Neuroimaging Studies of Reward Processing in Depression

Summary

Principal Investigator: Diego Pizzagalli
Affiliation: Harvard University
Country: USA
Abstract: [unreadable] DESCRIPTION (provided by applicant): The aim of this proposal is to investigate the functional neuroanatomy of depression. A promising strategy for parsing the heterogeneity of Major Depressive Disorder (MDD) is to identify phenotypes characterized by reliable functional brain abnormalities. Anhedonia, the lack of reactivity to pleasurable stimuli, is considered a trait marker for depression. Preclinical work suggests links among phenomena associated with depression - decreased hedonic responsiveness, exaggerated stress responsiveness, and dysfunction in the dopaminergic mesolimbic system - but in humans the neural underpinnings are largely unknown. Using behavioral, event-related potential (ERP), and functional magnetic resonance imaging (fMRI) techniques, this proposal aims to investigate these processes. A monetarily reinforced button-press task will be used to dissociate the neural circuitry involved in anticipation of and reactivity to reward or punishment. Experiment 1 addresses the spatio-temporal dynamics of brain mechanisms underlying anticipation of and reactivity to reward and punishment in subjects differing on objective measures of anhedonia, operationalized as decreased responsiveness to reward-related cues in a separate signal-detection task. Compared to controls, subjects with impaired reward responsiveness (n=20) are predicted to show lower activation in regions subserving reward processing (e.g., nucleus accumbens, medial prefrontal cortex) to reward-related, but not to punishment-related, cues. In the ERP data, decreased late frontal negativity wave to reward cues, and decreased medial-frontal negativity and P3 to reward feedbacks, are hypothesized. Experiment 2 extends this paradigm to subjects with a DSM-IV diagnosis of MDD. These subjects (n=23) are expected to show lower activation in regions subserving reward processing than controls (n=23) in response to reward-related cues, and higher activation in regions subserving processing of withdrawal-related cues. In the ERP data, medial-frontal negativity and P3 are predicted to differentiate the subject groups. Experiment 3 addresses the effects of mental stress on reward processing in MDD. Compared to controls (n=21), depressed subjects (n=21) are expected to show a larger stress-induced reduction of activation in regions subserving reward processing, and a larger activation in regions subserving punishment processing. Decreased gray matter density in medial and subgenual prefrontal regions, as assessed by voxel-based MRI morphometrical analyses, is expected to be associated with the detrimental effect of stress on reward responsiveness. Overall, the integration of techniques with high temporal (ERP) and spatial (fMRI) resolution will enhance understanding of the functional neuroanatomy of depression. [unreadable] [unreadable]
Funding Period: 2004-06-07 - 2009-04-30
more information: NIH RePORT

Top Publications

  1. pmc Adolescent depression: stress and reward dysfunction
    Randy P Auerbach
    From the Department of Psychiatry, Harvard Medical School Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA
    Harv Rev Psychiatry 22:139-48. 2014
  2. pmc Disrupted reinforcement learning and maladaptive behavior in women with a history of childhood sexual abuse: a high-density event-related potential study
    Pia Pechtel
    Center for Depression, Anxiety and Stress Research, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
    JAMA Psychiatry 70:499-507. 2013
  3. doi Dopamine-d2-receptor blockade reverses the association between trait approach motivation and frontal asymmetry in an approach-motivation context
    Jan Wacker
    Department of Psychology, Philipps Universitat Marburg, Marburg, Germany
    Psychol Sci 24:489-97. 2013
  4. pmc Reduced reward learning predicts outcome in major depressive disorder
    Elske Vrieze
    Department of Psychiatry, University Psychiatric Center, Campus Leuven, Belgium
    Biol Psychiatry 73:639-45. 2013
