Increased Activity Imbalance in Fronto-Subcortical Circuits in Adolescents with Major Depression

Background A functional discrepancy exists in adolescents between frontal and subcortical regions due to differential regional maturational trajectories. It remains unknown how this functional discrepancy alters and whether the influence from the subcortical to the frontal system plays a primacy role in medication naïve adolescent with major depressive disorder (MDD). Methodology/Principal Findings Eighteen MDD and 18 healthy adolescents were enrolled. Depression and anxiety severity was assessed by the Short Mood and Feeling Questionnaire (SMFQ) and Screen for Child Anxiety Related Emotional Disorders (SCARED) respectively. The functional discrepancy was measured by the amplitude of low-frequency fluctuations (ALFF) of resting-state functional MRI signal. Correlation analysis was carried out between ALFF values and SMFQ and SCARED scores. Resting brain activity levels measured by ALFF was higher in the frontal cortex than that in the subcortical system involving mainly (para) limbic-striatal regions in both HC and MDD adolescents. The difference of ALFF values between frontal and subcortical systems was increased in MDD adolescents as compared with the controls. Conclusions/Significance The present study identified an increased imbalance of resting-state brain activity between the frontal cognitive control system and the (para) limbic-striatal emotional processing system in MDD adolescents. The findings may provide insights into the neural correlates of adolescent MDD.

[1]  Manzar Ashtari,et al.  Neuroimaging Studies of Children with Serious Emotional Disturbances: A Selective Review , 2007, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[2]  Janet Thomas,et al.  The Developing Child , 1991 .

[3]  Cheng Pei.  Reliability and Validity of the Short Mood and Feelings Questionnaire in Chinese Adolescents , 2009 .

[4]  Suzanne E. Welcome,et al.  Mapping cortical change across the human life span , 2003, Nature Neuroscience.

[5]  Bryon A. Mueller,et al.  A preliminary study of functional connectivity in comorbid adolescent depression , 2009, Neuroscience Letters.

[6]  Bharat B. Biswal,et al.  The oscillating brain: Complex and reliable , 2010, NeuroImage.

[7]  B. Luna.  Developmental changes in cognitive control through adolescence. , 2009, Advances in child development and behavior.

[8]  Alan C. Evans,et al.  Growing Together and Growing Apart: Regional and Sex Differences in the Lifespan Developmental Trajectories of Functional Homotopy , 2010, The Journal of Neuroscience.

[9]  Chaozhe Zhu,et al.  An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: Fractional ALFF , 2008, Journal of Neuroscience Methods.

[10]  Yong He,et al.  Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. , 2007, Brain & development.

[11]  Aaron D. Boes,et al.  Rostral Anterior Cingulate Cortex Volume Correlates with Depressed Mood in Normal Healthy Children , 2008, Biological Psychiatry.

[12]  N. Raoux,et al.  Executive functioning and verbal memory in young patients with unipolar depression and schizophrenia , 1999, Psychiatry Research.

[13]  P. Renshaw,et al.  Smaller frontal lobe white matter volumes in depressed adolescents , 2002, Biological Psychiatry.

[14]  Thomas Weiss,et al.  How do brain areas communicate during the processing of noxious stimuli? An analysis of laser-evoked event-related potentials using the Granger causality index. , 2008, Journal of neurophysiology.

[15]  A. Kleinschmidt,et al.  Electroencephalographic signatures of attentional and cognitive default modes in spontaneous brain activity fluctuations at rest , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[16]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[17]  D. Rosenberg,et al.  Striatal volume abnormalities in treatment-naïve patients diagnosed with pediatric major depressive disorder. , 2008, Journal of child and adolescent psychopharmacology.

[18]  P. Fossati,et al.  [Executive functioning in unipolar depression: a review]. , 2002, L'Encephale.

[19]  G. Glover,et al.  Biological Substrates of Emotional Reactivity and Regulation in Adolescence During an Emotional Go-Nogo Task , 2008, Biological Psychiatry.

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

[21]  L. Steinberg.  Cognitive and affective development in adolescence , 2005, Trends in Cognitive Sciences.

[22]  L. Su,et al.  Reliability and validity of the screen for child anxiety related emotional disorders (SCARED) in Chinese children. , 2008, Journal of anxiety disorders.

[23]  Cheng Xu,et al.  Decreased regional homogeneity in insula and cerebellum: A resting-state fMRI study in patients with major depression and subjects at high risk for major depression , 2010, Psychiatry Research: Neuroimaging.

