Neural Processing of Reward and Punishment in Young People at Increased Familial Risk of Depression


      Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder.


      We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16–21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects.


      We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli.


      Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Epstein J.
        • Pan H.
        • Kocsis J.H.
        • Yang Y.
        • Butler T.
        • Chusid J.
        • et al.
        Lack of ventral striatal response to positive stimuli in depressed versus normal subjects.
        Am J Psychiatry. 2006; 163: 1784-1790
        • Keedwell P.A.
        • Andrew C.
        • Williams S.C.
        • Brammer M.J.
        • Phillips M.L.
        The neural correlates of anhedonia in major depressive disorder.
        Biol Psychiatry. 2005; 58: 843-853
        • Knutson B.
        • Bhanji J.P.
        • Cooney R.E.
        • Atlas L.Y.
        • Gotlib I.H.
        Neural responses to monetary incentives in major depression.
        Biol Psychiatry. 2008; 63: 686-692
        • Kumar P.
        • Waiter G.
        • Ahearn T.
        • Milders M.
        • Reid I.
        • Steele J.D.
        Abnormal temporal difference reward-learning signals in major depression.
        Brain. 2008; 131: 2084-2093
        • Pizzagalli D.A.
        • Holmes A.J.
        • Dillon D.G.
        • Goetz E.L.
        • Birk J.L.
        • Bogdan R.
        • et al.
        Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder.
        Am J Psychiatry. 2009; 166: 702-710
        • Steele J.D.
        • Kumar P.
        • Ebmeier K.P.
        Blunted response to feedback information in depressive illness.
        Brain. 2007; 130: 2367-2374
        • Hasler G.
        • Drevets W.C.
        • Manji H.K.
        • Charney D.S.
        Discovering endophenotypes for major depression.
        Neuropsychopharmacology. 2004; 29: 1765-1781
        • McCabe C.
        • Cowen P.J.
        • Harmer C.J.
        Neural representation of reward in recovered depressed patients.
        Psychopharmacology (Berl). 2009; 205: 667-677
        • Beardslee W.R.
        • Versage E.M.
        • Gladstone T.R.
        Children of affectively ill parents: A review of the past 10 years.
        J Am Acad Child Adolesc Psychiatry. 1998; 37: 1134-1141
        • McCabe C.
        • Rolls E.T.
        Umami: A delicious flavor formed by convergence of taste and olfactory pathways in the human brain.
        Eur J Neurosci. 2007; 25: 1855-1864
        • McCabe C.
        • Rolls E.T.
        • Bilderbeck A.
        • McGlone F.
        Cognitive influences on the affective representation of touch and the sight of touch in the human brain.
        Soc Cogn Affect Neurosci. 2008; 3: 97-108
        • O'Doherty J.
        • Rolls E.T.
        • Francis S.
        • Bowtell R.
        • McGlone F.
        Representation of pleasant and aversive taste in the human brain.
        J Neurophysiol. 2001; 85: 1315-1321
        • Rolls E.T.
        • McCabe C.
        Enhanced affective brain representations of chocolate in cravers vs. non-cravers.
        Eur J Neurosci. 2007; 26: 1067-1076
        • Eshel N.
        • Roiser J.P.
        Reward and punishment processing in depression.
        Biol Psychiatry. 2010; 68: 118-124
        • First M.B.
        • Spitzer R.L.
        • Gibbon M.
        • Williams J.B.W.
        Structured Clinical Interview for DSM-IV Axis I Disorders: Clinical Version.
        American Psychiatric Press, Washington, DC1997
        • Andreasen N.C.
        • Endicott J.
        • Spitzer R.L.
        • Winokur G.
        The family history method using diagnostic criteria.
        Arch Gen Psychiatry. 1977; 34: 1229-1235
        • Oldfield R.C.
        The assessment and analysis of handedness: The Edinburgh inventory.
        Neuropsychologia. 1971; 9: 97-113
        • Beck A.T.
        • Ward C.H.
        • Mendelson M.
        • Mock J.
        • Erbaugh J.
        An inventory for measuring depression.
        Arch Gen Psychiatry. 1961; 4: 561-571
        • Fawcett J.
        • Clark D.C.
        • Scheftner W.A.
        • Gibbons R.D.
        Assessing anhedonia in psychiatric patients.
        Arch Gen Psychiatry. 1983; 40: 79-84
        • Snaith R.P.
        • Hamilton M.
        • Morley S.
        • Humayan A.
        • Hargreaves D.
        • Trigwell P.
        A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale.
        Br J Psychiatry. 1995; 167: 99-103
        • de Araujo I.E.
        • Kringelbach M.L.
        • Rolls E.T.
        • Hobden P.
        Representation of umami taste in the human brain.
        J Neurophysiol. 2003; 90: 313-319
        • de Araujo I.E.
        • Kringelbach M.L.
        • Rolls E.T.
        • McGlone F.
        Human cortical responses to water in the mouth, and the effects of thirst.
        J Neurophysiol. 2003; 90: 1865-1876
        • Wilson J.L.
        • Jenkinson M.
        • de Araujo I.
        • Kringelbach M.L.
        • Rolls E.T.
        • Jezzard P.
        Fast, fully automated global and local magnetic field optimization for fMRI of the human brain.
        Neuroimage. 2002; 17: 967-976
        • Friston K.J.
        • Glaser D.E.
        • Henson R.N.
        • Kiebel S.
        • Phillips C.
        • Ashburner J.
        Classical and Bayesian inference in neuroimaging: applications.
        Neuroimage. 2002; 16: 484-512
        • Friston K.J.
        • Worsley K.J.
        • Frackowiak R.S.J.
        • Mazziotta J.C.