  5. pmc Behavioral and electrophysiological correlates of training-induced cognitive control improvements
    Alexander J Millner
    Department of Psychology, Harvard University, Cambridge, MA, USA
    Neuroimage 63:742-53. 2012
  6. pmc Neurogenetics of depression: a focus on reward processing and stress sensitivity
    Ryan Bogdan
    BRAIN Laboratory, Department of Psychology, Washington University in St Louis, Box 1125, One Brookings Drive, St Louis, MO 63130, USA
    Neurobiol Dis 52:12-23. 2013
  7. pmc Dopamine-related deficit in reward learning after catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa
    Simona Grob
    Department of Psychiatry and Psychotherapy, University Hospital, Zurich, Switzerland
    Neuropsychopharmacology 37:1945-52. 2012
  8. pmc Decreased cognitive control in response to negative information in patients with remitted depression: an event-related potential study
    Marie Anne Vanderhasselt
    Department of Psychology, Ghent University, Ghent, Belgium
    J Psychiatry Neurosci 37:250-8. 2012
  9. pmc Measuring extrastriatal dopamine release during a reward learning task
    Elske Vrieze
    Department of Psychiatry, University Hospital Leuven, Belgium
    Hum Brain Mapp 34:575-86. 2013
  10. pmc Neural responses to negative feedback are related to negative emotionality in healthy adults
    Diane L Santesso
    Department of Psychology, Harvard University, Cambridge, MA, USA
    Soc Cogn Affect Neurosci 7:794-803. 2012

Scientific Experts

  • Karolina M Lempert
  • Diego A Pizzagalli
  • Pia Pechtel
  • Pearl H Chiu
  • Michele Candrian
  • C M Deveney
  • Ryan Bogdan
  • Avram J Holmes
  • Daniel G Dillon
  • Diane L Santesso
  • Elske Vrieze
  • Sunny J Dutra
  • Jan Wacker
  • R Bogdan
  • Koen Demyttenaere
  • Stephan Claes
  • Jeffrey L Birk
  • Tiffany M Meites
  • P Kumar
  • Randy P Auerbach
  • Titia Hompes
  • Pascal Sienaert
  • Peter de Boer
  • Mark Schmidt
  • Lisa H Berghorst
  • Quentin Jm Huys
  • Daniel Gerard Dillon
  • A Der-Avakian
  • Yuliya Nikolova
  • Christopher G AhnAllen
  • Simona Grob
  • Alexander J Millner
  • Marie Anne Vanderhasselt
  • Michael J Frank
  • Katrina Koslov
  • Roy H Perlis
  • Jesen Fagerness
  • Erik M Mueller
  • Nancy Brooks
  • A Eden Evins
  • E M Mueller
  • Katherine M Putnam
  • Katherine T Steele
  • L H Berghorst
  • Roee Admon
  • Dirk Hermans
  • L D Nickerson
  • Ronny Bruffaerts
  • William D S Killgore
  • Isabelle M Rosso
  • D N Greve
  • F K Goer
  • Scott L Rauch
  • S J Dutra
  • Peter Dayan
  • Jenny Ceccarini
  • Gerhard Stemmler
  • Jurgen Hennig
  • Yuliya S Nikolova
  • M S D'Souza
  • Guy Bormans
  • A Markou
  • Koen Van Laere
  • Mathieu Vandenbulcke
  • Gregor Hasler
  • Elena L Goetz
  • Luke E Stoeckel
  • Jair Stern
  • Gary B Kaplan
  • Sara V Carlini
  • Adam C Jaroszewski
  • Hanspeter Mörgeli
  • Harish Chamarthi
  • James J Levitt
  • Gabriella Milos
  • Rudi De Raedt
  • Ulrich Schnyder
  • Kristin L Gregor
  • Vamsi K Koneru
  • Gabrielle I Liverant
  • Barbara W Kamholz
  • Suzy Bird Gulliver
  • Petra E Pajtas
  • Wendy Berry Mendes
  • R H Perlis
  • J Fagerness
  • Erika C Schetter
  • S Bitran
  • Karlen Lyons-Ruth
  • D L Santesso

Detail Information

Publications62

  1. pmc Adolescent depression: stress and reward dysfunction
    Randy P Auerbach
    From the Department of Psychiatry, Harvard Medical School Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA
    Harv Rev Psychiatry 22:139-48. 2014
    ..To highlight the translational potential of these insights, a hypothetical case study is provided as a means of demonstrating the importance of targeting reward dysfunction in both assessment and treatment of adolescent depression...
  2. pmc Disrupted reinforcement learning and maladaptive behavior in women with a history of childhood sexual abuse: a high-density event-related potential study
    Pia Pechtel
    Center for Depression, Anxiety and Stress Research, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
    JAMA Psychiatry 70:499-507. 2013
    ..Despite the epidemiological data available, the mechanisms underlying these maladaptive outcomes remain poorly understood...
