IJCM  Vol.3 No.7 , December 2012
Anhedonia and Reward System: Psychobiology, Evaluation, and Clinical Features

Anhedonia can be defined as a condition in which the hedonic capacity is totally or partially lost. From a psychobiological perspective, several researchers proposed that anhedonia has a putative neural substrate, the dopaminergic mesolimbic and mesocortical reward circuit, which involves the ventral tegmental area, the ventral striatum and part of the prefrontal cortex. Anhedonia is, besides depressed mood, one of the two core symptoms of depression; furthermore it is one of the most important negative symptom in schizophrenia. Anhedonia is also present in substance use disorders as part of the abstinence symptomatology, and interrelations between hedonic capability, craving and protracted withdrawal have been found, particularly in opiate-dependent subjects. Although anhedonia is regarded as an important symptom in psychopathology, so far it has received relatively little attention. In general, two main approaches have been utilized to investigate and assess anhedonia or hedonic capacity: laboratory-based measures and questionnaires. Among measurement scales, the most commonly used are the Snaith-Hamilton Pleasure Scale (SHAPS), the Fawcett-Clark Pleasure Scale (FCPS), and the Revised Chapman Physical Anhedonia Scale (CPAS). Nevertheless, other measurement scales, particularly used within broader psychopathological dimensions, are the Anhedonia-Asociality subscale (SANSanh) of the Scale for the Assessment of Negative Symptoms (SANS) and the Bech-Rafaelsen Melancholia Scale (BRMS). In this paper we analyze these different scales, individuating their strengths and limits and their current clinical applications.

Cite this paper
G. Martinotti, D. Hatzigiakoumis, O. Vita, M. Clerici, F. Petruccelli, M. Giannantonio and L. Janiri, "Anhedonia and Reward System: Psychobiology, Evaluation, and Clinical Features," International Journal of Clinical Medicine, Vol. 3 No. 7, 2012, pp. 697-713. doi: 10.4236/ijcm.2012.37125.
[1]   T. Ribot, “La Psychologie Des Sentiments, ” Felix Alcan, Paris, 1896.

[2]   G. Loas and A. Pierson, “Anhedonia in Psychiatry: A Review,” Annales Medico-Psychologiques, Vol. 147, No. 7, 1989, pp. 705-717.

[3]   American Psychiatric Association, “Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition, Text Revision (DSM-IV-TR),” American Psychiatric Press, Washington DC, 2000.

[4]   D. Klein, “Endogenomorphic Depression. A Conceptual and Terminological Revision,” Archives of General Psychiatry, Vol. 31, No. 4, 1974, pp. 447-454. doi:10.1001/archpsyc.1974.01760160005001

[5]   D. Klein, “Depression and Anhedonia,” In: C. Clark and J. Fawcett, Eds., Anhedonia and Affect Deficit States, PMA Publishing, New York, 1984, pp. 1-14.

[6]   G. Loas, J. M. Perot, P. Hardy and R. Jouvent, “Physical Anhedonia and Subtypes of Major Depressive Disorder,” European Psychiatry, Vol. 9, 1994, pp. 304-306.

[7]   G. D. Schrader, “Does Anhedonia Correlate with Depression Severity in Chronic Depression?” Comprehensive Psychiatry, Vol. 38, No. 5, 1997, pp. 260-263. doi:10.1016/S0010-440X(97)90057-2

[8]   N. C. Andreasen, “Negative Symptoms in Schizophrenia: Definition and Reliability,” Archives of General Psychiatry, Vol. 39, No. 7, 1982, pp. 784-788. doi:10.1001/archpsyc.1982.04290070020005

[9]   J. J. Blanchard, W. P. Horan and S. A. Brown, “Diagnostic Differences in Social Anhedonia: A Longitudinal Study of Schizophrenia and Major Depressive Disorder,” Journal of Abnormal Psychology, Vol. 110, No. 3, 2001, pp. 363-371. doi:10.1037/0021-843X.110.3.363

[10]   D. C. Gooding, K. A. Tallent and C. W. Matts, “Clinical Status of At-Risk Individuals 5 Years Later: Further Validation of the Psychometric High-Risk Strategy,” Journal of Abnormal Psychology, Vol. 114, No. 1, 2005, pp. 170-175. doi:10.1037/0021-843X.114.1.170

[11]   O. Mason, M. Startup, S. Halpin, U. Schall, A. Conrad and V. Carr, “Risk Factors for Transition to First Episode Psychosis among Individuals with ‘At-Risk Mental States’,” Schizophrenia Research, Vol. 71, No. 2-3, 2004, pp. 227-237. doi:10.1016/j.schres.2004.04.006

[12]   N. C. Andreasen and S. Olsen, “Negative versus Positive Schizophrenia: Definition and Validation,” Archives General Psychiatry, Vol. 39, No. 7, 1982, pp. 789-794. doi:10.1001/archpsyc.1982.04290070025006

[13]   J. J. Blanchard, “Hedonic Capacity: Implications for Understanding Emotional and Social Functioning in Schizophrenia,” In: W. F. Flack and J. D. Laird, Eds., Emotions in Psychopathology: Theory and Research, Oxford University Press, New York, 1998, pp. 336-352.