        • Evans A.C.
        Assessing the significance of focal activations using their spatial extent.
        Hum Brain Mapp. 1994; 1: 214-220
        • Mannie Z.N.
        • Norbury R.
        • Murphy S.E.
        • Inkster B.
        • Harmer C.J.
        • Cowen P.J.
        Affective modulation of anterior cingulate cortex in young people at increased familial risk of depression.
        Br J Psychiatry. 2008; 192: 356-361
        • Rolls E.T.
        • Kringelbach M.L.
        • de Araujo I.E.
        Different representations of pleasant and unpleasant odours in the human brain.
        Eur J Neurosci. 2003; 18: 695-703
        • Fitzgerald D.A.
        • Posse S.
        • Moore G.J.
        • Tancer M.E.
        • Nathan P.J.
        • Phan K.L.
        Neural correlates of internally-generated disgust via autobiographical recall: A functional magnetic resonance imaging investigation.
        Neurosci Lett. 2004; 370: 91-96
        • Gotlib I.H.
        • Hamilton J.P.
        • Cooney R.E.
        • Singh M.K.
        • Henry M.L.
        • Joormann J.
        Neural processing of reward and loss in girls at risk for major depression.
        Arch Gen Psychiatry. 2011; 67: 380-387
        • Preuschoff K.
        • Quartz S.R.
        • Bossaerts P.
        Human insula activation reflects risk prediction errors as well as risk.
        J Neurosci. 2008; 28: 2745-2752
        • Monk C.S.
        • Klein R.G.
        • Telzer E.H.
        • Schroth E.A.
        • Mannuzza S.
        • Moulton 3rd, J.L.
        • et al.
        Amygdala and nucleus accumbens activation to emotional facial expressions in children and adolescents at risk for major depression.
        Am J Psychiatry. 2008; 165: 90-98
        • Elliott R.
        • Friston K.J.
        • Dolan R.J.
        Dissociable neural responses in human reward systems.
        J Neurosci. 2000; 20: 6159-6165
        • Liu X.
        • Hairston J.
        • Schrier M.
        • Fan J.
        Common and distinct networks underlying reward valence and processing stages: A meta-analysis of functional neuroimaging studies.
        Neurosci Biobehav Rev. 2011; 35: 1219-1236
        • Zald D.H.
        Orbitofrontal cortex contributions to food selection and decision making.
        Ann Behav Med. 2009; 38: S18-S24
        • Murray E.A.
        • Wise S.P.
        Interactions between orbital prefrontal cortex and amygdala: Advanced cognition, learned responses and instinctive behaviors.
        Curr Opin Neurobiol. 2010; 20: 212-220
        • Rushworth M.F.
        • Noonan M.P.
        • Boorman E.D.
        • Walton M.E.
        • Behrens T.E.
        Frontal cortex and reward-guided learning and decision-making.
        Neuron. 2011; 70: 1054-1069
        • Rudebeck P.H.
        • Behrens T.E.
        • Kennerley S.W.
        • Baxter M.G.
        • Buckley M.J.
        • Walton M.E.
        • et al.
        Frontal cortex subregions play distinct roles in choices between actions and stimuli.
        J Neurosci. 2008; 28: 13775-13785
        • Kennerley S.W.
        • Walton M.E.
        • Behrens T.E.
        • Buckley M.J.
        • Rushworth M.F.
        Optimal decision making and the anterior cingulate cortex.
        Nat Neurosci. 2006; 9: 940-947
        • Glascher J.
        • Hampton A.N.
        • O'Doherty J.P.
        Determining a role for ventromedial prefrontal cortex in encoding action-based value signals during reward-related decision making.
        Cereb Cortex. 2009; 19: 483-495
        • Boes A.D.
        • McCormick L.M.
        • Coryell W.H.
        • Nopoulos P.
        Rostral anterior cingulate cortex volume correlates with depressed mood in normal healthy children.
        Biol Psychiatry. 2008; 63: 391-397
        • O'Doherty J.
        • Kringelbach M.L.
        • Rolls E.T.
        • Hornak J.
        • Andrews C.
        Abstract reward and punishment representations in the human orbitofrontal cortex.
        Nat Neurosci. 2001; 4: 95-102
        • McCabe C.
        • Mishor Z.
        • Cowen P.J.
        • Harmer C.J.
        Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment.
        Biol Psychiatry. 2010; 67: 439-445
        • Kendler K.S.
        • Thornton L.M.
        • Gardner C.O.
        Stressful life events and previous episodes in the etiology of major depression in women: An evaluation of the “kindling” hypothesis.
        Am J Psychiatry. 2000; 157: 1243-1251
        • Kendler K.S.
        • Karkowski-Shuman L.
        Stressful life events and genetic liability to major depression: Genetic control of exposure to the environment?.
        Psychol Med. 1997; 27: 539-547
        • Behrens T.E.
        • Hunt L.T.
        • Woolrich M.W.
        • Rushworth M.F.
        Associative learning of social value.
        Nature. 2008; 456: 245-249

      Linked Article

      • A “Taste” of What is to Come: Reward Sensitivity as a Potential Endophenotype for Major Depressive Disorder
        Biological PsychiatryVol. 72Issue 7
        • Preview
          Nearly 40% of patients diagnosed with major depressive disorder (MDD) experience a loss of interest and responsiveness to previously rewarding stimuli and activities, a condition referred to clinically as anhedonia (see [1] for review). Anhedonia is one of the most treatment-resistant aspects of depression (2), and there is good reason to believe that the pathophysiology underlying this symptom complex may at least partly involve hypoactivity within the mesolimbic dopamine pathway and related brain structures (3).
        • Full-Text
        • PDF