Trends in Neurosciences
ReviewSpecial Issue: Neuropsychiatric DisordersThe neurobiology of anhedonia and other reward-related deficits
Introduction
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.) [1]
Anhedonia, or loss of interest or pleasure in all or almost all activities, is a prominent symptom of many neuropsychiatric disorders, most notably major depressive disorder (MDD) and schizophrenia (see Glossary) [2]. Greek philosophers, such as Epicurus, contemplated the nature of pleasure (and the absence of pleasure) over 2000 years ago. 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. The current preclinical and clinical literature regarding the neural bases of the various aspects of reward processing, and the contribution of deficits in these reward processes to the clinical symptom of anhedonia, is reviewed here.
Section snippets
A brief history of anhedonia
Anhedonia as a psychopathological symptom was first noted in the early 19th century. Haslam, who documented the first complete study of a psychiatric patient in 1809 (suffering from schizophrenia), noted a ‘neglect [of] those objects and pursuits which formerly proved sources of delight and instruction’ [3]. The term anhedonie was later introduced by the French psychologist Ribot in 1896 to describe the counterpart to analgesia in his patients, for whom ‘it was impossible to find the least
Reward deficits beyond anhedonia
There are numerous published studies documenting the neurobiological changes associated with MDD, schizophrenia and other neuropsychiatric disorders characterized by anhedonia, but relatively few that specifically examined the presence or severity of anhedonia. Considering that MDD and schizophrenia are characterized by various symptoms, it is unlikely that the neural circuits mediating anhedonia are also involved in, for example, hallucinations or feelings of guilt. Thus, it is challenging to
Assessments of anhedonia in humans and experimental animals
Traditional subjective self-report measures of anhedonia assess the ability to experience pleasurable events. In these assessments, individuals respond to statements such as ‘I would enjoy being with my family or close friends’ [Snaith-Hamilton Pleasure Scale (SHAPS)]. The preclinical analogs to these anhedonia scales, and the procedures most commonly used to assess depression-like behavior in rodents, are the sucrose intake and preference tests, whereby decreased intake of or preference for a
Dissecting the circuits of anhedonia and other reward-related deficits
The majority of studies in humans to assess the neurobiology of anhedonia have involved MDD or schizophrenia patients, although we could extrapolate that the same circuits are likely to be involved in anhedonia exhibited in other neuropsychiatric disorders, such as PD and AD. Although 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
Constructing the circuits for anhedonia, anticipation, valuation, decision-making and avolition
Although distinct neural regions code for separate reward processes, the circuits connecting these regions allow an individual to: (i) sense a pleasant stimulus; (ii) compute reward value and associated costs; (iii) determine effort requirements to obtain that stimulus; (iv) decide to obtain that stimulus; and (v) anticipate and increase motivation to obtain that stimulus (Figure 2). The hedonic perception of rewards is mediated primarily by endogenous opioid, GABA and endocannabinoid systems
Concluding remarks and future considerations
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,
Disclosure statement
A.M. has received contract research support from Lundbeck, Bristol-Myers Squibb Co., F. Hoffman-La Roche, Pfizer, and Astra-Zeneca, and honoraria/consulting fees from Abbott GmbH and Company, AstraZeneca, and Pfizer during the past 3 years. A.M. has a patent application on the use of metabotropic glutamate compounds for the treatment of nicotine dependence.
Acknowledgments
This work was supported by National Institutes of Health grants R01MH62527 and R01MH087989 (to A.M.), and a National Research Service Award Individual Postdoctoral fellowship F32MH080585 (to A.D.) from the National Institute of Mental Health. The authors would like to thank Ms. Janet Hightower for her assistance with graphics.
Glossary
- Anhedonia
- markedly diminished interest or pleasure in all, or almost all, activities
- Avolition
- a reduction or difficulty in the ability to initiate and persist in goal-directed behavior; lack of motivation.
- Chapman Physical and Social Anhedonia Scales (CPAS/CSAS)
- self-report anhedonia scales that differentiate between physical (eating, sex) and social (expressing feelings and interacting with people) pleasures.
- Deep brain stimulation (DBS)
- clinical procedure involving surgical implantation of
References (132)
Neurobiological similarities in depression and drug dependence: a self-medication hypothesis
Neuropsychopharmacology
(1998)- et al.
Sensitivity to the rewarding effects of food and exercise in the eating disorders
Compr. Psychiatry
(2002) Psychiatric genetics: search for phenotypes
Trends Neurosci.
(1998)Sucrose consumption as an hedonic measure following chronic unpredictable mild stress
Physiol. Behav.
(1995)Measures of anhedonia and hedonic responses to sucrose in depressive and schizophrenic patients in comparison with healthy subjects
Eur. Psychiatry
(1998)Opioid modulation of taste hedonics within the ventral striatum
Physiol. Behav.