  3. doi Dopamine-d2-receptor blockade reverses the association between trait approach motivation and frontal asymmetry in an approach-motivation context
    Jan Wacker
    Department of Psychology, Philipps Universitat Marburg, Marburg, Germany
    Psychol Sci 24:489-97. 2013
    ....
  4. pmc Reduced reward learning predicts outcome in major depressive disorder
    Elske Vrieze
    Department of Psychiatry, University Psychiatric Center, Campus Leuven, Belgium
    Biol Psychiatry 73:639-45. 2013
    ..Our goal was to test whether MDD is characterized by reduced reward learning, especially in the presence of anhedonic symptoms, and to investigate the relationship between reward learning and MDD diagnosis after 8 weeks of treatment...
  5. pmc Behavioral and electrophysiological correlates of training-induced cognitive control improvements
    Alexander J Millner
    Department of Psychology, Harvard University, Cambridge, MA, USA
    Neuroimage 63:742-53. 2012
    ..Overall, results suggest that a brief training can improve cognitive control, specifically the ability to inhibit task-irrelevant information...
  6. pmc Neurogenetics of depression: a focus on reward processing and stress sensitivity
    Ryan Bogdan
    BRAIN Laboratory, Department of Psychology, Washington University in St Louis, Box 1125, One Brookings Drive, St Louis, MO 63130, USA
    Neurobiol Dis 52:12-23. 2013
    ..We conclude by highlighting challenges facing intermediate phenotype research and future development that will be required to propel this pivotal research into new directions...
  7. pmc Dopamine-related deficit in reward learning after catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa
    Simona Grob
    Department of Psychiatry and Psychotherapy, University Hospital, Zurich, Switzerland
    Neuropsychopharmacology 37:1945-52. 2012
    ..These deficits uncover disturbance of the central reward processing systems in rBN related to altered brain catecholamine levels, which might reflect a trait-like deficit increasing vulnerability to BN...
  8. pmc Decreased cognitive control in response to negative information in patients with remitted depression: an event-related potential study
    Marie Anne Vanderhasselt
    Department of Psychology, Ghent University, Ghent, Belgium
    J Psychiatry Neurosci 37:250-8. 2012
    ..To fill these gaps, we investigated cognitive control over emotional stimuli in participants with rMDD and controls without history of depression or psychopathology...
  9. pmc Measuring extrastriatal dopamine release during a reward learning task
    Elske Vrieze
    Department of Psychiatry, University Hospital Leuven, Belgium
    Hum Brain Mapp 34:575-86. 2013
    ..The purpose of this study was to examine presynaptic DA release in extrastriatal regions of the reward circuit by measuring displacement of the high affinity D(2) /D(3) radioligand [(18) F]Fallypride during a reward task...
  10. pmc Neural responses to negative feedback are related to negative emotionality in healthy adults
    Diane L Santesso
    Department of Psychology, Harvard University, Cambridge, MA, USA
    Soc Cogn Affect Neurosci 7:794-803. 2012
    ....
  11. pmc Evidence of successful modulation of brain activation and subjective experience during reappraisal of negative emotion in unmedicated depression
    Daniel Gerard Dillon
    Center for Depression, Anxiety and Stress Research and McLean Imaging Center, McLean Hospital, Department of Psychiatry, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA
    Psychiatry Res 212:99-107. 2013
    ..However, the negative relationship between depression severity and effects of reappraisal on brain activation indicates that group differences may be detectable in larger samples of more severely depressed participants...
  12. pmc Acute stress selectively reduces reward sensitivity
    Lisa H Berghorst
    Department of Psychology, Harvard University Cambridge, MA, USA Center for Depression, Anxiety and Stress Research, Harvard Medical School, McLean Hospital Belmont, MA, USA
    Front Hum Neurosci 7:133. 2013
    ..While such results highlight the possibility that stress-induced anhedonia might be an important mechanism linking stress to affective disorders, future studies are necessary to confirm this conjecture...
