Search

This paper aimed to find clues to treatment-resistant depression (TRD) solutions. Depression comorbid with anxiety is often treatment-resistant where anxious-depressive attack (ADA) often lurks. ADA is a recently proposed clinical idea for just a psychological version of a panic attack. It mostly begins with an abrupt surge of intense anxiety followed by uninterrupted intrusive thoughts; lasting ruminations about regret or worry produced by violent anxiety, agitation, and loneliness. Acting-out behaviors such as deliberate self-injury and over-dose may also be observed during the attack. As the basic psychopathology of ADA, rejection sensitivity (RS) was revealed by a structural equation model. It is said that the presence of RS in depressive disorders implies a poor prognosis. The following biological markers for RS were reviewed in the literature: first, the involvement of the μ-opioid receptor function in RS and, secondly, hypersensitivity of the dopamine D4 receptor (DRD4) in the medial prefrontal cortex. The latter has been suggested in fear-conditioned animal experiments. Manipulation of the μ-opioid receptor function together with the DRD4 function may culminate in a treatment for RS, which could contribute to the development of a treatment for TRD via the improvement of ADA., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)