The neural correlates of emotional face-processing in adolescent depression: a dimensional approach focusing on anhedonia and illness severity

Deficits in emotion processing, a known clinical feature of major depressive disorder (MDD), have been widely investigated using emotional face paradigms and neuroimaging. However, most studies have not accounted for the high inter-subject variability of symptom severity. Similarly, only sparse research has focused on MDD in adolescence, early in the course of the illness. Here we sought to investigate neural responses to emotional faces using both categorical and dimensional analyses with a focus on anhedonia, a core symptom of MDD associated with poor outcomes. Nineteen medication-free depressed adolescents and 18 healthy controls (HC) were scanned during presentation of happy, sad, fearful, and neutral faces. ANCOVAs and regressions assessed group differences and relationships with illness and anhedonia severity, respectively. Findings included a group by valence interaction with depressed adolescents exhibiting decreased activity in the superior temporal gyrus (STG), putamen and premotor cortex. Post-hoc analyses confirmed decreased STG activity in MDD adolescents. Dimensional analyses revealed associations between illness severity and altered responses to negative faces in prefrontal, cingulate, striatal, and limbic regions. However, anhedonia severity was uniquely correlated with responses to happy faces in the prefrontal, cingulate, and insular regions. Our work highlights the need for studying specific symptoms dimensionally in psychiatric research.

[1]  H. Critchley Neural mechanisms of autonomic, affective, and cognitive integration , 2005, The Journal of comparative neurology.

[2]  N. Yeung,et al.  Anterior Cingulate Cortex , 2002 .

[3]  J. Tanaka,et al.  The NimStim set of facial expressions: Judgments from untrained research participants , 2009, Psychiatry Research.

[4]  R. Adolphs,et al.  Social and monetary reward learning engage overlapping neural substrates. , 2012, Social cognitive and affective neuroscience.

[5]  Amy R. Johnson,et al.  A Preliminary Study of White Matter in Adolescent Depression: Relationships with Illness Severity, Anhedonia, and Irritability , 2013, Front. Psychiatry.

[6]  Pienie Zwitserlood,et al.  Automatic Mood-Congruent Amygdala Responses to Masked Facial Expressions in Major Depression , 2010, Biological Psychiatry.

[7]  M. Shad,et al.  Gray matter differences between healthy and depressed adolescents: a voxel-based morphometry study. , 2012, Journal of child and adolescent psychopharmacology.

[8]  E. Aarts,et al.  Attentional control of task and response in lateral and medial frontal cortex: Brain activity and reaction time distributions , 2009, Neuropsychologia.

[9]  John Suckling,et al.  Neural responses to happy facial expressions in major depression following antidepressant treatment. , 2007, The American journal of psychiatry.

[10]  T. Insel,et al.  Wesleyan University From the SelectedWorks of Charles A . Sanislow , Ph . D . 2010 Research Domain Criteria ( RDoC ) : Toward a New Classification Framework for Research on Mental Disorders , 2018 .

[11]  Benjamin A. Ely,et al.  The possible role of the kynurenine pathway in anhedonia in adolescents , 2012, Journal of Neural Transmission.

[12]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[13]  B. Biswal,et al.  Functional connectivity of human striatum: a resting state FMRI study. , 2008, Cerebral cortex.

[14]  Gregory G. Brown,et al.  Adolescents with major depression demonstrate increased amygdala activation. , 2010, Journal of the American Academy of Child and Adolescent Psychiatry.

[15]  A. Beck,et al.  Screening for major depression disorders in medical inpatients with the Beck Depression Inventory for Primary Care. , 1997, Behaviour research and therapy.

[16]  K. Dobson,et al.  A systematic meta-analysis of the Stroop task in depression. , 2012, Clinical psychology review.

[17]  Steven C. R. Williams,et al.  The Neural Correlates of Anhedonia in Major Depressive Disorder , 2005, Biological Psychiatry.

[18]  William D S Killgore,et al.  Ventromedial prefrontal activity correlates with depressed mood in adolescent children , 2006, Neuroreport.

[19]  K. Davis,et al.  Two systems of resting state connectivity between the insula and cingulate cortex , 2009, Human brain mapping.

[20]  Monique Ernst,et al.  Nucleus accumbens, thalamus and insula connectivity during incentive anticipation in typical adults and adolescents , 2013, NeuroImage.

[21]  Udo Dannlowski,et al.  Facial emotion processing in major depression: a systematic review of neuroimaging findings , 2011, Biology of Mood & Anxiety Disorders.

[22]  R. von Känel,et al.  BioPsychoSocial Medicine BioMed Central Review , 2007 .