  13. pmc Differential effects of acute stress on anticipatory and consummatory phases of reward processing
    P Kumar
    Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA Department of Psychiatry, Harvard Medical School, MA, USA Electronic address
    Neuroscience 266:1-12. 2014
    ..Given that stress is a pivotal vulnerability factor for depression, these results offer insight to better understand the etiology of this prevalent disorder. ..
  14. pmc Depression, stress, and anhedonia: toward a synthesis and integrated model
    Diego A Pizzagalli
    Department of Psychiatry, Harvard Medical School and McLean Hospital, Belmont, Massachusetts 02478 email
    Annu Rev Clin Psychol 10:393-423. 2014
    ..In the last section, we provide a synthesis of these four literatures, present initial evidence consistent with our model, and discuss directions for future research. ..
  15. pmc Dimensions in major depressive disorder and their relevance for treatment outcome
    Elske Vrieze
    Department of Psychiatry, University Psychiatric Center, Campus Leuven, Leuven, Belgium Electronic address
    J Affect Disord 155:35-41. 2014
    ..The first aim of this study was to find potential dimensions within a broad psychopathological assessment in depressed patients. Second, we aimed at examining how these dimensions predicted course in MDD...
  16. pmc Peril and pleasure: an rdoc-inspired examination of threat responses and reward processing in anxiety and depression
    Daniel G Dillon
    Center for Depression, Anxiety and Stress Research, McLean Hospital, Harvard Medical School, Boston, Massachusetts
    Depress Anxiety 31:233-49. 2014
    ..In addition to its basic scientific value, a better understanding of interactions between the neural systems that mediate threat and reward responses may offer relief from the burdensome condition of anxious depression. ..
  17. pmc Blunted reward responsiveness in remitted depression
    Pia Pechtel
    McLean Hospital and Harvard Medical School, USA Electronic address
    J Psychiatr Res 47:1864-9. 2013
    ..More research is warranted to investigate if blunted reward responsiveness may predict future depressive episodes and whether targeting reward-related deficits may prevent the re-occurrence of the disorder. ..
  18. pmc Assessment of reward responsiveness in the response bias probabilistic reward task in rats: implications for cross-species translational research
    A Der-Avakian
    Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 92093 0603, USA
    Transl Psychiatry 3:e297. 2013
    ..Thus, this new procedure in rats, which is conceptually and procedurally analogous to the one used in humans, provides a reverse translational platform to investigate abnormal reward responsiveness across species...
  19. pmc Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis
    Quentin Jm Huys
    Gatsby Computational Neuroscience Unit, UCL, London, UK
    Biol Mood Anxiety Disord 3:12. 2013
    ..We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge...
  20. pmc The impact of mineralocorticoid receptor ISO/VAL genotype (rs5522) and stress on reward learning
    R Bogdan
    Department of Psychology, Harvard University, Cambridge, MA 02138, USA
    Genes Brain Behav 9:658-67. 2010
    ..Future studies are warranted to evaluate whether rs5522 genotype interacts with naturalistic stressors to increase the risk of depression and whether stress-induced anhedonia might moderate such risk...
  21. pmc Frontocingulate dysfunction in depression: toward biomarkers of treatment response
    Diego A Pizzagalli
    Center for Depression, Anxiety, and Stress Research and Neuroimaging Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA
    Neuropsychopharmacology 36:183-206. 2011
    ..The review ends with a discussion of the limitations of current work and future directions...
  22. pmc Effects of early life stress on cognitive and affective function: an integrated review of human literature
    Pia Pechtel
    Center for Depression, Anxiety, and Stress Research, McLean Hospital, Harvard Medical School, Room 233C, De Marneffe Building, 115 Mill Street, Belmont, MA 02478 9106, USA
    Psychopharmacology (Berl) 214:55-70. 2011
    ..Emerging findings from longitudinal studies examining developmental trajectories of the brain in healthy samples may provide a new framework to understand mechanisms underlying ELS sequelae...
  23. pmc Asymmetry in resting intracortical activity as a buffer to social threat
    Katrina Koslov
    Department of Psychiatry, University of California, San Francisco, CA 94111, USA
    Psychol Sci 22:641-9. 2011
    ..Our data are the first to show that social context matters when attempting to link individual differences in cortical asymmetry with approach-related cardiovascular and emotional outcomes...
