Anhedonia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2]


Anhedonia is being studied with variety of neuropsychiatrie disorders. Behavioral, electrophysiological, hemodynamic, and interview-based measures, but the most interesting findings concern neuropharmacological and neuroanatomical studies. The prevalent recognizes key role of dopamine in the pathogenesis of anhedonia, anatomically there is a restricted activity of ventral striatum, including the nucleus accumbens and increased activation of ventral region of the prefrontal cortex, and the ventromedial prefrontal cortex and the orbitofrontal cortex.


  • Feeling a normal emotion requires three steps,
    1. Appraisal: Recognition of emotional importance of a stimulus
    2. Production: Generation of an affective state
    3. Regulation: Management at different levels.

These steps are considered to be organized via two different systems, which have a reciprocal relationship.

  • Activities within the nucleus accumbens, ventral caudate ,ventral putamen correspond to the euphoric response to various stimuli like dextroamphetamine, cocaine, financial gain, music etc. and are related to dopamine release in the ventral caudate and putamen.
  • Ventral striatum and nucleus accumbens employ a major role, in behavioral responses of anticipation and monitoring of errors in the prediction of reward.
  • The nucleus accumbens receives projections basically from four regions:
    1. Midbrain region (ventral tegmental area)
    2. Regions involved in emotion (amygdala, orbitofrontal& prefrontal cortex)
    3. Motor regions (dorsal caudate & globus pallidus)
    4. Regions involved in memory (hippocampus)
  • Furthermore the accumbens also indirectly projects to the regions implicated in emotion processing, namely:
    1. cortical regions.
    2. The cingular and medial prefrontal cortex
    3. The Ventral pallidum
    4. The Thalamus
    5. The Amygdala. &
    6. The hypothalamus


Anhedonia coexists with sleep disturbances, impairment in libido, changes in appetite and weight, and also the sense of satisfaction. There is a disturbance in the dopaminergic system, inflammatory processes, circadian rhythms, and melatonin. Anhedonia seems to be more prevalent in interferon-alpha induced depression than the patients of the major depressive disorder. Animal studies on anhedonia have demonstrated impairment in the cytokines. Also, cathecoalamine dysfunction is more pronounced in anhedonia than depression.[2]

Social anhedonia may represent a prodrome of psychotic disorders.[3]

Sex differences

Males tends to score higher in scoial anhedonia scales than females[4] irrespective of,

  • Age group (from adolescence into adulthood)
  • Co-occurance of the schizophrenia-spectrum disorders[5]

Males with schizophrenia are diagnosed at a younger age, have more severe symptoms, worse treatment outcomes, and a decrease in overall quality of life compared to females with the disorder.[6] More research needs to be done to explore possibility of genetic and hormonal role responsible for difference between males and females, and that may increase risk or resilience for mental illnesses such as schizophrenia.[7]

Genetic components

  • The DISC1 gene implicated in the etiology of schizophrenia-spectrum disorders and other mental illnesses[8], is also found to be associated with social anhedonia within the general population.[9]
  • A specific DISC1 allele associated with an increase in characteristics of social anhedonia, on the contrary another DISC1 allele, preferentially expressed in women, is associated with decreased characteristics of social anhedonia.
  • First-degree relatives of individuals with schizophrenia show elevated levels of social anhedonia,[10]
  • Higher baseline scores of social anhedonia are associated with later development of schizophrenia.[11] These findings provide support for the conjecture that it represents a genetic risk marker for schizophrenia-spectrum disorders.

More research needs to be conducted, but social anhedonia seems to be an important intermediate phenotype between genes associated with risk for schizophrenia and the phenotype of the disorder.

Anhedonia and Other Diseases

Anhedonia is implicated in the pathophysiology of many diseases.

Cardiovascular Diseases

The following findings have been observed in the patients suffering from cariovascular aliments and anhedonia,

  • Increased platelet reactivity
  • Hypercoaguability
  • Inflammatory activation, and endothelial or autonomic dysfunction
  • High catecholamine levels which in turn can trigger tachyarrhythmia, and promote platelet aggregation.

resulting in increased morbidity and mortality due to cardiovascular disease.[12]


  • Increased incedence of anhedonia is seen in the substance abuse, and substance dependance.
  • Anhedonia predicts drug craving attitude and probability of the relapse.
  • Anhedonia diminishes with abstinance.[13]


  • An increase in the hedonic set point is observed in chronic nicotine exposure, leading to a decreased reward potency. There is a increased difficulty to experience pleasure and stronger stimuli is needed to experience pleasure. Thus, over time person requires increased nicotine quantity to achieve similar reward stimulus.
  • In withdrawal, craving for smoking increases to achieve reward stimulus to accommodate hypo-functioning dopamine functioning.[14]


  1. "Neurobiological mechanisms of anhedonia".
  2. "Anhedonia Predicts Major Adverse Cardiac Events and Mortality in Patients 1 Year After Acute Coronary Syndrome".
  3. Silvia, P.J., & Thomas, R.K. (2011). Aberrant asociality: How individual differences in social anhedonia illuminate the need to belong. ‘’Journal of Personality, 79’’.
  4. Fonseca-Pedrero, E., Lemos-Giráldez, S., Muñiz, J., García-Cueto, E., & Campillo-Alvarez, A. (2008). Schizotypy in adolescence: the role of gender and age. The Journal of nervous and mental disease, 196(2), 161–165
  5. Miettunen, J., & Jääskeläinen, E. (2010). Sex differences in Wisconsin Schizotypy Scales--a meta-analysis. Schizophrenia bulletin, 36(2), 347–358
  6. Leung A, Chue P. Sex differences in schizophrenia, a review of the literature. Acta Psychiatr Scand. 2000;101:3–38
  7. Jessen, H. M., & Auger, A. P. (2011). Sex differences in epigenetic mechanisms may underlie risk and resilience for mental health disorders. Epigenetics: official journal of the DNA Methylation Society, 6(7), 857–861
  8. Brandon, Nicholas J, & Sawa, A. (2011). Linking neurodevelopmental and synaptic theories of mental illness through DISC1. Nature reviews. Neuroscience, 12(12), 707–722
  9. Tomppo, L., Hennah, W., Miettunen, J., Järvelin, M.-R., Veijola, J., Ripatti, S., … Ekelund, J. (2009). Association of variants in DISC1 with psychosis-related traits in a large population cohort. Archives of general psychiatry, 66(2), 134–141
  10. Cohen, A.S., Emmerson, L.C., Mann, M.C., Forbes, C.B., & Blanchard, J.J. (2010). Schizotypal, schizoid and paranoid characteristics in the biological parents of social anhedonics. ‘’Psychiatry Research, 178’’, 79-83.
  11. Gooding, D.C., Tallent, K.A., & Matts, C.W. (2005). Clinical status of at-risk individuals five years later: Further validation of the psychometric high-risk strategy. ‘’Journal of Abnormal Psychology, 114’’, 170-175.
  12. "Anhedonia Predicts Major Adverse Cardiac Events and Mortality in Patients 1 Year After Acute Coronary Syndrome".
  13. "Anhedonia in substance use disorders: A systematic review of its nature, course and clinical correlates".
  14. "Effects of anhedonia on days to relapse amo... [Nicotine Tob Res. 2010] - PubMed - NCBI".

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