[14]   J. J. Blanchard and A. S. Cohen, “The Structure of Negative Symptoms within Schizophrenia: Implications for Assessment,” Schizophrenia Bulletin, Vol. 32, No. 2, 2006, pp. 238-245. doi:10.1093/schbul/sbj013

[15]   I. Myin-Germeys, J. van Os, J. E. Schwartz, A. A. Stone and P. A. Delespaul, “Emotional Reactivity to Daily Life Stress in Psychosis,” Archives of General Psychiatry, Vol. 58, No. 12, 2001, pp. 1137-1144. doi:10.1001/archpsyc.58.12.1137

[16]   P. H. Silverstone, “Is Anhedonia a Good Measure of Depression?” Acta Psychiatrica Scandinavica, Vol. 83, No. 4, 1991, pp. 249-250. doi:10.1111/j.1600-0447.1991.tb05534.x

[17]   T. I. Oei, W. M. Verhoeven, H. G. Westenberg, F. M. Zwart and J. M. van Ree, “Anhedonia, Suicide Ideation and Dexamethasone Nonsuppression in Depressed Patients,” Journal of Psychiatric Research, Vol. 24, No. 1, 1990, pp. 25-35. doi:10.1016/0022-3956(90)90022-I

[18]   J. Fawcett, “The Morbidity and Mortality of Clinical Depression. Special Issue: Affective Disorders: Current and Future Perspectives,” International Clinical Psychopharmacology, Vol. 8, 1993, pp. 217-220. doi:10.1097/00004850-199300840-00002

[19]   G. Loas, “Vulnerability to Depression: A Model Centered on Anhedonia,” Journal of Affective Disorders, Vol. 41, No. 1, 1996, pp. 39-53. doi:10.1016/0165-0327(96)00065-1

[20]   F. H. Gawin and H. D. Kleber, “Abstinence Symptomatology and Psychiatric Diagnosis in Cocaine Abusers,” Archives of General Psychiatry, Vol. 43, No, 2, 1986, pp. 107-113. doi:10.1001/archpsyc.1986.01800020013003

[21]   G. F. Koob and M. Le Moal, “Drug Addiction, Dysregulation of Reward, and Allostasis,” Neuropsychopharmacology, Vol. 24, No. 2, 2001, pp. 97-129. doi:10.1016/S0893-133X(00)00195-0

[22]   N. D. Volkow, J. S. Fowler, G. J. Wang and R. Z. Goldstein, “Role of Dopamine, the Frontal Cortex and Memory Circuits in Drug Addiction: Insight from Imaging Studies,” Neurobiology of Learning and Memory, Vol. 78, No. 3, 2002, pp. 610-624. doi:10.1006/nlme.2002.4099

[23]   S. H. Ahmed and G. F. Koob, “Transition from Moderate to Excessive Drug Intake: Change in Hedonic Set Point,” Science, Vol. 282, No. 5387, 1998, pp. 298-300. doi:10.1126/science.282.5387.298

[24]   A. Heinz, L. G. Schmidt and F. M. Reischies, “Anhedonia in Schizophrenic, Depressed, or Alcohol Dependent patients: Neurobiological Correlates,” Pharmacopsychiatry, Vol. 27, Suppl. 1, 1994, pp. 7-10. doi:10.1055/s-2007-1014317

[25]   F. H. Gawin and E. H. Ellinwood Jr., “Cocaine and Other Stimulants. Actions, Abuse and Treatment,” The New England Journal of Medicine, Vol. 318, No. 18, 1988, pp. 1173-1182. doi:10.1056/NEJM198805053181806

[26]   N. S. Miller, G. L. Summers and M. S. Gold, “Cocaine Dependence: Alcohol and Other Drug Dependence and Withdrawal Characteristics,” Journal of Addictive Disorders, Vol. 12, No. 1, 1993, pp. 25-35. doi:10.1300/J069v12n01_03

[27]   G. B. Bovasso, “Cannabis Abuse as a Risk Factor for Depressive Symptoms,” American Journal of Psychiatry, Vol. 158, No. 12, 2001, pp. 2033-2037. doi:10.1176/appi.ajp.158.12.2033

[28]   G. Martinotti, V. Carli, D. Tedeschi, M. Di Giannantonio, A. Roy, L. Janiri and M. Sarchiapone, “Mono- and Polysubstance Dependent Subjects Differ on Social Factors, Childhood Trauma, Personality, Suicidal Behaviour, and Comorbid Axis I Diagnoses,” Addictive Behaviors, Vol. 34, No. 9, 2009, pp. 790-793. doi:10.1016/j.addbeh.2009.04.012

[29]   H. Jaffe, C. M. Knappe and D. A. Ciraulo, “Opiates: Clinical Aspects,” In: J. H. Lowinson, P. Ruiz, R. B. Millman and J. G. Langrod, Eds., Substance Abuse—A Comprehensive Textbook, 3rd Edition, Williams & Wilkins, Baltimore, 1997, pp. 158-166.

[30]   L. Janiri, G. Martinotti, T. Dario, D. Reina, F. Paparello, G. Pozzi, G. Addolorato, M. Di Giannantonio and S. De Risio, “Anhedonia and Substance-Related Symptoms in Detoxified Substance Dependent Subjects: A Correlation Study,” Neuropsychobiology, Vol. 52, No. 1, 2005, pp. 37-44. doi:10.1159/000086176

[31]   G. Martinotti, M. Di Nicola, D. Reina, S. Andreoli, F. Focà, A. Cunniff, F. Tonioni, P. Bria and L. Janiri, “Alcohol Protracted Withdrawal Syndrome: The Role of Anhedonia,” Substance Use & Misuse, Vol. 43, No. 3-4, 2008, pp. 271-284. doi:10.1080/10826080701202429

[32]   K. Bott, C. Meyer, H. J. Rumpf, U. Hapke and U. John, “Psychiatric Disorders among At-Risk Consumers of Alcohol in the General Population,” Journal of Studies on Alcohol, Vol. 66, No. 2, 2005, pp. 246-253.