  24. pmc Varenicline as a smoking cessation aid in schizophrenia: effects on smoking behavior and reward sensitivity
    Sunny J Dutra
    Department of Psychology, Yale University, P O Box 208205, New Haven, CT 06520, USA
    Psychopharmacology (Berl) 219:25-34. 2012
    ..To maximize treatment efficacy while minimizing risks, it is critical to identify reliable predictors of positive response to varenicline in smokers with schizophrenia...
  25. pmc Perception of a naturalistic stressor interacts with 5-HTTLPR/rs25531 genotype and gender to impact reward responsiveness
    Yuliya Nikolova
    Affective Neuroscience Laboratory, Department of Psychology, Harvard University, Cambridge, MA, USA
    Neuropsychobiology 65:45-54. 2012
    ....
  26. pmc The relationship between reward-based learning and nicotine dependence in smokers with schizophrenia
    Christopher G AhnAllen
    VA Boston Healthcare System, Brockton, MA 02301 5596, USA
    Psychiatry Res 196:9-14. 2012
    ..These findings emphasize the importance of targeting reward system functioning in smoking cessation treatment for individuals with schizophrenia...
  27. pmc Effects of task-relevant incentives on the electrophysiological correlates of error processing in major depressive disorder
    Avram J Holmes
    Harvard University, Cambridge, Massachusetts, USA
    Cogn Affect Behav Neurosci 10:119-28. 2010
    ..The present findings highlight distinct effects of task incentives on electrophysiological components of error processing and are interpreted within current theories of action monitoring and incentive processing in depression...
  28. pmc Delay discounting and future-directed thinking in anhedonic individuals
    Karolina M Lempert
    Department of Psychology, Harvard University, 1220 William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
    J Behav Ther Exp Psychiatry 41:258-64. 2010
    ..The current findings provide preliminary evidence indicating that anhedonic individuals make less myopic decisions about their future, possibly due to their decreased responsiveness to immediate rewards...
  29. pmc Serotonin transporter genotype and action monitoring dysfunction: a possible substrate underlying increased vulnerability to depression
    Avram J Holmes
    Department of Psychology, Harvard University, Cambridge, MA 02138, USA
    Neuropsychopharmacology 35:1186-97. 2010
    ....
  30. pmc Corticotropin-releasing hormone receptor type 1 (CRHR1) genetic variation and stress interact to influence reward learning
    Ryan Bogdan
    Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, USA
    J Neurosci 31:13246-54. 2011
    ..Homozygosity for the A allele at rs12938031 may increase risk for psychopathology via stress-induced reward learning deficits...
  31. pmc Spatiotemporal dynamics of error processing dysfunctions in major depressive disorder
    Avram J Holmes
    Department of Psychology, Harvard University, Cambridge, MA 02138, USA
    Arch Gen Psychiatry 65:179-88. 2008
    ..Depression is characterized by executive dysfunctions and abnormal reactions to errors; however, little is known about the brain mechanisms that underlie these deficits...
  32. pmc Electrophysiological correlates of spatial orienting towards angry faces: a source localization study
    Diane L Santesso
    Department of Psychology, Harvard University, Cambridge, MA, USA
    Neuropsychologia 46:1338-48. 2008
    ..Results suggest that the earliest modulation of spatial attention by face stimuli is manifested in the P1 component, and provide insights about mechanisms underlying attentional orienting toward cues of threat and social disapproval...
  33. pmc Euthymic patients with bipolar disorder show decreased reward learning in a probabilistic reward task
    Diego A Pizzagalli
    Department of Psychology, Harvard University, Cambridge, MA 02138, USA
    Biol Psychiatry 64:162-8. 2008
    ..Our goal was to test the hypothesis that BPD is characterized by impairments in adjusting behavior as a function of prior reinforcement history, particularly in the presence of residual anhedonic symptoms...
  34. pmc The cognitive consequences of emotion regulation: an ERP investigation
    C M Deveney
    Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, USA
    Psychophysiology 45:435-44. 2008
    ..Results are discussed in the context of the developing ER literature, as well as theories of emotional incongruity (N400) and resource allocation (P300)...
