Anhedonia

While anhedonia was originally defined in 1896 by Théodule-Armand Ribot as the reduced ability to experience pleasure, it has been used to refer to deficits in multiple facets of reward. Reconceptualizations of anhedonia highlight the independence of "wanting" and "liking". "Wanting" is a component of anticipatory positive affect, mediating both the motivation (i.e. incentive salience) to engage with reward, as well as the positive emotions associated with anticipating a reward. "Liking", though, is associated with the pleasure derived from consuming a reward. The consciousness of reward-related processes has also been used to categorize reward in the context of anhedonia, as studies comparing implicit behavior versus explicit self-reports demonstrate a dissociation of the two. Learning has also been proposed as an independent facet of reward that may be impaired in conditions associated with anhedonia, but empirical evidence dissociating learning from either "liking" or "wanting" is lacking.

Anhedonia has also been used to refer to "affective blunting", "restricted range of affect", "emotional numbing", and "flat affect", particularly in the context of post-traumatic stress disorder (PTSD). In PTSD patients, scales measuring these symptoms correlate strongly with scales that measure more traditional aspects of anhedonia, supporting this association.

Studies in clinical populations, healthy populations, and animal models have implicated a number of neurobiological substrates in anhedonia. Regions implicated in anhedonia include the prefrontal cortex as a whole, particularly the orbitofrontal cortex (OFC), the striatum, amygdala, anterior cingulate cortex (ACC), hypothalamus, and ventral tegmental area (VTA). Neuroimaging studies in humans have reported that deficits in consummatory aspects of reward are associated with abnormalities in the ventral striatum and medial prefrontal cortex, while deficits in anticipatory aspects of reward are related to abnormalities in hippocampal, dorsal ACC and prefrontal regions. These abnormalities are generally consistent with animal models, except for inconsistent findings with regard to the OFC. This inconsistency may be related to the difficulty in imaging the OFC due to its anatomical location, or the small number of studies performed on anhedonia; a number of studies have reported reduced activity in the OFC in schizophrenia and major depression, as well as a direct relationship between reduced activity and anhedonia. Researchers theorize that anhedonia may result from the breakdown in the brain's reward system, involving the neurotransmitter dopamine. Anhedonia can be characterised as "impaired ability to pursue, experience or learn about pleasure, which is often, but not always accessible to conscious awareness".

The conditions of akinetic mutism and negative symptoms are closely related. In akinetic mutism, a stroke or other lesion to the anterior cingulate cortex causes reduction in movement (akinetic) and speech (mutism).

Anhedonia occurs in roughly 70% of people with a major depressive disorder. It is a core symptom of major depressive disorder, so individuals experiencing this symptom can be diagnosed with depression, even in the absence of low/depressed mood. The Diagnostic and Statistical Manual of Mental Disorders (DSM) describes a "lack of interest or pleasure", but these can be difficult to discern given that people tend to become less interested in things that do not give them pleasure. The DSM criterion of weight loss is probably related, and many individuals with this symptom describe a lack of enjoyment of food. They can portray any of the non-psychotic symptoms and signs of depression.

Anhedonia is one of the negative symptoms of schizophrenia. Although five domains are usually used to classify negative symptoms, factor analysis of questionnaires yield two factors, with one including deficits in pleasure and motivation. People with schizophrenia retrospectively report experiencing fewer positive emotions than healthy individuals, but "liking" or consummatory pleasure is intact in people with schizophrenia, as they report experiencing the same degree of positive affect when presented with rewarding stimuli. Neuroimaging studies support this behavioral observation, as most studies report intact responses in the reward system (i.e. ventral striatum, VTA) to simple rewards. However, studies on monetary rewards sometimes report reduced responsiveness. More consistent reductions are observed with regard to emotional response during reward anticipation, which is reflected in a reduced responsiveness of both cortical and subcortical components of the reward system. Schizophrenia is associated with reduced positive prediction errors (a normal pattern of response to an unexpected reward), which a few studies have demonstrated to be correlated with negative symptoms. People with schizophrenia demonstrate impairment in reinforcement learning tasks only when the task requires explicit learning, or is sufficiently complex. Implicit reinforcement learning, on the other hand, is relatively intact. These deficits may be related to dysfunction in the ACC, OFC and dlPFC leading to abnormal representation of reward and goals.

Anhedonia is common in people who are dependent upon any one or more of a wide variety of drugs, including alcohol, opioids, cannabinoids, and nicotine. …

In a meta-analysis conducted in 2023, anhedonia was found to be a risk factor for suicidal behaviors. In another research article, a robust association was found between anhedonia and suicidal ideation, independently of depression.

The anhedonia experienced by individuals with major depressive disorder (MDD) has been difficult to treat using traditional pharmacotherapies, including dopaminergic therapies. A network meta-analysis published in 2024 revealed that pro-dopaminergic strategies, including bupropion, resulted in small improvements in anhedonia symptoms, with confidence intervals suggesting the possibility of non-response. Non-dopaminergic antidepressants showed comparatively larger effects, suggesting that anhedonia may not respond robustly to dopamine-targeted therapies alone.

A 2024 meta-analysis suggested that ketamine may exert anti-anhedonic effects in patients experiencing depressive episodes amid unipolar or bipolar affective disorders. Supporting neuroimaging evidence highlights ketamine's influence on neuroplasticity, evidenced by changes in functional connectivity that align with improvements in anhedonia symptoms. A systematic review conducted in 2021 suggested improvement in suicidal ideation and anhedonia after ketamine infusion for bipolar depression.

In a meta-analysis conducted in 2019, minocycline reduced both immobility and anhedonia-related outcomes, indicating its potential as an effective treatment for core depressive symptoms.

Amantadine has shown potential to reduce anhedonia through preclinical studies demonstrating its antidepressant-like effects. In animal models like chronic unpredictable mild stress (CUMS), amantadine reversed reductions in sucrose preference (an indicator of anhedonia) by modulating glutamatergic systems via NMDA receptor antagonism and enhancing synaptic plasticity through increased BDNF expression. Additionally, in traumatic brain injury models inducing depressive behaviors, it preserved dopamine levels and boosted sucrose intake, suggesting dopaminergic mechanisms contribute to alleviating anhedonia. While clinical trials support amantadine's role in improving overall depressive symptoms, often as an adjunct to antidepressants.

Sirukumab, a monoclonal antibody targeting interleukin-6 (IL-6), may reduce anhedonia in major depressive disorder (MDD) by modulating inflammatory pathways linked to reward and hedonic processes. …