[33]   G. E. Simon, M. VonKorff, M. Piccinelli, C. Fullerton and J. Ormel, “An International Study of the Relation between Somatic Symptoms and Depression,” The New England Journal of Medicine, Vol. 341, No. 18, 1999, pp. 1329-1335. doi:10.1056/NEJM199910283411801

[34]   G. Martinotti, C. R. Cloninger and L. Janiri, “Temperament and Character Inventory Dimensions and Anhedonia in Detoxified Substance-Dependent Subjects,” American Journal of Drug and Alcohol Abuse, Vol. 34, No. 2, 2008, pp. 177-183. doi:10.1080/00952990701877078

[35]   C. R. Cloninger, D. M. Svrakic and T. R. Przybeck, “A Psychobiological Model of Temperament and Character,” Archives of General Psychiatry, Vol. 50, No. 12, 1993, pp. 975-989.doi:10.1001/archpsyc.1993.01820240059008

[36]   G. Pozzi, G. Martinotti, D. Reina, T. Dario, A. Frustaci, L. Janiri and P. Bria, “The Assessment of Post-Detoxification Anhedonia: Influence of Clinical and Psychosocial Variables,” Substance Use & Misuse, Vol. 43, No. 2, 2008, pp. 722-732. doi:10.1080/00952990701202954

[37]   K. Schmidt, B. Nolte-Zenker, J. Patzer, M. Bauer, L. G. Schmid and A. Heinz, “Psychopathological Correlates of Reduced Dopamine Receptor Sensitivity in Depression, Schizophrenia, and Opiate and Alcohol Dependence,” Pharmacopsychiatry, Vol. 34, No. 2, 2001, pp. 66-72. doi:10.1055/s-2001-15184

[38]   A. Guyon, F. Assouly-Besse, G. Biala, A. J. Puech and M.-H. Thiébot, “Potentiation by Low Doses of Selected Neuroleptics of Food-Induced Conditioned Place Preference in Rats,” Psychopharmacology, Vol. 110, No. 4, 1993, pp. 460-466. doi:10.1007/BF02244653

[39]   P. Willner, “Validity, Reliability and Utility of the Chronic Mild Stress Model of Depression: A 10-Year Review and Evaluation,” Psychopharmacology, Vol. 134, No. 4, 1997, pp. 319-329. doi:10.1007/s002130050456

[40]   M. Diana, M. Pistis, A. Muntoni and G. Gessa, “Mesolimbic Dopaminergic Reduction Outlasts Ethanol Withdrawal Syndrome: Evidence of Protracted Abstinence,” Neuroscience, Vol. 71, No. 2, 1996, pp. 411-415. doi:10.1016/0306-4522(95)00482-3

[41]   M. W. Robertson, C. A. Leslie and J. P. Benne Jr., “Apparent Synaptic Dopamine Deficiency Induced by Withdrawal from Chronic Cocaine Treatment,” Brain Research, Vol. 538, No. 2, 1991, pp. 337-339. doi:10.1016/0006-8993(91)90451-Z

[42]   N. S. Miller, C. A. Dackis and M. S. Gold, “The Relationship of Addiction, Tolerance, and Dependence to Alcohol and Drugs: A Neurochemical Approach,” Journal of Substance Abuse Treatment, Vol. 4, No. 3-4, 1987, pp. 197-207. doi:10.1016/S0740-5472(87)80014-4

[43]   C. Martin-Soelch, A. F. Chevalley, G. Kunig, J. Missimer, S. Magyar and A. Mino, “Changes in Reward-Induced brain Activation in Opiate Addicts,” The European Journal of Neuroscience, Vol. 14, No. 8, 2001, pp. 1360-1368. doi:10.1046/j.0953-816x.2001.01753.x

[44]   N. D. Volkow, G. J. Wang, J. S. Fowler, J. Logan, S. J. Gatley, R. Hitzemann, A. D. Chen, S. L. Dewey and N. Pappas, “Decreased Striatal Dopaminergic Responsiveness in Detoxified Cocaine-Dependent Subjects,” Nature, Vol. 386, No. 6627, 1997, pp. 830-833. doi:10.1038/386830a0

[45]   V. Isella, S. Iurlaro, R. Piolti, C. Ferrarese, L. Frattola, I. Appollonio, P. Melzi and M. Grimaldi, “Physical Anhedonia in Parkinson’s Disease,” Journal of Neurology, Neurosurgery, and Psychiatry, Vol. 74, No. 9, 2003, pp. 1308-1311. doi:10.1136/jnnp.74.9.1308

[46]   C. Davis and D. B. Woodside, “Sensitivity to the Rewarding Effects of Food and Exercise in the Eating Disorders,” Comprehensive Psychiatry, Vol. 43, No. 3, 2002, pp. 189-194. doi:10.1053/comp.2002.32356

[47]   I. H. A. Franken, C. Zijlstra and P. Muris, “Are Nonpharmacological Induced Rewards Related to Anhedonia? A Study among Skydivers,” Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 30, No. 2, 2006, pp. 297-300. doi:10.1016/j.pnpbp.2005.10.011

[48]   J. C. Bucknill and D. H. Tuke, “A Manual of Psychological Medicine,” Churchill, London, 1874.

[49]   T. S. Clouston, “Clinical Lectures on Mental Diseases,” Churchill, London, 1896.

[50]   L. W. Bevan, “A Textbook of Mental Diseases,” Charles Griffin, London, 1899.

[51]   E. Kraepelin, “Dementia Praecox and Paraphrenia,” Huntington, New York, 1919.

[52]   E. Bleuler, “Dementia Praecox Oder Gruppe der Schizophrenien/Dementia Praecox or the Group of Schizophrenias,” International Universities Press, New York, 1911.

[53]   A. Myerson, “Anhedonia,” The American Journal of Psychiatry, Vol. 2, 1923, pp. 87-103.

[54]   K. Jaspers, “Allgemeine Psychopathologie. Ein Leitfaden für Studierende, ?rzte und Psychologen. 1. Auflage,” Springer, Berlin, 1913.

[55]   World Health Organisation, “Mental Disorders: Glossary and Guide to Their Classification with the Ninth Revision of the International Classification of Diseases,” WHO, Genève, 1978.

[56]   S. Rado, “Psychoanalysis of Behavior: Collected Papers,” Grune & Stratton, New York, 1956.

[57]   S. Rado, “Psychoanalysis of Behavior: Collected Papers),” Vol. 2, Grune & Stratton, New York, 1962.

[58]   P. E. Meehl, “Schizotaxia, Schizotypy, Schizophrenia,” The American Psychologist, Vol. 17, 1962, pp. 827-838. doi:10.1037/h0041029

[59]   P. E. Meehl, “Psychodiagnosis. Selected Papers,” University of Minnesota Press, Minneapolis, 1973.