  35. ncbi Perceived stress and cognitive vulnerability mediate the effects of personality disorder comorbidity on treatment outcome in major depressive disorder: a path analysis study
    Michele Candrian
    Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
    J Nerv Ment Dis 195:729-37. 2007
    ..Depressogenic cognitions might be continuously activated by chronic distress in MDD subjects reporting axis II pathology, leading to stress exacerbation and eventually poorer treatment outcome...
  36. pmc Single dose of a dopamine agonist impairs reinforcement learning in humans: behavioral evidence from a laboratory-based measure of reward responsiveness
    Diego A Pizzagalli
    Department of Psychology, Harvard University, 1220 William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
    Psychopharmacology (Berl) 196:221-32. 2008
    ..Animal studies have emphasized the role of phasic dopamine (DA) signaling in reward-related learning, but these processes remain largely unexplored in humans...
  37. pmc Increased perceived stress is associated with blunted hedonic capacity: potential implications for depression research
    Diego A Pizzagalli
    Department of Psychology, Harvard University, 1220 William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
    Behav Res Ther 45:2742-53. 2007
    ..These findings are consistent with preclinical data highlighting links between stress and anhedonia, and offer promising insights into potential mechanisms linking stress to depression...
  38. pmc Dissociation of neural regions associated with anticipatory versus consummatory phases of incentive processing
    Daniel G Dillon
    Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, USA
    Psychophysiology 45:36-49. 2008
    ..Although the study features several methodological improvements and helps clarify the neural basis of incentive processing, replications in larger samples are needed...
  39. pmc Task feedback effects on conflict monitoring and executive control: relationship to subclinical measures of depression
    Avram J Holmes
    Department of Psychology, Harvard University, Cambridge, MA 02138, USA
    Emotion 7:68-76. 2007
    ..These findings suggest that subclinical depression is associated with impairments in behavioral adjustments after internal (perceived failure) and external feedback about deficient task performance...
  40. pmc Acute stress reduces reward responsiveness: implications for depression
    Ryan Bogdan
    Department of Psychology, Harvard University, 33 Kirkland Street, Cambridge, MA 02138, USA
    Biol Psychiatry 60:1147-54. 2006
    ..Stress, one of the strongest risk factors for depression, has been linked to "anhedonic" behavior and dysfunctional reward-related neural circuitry in preclinical models...
  41. ncbi Frontal brain asymmetry and reward responsiveness: a source-localization study
    Diego A Pizzagalli
    Department of Psychology, Harvard University, Cambridge, MA 02138, USA
    Psychol Sci 16:805-13. 2005
    ..8% of the variance in reward bias. These findings not only confirm that frontal EEG asymmetry modulates the propensity to engage in appetitively motivated behavior, but also provide anatomical details about the underlying brain systems...
  42. ncbi Resting anterior cingulate activity and abnormal responses to errors in subjects with elevated depressive symptoms: a 128-channel EEG study
    Diego A Pizzagalli
    Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, USA
    Hum Brain Mapp 27:185-201. 2006
    ..Because rostral ACC regions have been implicated in treatment response in depression, our findings provide initial insight into putative mechanisms fostering treatment response...
  43. pmc Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task
    Diego A Pizzagalli
    Department of Psychology, Harvard University, 1220 William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
    J Psychiatr Res 43:76-87. 2008
    ..The goal of the present study was to test the hypothesis that individuals with major depression are characterized by blunted reward responsiveness, particularly when anhedonic symptoms are prominent...
  44. pmc The heritability of hedonic capacity and perceived stress: a twin study evaluation of candidate depressive phenotypes
    R Bogdan
    Department of Psychology, Harvard University, Cambridge, MA, USA
    Psychol Med 39:211-8. 2009
    ..The present proof-of-concept study assessed whether hedonic capacity and stress perception are heritable and whether their genetic and environmental contributions are shared...
  45. pmc Dissociable recruitment of rostral anterior cingulate and inferior frontal cortex in emotional response inhibition
    Pearl H Chiu
    Department of Psychology, Harvard University, Cambridge, MA 02138, USA
    Neuroimage 42:988-97. 2008
    ....
  46. pmc Variation in TREK1 gene linked to depression-resistant phenotype is associated with potentiated neural responses to rewards in humans
    Daniel G Dillon
    Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, USA
    Hum Brain Mapp 31:210-21. 2010
    ..Future studies in depressed samples should evaluate whether variation in neural responses to rewards may contribute to the association between TREK1 and antidepressant response in humans...