(2002)The neural correlates of anhedonia in major depressive disorder
Biol. Psychiatry
(2005)Functional neural substrates of self-reported physical anhedonia in non-clinical individuals and in patients with schizophrenia
J. Psychiatr. Res.
(2010)Medial prefrontal default-mode hypoactivity affecting trait physical anhedonia in schizophrenia
Psychiatry Res.
(2009)The role of the nucleus accumbens and rostral anterior cingulate cortex in anhedonia: integration of resting EEG, fMRI, and volumetric techniques
Neuroimage
(2009)
Regional prefrontal cortex gray matter volumes in youth at familial risk for schizophrenia from the Harvard Adolescent High Risk Study
Schizophr. Res.
Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males
Drug Alcohol Depend.
Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response
Biol. Psychiatry
Deep brain stimulation for treatment-resistant depression
Neuron
Value, pleasure and choice in the ventral prefrontal cortex
Trends Cogn. Sci.
Anhedonia and emotional experience in schizophrenia: neural and behavioral indicators
Biol. Psychiatry
What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?
Brain Res. Brain Res. Rev.
Neural mechanisms of acquired phasic dopamine responses in learning
Neurosci. Biobehav. Rev.
Anhedonia or anergia? Effects of haloperidol and nucleus accumbens dopamine depletion on instrumental response selection in a T-maze cost/benefit procedure
Behav. Brain Res.
Nucleus accumbens dopamine and work requirements on interval schedules
Behav. Brain Res.
Beyond the reward hypothesis: alternative functions of nucleus accumbens dopamine
Curr. Opin. Pharmacol.
Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration
Brain Res.
Fluoxetine combined with a serotonin-1A receptor antagonist reversed reward deficits observed during nicotine and amphetamine withdrawal in rats
Neuropsychopharmacology
Withdrawal from chronic cocaine administration induces deficits in brain reward function in C57BL/6J mice
Behav. Brain Res.
Increased successive negative contrast in rats withdrawn from an escalating-dose schedule of d-amphetamine
Pharmacol. Biochem. Behav.
Neurochemical and behavioral effects elicited by bupropion and diethylpropion in rats
Behav. Brain Res.
Acute effect of the anti-addiction drug bupropion on extracellular dopamine concentrations in the human striatum: an [11C]raclopride PET study
Neuroimage
Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression
Biol. Psychiatry
Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression
Biol. Psychiatry
Parallel incentive processing: an integrated view of amygdala function
Trends Neurosci.
The amygdala, reward and emotion
Trends Cogn. Sci.
Glutamate-based antidepressants: 20 years on
Trends Pharmacol. Sci.
Antidepressant effects of ketamine in depressed patients
Biol. Psychiatry
Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid acting agents
Trends Neurosci.
Interactive effects of the mGlu5 receptor antagonist MPEP and the mGlu2/3 receptor antagonist LY341495 on nicotine self-administration and reward deficits associated with nicotine withdrawal in rats
Eur. J. Pharmacol.
Two-week administration of the combined serotonin–noradrenaline reuptake inhibitor duloxetine augments functioning of mesolimbic incentive processing circuits
Biol. Psychiatry
Chronic agomelatine and fluoxetine induce antidepressant-like effects in H/Rouen mice, a genetic mouse model of depression
Pharmacol. Biochem. Behav.
Hyperfunctionality of serotonin-2C receptor-mediated inhibition of accumbal dopamine release in an animal model of depression is reversed by antidepressant treatment
Neuropharmacology
Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient
Biol. Psychiatry
The hidden island of addiction: the insula
Trends Neurosci.
The neurobiology of decision: consensus and controversy
Neuron
Epicurus, The Extant Remains
Diagnostic and Statistical Manual of Mental Disorders: DSM-IV
Observations on Madness and Melancholy; Including Practical Remarks on those Diseases, together with Cases, and an Account of the Morbid Appearances on Dissection
La Psychologie des Sentiments
Psychoanalysis of Behavior; Collected Papers
Schizotaxia, schizotypy, schizophrenia
Am. Psychol.
Scales for physical and social anhedonia
J. Abnorm. Psychol.
Endogenomorphic depression. A conceptual and terminological revision
Arch. Gen. Psychiatry
Diagnostic and Statistical Manual of Mental Disorders
Cited by (721)
Construction of a depression risk prediction model for type 2 diabetes mellitus patients based on NHANES 2007–2014
2024, Journal of Affective DisordersBehavioral, neurochemical and neuroimmune features of RasGEF1b deficient mice
2024, Progress in Neuro-Psychopharmacology and Biological PsychiatryIncreased brain nucleus accumbens functional connectivity in melancholic depression
2024, NeuropharmacologyNeural reward responsiveness and daily positive affect functioning in adolescent girls
2024, International Journal of Psychophysiology