Vol 10, N°3 Dialogues in Clinical Neuroscience - The Core of Depression
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The concept of anhedonia nhedonia refers to the reduced ability to expe- rience pleasure.1 It has had an important place in many aspects of psychopathology since it was first described in the previous century,2 and is still a feature of several types of psychiatric disorders and maladaptive behaviors.3-5 Anhedonia has been the most extensively studied in major depression,6 but, as it also constitutes one impor- tant negative symptom of schizophrenia, much literature has also been devoted to anhedonia in psychosis.3,7 Anhedonia has in fact been studied in a large range of neuropsychiatric disorders, including substance use dis- order,8-10 Parkinson's disease,11 overeating,12 and various risky behaviors.13 Anhedonia is nevertheless considered to be a core fea- ture of major depressive disorder as, for example, the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM-IV)14 requires that either depressed mood or anhedonia be present to propose this diagnosis. Furthermore, lack of reactivity and anhedonia are key diagnostic criteria for the DSM-IV melancholic subtype of major depression,14 and presence of anhedonia has been shown to be predictive of antidepressant response.15 The absence of diagnostic specificity could be regarded as a limiting factor when trying to define anhedonia as a pivotal feature of major depressive disorder.The devel- opment of the “endophenotype” concept may help to overtake such limits, on the basis of three notions.16 T r a n s l a t i o n a l  r e s e a r c h A Copyright © 2008 LLS SAS. All rights reserved www.dialogues-cns.org Neurobiological mechanisms of anhedonia Philip Gorwood, MD, PhD Keywords: depression; mood; striatum; orbitofrontal; anhedonia; accumbens Author affiliations: INSERM U675, Institut Fédératif de Recherche (IFR 02), Faculty, Xavier Bichat, Paris, France; AP-HP, Service de Psychiatrie Adulte, Louis Mourier, Hospital (Paris Diderot), Colombes, France Address for correspondence: Philip Gorwood, MD, PhD, INSERM U675, Faculty of Medicine Bichat (IFR02). 16 rue Henri Huchard, 75018 Paris, France (e-mail: philip.gorwood@lmr.aphp.fr) Anhedonia refers to the reduced ability to experience pleasure, and has been studied in different neuropsychi- atric disorders. Anhedonia is nevertheless considered as a core feature of major depressive disorder, according to DSM-IV criteria for major depression and the definition of melancholic subtype, and regarding its capacity to predict antidepressant response. Behavioral, electrophysiological, hemodynamic, and interview-based measures and self- reports have been used to assess anhedonia, but the most interesting findings concern neuropharmacological and neuroanatomical studies. The analyses of anhedonic non- clinical subjects, nonanhedonic depressed patients, and depressed patients with various levels of anhedonia seem to favor the hypothesis that the severity of anhedonia is associated with a deficit of activity of the ventral striatum (including the nucleus accumbens) and an excess of activ- ity of ventral region of the prefrontal cortex (including the ventromedial prefrontal cortex and the orbitofrontal cor- tex), with a pivotal, but not exclusive, role of dopamine.  © 2008, LLS SAS Dialogues Clin Neurosci. 2008;10:291-299.