A study of people with major depression (who weren’t on meds) found they had higher blood levels of oxytocin and lower ability to understand others' thoughts (cognitive empathy) compared to healthy folks. The link between oxytocin and empathy was weak, and the research didn’t test any treatments, just measured natural levels.

Major depressive disorder (MDD) is a common disorder influenced by biopsychosocial factors. There is conflicting and insufficient evidence regarding the role of neuropeptides such as Orexin-A and Oxytocin (OCT) and its association with empathy in MDD. This study aimed to address this question which is not only important for a better neurobiological understanding but could also lead to novel biomarkers. Sixty-nine antidepressant-free patients (48 females, 21 males) diagnosed with MDD according to DSM-5 criteria and 32&#xa0;healthy controls (19 females, 13 males) were included. Serum Orexin-A and OCT levels were measured, and empathy and depression were assessed using the Basic Empathy Scale and the Hamilton Depression Rating Scale. Patients showed lower cognitive empathy than controls (Z&#x2009;=&#x2009;4.161, <i>p</i>&#x2009;&lt;&#x2009;0.001), with significant differences only in females. Emotional and total empathy scores did not differ between groups. Patients had higher serum OCT levels (Z&#x2009;=&#x2009;1.989, <i>p</i>&#x2009;=&#x2009;0.047), while Orexin-A levels showed no clear group differences. Longer illness duration and more depressive episodes were modestly associated with higher emotional and total empathy. OCT levels showed a weak positive association with cognitive empathy. Lower cognitive empathy and elevated OCT levels may relate to depressive pathology, but further studies are needed to clarify these relationships.