[24]  Huafu Chen,et al.  fMRI study of mesial temporal lobe epilepsy using amplitude of low‐frequency fluctuation analysis , 2010, Human brain mapping.

[25]  H. Meltzer,et al.  The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology. , 2000, Journal of child psychology and psychiatry, and allied disciplines.

[26]  Sandra M. Neer,et al.  The Screen for Child Anxiety Related Emotional Disorders (SCARED): scale construction and psychometric characteristics. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[27]  A. Pickles,et al.  Psychiatric disorders in the relatives of depressed probands. I. Comparison of prepubertal, adolescent and early adult onset cases. , 1997, Journal of affective disorders.

[28]  Benjamin J. Tamber-Rosenau,et al.  Avoiding non-independence in fMRI data analysis: Leave one subject out , 2010, NeuroImage.

[29]  R. V. Van Heertum,et al.  Response of cortical metabolic deficits to serotonergic challenge in familial mood disorders. , 2003, The American journal of psychiatry.

[30]  Yong He,et al.  Erratum to “Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI” [Brain Develop 29 (2) (2007) 83–91] , 2012, Brain and Development.

[31]  D. Yurgelun-Todd,et al.  Depressed mood and lateralized prefrontal activity during a Stroop task in adolescent children , 2007, Neuroscience Letters.

[32]  Yongmei Shi,et al.  Abnormal neural activity in the patients with remitted geriatric depression: a resting-state functional magnetic resonance imaging study. , 2008, Journal of affective disorders.

[33]  M. Raichle,et al.  Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism , 2002, European Neuropsychopharmacology.

[34]  M E Phelps,et al.  Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. , 2001, Archives of general psychiatry.

[35]  Thomas F. Nugent,et al.  Dynamic mapping of human cortical development during childhood through early adulthood. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Adriana Galvan,et al.  The adolescent brain. , 2008, Developmental review : DR.

[37]  J. Giedd.  Structural Magnetic Resonance Imaging of the Adolescent Brain , 2004, Annals of the New York Academy of Sciences.

[38]  Yufeng Zang,et al.  DPARSF: A MATLAB Toolbox for “Pipeline” Data Analysis of Resting-State fMRI , 2010 .

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

[40]  W. Drevets,et al.  Orbitofrontal Cortex Function and Structure in Depression , 2007, Annals of the New York Academy of Sciences.

[41]  Adrian Angold,et al.  Development of a Short Questionnaire for Use in Epidemiological Studies of Depression in Children and Adolescents: Factor Composition and Structure Across Development. , 1995 .

[42]  P. Huttenlocher.  Synaptic density in human frontal cortex - developmental changes and effects of aging. , 1979, Brain research.

[43]  Y. Zang,et al.  Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI , 2007, Brain and Development.

[44]  Y. Levkovitz,et al.  rTMS for adolescents: Safety and efficacy considerations , 2010, Psychiatry Research.

[45]  Chaogan Yan,et al.  DPARSF: A MATLAB Toolbox for “Pipeline” Data Analysis of Resting-State fMRI , 2010, Front. Syst. Neurosci..

[46]  Qiyong Gong,et al.  High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China , 2009, Proceedings of the National Academy of Sciences.

[47]  V. Kusumakar,et al.  MRI study of the pituitary gland in adolescent depression. , 2004, Journal of psychiatric research.

[48]  John Suckling,et al.  Brain Imaging Correlates of Depressive Symptom Severity and Predictors of Symptom Improvement After Antidepressant Treatment , 2007, Biological Psychiatry.

[49]  L. Somerville,et al.  Developmental neurobiology of cognitive control and motivational systems , 2010, Current Opinion in Neurobiology.

[50]  David R Rosenberg,et al.  Increased amygdala: hippocampal volume ratios associated with severity of anxiety in pediatric major depression. , 2003, Journal of child and adolescent psychopharmacology.

[51]  M. Delgado,et al.  Event-related functional magnetic resonance imaging of reward-related brain circuitry in children and adolescents , 2004, Biological Psychiatry.

[52]  P Videbech,et al.  The Danish PET/depression project: PET findings in patients with major depression , 2001, Psychological Medicine.

[53]  P. Boesiger,et al.  Imbalance between Left and Right Dorsolateral Prefrontal Cortex in Major Depression Is Linked to Negative Emotional Judgment: An fMRI Study in Severe Major Depressive Disorder , 2008, Biological Psychiatry.