A Systematic Review: Investigating Biomarkers of Anhedonia and Amotivation in Depression and Cannabis Use.

Objective: To assess biological factors associated with anhedonia in depression and amotivation in cannabis use (PROSPERO: CRD42023422438). Method: A systematic review was conducted of 8 electronic databases. Inclusion criteria included original research studies that investigated the association of biological factors or behavioral tasks with depression combined with concepts of anhedonia or cannabis combined with concepts of amotivation including apathy. Results: The review included 44 articles that evaluated biological factors associated with anhedonia in depression and 2 articles that evaluated biological factors associated with amotivation in cannabis use. Overall, anhedonia was operationalized as loss of anticipatory pleasure or consummatory pleasure using a range of measures. No biological factor or behavioral task was consistently associated with anhedonia in depression. Neuroimaging studies encompassed heterogeneous study designs and analytic approaches, with little overlap among findings of brain regions associated with anhedonia. Regions of interest most frequently associated with anhedonia across functional and structural neuroimaging and tasked-based neuroimaging studies included the anterior cingulate cortex, nucleus accumbens, and medial prefrontal cortex. No biochemical marker, including interleukin-6 or C-reactive protein, was consistently associated with anhedonia, and most tested associations between biochemical markers and anhedonia were not significant. Conclusion: Heterogeneous study designs and self-reported assessments of anhedonia have yielded variable findings across the literature. Neuroimaging studies of adolescents with depression and cannabis use reveal similar neurobiological deficits in reward processing. Prospectively examining these deficits may inform developmental pathways that underlie the etiology of these disorders and identify novel treatment targets. Study preregistration information: A systematic review of anhedonia and amotivation in depression and cannabis use; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023422438. Diversity & Inclusion Statement: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list.