Characterizing anhedonia: A systematic review of neuroimaging across the subtypes of reward processing deficits in depression

Abstract

Anhedonia is a key symptom of major depressive disorder (MDD) and comprises behavioural deficits in three reward processing subtypes: reward liking, reward wanting, and reward learning. However, neuroimaging findings regarding the neural abnormalities underpinning these deficits are complex. We have conducted a systematic review to update, reframe and summarize neuroimaging findings across the three subtypes of anhedonia in MDD. Using PubMed, The Cochrane Library, PsycINFO, and Web of Science databases, we identified 59 fMRI studies comparing participants with current or remitted MDD with controls, using reward processing tasks. For reward liking and wanting, striatal hypoactivation was observed, alongside hypoactivation and hyperactivation across frontal regions. For reward learning, blunted frontostriatal sensitivity to positive feedback was observed. These findings highlight the importance of studying anhedonia not only as a clinical manifestation but also as a neurobiological mechanism underlying depressive disorder and other broader psychiatric conditions. Keywords Anhedonia. Depression. Neuroimaging. fMRI. Reward processing Major depressive disorder (MDD) is both common, with a lifetime prevalence of 16.6% in the USA (Kessler, Petukhova, Sampson, Zaslavsky, & Wittchen, 2012), and consequential, being the second leading contributor to global years lived with disability (YLDs) worldwide (Ferrari et al., 2013). Anhedonia is one of two key symptoms required for a diagnosis of MDD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5; American Psychiatric Association, 2013), and is defined as 'markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day' (American Psychiatric Association, 2013), and so represents a deficit in reward processing. In a study examining the factor structure for DSM-IV, MDD symptoms in a sample 2,615 army recruits, the best fit for the data indicated that MDD consisted of both a somatic and nonsomatic component (Elhai et al., 2012), and anhedonia had the second highest factor weighting (Beta = 0.76) for the nonsomatic component (after depressed mood), as well as the second highest factor weighting of all symptoms (Elhai et al., 2012). This suggests that anhedonia is a core feature of depression. Anhedonia is a symptom which warrants attention; indeed, reward processing deficits are associated with increased risk of new onset MDD (Rawal, Collishaw, Thapar, & Rice, 2013), anhedonia may precede illness onset, and, moreover, it can often persist past the remission of other depressive symptoms (Schrader, 1997), as do deficits on reward processing tasks (Pechtel, Dutra, Goetz, & Pizzagalli, 2013). Three subtypes of anhedonia In DSM-5, anhedonia comprises deficits in hedonic experience of rewards and motivation for rewards (American Psychiatric Association, 2013). However, reviews have called for research to conceptualize anhedonia as comprising deficits across three partially separable subtypes of reward processing:

Human Fronto-Striatal Connectivity is Organized into Discrete Functional Subnetworks

“…The integrity of cortico-striatal connectivity is critical for healthy brain function, as its disruption causes devastating neurological and psychiatric symptoms in disorders such as Parkinson's and Huntington's disease (Blumenstock and Dudanova, 2020;Bunner and Rebec, 2016). Even relatively minor alterations in cortico-striatal circuitry are thought to play a major role in symptoms observed in Tourette syndrome (Greene et al, 2017;Mink, 2001), schizophrenia (Simpson et al, 2010), obsessive-compulsive disorder (Harrison et al, 2009), depression (Borsini et al, 2020), and autism (Li and Pozzo-Miller, 2019). However, cortico-striatal circuits are some of the least well-understood pathways in the human brain, as their striatal elements are small and exceedingly difficult to dissociate from each other using non-invasive imaging.…”

Increased Functional Coupling between VTA and Hippocampus during Rest in First-Episode Psychosis

“…Reduced VTA-NAcc connectivity has also been shown during resting state in psychosis-related populations with general severity of symptoms (Nakamura et al, 2020), as well as during salience detection in CHR (Modinos et al, 2020). Connectivity between the VTA and NAcc is known to be critical for initiating and maintaining goal-oriented behavior (Shohamy and Adcock, 2010;Ballard et al, 2011;Berridge, 2012;Wise and Robble, 2020) and alterations in NAcc engagement has been associated with symptoms of anhedonia (Lee et al, 2015;Zhang et al, 2016;Barkus and Badcock, 2019;Borsini et al, 2020), which are prominent in psychosis (Kirkpatrick and Buchanan, 1990;Strauss and Gold, 2012). Together, these findings suggest that psychosis is associated with increased functional coupling between the VTA and hippocampus, and decreased functional coupling between the VTA and striatum.…”

Kognitive Neurowissenschaft der psychischen Resilienz

“…Funktionelle Veränderungen des Belohnungssystems sind bei verschiedenen psychiatrischen Störungsbildern beschrieben [67][68][69][70][71][72]. Bei Suchterkrankungen kommt es in frühen Stadien zu einer Übersensitivierung des Assoziationssystems für Belohnungsanrei ze, was mit exzessivem "Wollen" einhergeht [66].…”

“…Bei Suchterkrankungen kommt es in frühen Stadien zu einer Übersensitivierung des Assoziationssystems für Belohnungsanrei ze, was mit exzessivem "Wollen" einhergeht [66]. Bei Anhedonie, also der gestörten Fähigkeit Genuss anzustreben und zu erleben, ist während der Antizipation und Verarbeitung von Belohnung die striatale Reaktion verringert und die präfrontale Aktivierung er höht, und beim Belohnungslernen die fronto-striatale Sensitivi tät verringert [68,72]. Neurowissenschaftliche Experimente zei gen, dass eine positive Erwartungshaltung erfolgreich trainiert wer den und gegen Depression helfen bzw.…”