The 10 most-cited articles in American Journal of Psychiatry, 2020

OBJECTIVE: New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression. METHODS: Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the…

Objective: The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders. Methods: Searches of PubMed and PsycINFO via Ovid were conducted for articles in English, in peer-reviewed journals, reporting on “psilocybin,” “lysergic acid diethylamide,” “LSD,” “ayahuasca,” “3,4-methylenedioxymethamphetamine,” and “MDMA,” in human subjects, published between 2007 and July 1, 2019. A total of 1,603 articles were identified and screened. Articles that did not contain the terms “clinical trial,” “therapy,” or “imaging” in the title or abstract were filtered out. The 161 remaining articles were reviewed by two or more authors. The authors identified 14 articles reporting on well-designed clinical trials investigating the efficacy of lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin, and ayahuasca for the treatment of mood and anxiety disorders, trauma and stress-related disorders, and substance-related and addictive disorders as well as in end-of-life care. Results: The most…

OBJECTIVE: Imaging studies of major depressive disorder have reported structural and functional abnormalities in a variety of spatially diverse brain regions. Quantitative meta-analyses of this literature, however, have failed to find statistically significant between-study spatial convergence, other than transdiagnostic-only effects. In the present study, the authors applied a novel multimodal meta-analytic approach to test the hypothesis that major depression exhibits spatially convergent structural and functional brain abnormalities. METHODS: This coordinate-based meta-analysis included voxel-based morphometry (VBM) studies and resting-state voxel-based pathophysiology (VBP) studies of blood flow, glucose metabolism, regional homogeneity, and amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF). Input data were grouped into three primary meta-analytic classes: gray matter atrophy, increased function, and decreased function in patients with major depression relative to healthy control subjects. In secondary meta-analyses, the data were grouped across primary…

OBJECTIVE: Disrupted emotional processing is a common feature of many psychiatric disorders. The authors investigated functional disruptions in neural circuitry underlying emotional processing across a range of tasks and across psychiatric disorders through a transdiagnostic quantitative meta-analysis of published neuroimaging data. METHODS: A PubMed search was conducted for whole-brain functional neuroimaging findings published through May 2018 that compared activation during emotional processing tasks in patients with psychiatric disorders (including schizophrenia, bipolar or unipolar depression, anxiety, and substance use) to matched healthy control participants. Activation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates to identify spatial convergence. RESULTS: The 298 experiments submitted to meta-analysis included 5,427 patients and 5,491 control participants. ALE across diagnoses and patterns of patient hyper- and hyporeactivity demonstrated abnormal activation in the amygdala, the hippocampal/parahippocampal gyri, the dorsomedial/pulvinar…

OBJECTIVE: Treatment of different depression symptoms may require different brain stimulation targets with different underlying brain circuits. The authors sought to identify such targets, which could improve the efficacy of therapeutic brain stimulation and facilitate personalized therapy. METHODS: The authors retrospectively analyzed two independent cohorts of patients who received left prefrontal transcranial magnetic stimulation (TMS) for treatment of depression (discovery sample, N=30; active replication sample, N=81; sham replication sample, N=87). Each patient's TMS site was mapped to underlying brain circuits using functional connectivity MRI from a large connectome database (N=1,000). Circuits associated with improvement in each depression symptom were identified and then clustered based on similarity. The authors tested for reproducibility across data sets and whether symptom-specific targets derived from one data set could predict symptom improvement in the other independent cohort. RESULTS: The authors identified two distinct circuit targets effective for two discrete…

Abstract We used GWAS in the Million Veteran Program sample (nearly 200,000 informative individuals) using a continuous trait for anxiety (GAD-2) to identify 5 genome-wide significant (GWS) signals for European Americans (EA) and 1 for African Americans. The strongest findings were on chromosome 3 (rs4603973, p=7.40×10 −11 ) near the SATB1 locus, a global regulator of gene expression and on chromosome 6 (rs6557168, p=1.04×10 −9 ) near ESR1 which encodes estrogen receptor α. A locus identified on chromosome 7 near MADIL1 (p=1.62×10 −8 ) has been previously identified in GWAS of bipolar disorder and of schizophrenia and may represent a risk factor for psychiatric disorders broadly. SNP-based heritability was estimated to be ~6% for GAD-2. We also GWASed for self-reported anxiety disorder diagnoses (N=224,330) and identified two GWS loci, one (rs35546597, MAF=0.42, p=1.88×10 −8 ) near the AURKB locus, and the other (rsl0534613, MAF=0.41, p=4.92×10 −8 ) near the IQCHE and MADIL1 locus identified in the GAD-2 analysis. We demonstrate reproducibility by replicating our top findings in the…

Back to table of contents Previous article Next article CommentaryFull AccessMental Health Response to the COVID-19 Outbreak in ChinaJunying Zhou, M.D., Ph.D., Liu Liu, M.D., Pei Xue, M.D., Xiaorong Yang, B.N., Xiangdong Tang, M.D., Ph.D.Junying Zhou, M.D., Ph.D., Liu Liu, M.D., Pei Xue, M.D., Xiaorong Yang, B.N., Xiangdong Tang, M.D., Ph.D.Published Online:7 May 2020https://doi.org/10.1176/appi.ajp.2020.20030304AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Transmission of the 2019 novel coronavirus (COVID-19) (1) has now widely and rapidly spread around the world. On March 11, 2020, the World Health Organization announced that COVID-19 is a pandemic (2). The rapid transmission and mortality risk of the COVID-19 infection may increase the risk of mental health problems among healthy individuals in the general public and worsen preexisting psychiatric problems in psychiatric patients, although data are still being gathered. A constellation of difficult feelings and psychological distress, including panic,…

OBJECTIVE: Although anxiety can be an adaptive response to unpredictable threats, pathological anxiety disorders occur when symptoms adversely affect daily life. Whether or not adaptive and pathological anxiety share mechanisms remains unknown, but if they do, induced (adaptive) anxiety could be used as an intermediate translational model of pathological anxiety to improve drug development pipelines. The authors therefore compared meta-analyses of functional neuroimaging studies of induced and pathological anxiety. METHODS: A systematic search of the PubMed database was conducted in June 2019 for whole-brain functional MRI articles. Eligible articles contrasted either anxious patients to control subjects or an unpredictable-threat condition to a safe condition in healthy participants. Five anxiety disorders were included: posttraumatic stress disorder, social anxiety disorder, generalized anxiety disorder, panic disorder, and specific phobia. A total of 3,433 records were identified, 181 articles met selection criteria, and the largest subset of task type was emotional (N=138).…