Adolescent depression is a major public health problem that frequently recurs in the patient's life with significant costs to the adolescent and society. Presently, our understanding of the underlying neural substrates of adolescent depression is very limited. The number of pediatric functional neuroimaging studies is extremely sparse. The few functional magnetic resonance imaging (fMRI) studies of the amygdala in pediatric depression have reported opposite results. There are no published fMRI studies examining the subgenual anterior cingulate or dorsal lateral prefrontal cortex in depressed adolescents relative to matched, healthy adolescents except for the recent publication by the Principal Investigator (Dr. Yang). Furthermore, there are no published functional neuroimaging studies in depressed adolescents examining possible brain regions that might be predictors of future clinical response to treatment. Description: This proposal is both a cross-sectional and longitudinal follow-up study. In this application, we plan to: (1) recruit 64adolescents with major depressive disorder (MDD) and 64 healthy, control adolescents;and (2) follow the depressed adolescents longitudinally over 6 months after the initial assessment. MDD and healthy adolescents ages 13 to 17 years will participate in this study. Both genders and all ethnicities will be included. Recruitment will be through several major sources using the same approach as established in 5K23MH070791. Similarly, using the same approach established in 5K23MH070791, all adolescents will be carefully screened and undergo a series of interviews, questionnaires, and assessments to obtain information pertinent to this study. Adolescents will be scanned using fMRI tasks that activate the adolescent amygdala, dorsal lateral prefrontal cortices, and subgenual anterior cingulate cortex. A single fMRI scan will occur at baseline. Clinical assessments will occur at baseline, 3 months, and 6 months. The 6-month clinical assessment will be the primary time point of interest for the longitudinal study. The Children's Depression Rating Scale-Revised (CDRS-R) will be the primary clinical outcome measure. The Beck Depression Inventory II and Children's Global Assessment Scale will be the secondary clinical outcome measures.
Aims :
Aims of the current proposal are to: (1) contrast brain activation in the amygdala, dorsal lateral prefrontal cortices (DLPFC), and subgenual anterior cingulate cortex (sgACC) using fMRI between adolescents with MDD and matched healthy controls, and (2) evaluate the relationship between fMRI activation in the amygdala, DLPFC, and sgACC at baseline and the future clinical response to treatment in adolescents with MDD. Accomplishing these aims will advance the neurobiology of adolescent depression by: (1) contributing to an overall understanding and model of adolescent depression that can be used to develop clinically relevant tools, and (2) taking the necessary first steps towards the translation of basic functional neuroimaging findings into a useful clinical tool that can predict future treatment response in depressed adolescents.

Public Health Relevance

Depression is a major public health problem that frequently recurs in the patient's life with significant costs to the adolescent and society. This functional magnetic resonance imaging study will advance the understanding and treatment of adolescent depression by: (1) further elucidating the underlying network of cortical and subcortical brain structures that are affected in adolescent depression by performing a cross- sectional study in depressed and healthy adolescents, and (2) taking the initial steps towards utilizing the knowledge gained from a deeper understanding of which brain structures are affected in depressed adolescents to aid the development of a clinically relevant fMRI tool that has the potential to predict future treatment response in depressed adolescents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH085734-05
Application #
8456199
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Garriock, Holly A
Project Start
2010-07-01
Project End
2015-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2013
Total Cost
$502,678
Indirect Cost
$182,246
Name
University of California San Francisco
Department
Psychiatry
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Ho, Tiffany C; Sacchet, Matthew D; Connolly, Colm G et al. (2017) Inflexible Functional Connectivity of the Dorsal Anterior Cingulate Cortex in Adolescent Major Depressive Disorder. Neuropsychopharmacology 42:2434-2445
DeGuzman, Marisa; Shott, Megan E; Yang, Tony T et al. (2017) Association of Elevated Reward Prediction Error Response With Weight Gain in Adolescent Anorexia Nervosa. Am J Psychiatry 174:557-565
Tymofiyeva, Olga; Connolly, Colm G; Ho, Tiffany C et al. (2017) DTI-based connectome analysis of adolescents with major depressive disorder reveals hypoconnectivity of the right caudate. J Affect Disord 207:18-25
Connolly, Colm G; Ho, Tiffany C; Blom, Eva Henje et al. (2017) Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression. J Affect Disord 207:86-94
Shott, Megan E; Pryor, Tamara L; Yang, Tony T et al. (2016) Greater Insula White Matter Fiber Connectivity in Women Recovered from Anorexia Nervosa. Neuropsychopharmacology 41:498-507
Yamagata, Bun; Murayama, Kou; Black, Jessica M et al. (2016) Female-Specific Intergenerational Transmission Patterns of the Human Corticolimbic Circuitry. J Neurosci 36:1254-60
Ho, Tiffany C; Zhang, Shunan; Sacchet, Matthew D et al. (2016) Fusiform Gyrus Dysfunction is Associated with Perceptual Processing Efficiency to Emotional Faces in Adolescent Depression: A Model-Based Approach. Front Psychol 7:40
Henje Blom, Eva; Tymofiyeva, Olga; Chesney, Margaret A et al. (2016) Feasibility and Preliminary Efficacy of a Novel RDoC-Based Treatment Program for Adolescent Depression: ""Training for Awareness Resilience and Action"" (TARA)-A Pilot Study. Front Psychiatry 7:208
Henje Blom, Eva; Ho, Tiffany C; Connolly, Colm G et al. (2016) The neuroscience and context of adolescent depression. Acta Paediatr 105:358-65
Sacchet, Matthew D; Ho, Tiffany C; Connolly, Colm G et al. (2016) Large-Scale Hypoconnectivity Between Resting-State Functional Networks in Unmedicated Adolescent Major Depressive Disorder. Neuropsychopharmacology 41:2951-2960

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