From Stress to Anhedonia: Molecular Processes through Functional Circuits

Abstract

Converging evidence across species highlights the contribution of environmental stress to anhedonia (loss of pleasure and/or motivation). However, despite a clear link between stress and the emergence of anhedonic-like behavior in both human and animal models, the underlying biological pathways remain elusive. Here, we synthesize recent findings across multiple levels, from molecular signaling pathways through whole-brain networks, to discuss mechanisms through which stress may influence anhedonia. Recent work suggests the involvement of diverse systems that converge on the mesolimbic reward pathway, including medial-prefrontal cortical circuitry, neuroendocrine stress responses, homeostatic energy regulation systems, and inflammation. We conclude by emphasizing the need to disentangle the influences of key dimensions of stress on specific aspects of reward processing, taking into account individual differences that could moderate this relationship.

Associations of neural processing of reward with posttraumatic stress disorder and secondary psychotic symptoms in trauma-affected refugees

“…However, this is not surprising, as similar psychopathology across psychiatric conditions is likely to share neuropathogenic mechanisms (Insel et al, 2010). In this vein, it is interesting to consider systemic inflammation as a mediating link between anhedonia and diminished prefrontal activity across psychiatric conditions (Bauer & Teixeira, 2019;Freed et al, 2018;Stanton, Holmes, Chang, & Joormann, 2019). In this regard, anti-inflammatory treatment might be promising in treating anhedonia in some PTSD patients, as preliminary studies have shown it to be efficient in treating subgroups of patients with depression and schizophrenia (Khandaker et al, 2015;Miller & Raison, 2016).…”

“…Since trauma exposure has been associated with reward processing deficits irrespective of a PTSD diagnosis (Stanton et al, 2019), use of trauma-affected healthy controls (though less affected than the PTSD participants) in this study may conceal any potential effects of the traumatic events per se. Therefore, the results are likely to primarily concern changes in neural activation either related to having experienced multiple traumas and/or the transition from being traumaaffected to developing PTSD.…”

Can Understanding Reward Help Illuminate Anhedonia?

“…There are many theories as to what might cause anhedonia, such as stress [18,19], genetic variations [20••], and dysfunction in brain activity [21,22]. The brain's response to reward during depression is of interest in relation to understanding the causes of anhedonia [23] as it is thought that anhedonia comes about by dysfunctional reward mechanisms in the brain [24].…”

“…It is suggested that stress can disrupt reward processing [19], and preclinical work shows that physical stress (e.g. foot shock) decreases consummatory behaviour in rats (decreased saccharine consumption) [42] and exploratory behaviour [43,44].…”

“…They found that as activation in the VS of individuals exposed to early life stress (ELS) decreased, the risk for anhedonia increased [47]. However, the authors point out that more work needs to be done to elucidate the relationship between stress and anhedonia in more detail; for example, it is not known which types of stress lead to changes in motivation and reward processing at the molecular and neural levels [19]. Further studies in humans have found that ELS is associated with reward dysfunction, as evidenced by blunted activation during both reward anticipation in the dorsal striatum [48,49] and reward receipt in the ventral striatum [50][51][52].…”