A preliminary study of functional connectivity in comorbid adolescent depression

Major depressive disorder (MDD) begins frequently in adolescence and is associated with severe outcomes, but the developmental neurobiology of MDD is not well understood. Research in adults has implicated fronto-limbic neural networks in the pathophysiology of MDD, particularly in relation to the subgenual anterior cingulate cortex (ACC). Developmental changes in brain networks during adolescence highlight the need to examine MDD-related circuitry in teens separately from adults. Using resting state functional magnetic resonance imaging (fMRI), this study examined functional connectivity in adolescents with MDD (n=12) and healthy adolescents (n=14). Seed-based connectivity analysis revealed that adolescents with MDD have decreased functional connectivity in a subgenual ACC-based neural network that includes the supragenual ACC (BA 32), the right medial frontal cortex (BA 10), the left inferior (BA 47) and superior frontal cortex (BA 22), superior temporal gyrus (BA 22), and the insular cortex (BA 13). These preliminary data suggest that MDD in adolescence is associated with abnormal connectivity within neural circuits that mediate emotion processing. Future research in larger, un-medicated samples will be necessary to confirm this finding. We conclude that hypothesis-driven, seed-based analyses of resting state fMRI data hold promise for advancing our current understanding of abnormal development of neural circuitry in adolescents with MDD.

[1]  Daniel S. Margulies,et al.  Mapping the functional connectivity of anterior cingulate cortex , 2007, NeuroImage.

[2]  Sarah A. Mustillo,et al.  Prevalence and development of psychiatric disorders in childhood and adolescence. , 2003, Archives of general psychiatry.

[3]  S. Rauch,et al.  Neurobiology of emotion perception II: implications for major psychiatric disorders , 2003, Biological Psychiatry.

[4]  S. Faraone,et al.  Psychiatric comorbidity among referred juveniles with major depression: fact or artifact? , 1995, Journal of the American Academy of Child and Adolescent Psychiatry.

[5]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[6]  M. Raichle,et al.  Subgenual prefrontal cortex abnormalities in mood disorders , 1997, Nature.

[7]  M M Weissman,et al.  Depressed adolescents grown up. , 1999, JAMA.

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

[9]  Danielle S. Bassett,et al.  A validated network of effective amygdala connectivity , 2007, NeuroImage.

[10]  P. Jerabek,et al.  Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response , 2000, Biological Psychiatry.

[11]  C. Murray,et al.  A critical examination of summary measures of population health. , 2000, Bulletin of the World Health Organization.

[12]  Steven C. R. Williams,et al.  A functional MRI study of happy and sad affective states induced by classical music , 2007, Human brain mapping.

[13]  A. Craig.  How do you feel? Interoception: the sense of the physiological condition of the body , 2002, Nature Reviews Neuroscience.

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

[15]  G. Glover,et al.  Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus , 2007, Biological Psychiatry.

[16]  Lisa Feldman Barrett,et al.  Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies , 2008, NeuroImage.

[17]  S. Petersen,et al.  The maturing architecture of the brain's default network , 2008, Proceedings of the National Academy of Sciences.

[18]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[19]  F. Benes,et al.  Amygdalo‐cortical sprouting continues into early adulthood: Implications for the development of normal and abnormal function during adolescence , 2002, The Journal of comparative neurology.

[20]  Yuan Zhou,et al.  The relationship within and between the extrinsic and intrinsic systems indicated by resting state correlational patterns of sensory cortices , 2007, NeuroImage.

[21]  A. Lozano,et al.  Deep Brain Stimulation for Treatment-Resistant Depression , 2005, Neuron.

[22]  D. Yurgelun-Todd,et al.  Fear-related activity in the prefrontal cortex increases with age during adolescence: A preliminary fMRI study , 2006, Neuroscience Letters.

[23]  B. Biswal,et al.  Cingulate-Precuneus Interactions: A New Locus of Dysfunction in Adult Attention-Deficit/Hyperactivity Disorder , 2008, Biological Psychiatry.

[24]  W. Drevets,et al.  The Subgenual Anterior Cingulate Cortex in Mood Disorders , 2008, CNS Spectrums.

[25]  J. Talbott,et al.  Prevalence and Co-occurrence of Substance Use Disorders and Independent Mood and Anxiety Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions , 2006 .

[26]  H. Mayberg.  Limbic-cortical dysregulation: a proposed model of depression. , 1997, The Journal of neuropsychiatry and clinical neurosciences.

[27]  M. Lowe,et al.  Activity and Connectivity of Brain Mood Regulating Circuit in Depression: A Functional Magnetic Resonance Study , 2005, Biological Psychiatry.

[28]  D. Margulies,et al.  Development of anterior cingulate functional connectivity from late childhood to early adulthood. , 2009, Cerebral cortex.

[29]  S. Petersen,et al.  Development of distinct control networks through segregation and integration , 2007, Proceedings of the National Academy of Sciences.

[30]  M. Constantine-Paton,et al.  Development of hemodynamic responses and functional connectivity in rat somatosensory cortex , 2008, Nature Neuroscience.

[31]  Martin P Paulus,et al.  Decreased functional coupling of the amygdala and supragenual cingulate is related to increased depression in unmedicated individuals with current major depressive disorder. , 2008, Journal of affective disorders.

[32]  B. Grant,et al.  Prevalence and Co-Occurrence of Substance Use Disorders and Independent Mood and Anxiety Disorders , 2004, Archives of general psychiatry.

[33]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[34]  Timothy Edward John Behrens,et al.  A Tractography Analysis of Two Deep Brain Stimulation White Matter Targets for Depression , 2009, Biological Psychiatry.

[35]  W. Drevets.  Prefrontal Cortical‐Amygdalar Metabolism in Major Depression , 1999, Annals of the New York Academy of Sciences.

[36]  Heather L. Urry,et al.  Failure to Regulate: Counterproductive Recruitment of Top-Down Prefrontal-Subcortical Circuitry in Major Depression , 2007, The Journal of Neuroscience.

[37]  S. Rauch,et al.  Neurobiology of emotion perception I: the neural basis of normal emotion perception , 2003, Biological Psychiatry.

[38]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version , 2011 .