Neuroscientific Advances Supporting New Treatments for Major Depression

Article Psychiatry

Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial

Herriot Tabuteau et al.

Summary: This study evaluated the efficacy and safety of dextromethorphan-bupropion in the treatment of major depressive disorder, with results showing that dextromethorphan-bupropion was more effective in improving depressive symptoms compared to bupropion, and was generally well tolerated.

AMERICAN JOURNAL OF PSYCHIATRY (2022)

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Article Psychiatry

Digital Intervention for Cognitive Deficits in Major Depression: A Randomized Controlled Trial to Assess Efficacy and Safety in Adults

Richard S. E. Keefe et al.

Summary: AKL-T03, a digital intervention delivered through a video game-based interface, was evaluated for its effectiveness in enhancing attentional control and cognitive functioning in adult patients with major depressive disorder and cognitive impairment. The study results showed significant improvement in sustained attention and overall cognitive functioning with AKL-T03 compared to a control intervention.

AMERICAN JOURNAL OF PSYCHIATRY (2022)

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Article Psychiatry

Predictive Value of Acute Neuroplastic Response to rTMS in Treatment Outcome in Depression: A Concurrent TMS-fMRI Trial

Ruiyang Ge et al.

Summary: The study investigated the predictive value of functional connectivity changes induced by acute repetitive transcranial magnetic stimulation (rTMS) for clinical response in treatment-resistant depression. The findings suggest that these connectivity changes may serve as predictors of treatment response and can inform prospective clinical trials.

AMERICAN JOURNAL OF PSYCHIATRY (2022)

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Article Psychiatry

Longitudinal Trajectory of the Link Between Ventral Striatum and Depression in Adolescence

Pedro Mario Pan et al.

Summary: This study found associations between right VS connectivity and baseline depressive disorders, and between left VS connectivity and anhedonia at 2 years, as well as between right VS connectivity and anhedonia at 4 years.

AMERICAN JOURNAL OF PSYCHIATRY (2022)

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Article Multidisciplinary Sciences

Reproducible brain-wide association studies require thousands of individuals

Scott Marek et al.

Summary: Magnetic resonance imaging (MRI) has greatly advanced our understanding of the human brain, but similar progress has not been made in mental health research. By analyzing three large neuroimaging datasets, researchers found that brain-wide association studies (BWAS) had smaller effect sizes than previously thought, leading to underpowered studies, inflated effect sizes, and replication failures. As sample sizes increased, replication rates improved and effect size inflation decreased. Functional MRI, cognitive tests, and multivariate methods showed more robust effects in BWAS. Smaller than expected brain-phenotype associations and population subsample variability explain the widespread replication failures in BWAS. Reproducibility in BWAS requires samples with thousands of individuals.

NATURE (2022)

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Editorial Material Psychiatry

Understanding the Efficacy and Mechanism of Action of a Dextromethorphan-Bupropion Combination: Where Does It Fit in the NMDA Versus mu-Opioid Story?

Alan F. Schatzberg

AMERICAN JOURNAL OF PSYCHIATRY (2022)

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Review Psychiatry

Toward a Better Understanding of the Mechanisms and Pathophysiology of Anhedonia: Are We Ready for Translation?

Diego A. Pizzagalli

Summary: Anhedonia, the loss of pleasure or lack of reactivity to pleasurable stimuli, is a significant challenge in neuropsychiatric disorders. It is associated with poor disease course and treatment response in major depressive disorder, and has been linked to neural abnormalities that may be targets for prevention. Gaps in understanding anhedonia remain, and the author highlights the need for controlled clinical trials, relevant preclinical models, and clinical scales that incorporate advances in neuroscientific understanding. The author emphasizes the importance of an integrated, collaborative, cross-species, and multilevel approach to tackling anhedonia.

AMERICAN JOURNAL OF PSYCHIATRY (2022)

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Editorial Material Psychiatry