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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.

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Supplementary Material

File (appi.ajp.2017.17040430.ds001.pdf)

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 1112 - 1119
PubMed: 28946760

History

Received: 17 April 2017
Revision received: 28 May 2017
Accepted: 3 July 2017
Published online: 26 September 2017
Published in print: November 01, 2017

Keywords

  1. Mood Disorders-Unipolar
  2. Brain Imaging Techniques
  3. Adolescents
  4. Depression
  5. Reward
  6. Cohort

Authors

Affiliations

Pedro Mario Pan, M.D. [email protected]
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.
João R. Sato, Ph.D.
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.
Giovanni A. Salum, M.D., Ph.D.
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.
Luis A. Rohde, M.D., Ph.D.
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.
Ary Gadelha, M.D., Ph.D.
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.
Andre Zugman, M.D., Ph.D.
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.
Jair Mari, M.D., Ph.D.
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.
Andrea Jackowski, Ph.D.
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.
Felipe Picon, M.D.
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.
Eurípedes C. Miguel, M.D., Ph.D.
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.
Daniel S. Pine, M.D.
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.
Ellen Leibenluft, M.D.
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.
Rodrigo A. Bressan, M.D., Ph.D.
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.
Argyris Stringaris, M.D., Ph.D.
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.

Notes

Address correspondence to Dr. Pan ([email protected]).

Funding Information

Fundação de Amparo à Pesquisa do Estado de São Paulo10.13039/501100001807: INPD (# 2014/50917-0), INPD (#2013/08531-5)
Conselho Nacional de Desenvolvimento Científico e Tecnológico10.13039/501100003593: INPD (#465550/2014-2).
Supported by the National Institute of Developmental Psychiatry for Children and Adolescents, São Paulo, with grants from the São Paulo Research Foundation (Fapesp 2014/50917-0; 2013/08531-5) and the Brazilian National Council for Scientific and Technological Development (CNPq 465550/2014-2).Dr. Rohde has received grant or research support from, served as a consultant for, and served on speakers bureaus for Eli Lilly, Janssen, Medice, Novartis, and Shire, and he has received travel grants from Shire and royalties from Artmed Editora and Oxford University Press; the ADHD and juvenile bipolar disorder outpatient programs chaired by Dr. Rohde have received unrestricted educational and research support from Eli Lilly, Janssen, Novartis, and Shire. Dr. Gadelha has served on advisory boards for Janssen and Daiichi Sankyo and he has served as a speaker for Janssen and Aché. Dr. Bressan has received funding from the São Paulo Research Foundation, honoraria for educational input and nonfinancial support from Aché, honoraria from Lundbeck, and grants, honoraria, and nonfinancial support from Janssen. Dr. Stringaris has received funding from the Wellcome Trust and the U.K. National Institutes of Health Research, funds from University College London for a joint project with Johnson & Johnson, and royalties from Cambridge University Press and Oxford University Press. The other authors report no financial relationships with commercial interests.

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