Altered Brain Activity in Unipolar Depression Revisited

Abstract

IMPORTANCE 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. DATA SOURCES 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. STUDY SELECTION 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. DATA EXTRACTION AND SYNTHESIS 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. MAIN OUTCOMES AND MEASURES 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 AND RELEVANCE Inconsistencies exist across individual experiments investigating aberrant brain activity in UD and replication problems across previous neuroimaging meta-analyses. For individual ex...

Application of functional magnetic resonance imaging in psychiatric clinical evaluation: Controversies and avenues

“…The most recent meta‐analysis of 65 neuroimaging studies on emotional processing in unipolar depression published by Müller et al has failed to reveal any significant results across all experiments and separately for those reporting increases and decreases in patients compared with healthy controls as well as for Neg and Pos valence, emotional faces, and sex discrimination tasks. As the authors argue, this failure might be explained by the differences in experimental designs, study populations, sample size, and statistical inference.…”

Guidelines of the Polish Psychiatric Association – Wroclaw Division, the Polish Society of Family Medicine and the College of Family Physicians in Poland for diagnosis and treatment of depressive disorders in primary health care

“…the current reports on neuroimaging in unipolar depression provide no explicit data [45]. the criteria for diagnosing depression do not include the results of any neuroimaging studies, but these examinations may be useful in the exclusion of organic disorders in which mood changes may occur.…”

Subtle Scientific Fallacies Undermine the Validity of Neuroendocrinological Research: Do Not Draw Premature Conclusions on the Role of Female Sex Hormones

“…A systematic review of the literature indicates that most published findings are anecdotal, irreproducible and inconsistent, especially in the behavioral neurosciences (Ioannidis, 2011; Rosmalen and Oldehinkel, 2011; Ioannidis et al, 2014b; Sundström Poromaa and Gingnell, 2014; Müller et al, 2017). Nevertheless, many researchers tend to selectively review the literature (Tatsioni et al, 2007; Jannot et al, 2013) and to uncritically draw conclusions that are not sufficiently supported by the literature (Ioannidis et al, 2007; Saraga and Stiefel, 2011; Chalmers et al, 2014).…”

“…Original studies subjecting psychological and medical research to close scrutiny have indeed provided ample evidence that many, and sometimes even a majority, of published findings are irreproducible, false positive, or severely inflated (Ioannidis, 2005b; Turner et al, 2008; Munafo et al, 2009; Bakker et al, 2012; Begley and Ellis, 2012; Open Science Collaboration, 2015; Müller et al, 2017); for reviews see (Nosek et al, 2012; Macleod et al, 2014; Naci and Ioannidis, 2015). More specifically, Open Science Collaboration (2015) tried to replicate 100 original studies published in 2008 in three leading psychology journals.…”

“…Moreover, in the original studies the average effect size was r = 0.403 (SD = 0.188), whereas in the replication studies it was only r = 0.197 (SD = 0.257), suggesting that the evidence for the original findings is rather weak (Open Science Collaboration, 2015). Very recently, Müller et al (2017) meta-analyzed neuroimaging studies in persons with unipolar depression conducted between 1997 and 2015 and found not a single functional neuro-pattern that replicated consistently across studies, suggesting that the grand majority of published findings are irreproducible or false-positives. Finally, Contopoulos-Ioannidis et al (2003) identified a total of 101 articles published between 1979 and 1983 in six leading biomedical journals, which clearly stated that the technology studied had novel therapeutic or preventive promises.…”