  47. pmc The role of the nucleus accumbens and rostral anterior cingulate cortex in anhedonia: integration of resting EEG, fMRI, and volumetric techniques
    Jan Wacker
    Department of Psychology, Philipps Universitaet, Marburg, Germany
    Neuroimage 46:327-37. 2009
    ..Taken together, these results help elucidate the neural basis of anhedonia and strengthen the argument for anhedonia as an endophenotype for depression...
  48. pmc Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder
    Diego A Pizzagalli
    Department of Psychology, Harvard University, 1220 William James Hall, 33 Kirkland St, Cambridge, MA 02138, USA
    Am J Psychiatry 166:702-10. 2009
    ....
  49. pmc Electrophysiological evidence of attentional biases in social anxiety disorder
    E M Mueller
    Department of Psychology, Boston University, Boston, MA, USA
    Psychol Med 39:1141-52. 2009
    ..We used a dot-probe task in conjunction with high-density ERPs and source localization to investigate attentional biases in SAD...
  50. pmc Childhood adversity is associated with left basal ganglia dysfunction during reward anticipation in adulthood
    Daniel G Dillon
    Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, USA
    Biol Psychiatry 66:206-13. 2009
    ..In animal models, early adversity is associated with dysfunction in basal ganglia regions involved in reward processing, but this relationship has not been established in humans...
  51. pmc Neural activity and diurnal variation of cortisol: evidence from brain electrical tomography analysis and relevance to anhedonia
    Katherine M Putnam
    National Center for PTSD, VA Boston Healthcare Center, Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02130, USA katherine putnam va gov
    Psychophysiology 45:886-95. 2008
    ..For the anhedonic group, the mPFC finding was absent. Anhedonia may be characterized by disruptions of mPFC-mediated neuroendocrine regulation, which could constitute a vulnerability to the development of stress-related disorders...
  52. pmc Single dose of a dopamine agonist impairs reinforcement learning in humans: evidence from event-related potentials and computational modeling of striatal-cortical function
    Diane L Santesso
    Department of Psychology, Harvard University, Cambridge, MA 02138, USA
    Hum Brain Mapp 30:1963-76. 2009
    ..These preliminary findings offer important insights on the role of phasic DA signals on reinforcement learning in humans and provide initial evidence regarding the spatiotemporal dynamics of brain mechanisms underlying these processes...
  53. pmc Implicit depression and hopelessness in remitted depressed individuals
    Tiffany M Meites
    Harvard University, Psychology Department, 1220 William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
    Behav Res Ther 46:1078-84. 2008
    ..Results extend prior IAT research by documenting the presence of a reduced tendency to associate the self with happiness in a sample at increased risk for depression...
  54. pmc Individual differences in reinforcement learning: behavioral, electrophysiological, and neuroimaging correlates
    Diane L Santesso
    Department of Psychology, Harvard University, 1220 William James Hall, 33 Kirkland Street, Cambridge, MA 02138, USA
    Neuroimage 42:807-16. 2008
    ..Furthermore, these results highlight the importance of the dACC to probabilistic reward learning in humans...
  55. pmc Enhanced negative feedback responses in remitted depression
    Diane L Santesso
    Department of Psychology, Harvard University, Cambridge, Massachusetts 02138, USA
    Neuroreport 19:1045-8. 2008
    ..The present findings suggest that abnormal responses to negative feedback extend to samples at increased risk for depressive episodes in the absence of current symptoms...
  56. pmc Response conflict and frontocingulate dysfunction in unmedicated participants with major depression
    Avram J Holmes
    Department of Psychology, Harvard University, Cambridge, MA 02138, USA
    Neuropsychologia 46:2904-13. 2008
    ....
  57. pmc Toward an objective characterization of an anhedonic phenotype: a signal-detection approach
    Diego A Pizzagalli
    Department of Psychology, Harvard University, Cambridge, Massachusetts, USA
    Biol Psychiatry 57:319-27. 2005
    ..Decreased approach-related behavior and anhedonia (lack of responsiveness to pleasure) are considered cardinal features of depression, but few studies have used laboratory-based measures to objectively characterize these constructs...