[60]   P. Snaith, “Anhedonia: Exclusion from the Pleasure Dome,” British Medical Journal, Vol. 305, No. 6846, 1992, p. 134. doi:10.1136/bmj.305.6846.134

[61]   M. Leboyer, F. Bellivier, M. Nosten-Bertrand, R. Jouvent, D. Pauls and J. Mallet, “Psychiatric Genetics: Search for Phenotypes,” Trends in Neurosciences, Vol. 21, No. 3, 1998, pp. 102-105. doi:10.1016/S0166-2236(97)01187-9

[62]   G. Hasler, W. C. Drevets, H. K. Manji and D. S. Charney, “Discovering Endophenotypes for Major Depression,” Neuropsychopharmacology, Vol. 29, No. 10, 2004, pp. 1765-1781. doi:10.1038/sj.npp.1300506

[63]   A. Markou and G. F. Koob, “Postcocaine Anhedonia. An Animal Model of Cocaine Withdrawal,” Neuropsychopharmacology, Vol. 4, No. 1, 1991, pp. 17-26.

[64]   P. Willner, A. S. Hale and S. Argyropoulos, “Dopaminergic Mechanism of Antidepressant Action in Depressed Patients,” Journal of Affective Disorders, Vol. 86, No. 1, 2005, pp. 37-45. doi:10.1016/j.jad.2004.12.010

[65]   J. C. Cooper, F. E. Bloom and R. H. Roth, “The Biochemical Basis of Neuropharmacology,” 8th Edition, Oxford University Press, New York, 2003.

[66]   D. J. Surmeier, J. Ding, M. Day, Z. Wang and W. Shen, “D1 and D2 Dopamine-Receptor Modulation of Striatal Glutamatergic Signaling in Striatal Medium Spiny Neurons,” Trends in Neuroscience, Vol. 30, No. 5, 2007, pp. 228-235. doi:10.1016/j.tins.2007.03.008

[67]   S. Hernandez-Lopez, T. Tkatch, E. Perez-Garci, E. Galarraga, J. Bargas, H. Hamm and D. J. Surmeier, “D2 Dopamine Receptors in Striatal Medium Spiny Neurons Reduce L-Type Ca2+ Currents and Excitability via a Novel PLC[beta]1-IP3-calcineurin-signaling Cascade,” The Journal of Neuroscience, Vol. 20, No. 24, 2000, pp. 8987-8995.

[68]   P. Willner, “Dopaminergic Mechanism in Depression and Mania,” In: F. E. Bloom and D. J. Kupfer, Eds., Psychopharmacology: The Fourth Generation of Progress, Raven Press, New York, 1995, pp. 921-931.

[69]   P. Boyer, Y. Lecrubier, A. J. Puech, J. Dewailly and F. Aubin, “Treatment of Negative Symptoms in Schizophrenia with Amisulpride,” The British Journal of Psychiatry, Vol. 166, No. 1, 1995, pp. 68-72. doi:10.1192/bjp.166.1.68

[70]   E. Smeraldi, “Amisulpride versus Fluoxetine in Patients with Dysthymia or Major Depression in Partial Remission: A Double-Blind, Comparative Study,” Journal of Affective Disorders, Vol. 48, No. 1, 1998, pp. 47-56. doi:10.1016/S0165-0327(97)00139-0

[71]   N. Brunello, H. Akiskal, P. Boyer, G. L. Gessa, R. H. Howland, S. Z. Langer, J. Mendlewicz, M. Paes de Souza, G. F. Placidi, G. Racagni and S. Wessely, “Dysthymia: Clinical Picture, Extent of Overlap with Chronic Fatigue Syndrome, Neuropsychopharmacological Considerations, and New Therapeutic Vistas,” Journal of Affective Disorders, Vol. 52, No. 1-3, 1999, pp. 275-290. doi:10.1016/S0165-0327(98)00163-3

[72]   J. D. Salamone, M. S. Cousins and B. J. Snyder, “Behavioral Functions of Nucleus Accumbens Dopamine: Empirical and Conceptual Problems with the Anhedonia Hypothesis,” Neuroscience and Biobehavioral Reviews, Vol. 21, No. 3, 1997, pp. 341-559. doi:10.1016/S0149-7634(96)00017-6

[73]   R. A. Wise, “Neuroleptics and Operant Behaviour: The Anhedonia Hypothesis,” Behavioral and Brain Sciences, Vol. 5, No. 1, 1982, pp. 39-88. doi:10.1017/S0140525X00010372

[74]   J. H. Meyer, S. Kruger, A. A. Wilson, B. K. Christensen, V. S. Goulding, A. Schaffer, C. Minifie, S. Houle, D. Hussey and S. H. Kennedy, “Lower Dopamine Transporter Binding Potential in Striatum during Depression,” Neuroreport, Vol. 12, No. 18, 2001, pp. 4121-4125. doi:10.1097/00001756-200112210-00052

[75]   J. D. Amsterdam and A. B. Newberg, “A Preliminary study of Dopamine Transporter Binding in Bipolar and Unipolar Depressed Patients and Healthy Controls,” Neuropsychobiology, Vol. 55, No. 3-4, 2007, pp. 167-170. doi:10.1159/000106476

[76]   T. Laasonen-Balk, J. Kuikka, H. Viinamaki, M. Husso-Saastamoinen, J. Lehtonen and J. Tiihonen, “Striatal Dopamine Transporter Density in Major Depression,” Psychopharmacology, Vol. 144, No. 3, 1999, pp. 282-285. doi:10.1007/s002130051005

[77]   Y. K. Yang, T. L. Yeh, W. J. Yao, I. H. Lee, P. S. Chen, N. T. Chiu and R. B. Lu, “Greater Availability of Dopamine Transporters in Patients with Major Depression—A Dual-Isotope SPECT Study,” Psychiatry Research, Vol. 162, No. 3, 2008, pp. 230-235. doi:10.1016/j.pscychresns.2007.08.008

[78]   M. J. Bannon, P. Sacchetti and J. Granneman, “The Dopamine Transporter: Potential Involvement in Neuropsychiatric Disorders,” In: F. E. Bloom and D. J. Kupfer, Eds., Psychopharmacology: The Fourth Generation of Progress, Raven Press, New York, 1995, pp. 179-188.

