Year 2021
September 2021


Abstract Title
A systematic review on the association between endogenous opioid neural pathways and negative symptoms



National University of Singapore1, Institute of Mental Health2 

Background & Hypothesis

Negative symptoms consisting of avolition-apathy and diminished expressivity are unmet treatment needs in psychiatry. Opioid systems in humans mediate reward processing pathways and produce euphoria, overlapping with negative symptom behavior. This review aimed to examine the association between the endogenous opioid system and negative symptoms in humans, highlighting whether these are viable targets for future intervention.


A systematic search was conducted via a database search of PubMed, Embase and PsychInfo. After reviewing the papers found, 10 articles that met the inclusion and exclusion criteria were included in this review. The opioid systems mentioned in each were explored, as well as their relation to the experience of negative symptoms.


Most of the studies provided information about the kappa-opioid receptors (KOR) and Mu-opioid receptors (MOR) systems, but there was limited information on the Delta-opioid receptors (DOR) system. The KOR system is primarily seen to produce dysphoria and negative symptoms such as anhedonia when dynorphin stimulation is increased. Simultaneously, hypocretin stimulation within the KOR system helps to modulate mood and attention. The MOR system on the other hand seems to promote more ‘orexigenic effects’ and helps to modulate the perception of reward when it is upregulated.

Discussion & Conclusion

The limited available evidence suggested that the KOR system is more involved in the production of negative symptoms, while the MOR system seeks to attenuate them and provide motivation through reward perception. More studies are needed to understand the association between endogenous opioids and negative symptoms in human beings.