Anhedonia and Depressive Disorders

Abstract

Anhedonia is a core symptom of depression and of several psychiatric disorders. Anhedonia has however expanded from its original definition to encompass a spectrum of reward processing deficits that received much interest in the last decades. It is a relevant risk factor for possible suicidal behaviors, and that it may operate as an independent risk factor for suicidality apart from the episode severity. Anhedonia has also been linked to inflammation with a possible reciprocal deleterious effect on depression. Its neurophysiological bases mainly include alterations in striatal and prefrontal areas, with dopamine being the most involved neurotransmitter. Anhedonia is thought to have a significant genetic component and polygenic risk scores are a possible tool for predicting an individual’s risk for developing anhedonia. Traditional antidepressants, such as selective serotonin reuptake inhibitors, showed a limited benefit on anhedonia, also considering their potential pro-anhedonic effect in some subjects. Other treatments may be more effective in treating anhedonia, such as agomelatine, vortioxetine, ketamine and transcranial magnetic stimulation. Psychotherapy is also widely supported, with cognitive-behavioral therapy and behavioral activation both showing benefit. In conclusion, a large body of evidence suggests that anhedonia is, at least partially, independent from depression, therefore it needs careful assessment and targeted treatment.

The role of IL-6 in dopamine dysregulation underlying anhedonia phenotype in rats

“…Anhedonia is a DA-dependent behaviour and a core feature for depression disorders. In both animal models and depressive patients, the most relevant biological mechanism of anhedonia is the ventral striatal hypoactivation, but dysfunctions in prefrontal cortex also play an important role in abnormal reward processing and impaired reward-related decision making [30]. In addition to changes in behavioural phenotype, our results demonstrated that chronic ACTH injection decreased TH levels in NAcS and ILC.…”

Effect of venlafaxine on anhedonia and amotivation in patients with major depressive disorder

“…21,22 Both pharmacological and non-pharmacological treatment approaches have been evaluated for treating anhedonia. 23,24 Selective serotonin reuptake inhibitors (SSRIs) are frequently used as first-line agents in the management of MDD. 25,26 They have been shown to have a more pronounced role in reducing the negative affect compared to their role in improving the positive affect or ability of pleasure (ie, improving reward processing and motivation).…”

“…Sertraline and fluoxetine, which interact with the dopaminergic system, are reported to be somewhat effective in improving anhedonia. 24 Overall, SSRIs may be of limited clinical utility in the management of anhedonia and amotivation. 12,[26][27][28] A few studies on serotonin-norepinephrine reuptake inhibitors (SNRIs) have reported that they may have a role in improving these symptoms in patients with MDD.…”

“…12,28,30,31 Other antidepressants that have been reported to be beneficial in improving anhedonia are bupropion, either alone or in combination with dextromethorphan, agomelatine, and vortioxetine. 24 Ketamine, with a faster onset of action, may have a rapid anti-anhedonic effect. 24 Other classes of drugs which have been evaluated include stimulants such as methylphenidate.…”

“…24 Ketamine, with a faster onset of action, may have a rapid anti-anhedonic effect. 24 Other classes of drugs which have been evaluated include stimulants such as methylphenidate. An RCT reported its beneficial effect on anhedonia when concomitantly used with an antidepressant.…”