[79]   M. Sarchiapone, V. Carli, G. Camardese, C. Cuomo, D. Di Giuda, M. L. Calcagni, C. Focacci and S. De Risio, “Dopamine Transporter Binding in Depressed Patients with Anhedonia,” Psychiatry Research, Vol. 147, No. 2-3, 2006, pp. 243-248. doi:10.1016/j.pscychresns.2006.03.001

[80]   R. P. Snaith, M. Hamilton, S. Morley, A. Humayan, D. Hargreaves and P. Trigwell, “A Scale for the Assessment of Hedonic Tone: The Snaith-Hamilton Pleasure Scale,” The British Journal of Psychiatry, Vol. 167, No. 1, 1995, pp. 99-103. doi:10.1192/bjp.167.1.99

[81]   M. Hamilton, “A Rating Scale for Depression,” Journal of Neurology, Neurosurgery, and Psychiatry, Vol. 23, 1960, pp. 56-62. doi:10.1136/jnnp.23.1.56

[82]   S. Pecina, K. S. Smith and K. C. Berridge, “Hedonic Hot spots in the Brain,” The Neuroscientist: A Review Journal Bringing Neurobiology, Neurology and Psychiatry, Vol. 12, No. 6, 2006, pp. 500-511.

[83]   S. Pecina and K. C. Berridge, “Hedonic Hot Spot in Nucleus Accumbens Shell: Where Do Mu-Opioids Cause Increased Hedonic Impact of Sweetness?” The Journal of Neuroscience, Vol. 25, No. 50, 2005, pp. 11777-11786. doi:10.1523/JNEUROSCI.2329-05.2005

[84]   K. S. Smith, A. J. Tindell, J. W. Aldridge and K. C. Berridge, “Ventral Pallidum Roles in Reward and Motivation,” Behavioural Brain Research, Vol. 196, No. 2, 2009, pp. 155-167. doi:10.1016/j.bbr.2008.09.038

[85]   D. H. Zald and S. W. Kim, “Anatomy and Function of the Orbital Frontal Cortex. I. Anatomy, Neurocircuitry; and Obsessive-Compulsive Disorder,” The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 8, No. 2, 1996, pp. 125-138.

[86]   D. H. Zald and S. W. Kim, “Anatomy and Function of the Orbital Frontal Cortex. II. Function and Relevance to Obsessive-Compulsive Disorder,” The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 8, No. 3, 1996, pp. 249-261.

[87]   B. Knutson, J. Taylor, M. Kaufman, R. Peterson and G. Glover, “Distributed Neural Representation of Expected Value,” The Journal of Neuroscience, Vol. 25, No. 19, 2005, pp. 4806-4812. doi:10.1523/JNEUROSCI.0642-05.2005

[88]   A. G. Sanfey, J. K. Rilling, J. A. Aronson, L. E. Nystrom and J. D. Cohen, “The Neural Basis of Economic Decision-Making in the Ultimatum Game,” Science, Vol. 300, No. 5626, 2003, pp. 1755-1758. doi:10.1126/science.1082976

[89]   S. W. Kennerley, A. F. Dahmubed, A. H. Lara and J. D. Wallis, “Neurons in the Frontal Lobe Encode the Value of Multiple Decision Variables,” Journal of Cognitive Neuroscience, Vol. 21, No. 6, 2009, pp. 1162-1178. doi:10.1162/jocn.2009.21100

[90]   M. F. Rushworth and T. E. Behrens, “Choice, Uncertainty and Value in Prefrontal and Cingulate Cortex,” Nature Neuroscience, Vol. 11, No. 4, 2008, pp. 389-397. doi:10.1038/nn2066

[91]   B. W. Balleine and S. Killcross, “Parallel Incentive Processing: An Integrated View of Amygdala Function,” Trends in Neuroscience, Vol. 29, No. 5, 2006, pp. 272-279. doi:10.1016/j.tins.2006.03.002

[92]   M. G. Baxter and E. A. Murray, “The Amygdala and Reward,” Nature Reviews, Neuroscience, Vol. 3, No. 7, 2002, pp. 563-573. doi:10.1038/nrn875

[93]   E. A. Murray, “The Amygdala, Reward and Emotion,” Trends in Cognitive Sciences, Vol. 11, No. 11, 2007, pp. 489-497. doi:10.1016/j.tics.2007.08.013

[94]   M. T. Treadway and D. H. Zald, “Reconsidering Anhedonia in Depression: Lessons from Translational Neuroscience,” Neuroscience and Biobehavioral Reviews, Vol. 35, No. 3, 2011, pp. 537-555. doi:10.1016/j.neubiorev.2010.06.006

[95]   K. C. Berridge and T. E. Robinson, “What Is the Role of Dopamine in Reward: Hedonic Impact, Reward Learning, or Incentive Salience?” Brain Research Reviews, Vol. 28, No. 3, 1998, pp. 309-369. doi:10.1016/S0165-0173(98)00019-8

[96]   R. A. Depue and P. F. Collins, “Neurobiology of the Structure of Personality: Dopamine, Facilitation of Incentive Motivation, and Extraversion,” The Behavioral and Brain Sciences, Vol. 22, No. 3, 1999, pp. 491-569. doi:10.1017/S0140525X99002046

[97]   H. Berenbaum, C. Raghavan, H. N. Le, L. L. Vernon and J. J. Gomez, “A Taxonomy of Emotional Disturbances,” Clinical Psychology: Science and Practice, Vol. 10, No. 2, 2003, pp. 206-226. doi:10.1093/clipsy.bpg011

[98]   R. P. Snaith, “Anhedonia: A Neglected Symptom of Psychopathology,” Psychological Medicine, Vol. 23, No. 4, 1993, pp. 957-966. doi:10.1017/S0033291700026428

