxytocin measures that could be noninvasively collected. The biological validity of peripheral oxytocin measurements with respect to central oxytocin patterns nonetheless is debated (33)(34)(35). However, an increasing body of evidence shows that oxytocin pathways can involve coordinated central and peripheral oxytocin release, indicating that high peripheral measures reflect the release of central oxytocin.…”