For it is then that we have need of pleasure, when we feel pain owing to the absence of pleasure. Epicurus (341–270 B.C.)
Anhedonia is defined as the inability to experience pleasure from activities usually found enjoyable and is a prominent symptom of many neuropsychiatric disorders, most notably major depressive disorder (MDD) and schizophrenia .
Today, however, reward-related deficits experienced by individuals with MDD, schizophrenia and other neuropsychiatric disorders involve more than just an absence or loss of pleasure. Anhedonia is a core feature of reward deficits because the capacity to feel pleasure is a critical step during the normal processing of rewards. However, having the motivation to seek out pleasurable experiences and making appropriate decisions based on those previous experiences are important processes that are equally, if not more in some cases, disturbed in individuals with MDD or schizophrenia. Deficits in these reward processes are often inappropriately labeled under the umbrella of anhedonia.
In the general population, males score higher than females on measures of social anhedonia.This sex difference is stable throughout time (from adolescence into adulthood) and is also seen in people with schizophrenia-spectrum disorders. These results may reflect a more broad pattern of interpersonal and social deficits seen in schizophrenia-spectrum disorders. On average, males with schizophrenia are diagnosed at a younger age, have more severe symptomology, worse treatment prognosis, and a decrease in overall quality of life compared to females with the disorder. These results, coupled with the sex difference seen in social anhedonia, outline the necessity for research on genetic and hormonal characteristics that differ between males and females, and that may increase risk or resilience for mental illnesses such as schizophrenia.
Importantly, the term anhedonia does not adequately capture the complex and multifaceted reward-related deficits observed in neuropsychiatric disorders. Besides the specific loss of an ability to experience pleasure, deficits in other discrete reward-related processes can lead to behaviors that may be interpreted as a loss of interest or pleasure. For example, individuals may lack the ability to: anticipate or predict expected rewards; associate relative values and costs with rewards; determine the effort required to obtain rewards; integrate this information to decide whether it is worthwhile to obtain rewards; or become motivated to perform the necessary actions to obtain rewards.
Anhedonia in clinical populations is primarily defined by subjective responses to self-report questionnaires, these purported measures of anhedonia may also reflect deficits in other reward processes, such as motivation, valuation and decision-making, that are implicitly assessed by these scales. Studies in experimental animals have probed neural markers of these discrete reward processes, and these can be compared with imaging studies of anhedonic humans.
The ventral striatum and orbitofrontal cortex (OFC) contribute to experiences of pleasure. In particular, μ opioid and endocannabinoid receptors in the nucleus accumbens (NAc) and ventral pallidum mediate hedonic perception of rewards, such that activation of these receptors enhances the affective response for highly palatable rewards such as sucrose.
Activation of GABAA receptors in the NAc is also known to regulate the affective response to sucrose.
Activity of the ventral striatum and OFC is decreased in anhedonic individuals with MDD or schizophrenia (The neural correlates of anhedonia in major depressive disorder,2005), although it is debated whether schizophrenia is associated with impaired reward valuation and motivation rather than decreased hedonic capacity.
Investigation of the neurobiological bases of anhedonia has traditionally centered on the neurotransmitter dopamine and the mesolimbic circuit consisting of dopaminergic projections from the ventral tegmental area (VTA) to the ventral striatum, including the NAc. In addition, there are dopaminergic projections from the substantia nigra to areas such as the dorsal striatum, also called caudate putamen. The latter dopaminergic projections may also be involved in anhedonic responses, particularly in individuals suffering from Parkinsonism, which is characterized by gradual degeneration of the substantia nigra dopaminergic projections.
Research in experimental animals indicates that although dopamine does not mediate the perception of pleasure (What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?, 1998), it is associated with prediction or anticipation of and motivation to obtain rewards.
Although administration of addictive drugs that increase synaptic dopamine levels leads to feelings of euphoria in humans, it is unclear if this dopamine release mediates hedonic arousal.
It is well established that dopamine projections from the VTA to the ventral striatum fire in response to unpredicted rewards(Predictive reward signal of dopamine neurons,1998).
Subsequently, dopaminergic neurons fire in response to cues that predict rewards. Thus, it is hypothesized that one role of dopamine is to transfer positive incentive value from the reward to the cue that predicts the reward. Conversely, when predicted rewards are not presented, dopamine firing is blunted. Hence, ventral striatal dopamine regulates the prediction and anticipation of rewards, two mechanisms responsible for basic reinforcement learning.
With regard to motivation, studies have shown that dopamine depletion or antagonists in the NAc of rats decrease responses for large rewards requiring greater effort to obtain, but increase responses for smaller rewards requiring less effort(Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost/benefit procedure.,1994). Similarly, dopamine lesions decreased responses for rewards requiring five, but not one, successive responses; indicating that NAc dopamine is necessary to elicit responses for rewards when the effort required is increased. In human imaging studies, the appearance of food that was unavailable for consumption elicited an increased striatal dopamine response in fasting subjects, which points to a role for dopamine in motivated behavior and anticipation of reward.
The role of dopamine in motivation for food in humans: implications for obesity, 2002
Thus, deficits in dopamine neurotransmission in the ventral striatum may impair reinforcement learning and increase avolition, whereby unconditioned or conditioned rewards fail to stimulate responses to obtain those rewards.
Although distinct neural regions code for separate reward processes, the circuits connecting these regions allow an individual to: sense a pleasant stimulus; compute reward value and associated costs; determine effort requirements to obtain that stimulus; decide to obtain that stimulus; and anticipate and increase motivation to obtain that stimulus. The hedonic perception of rewards is mediated primarily by endogenous opioid, GABA and endocannabinoid systems in the NAc, ventral pallidum and OFC (orbitofrontal cortex).