[99]   I. H. A. Franken, E. Rassin and P. Muris, “The Assessment of Anhedonia in Clinical and Non-Clinical Populations: Further Validation of the Snaith-Hamilton Pleasure Scale (SHAPS),” Journal of Affective Disorders, Vol. 99, No. 1-3, 2007, pp. 83-89. doi:10.1016/j.jad.2006.08.020

[100]   H. Berenbaum, R. Snowhite and T. F. Oltmanns, “Anhedonia and Emotional Responses to Affect Evoking Stimuli,” Psychological Medicine, Vol. 17, No. 3, 1987, pp. 677-684. doi:10.1017/S0033291700025915

[101]   I. Berlin, L. Givry-Steiner, Y. Lecrubier and A. J. Puech, “Measures of Anhedonia and Hedonic Responses to Sucrose in Depressive and Schizophrenic Patients in Comparison with Healthy Subjects,” European Psychiatry, Vol. 13, No. 6, 1998, pp. 303-309. doi:10.1016/S0924-9338(98)80048-5

[102]   M. L. Ferguson and E. S. Katkin, “Visceral Perception, Anhedonia, and Emotion,” Biological Psychology, Vol. 42, No. 1-2, 1996, pp. 131-145. doi:10.1016/0301-0511(95)05151-1

[103]   E. R. Fiorito and R. F. Simons, “Emotional Imagery and Physical Anhedonia,” Psychophysiology, Vol. 31, No. 5, 1994, pp. 513-521. doi:10.1111/j.1469-8986.1994.tb01055.x

[104]   D. A. Pizzagalli, A. L. Jahn and J. P. O’Shea, “Toward an Objective Characterization of an Anhedonic Phenotype: A Signal-Detection Approach,” Biological Psychiatry, Vol. 57, No. 4, 2005, pp. 319-327. doi:10.1016/j.biopsych.2004.11.026

[105]   L. J. Chapman, J. P. Chapman and M. L. Raulin, “Scales for Physical and Social Anhedonia,” Journal of Abnormal Psychology, Vol. 85, No. 4, 1976, pp. 374-382. doi:10.1037/0021-843X.85.4.374

[106]   L. J. Chapman and J. P. Chapman, “The Revised Physical Anhedonia Scale,” University of Wisconsin, Madison, 1982.

[107]   J. Fawcett, D. C. Clark, W. A. Scheftner and R. D. Gibbons, “Assessing Anhedonia in Psychiatric Patients,” Archives of General Psychiatry, Vol. 40, No. 1,1983, pp. 79-84. doi:10.1001/archpsyc.1983.01790010081010

[108]   J. D. Amsterdam, R. G. Settle, R. L. Doty, E. Abelman and A. Winokur, “Taste and Smell Perception in Depression,” Biological Psychiatry, Vol. 22, No. 12, 1987, pp. 1481-1485. doi:10.1016/0006-3223(87)90108-9

[109]   M. Kazes, J. M. Danion, D. Grange, A. Pradignac, C. Simon, F. Burrus-Mehl, J. L. Schlienger and L. Singer, “Eating Behaviour and Depression before and after Antidepressant Treatment: A Prospective, Naturalistic Study,” Journal of Affective Disorders, Vol. 30, No. 3, 1994, pp. 193-207. doi:10.1016/0165-0327(94)90080-9

[110]   G. S. Dichter, M. J. Smoski, A. B. Kampov-Polevoy, R. Gallop and J. C. Garbutt, “Unipolar Depression Does Not Moderate Responses to the Sweet Taste Test,” Depression and Anxiety, Vol. 27, No. 9, 2010, pp. 859-863. doi:10.1002/da.20690

[111]   W. James, “The Principles of Psychology. 2 Voll,” Macmillan, London, 1890.

[112]   S. Dubal, A. Pierson and R. Jouvent, “Focussed Attention in Anhedonia: A P3 Study,” Psychophysiology, Vol. 37, No. 5, 2000, pp. 711-714. doi:10.1111/1469-8986.3750711

[113]   I. H. A. Franken, J. W. Van Strien and I. Nijs, “Effect of Hedonic Tone on Event-Related Potential Measures of Cognitive Processing,” Psychiatry Research, Vol. 142, No. 2, 2006, pp. 233-239. doi:10.1016/j.psychres.2005.08.013

[114]   R. F. Simons, F. W. MacMillan III and F. B. Ireland, “Anticipatory Pleasure Deficit in Subjects Reporting Physical Anhedonia: Slow Cortical Evidence,” Biological Psychology, Vol.14, No. 3-4, 1982, pp. 297-310. doi:10.1016/0301-0511(82)90010-2

[115]   B. Crespo-Facorro, S. Paradiso, N. C. Andreasen, D. S. O’Leary, G. L. Watkins, L. L. Ponto and R. D. Hichwa, “Neural Mechanism of Anhedonia in Schizophrenia: A PET Study of Response to Unpleasant and Pleasant Odors,” Journal of American Medical Association, Vol. 286, No. 4, 2001, pp. 427-435. doi:10.1001/jama.286.4.427

[116]   P. A. Keedwell, C. Andrew, S. C. Williams, M. J. Brammer and M. L. Phillips, “The Neural Correlates of Anhedonia in Major Depressive Disorder,” Biological Psychiatry, Vol. 58, No. 11, 2005, pp. 843-853. doi:10.1016/j.biopsych.2005.05.019

[117]   M. T. Mitterschiffthaler, V. Kumari, G. S. Malhi, R. G. Brown, V. P. Giampietro, M. J. Brammer, J. Suckling, L. Poon, A. Simmons, C. Andrew and T. Sharma, “Neural Response to Pleasant Stimuli in Anhedonia: An fMRI Study,” Neuroreport, Vol. 14, No. 2, 2003, pp. 177-182. doi:10.1097/00001756-200302100-00003

[118]   N. C. Andreasen, “The Scale for the Assessment of Negative Symptoms (SANS): Conceptual and Theoretical Foundations,” British Journal of Psychiatry, Vol. 7, 1989, pp. 49-58.

