Pedro Mario Pan1, João R Sato1, Giovanni A Salum1, Luis A Rohde1, Ary Gadelha1, Andre Zugman1, Jair Mari1, Andrea Jackowski1, Felipe Picon1, Eurípedes C Miguel1, Daniel S Pine1, Ellen Leibenluft1, Rodrigo A Bressan1, Argyris Stringaris1. 1. From the Department of Psychiatry, Laboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de São Paulo, São Paulo, Brazil; the Mood, Brain, and Development Unit, Emotion and Development Branch, NIMH, Bethesda, Md.; Center for Mathematics, Computing, and Cognition, Universidade Federal do ABC, Santo André, Brazil; the Department of Psychiatry, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; the Department and Institute of Psychiatry, Universidade de São Paulo, São Paulo, Brazil; the Section on Development and Affective Neuroscience and the Section on Mood Dysregulation and Neuroscience, Emotion and Development Branch, NIMH, Bethesda, Md.; the Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London; and the Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil.
Abstract
OBJECTIVE: Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. METHOD: A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. RESULTS: Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. CONCLUSIONS: Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.
OBJECTIVE: Previous studies have implicated aberrant reward processing in the pathogenesis of adolescent depression. However, no study has used functional connectivity within a distributed reward network, assessed using resting-state functional MRI (fMRI), to predict the onset of depression in adolescents. This study used reward network-based functional connectivity at baseline to predict depressive disorder at follow-up in a community sample of adolescents. METHOD: A total of 637 children 6-12 years old underwent resting-state fMRI. Discovery and replication analyses tested intrinsic functional connectivity (iFC) among nodes of a putative reward network. Logistic regression tested whether striatal node strength, a measure of reward-related iFC, predicted onset of a depressive disorder at 3-year follow-up. Further analyses investigated the specificity of this prediction. RESULTS: Increased left ventral striatum node strength predicted increased risk for future depressive disorder (odds ratio=1.54, 95% CI=1.09-2.18), even after excluding participants who had depressive disorders at baseline (odds ratio=1.52, 95% CI=1.05-2.20). Among 11 reward-network nodes, only the left ventral striatum significantly predicted depression. Striatal node strength did not predict other common adolescent psychopathology, such as anxiety, attention deficit hyperactivity disorder, and substance use. CONCLUSIONS: Aberrant ventral striatum functional connectivity specifically predicts future risk for depressive disorder. This finding further emphasizes the need to understand how brain reward networks contribute to youth depression.
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