Altered Brain Activity in Unipolar Depression Revisited: Meta-analyses of Neuroimaging Studies.
OBJECTIVE
During the past 20 years, numerous neuroimaging experiments have investigated aberrant brain activation during cognitive and emotional processing in patients with unipolar depression (UD). The results of those investigations, however, vary considerably; moreover, previous meta-analyses also yielded inconsistent findings.


OBJECTIVE
To readdress aberrant brain activation in UD as evidenced by neuroimaging experiments on cognitive and/or emotional processing.


METHODS
Neuroimaging experiments published from January 1, 1997, to October 1, 2015, were identified by a literature search of PubMed, Web of Science, and Google Scholar using different combinations of the terms fMRI (functional magnetic resonance imaging), PET (positron emission tomography), neural, major depression, depression, major depressive disorder, unipolar depression, dysthymia, emotion, emotional, affective, cognitive, task, memory, working memory, inhibition, control, n-back, and Stroop.


METHODS
Neuroimaging experiments (using fMRI or PET) reporting whole-brain results of group comparisons between adults with UD and healthy control individuals as coordinates in a standard anatomic reference space and using an emotional or/and cognitive challenging task were selected.


METHODS
Coordinates reported to show significant activation differences between UD and healthy controls during emotional or cognitive processing were extracted. By using the revised activation likelihood estimation algorithm, different meta-analyses were calculated.


METHODS
Meta-analyses tested for brain regions consistently found to show aberrant brain activation in UD compared with controls. Analyses were calculated across all emotional processing experiments, all cognitive processing experiments, positive emotion processing, negative emotion processing, experiments using emotional face stimuli, experiments with a sex discrimination task, and memory processing. All meta-analyses were calculated across experiments independent of reporting an increase or decrease of activity in major depressive disorder. For meta-analyses with a minimum of 17 experiments available, separate analyses were performed for increases and decreases.


RESULTS
In total, 57 studies with 99 individual neuroimaging experiments comprising in total 1058 patients were included; 34 of them tested cognitive and 65 emotional processing. Overall analyses across cognitive processing experiments (P > .29) and across emotional processing experiments (P > .47) revealed no significant results. Similarly, no convergence was found in analyses investigating positive (all P > .15), negative (all P > .76), or memory (all P > .48) processes. Analyses that restricted inclusion of confounds (eg, medication, comorbidity, age) did not change the results.


CONCLUSIONS
Inconsistencies exist across individual experiments investigating aberrant brain activity in UD and replication problems across previous neuroimaging meta-analyses. For individual experiments, these inconsistencies may relate to use of uncorrected inference procedures, differences in experimental design and contrasts, or heterogeneous clinical populations; meta-analytically, differences may be attributable to varying inclusion and exclusion criteria or rather liberal statistical inference approaches.
Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany2Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
Veronika I
VI
Müller
Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany2Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
Edna C
EC
Cieslik
Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Ilinca
I
Serbanescu
Department of Physics, Florida International University, Miami.
Angela R
AR
Laird
Research Imaging Institute, University of Texas Health Science Center, San Antonio5Research Service, South Texas Veterans Administration Medical Center, San Antonio6State Key Laboratory for Brain and Cognitive Sciences, University of Hong Kong, Hong Kong, China.
Peter T
PT
Fox
Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany2Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
Simon B
SB
Eickhoff
D000328:Adult; D001143:Arousal / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D003866:Depressive Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D004644:Emotions / Q000502:physiology; D059907:Functional Neuroimaging; D006801:Humans; D016013:Likelihood Functions; D008279:Magnetic Resonance Imaging; D012016:Reference Values; D009435:Synaptic Transmission / Q000502:physiology