[119]   G. Bersani, V. Orlandi, S. Gherardelli and P. Pancheri, “Cannabis and Neurogical Soft Signs in Schizophrenia: Absence of Relationship and Influence on Psychopathology,” Psychopathology, Vol. 35, No. 5, 2002, pp. 289-295. doi:10.1159/000067064

[120]   S. Dollfus and M. Petit, “Negative Symptoms in Schizophrenia: Their Evolution during an Acute Phase,” Schizophrenia Research, Vol. 17, No. 2, 1995, pp. 187-194. doi:10.1016/0920-9964(94)00087-O

[121]   G. D. Tollefson and T. M. Sanger, “Negative Symptoms: A Path Analytic Approach to a Double-Blind, Placebo- and Haloperidol-Controlled Clinical Trial with Olanzapine,” American Journal of Psychiatry, Vol. 154, No. 4, 1997, pp. 466-474.

[122]   P. Bech and O. J. Rafaelsen, “The Use of Rating Scales Exemplified by a Comparison of the Hamilton and the Bech-Rafaelsen Melancholia Scale,” Acta Psychiatrica Scandinavica, Vol. 62, No. S285, pp. 128-132. doi:10.1111/j.1600-0447.1980.tb07683.x

[123]   P. Bech, “The Bech-Rafaelsen Melancholia Scale (MES) in Clinical Trials of Therapies in Depressive Disorders: A 20-Year Review of Its Use as Outcome Measure,” Acta Psychiatrica Scandinavica, Vol. 106, No. 4, pp. 252-264. doi:10.1034/j.1600-0447.2002.01404.x

[124]   M. J. Muller, H. Wetzel and O. Benkert, “Differential Effects of High-Dose Amisulpride versus Flupentixol on Latent Dimensions of Depressive and Negative Symptomatology in Acute Schizophrenia: An Evaluation Using Confirmatory Factor Analysis,” International Clinical Psychopharmacology, Vol. 17, No. 5, 2002, pp. 249-261. doi:10.1097/00004850-200209000-00005

[125]   R. C. B. Aitken, “Measurement of Feelings Using Visual Analogue Scales,” Journal of the Royal Society of Medicine, Vol. 62, No. 10, 1969, pp. 989-993.

[126]   C. A. Mottola, “Measurement Strategies: The Visual Analogue Scale,” Decubitus, Vol. 6, No. 5, 1993, pp. 56-58.

[127]   D. E. Gard, M. G Gard, A. M. Kring and O. P. John, “Anticipatory and Consummatory Components of the Experience of Pleasure: A Scale Development Study,” Journal of Research in Personality, Vol. 40, 2006, pp. 1086-1102. doi:10.1016/j.jrp.2005.11.001

[128]   P. Gilbert, S. Allan, S. Brough, S. Melley and J. N. V. Miles, “Relationship of Anhedonia and Anxiety to Social rank, Defeat, and Entrapment,” Journal of Affective Disorders, Vol. 7, No. 9 , 2002, pp. 141-151. doi:10.1016/S0165-0327(01)00392-5

[129]   A. M. Leventhal, G. S. Chasson, E. Tapia, E. K. Miller and J. W. Pettit, “Measuring Hedonic Capacity in Depression: A Psychometric Analysis of Three Anhedonia Scales,” Journal of Clinical Psychology, Vol. 62, No. 12, 2006, pp.1545-1558. doi:10.1002/jclp.20327

[130]   S. A. Montgomery and M. Asberg, “A New Depression Scale Designed to Be Sensitive to Change,” British Journal of Psychiatry, Vol. 134, 1979, pp. 382-389. doi:10.1192/bjp.134.4.382

[131]   G. Loas, E. Salinas, A. Pierson and J. D. Guelfi, “Anhedonia and Blunted Affect in Major Depressive Disorder,” Comprehensive Psychiatry, Vol. 35, No. 5, 1994, pp. 366-372. doi:10.1016/0010-440X(94)90277-1

[132]   G. Loas and P. Boyer, “Anhedonia in Endogenomorphic Depression,” Psychiatry Research, Vol. 60, No. 1, 1996, pp. 57-65. doi:10.1016/0165-1781(95)02748-3

[133]   D. C. Clark, J. Fawcett, E. Salazar-Grueso and E. Fawcett, “Seven-Month Clinical Outcome of Anhedonic and Normally Hedonic Depressed Inpatients,” American Journal of Psychiatry, Vol. 141, No. 10, 1984, pp. 1216-1220.

[134]   M. K. Germans and A. M. Kring, “Hedonic Deficit in Anhedonia: Support for the Role of Approach Motivation,” Personality and Individual Differences, Vol. 28, No. 4, 2000, pp. 659-672. doi:10.1016/S0191-8869(99)00129-4

[135]   B. Bailey, K. Y. West, T. A. Widiger and K. Freiman, “The Convergent and Discriminant Validity of the Chapman Scales,” Journal of Personality Assessment, Vol. 61, No. 1, 1993, pp.121-135. doi:10.1207/s15327752jpa6101_9

[136]   J. R. Schuck, D. Leventhal, H. Rothstein and V. Irizarry, “Physical Anhedonia and Schizophrenia,” Journal of Abnormal Psychology, Vol. 93, No. 3, 1984, pp. 342-344. doi:10.1037/0021-843X.93.3.342

[137]   J. Katsanis, W. G. Iacono and M. Beiser, “Anhedonia and Perceptual Aberration in First Episode Psychotic Patients and Their Relatives,” Journal of Abnormal Psychology, Vol. 99, No. 2, 1990, pp. 202-206. doi:10.1037/0021-843X.99.2.202

[138]   H. D’Haenen, “Measurement of Anhedonia,” European Psychiatry, Vol. 11, No. 7, 1996, pp. 335-343. http://dx.doi.org/10.1016/S0924-9338(97)81056-5

[139]   G. K. Leak, “An Examination of the Construct Validity of the Social Anhedonia Scale,” Journal of Personality Assessment, Vol. 56, No. 1, 1991, pp. 84-95. doi:10.1207/s15327752jpa5601_8

[140]   W. P. Horan, A. M. Kring and J. J. Blanchard, “Anhedonia in Schizophrenia: A Review of Assessment Strategies,” Schizophrenia Bulletin, Vol. 32, No. 2, 2006, pp. 259-273. doi:10.1093/schbul/sbj009

[141]   R. R. J. Lewine, “A Discriminant Validity Study of Negative Symptoms with a Special Focus on Depression and Antipsychotic Medication,” American Journal of Psychiatry, Vol. 147, No. 11, 1990, pp. 1463-1466.

