Meta-analysis of functional neuroimaging of major depressive disorder in youth
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IMPORTANCE: Despite its high prevalence and morbidity, the underlying neural basis of major depressive disorder (MDD) in youth is not well understood. OBJECTIVES: To identify in youth diagnosed as having MDD the most reliable neural abnormalities reported in existing functional neuroimaging studies and characterize their relations with specific psychological dysfunctions. DATA SOURCES: Searches were conducted in PubMed and Web of Science to identify relevant studies published from November 2006 through February 2015. The current analysis took place from August 21, 2014, to March 28, 2015. STUDY SELECTION: We retained articles that conducted a comparison of youth aged 4 to 24 years diagnosed as having MDD and age-matched healthy controls using task-based functional magnetic resonance imaging and a voxelwise whole-brain approach. DATA EXTRACTION AND SYNTHESIS: We extracted coordinates of brain regions exhibiting differential activity in youth with MDD compared with healthy control participants. Multilevel kernel density analysis was used to examine voxelwise between-group differences throughout the whole brain. Correction for multiple comparisons was performed by computing null hypothesis distributions from 10 000 Monte Carlo simulations and calculating the cluster size necessary to obtain the familywise error rate control at P < .05. MAIN OUTCOMES AND MEASURES: Abnormal levels of activation in youth diagnosed as having MDD compared with control participants during a variety of affective processing and executive functioning tasks. RESULTS: Compared with age-matched healthy control participants (n = 274), youth with MDD (n = 246) showed reliable patterns of abnormal activation, including the following task-general and task-specific effects: hyperactivation in subgenual anterior cingulate cortex (P < .05) and ventrolateral prefrontal cortex (P < .05) and hypoactivation in caudate (P < .01) across aggregated tasks; hyperactivation in thalamus (P < .03) and parahippocampal gyrus (P < .003) during affective processing tasks; hypoactivation in cuneus (P < .001), dorsal cingulate cortex (P < .05), and dorsal anterior insula (P < .05) during executive functioning tasks; hypoactivity in posterior insula (P < .005) during positive valence tasks; and hyperactivity in dorsolateral prefrontal cortex (P < .001) and superior temporal cortex (P < .003) during negative valence tasks. CONCLUSIONS AND RELEVANCE: Altered activations in several distributed brain networks may help explain the following seemingly disparate symptoms of MDD in youth: hypervigilance toward emotional stimuli from the overactivation of central hubs in the subgenual anterior cingulate cortex and thalamus that lead to a cascade of other symptoms; ineffective emotion regulation despite increased activation of the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during affective processing, which may reverse across development or the clinical course; maladaptive rumination and poor executive control from difficulties shifting from default mode network activity to task-positive network activity during cognitively demanding tasks; and anhedonia from hypoactivation of the cuneus and posterior insula during reward processing.
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Intimate partner violence and sexual abuse, which are endemic globally, are major risk factors for depression, particularly in women, who are more likely to experience such violence, including coercive controlling behaviours.
“There is now a large evidence base that intimate partner violence and sexual abuse, which are endemic globally, are major risk factors for depression, particularly in women, 280,281 who are more likely to experience such violence, including coercive controlling behaviours. 282”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [280]
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- Authors
- Miller, C. H., Hamilton, J. P., Sacchet, M. D., & Gotlib, I. H.
- Affiliations
- Stanford University (US)
- Laureate Institute for Brain Research (US)
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2015-10-01
- Volume
- 72
- Issue
- 10
- Pages
- 1045
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC11890701
- OpenAlex
- W1696318955
- Cited by
- 229
- References
- 51
- Citations by year
- 2026: 17 · 2025: 21 · 2024: 18 · 2023: 23 · 2022: 24 · 2021: 24 · 2020: 17 · 2019: 25 · 2018: 18 · 2017: 23 · 2016: 16 · 2015: 2
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r21mh101545-02)
- National Institute of Mental Health (MH101545, R21-MH101545, MH74849, R01MH074849, R37MH101495)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- major depressive disorder, youth, subgenual anterior cingulate cortex, ventrolateral prefrontal cortex, caudate nucleus, thalamus, parahippocampal gyrus, dorsal anterior insula, posterior insula, dorsolateral prefrontal cortex, emotional processing, executive function, task-based fMRI
- MeSH terms
- Adolescent, Affect, Brain, Caudate Nucleus, Cerebral Cortex, Child, Child, Preschool, Major Depressive Disorder, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Occipital Lobe, Temporal Lobe, Thalamus, Case-Control Studies, Prefrontal Cortex, Parahippocampal Gyrus, Young Adult, Executive Function, Functional Neuroimaging
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