Journal
AMERICAN JOURNAL OF PSYCHIATRY
Volume 172, Issue 12, Pages 1215-1223Publisher
AMER PSYCHIATRIC PUBLISHING, INC
DOI: 10.1176/appi.ajp.2015.14101298
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Funding
- European Union [LSHM-CT-2007-037286]
- FP7 project IMAGEMEND (Imaging Genetics for Mental Disorders)
- Innovative Medicine Initiative Project EU-AIMS [115300-2]
- Medical Research Council Programme Grant Developmental pathways into adolescent substance abuse [93558]
- Swedish funding agency FORMAS
- Wellcome Trust (Behavioural and Clinical Neuroscience Institute, University of Cambridge)
- National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
- U.K. Department of Health
- Bundesministerium fur Bildung und Forschung (BMBF) [01GS08152, 01EV0711, eMED SysAlc01ZX1311A]
- NIH [RO1 MH085772-01A1]
- French funding agency ANR [RO1 MH085772-01A1, ANR-12-SAMA-0004]
- Eranet-Neuron grant [AF12-NEUR0008-01-WM2NA]
- Assistance Publique Hopitaux de Paris
- Paris Descartes University
- Paris Sud University [IDEX-2012]
- Fondation de France
- Mission Interministerielle de Lutte Contre la Drogue et La Toxicomanie
- Wellcome Trust
- U.K. National Institutes of Health Research
- University College London
- Alicia Koplowitz Foundation
- Eli Lilly
- Medice
- Novartis
- Shire
- German Federal Ministry of Education and Research
- German Science Foundation
- AstraZeneca
- Janssen-Cilag
- Bristol-Myers Squibb
- Janssen-Citag
- INSERM (interface grant)
- Medical Research Council [G0901858] Funding Source: researchfish
- MRC [G0901858] Funding Source: UKRI
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Objective: The authors examined whether alterations in the brain's reward network operate as a mechanism across the spectrum of risk for depression. They then tested whether these alterations are specific to anhedonia as compared with low mood and whether they are predictive of depressive outcomes. Method: Functional MRI was used to collect blood-oxygen-level-dependent (BOLD) responses to anticipation of reward in the monetary incentive task in 1,576 adolescents in a community-based sample. Adolescents with current subthreshold depression and clinical depression were compared with matched healthy subjects. In addition, BOLD responses were compared across adolescents with anhedonia, low mood, or both symptoms, cross-sectionally and longitudinally. Results: Activity in the ventral striatum was reduced in participants with subthreshold and clinical depression relative to healthy comparison subjects. Low ventral striatum activation predicted transition to subthreshold or clinical depression in previously healthy adolescents at 2-year follow-up. Brain responses during reward anticipation decreased in a graded manner between healthy adolescents, adolescents with current or future subthreshold depression, and adolescents with current or future clinical depression. Low ventral striatum activity was associated with anhedonia but not low mood; however, the combined presence of both symptoms showed the strongest reductions in the ventral striatum in all analyses. Conclusions: The findings suggest that reduced striatal activation operates as a mechanism across the risk spectrum for depression. It is associated with anhedonia in healthy adolescents and is a behavioral indicator of positive valence systems, consistent with predictions based on the Research Domain Criteria.
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