[142]   D. Schuldberg, D. M. Quinlan, H. Morgenstern and W. Glazer, “Positive and Negative Symptoms in Chronic Psychiatric Outpatients: Reliability, Stability, and Factor Structure,” Psychological Assessment: A Journal of Consulting and Clinical Psychology, Vol. 2, No. 3, 1990, pp. 262-268.

[143]   K. T. Mueser, S. L. Sayers, N. R. Schooler, R. M. Mance and G. L. Haas, “A Multisite Investigation of the Reliability of the Scale for the Assessment of Negative Symptoms,” American Journal of Psychiatry, Vol. 151, No. 10, 1994, pp. 1453-1462.

[144]   R. M. G. Norman, A. K. Malla, L. Cortese and F. Diaz, “A Study of the Interrelationship between and Comparative Interrater Reliability of the SAPS, SANS, and PANSS,” Schizophrenia Research, Vol. 19, No. 1, 1996, pp. 73-85. doi:10.1016/0920-9964(95)00055-0

[145]   V. Peralta and M. J. Cuesta, “Dimensional Structure of Psychotic Symptoms: An Item-Level Analysis of SAPS and SANS Symptoms in Psychotic Disorders,” Schizophrenia Research, Vol. 38, No. 1, 1999, pp. 13-26. doi:10.1016/S0920-9964(99)00003-1

[146]   J. Addington and D. Addington, “Positive and Negative Symptoms of Schizophrenia: Their Course and Relationship over Time,” Schizophrenia Research, Vol. 5, No. 1, 1991, pp. 51-59. doi:10.1016/0920-9964(91)90053-T

[147]   S. L. Eckert, P. M. Diamond, A. L. Miller and D. I. Velligan, “A Comparison of Instrument Sensitivity to Negative Symptom Change,” Psychiatry Research, Vol. 63, No. 1, 1996, pp. 67-75. doi:10.1016/0165-1781(96)02870-3

[148]   H. Silver, N. Aharon and A. Kaplan, “Add-On Fluvoxamine Improves Primary Negative Symptoms: Evidence for Specificity from Response Analysis of Individual Symptoms,” Schizophrenia Bulletin, Vol. 29, No. 3, 2003, pp. 541-546. doi:10.1093/oxfordjournals.schbul.a007026

[149]   P. Bech, L. F. Gram, E. Dein, O. Jacobsen, J. Vitger and G. Bolwig, “Quantitative Rating of Depressive States,” Acta Psychiatrica Scandinavica, Vol. 51, No. 3, 1975, pp. 161-170. doi:10.1111/j.1600-0447.1975.tb00002.x

[150]   M. ?sberg, P. Kragh-Sorensen, R. H. Mindham and J. R. Tuck, “International Reliability and Communicability of a Rating Scale for Depression,” Psychological Medicine, Vol. 3, No. 4, 1973, pp. 458-465. doi:10.1017/S003329170005426X

[151]   P. Bech, O. J. Rafaelsen, P. Kramp and T. G. Bolwig, “The Mania Rating Scale: Scale Construction and Inter-Observer Agreement,” Neuropharmacology, Vol. 17, No. 6, 1978, pp. 430-431. doi:10.1016/0028-3908(78)90022-9

[152]   B. Knutson, C. M. Adams, G. W. Fong and D. Hommer, “Anticipation of Increasing Monetary Reward Selectively Recruits Nucleus Accumbens,” The Journal of Neuroscience, Vol. 21, No. 16, 2001, pp. 159-163.

[153]   D. T. Gilbert and T. D. Wilson, “Miswanting: Some Problems in the Forecasting of Future Affective States,” In: E. Joseph and P. Forgas, Eds., Feeling and Thinking: The Role of Affect in Social Cognition, Cambridge University Press, New York, 2000, pp. 178-197.

[154]   S. R. Briggs and J. M. Cheek, “The Role of Factor Analysis in the Development and Evaluation of Personality scales,” Journal of Personality, Vol. 54, No. 1, 1986, pp. 106-148. doi:10.1111/j.1467-6494.1986.tb00391.x

[155]   M. Di Giannantonio, G. Di Iorio, R. Guglielmo, D. De Berardis, C. M. Conti, T. Acciavatti, M. Cornelio and G. Martinotti, “Major Depressive Disorder, Anhedonia and Agomelatine: An Open-Label Study,” Journal of Biological Regulators and Homeostatic Agents, Vol. 25, No. 1, 2011, pp. 109-114.

[156]   D. De Berardis, G. Di Iorio, T. Acciavatti, C. Conti, N. Serroni, L. Olivieri, M. Cavuto, G. Martinotti, L. Janiri, F. S. Moschetta, P. Conti and M. Di Giannantonio, “The Emerging Role of Melatonin Agonists in the Treatment of Major Depression: Focus on Agomelatine,” CNS & Neurological Disorders Drug Targets, Vol. 10, No. 1, 2011, pp. 119-132. doi:10.2174/187152711794488674

[157]   G. Martinotti, M. Di Nicola, M. Di Giannantonio and L. Janiri, “Aripiprazole in the Treatment of Patients with Alcohol Dependence: A Double-Blind, Comparison Trial vs. Naltrexone,” Journal of Psychopharmacology, Vol. 23, No. 2, 2009, pp. 123-129. doi:10.1177/0269881108089596