[23]  M. Mintun,et al.  Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study , 2001, Biological Psychiatry.

[24]  A. Young,et al.  A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder , 2005, Biological Psychiatry.

[25]  P. Fox,et al.  Amygdala hyperactivation in untreated depressed individuals , 2009, Psychiatry Research: Neuroimaging.

[26]  D. Pine,et al.  Adolescent depressive symptoms as predictors of adult depression: moodiness or mood disorder? , 1999, The American journal of psychiatry.

[27]  Katherine H. Taber,et al.  Anterior Cingulate Cortex: Unique Role in Cognition and Emotion , 2011 .

[28]  D. Pine,et al.  Face-memory and emotion: associations with major depression in children and adolescents. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[29]  Angela R Laird,et al.  A meta‐analytic study of changes in brain activation in depression , 2008, Human brain mapping.

[30]  Michael P Milham,et al.  Striatum-based circuitry of adolescent depression and anhedonia. , 2013, Journal of the American Academy of Child and Adolescent Psychiatry.

[31]  R. Adolphs Neural systems for recognizing emotion , 2002, Current Opinion in Neurobiology.

[32]  Michael S. Gaffrey,et al.  Association between depression severity and amygdala reactivity during sad face viewing in depressed preschoolers: an fMRI study. , 2011, Journal of affective disorders.

[33]  Kathryn R. Cullen,et al.  An Fmri Study of Emotional Face Processing in Adolescent Major Depression in Partial Fulfillment of the Requirements for the Degree of Master of Arts Emotion Face Processing in Adolescent Depression Emotion Face Processing in Adolescent Depression , 2022 .

[34]  A. Song,et al.  The involvement of the dopaminergic midbrain and cortico-striatal-thalamic circuits in the integration of reward prospect and attentional task demands. , 2012, Cerebral cortex.

[35]  Simon B. Eickhoff,et al.  A quantitative meta-analysis and review of motor learning in the human brain , 2013, NeuroImage.

[36]  Kevin J. Grimm,et al.  Emerging depression is associated with face memory deficits in adolescent girls. , 2011, Journal of the American Academy of Child and Adolescent Psychiatry.

[37]  D. Hedeker,et al.  Differences between anhedonic and normally hedonic depressive states. , 1983, The American journal of psychiatry.

[38]  Wang Xiang,et al.  Elevated amygdala activity to negative faces in young adults with early onset major depressive disorder , 2012, Psychiatry Research: Neuroimaging.

[39]  W. Nolen,et al.  Predictors of suicidality in depressive spectrum disorders in the general population: results of the Netherlands Mental Health Survey and Incidence Study , 2010, Social Psychiatry and Psychiatric Epidemiology.

[40]  J. Anthony,et al.  Child and adolescent clinical features as forerunners of adult-onset major depressive disorder: retrospective evidence from an epidemiological sample. , 2004, Journal of affective disorders.

[41]  G. MacQueen,et al.  Systematic review of the neural basis of social cognition in patients with mood disorders. , 2012, Journal of psychiatry & neuroscience : JPN.

[42]  M A Young,et al.  Time-related predictors of suicide in major affective disorder. , 1990, The American journal of psychiatry.

[43]  V. Diwadkar,et al.  fMRI responses to emotional faces in children and adolescents at genetic risk for psychiatric illness share some of the features of depression. , 2012, Journal of Affective Disorders.

[44]  A. Beck,et al.  Assessment of suicidal intention: the Scale for Suicide Ideation. , 1979, Journal of consulting and clinical psychology.

[45]  Jin Fan,et al.  Common and distinct networks underlying reward valence and processing stages: A meta-analysis of functional neuroimaging studies , 2011, Neuroscience & Biobehavioral Reviews.

[46]  G. Gründer,et al.  Differential patterns of nucleus accumbens activation during anticipation of monetary and social reward in young and older adults. , 2014, Social cognitive and affective neuroscience.

[47]  N. Ryan,et al.  Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor treatment-resistant depression. , 2012, Journal of the American Academy of Child and Adolescent Psychiatry.

[48]  Benjamin A. Ely,et al.  Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia. , 2012, Archives of general psychiatry.

[49]  Michael S. Gaffrey,et al.  Functional Brain Activation to Emotionally Valenced Faces in School-Aged Children with a History of Preschool-Onset Major Depression , 2012, Biological Psychiatry.

[50]  M. Phillips,et al.  Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression , 2004, Biological Psychiatry.

[51]  Christopher S. Monk,et al.  Increased Amygdala Activity During Successful Memory Encoding in Adolescent Major Depressive Disorder: An fMRI Study , 2006, Biological Psychiatry.