The OFC and ventral striatum receive inputs from sensory cortices and calculate the reward values. The OFC then projects reward value information to the ACC (anterior cingulate cortex) to incorporate costs, benefits and reinforcement history to determine the effort required for different possible actions.
The ACC sends projections to the anterior vmPFC (ventromedial prefrontal cortex) and dlPFC (dorsolateral prefrontal cortex), which are involved in decision-making based on reward value, effort and reinforcement history regarding future actions.
Glutamatergic efferents relay this information to the NAc (nucleus Accumbens), which receives dopaminergic and glutamatergic inputs from the VTA (ventral tegmental area) and amygdala, respectively; these provide incentive salience properties and increase motivation to carry out the goal-directed action planned in the PFC.
Indeed, there is focus on glutamate because of its putative antidepressant properties. Ketamine, an NMDA receptor antagonist, produces rapid antidepressant effects and it is hypothesized that these are partly mediated by increased glutamatergic signaling via AMPA receptors. In animal studies, disruption of glutamatergic signaling between the mPFC and NAc or administration of an AMPA receptor antagonist in the NAc shell resulted in avolition for rewards.
Desire and dread from the nucleus accumbens: cortical glutamate and subcortical GABA differentially generate motivation and hedonic impact in the rat, 2010
Disruption in any of these circuits can lead to different types of reward deficits. For example, blocking of dopaminergic transmission from the VTA to NAc or glutamate transmission from the vmPFC to NAc each decreased motivation for a large reward.
Serotonin (5-HT) originating from the midbrain raphe nuclei (RN) also regulates reward processing and anhedonic behaviors.
5-HT2C receptors inhibit NAc dopamine release, and antidepressant treatment increases striatal dopamine levels by decreasing 5-HT2C-mediated dopamine inhibition.
Hyperfunctionality of serotonin-2C receptor-mediated inhibition of accumbal dopamine release in an animal model of depression is reversed by antidepressant treatment, 2005.
The lateral habenula (LHb) may also play an important role in reward processes given its reciprocal connections with the VTA and RN. LHb neurons inhibit dopaminergic and 5-HT cells in the VTA and RN, respectively. Consequently, DBS (deep brain stimulation) of the LHb, purported to inhibit LHb activity and disinhibit dopamine and 5-HT activity, has antidepressant effects.
Deep brain stimulation of the lateral habenula in treatment resistant major depression, 2007
|BRAIN AREA||ROLE (in hedonic circuits)||Efferents and neurotransmitters|
|Orbitofrontal cortex||calculate the reward values||ACC, glutamate,excitatory|
|Ventral striatum||calculate the reward values||//|
|Anterior cingulate cortex||determine effort required for different actions||vmPFC, dlPFC, glutamate, excitatory|
|vmPFC and dlPFC:||make deciosn based on reward value, efforts and reinforcments||NAc, glutamate,excitatory|
|Nucleus Accumbens||increase motivation to carry out the goal-directed action||VTA, vmPFC, GABA, excitatory|
|Raphe nuclei||modulate reward processing||VTA, serotonin,inhibitory|
|Lateral habenula||inhibit RN and VTA||VTA, RN, glutamate,inhibitory|
Unfortunately, there is no validated treatment for social anhedonia. Future research should focus on genetic and environmental risk factors to hone in on specific brain regions and neurotransmitters that may be implicated in social anhedonia etiology and could be targeted with specialized pharmacological or behavioral treatments. Social support may also play a valuable role in the treatment of social anhedonia. Therefore, future studies should also examine ways to increase social support among individuals with social anhedonia in order to alleviate some of the symptoms.
Some studies explain how exercise training could help: Molecular aspects involved in swimming exercise training reducing anhedonia in a rat model of depression, 2011
Agomelatine seems usefull: Major depressive disorder, anhedonia and agomelatine: an open-label study,2011
Normally, a human being is able to feel pleasure from an orgasm. Upon reaching a climax, chemicals are released in the brain and motor signals are activated that will cause quick cycles of muscle contraction in the corresponding areas of both males and females. Sometimes, these signals can cause other involuntary muscle contractions such as body movements and vocalization. Finally, during orgasm, upward neural signals go to the cerebral cortex and feelings of intense pleasure are experienced. People who have this disorder are aware of reaching an orgasm, as they can feel the physical effects of it, but they are unable to experience any sort of pleasure.
It is thought that depression, drug addiction, high levels of prolactin, low testosterone, and uses of certain medications might play a role in inhibiting dopamine, released by nucleus acumbens. A spinal cord injury or chronic fatigue syndrome might also occasionally cause this disorder. Age may also be a cause of this disorder.
The focus on neurobiological markers of specific behaviors, rather than entire disorders, has led to significant advances in our understanding of anhedonia and related reward deficits in neuropsychiatric disorders. One advantage for clinical researchers is that preclinical research has provided a wealth of information regarding the neurobiology of reward-related processes, from perceiving pleasure to coding reward value, assessing costs and benefits, learning from prior reinforcement, evaluating effort, and making decisions that lead to action. Each process is regulated by specific neural circuits.
Given what is known about the sophisticated nature of reward deficits in neuropsychiatric disorders, it would be beneficial to limit the term anhedonia to describe only deficits in hedonic capacity and to incorporate additional terms to describe other aspects of reward-related processes that are compromised in neuropsychiatric disorders.