The 10 most-cited articles in American Journal of Psychiatry, 2023

OBJECTIVE: Childhood maltreatment is associated with mental health problems, but the extent to which this relationship is causal remains unclear. To strengthen causal inference, the authors conducted a systematic review and meta-analysis of quasi-experimental studies examining the relationship between childhood maltreatment and mental health problems. METHODS: A search of PubMed, PsycINFO, and Embase was conducted for peer-reviewed, English-language articles from database inception until January 1, 2022. Studies were included if they examined the association between childhood maltreatment and mental health problems using a quasi-experimental method (e.g., twin/sibling differences design, children of twins design, adoption design, fixed-effects design, random-intercept cross-lagged panel model, natural experiment, propensity score matching, or inverse probability weighting). RESULTS: Thirty-four quasi-experimental studies were identified, comprising 54,646 independent participants. Before quasi-experimental adjustment for confounding, childhood maltreatment was moderately associated…

OBJECTIVE: receptors and neuroactive steroid, as an oral, once-daily, 14-day treatment course for patients with severe PPD. METHODS: In this double-blind phase 3 trial, women with severe PPD were randomized in a 1:1 ratio to receive zuranolone 50 mg/day or placebo for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15; key secondary endpoints were change from baseline in HAM-D score at days 3, 28, and 45 and change from baseline in Clinical Global Impressions severity (CGI-S) score at day 15. Adverse events were monitored. RESULTS: Among 196 patients randomized (zuranolone, N=98; placebo, N=98), 170 (86.7%) completed the 45-day study. Treatment with zuranolone compared with placebo resulted in statistically significant improvement in depressive symptoms at day 15 (least squares mean [LSM] change from baseline in HAM-D score, -15.6 vs. -11.6; LSM difference, -4.0, 95% CI=-6.3, -1.7); significant improvement in depressive symptoms was also reported at days 3, 28, and 45. CGI-S score at day 15…

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: ). Significant brain tissue gene expression and drug set enrichment were…

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) protocols increasingly use subgenual anterior cingulate cortex (sgACC) functional connectivity to individualize treatment targets. However, the efficacy of this approach is unclear, with conflicting findings and varying effect sizes across studies. Here, the authors investigated the effect of the stimulation site's functional connectivity with the sgACC (sgACC-StimFC) on treatment outcome to rTMS in 295 patients with major depression. METHODS: The reliability and accuracy of estimating sgACC functional connectivity were validated with data from individuals who underwent extensive functional MRI testing. Electric field modeling was used to analyze associations between sgACC-StimFC and clinical improvement using standardized assessments and to evaluate sources of heterogeneity. RESULTS: An imputation-based method provided reliable and accurate sgACC functional connectivity estimates. Treatment responses weakly but robustly correlated with sgACC-StimFC (r=-0.16), but only when the stimulated cortex was identified using…

OBJECTIVE: Black Americans in the United States are disproportionately exposed to childhood adversity compared with White Americans. Such disparities may contribute to race-related differences in brain structures involved in regulating the emotional response to stress, such as the amygdala, hippocampus, and prefrontal cortex (PFC). The authors investigated neuroanatomical consequences of racial disparities in adversity. METHODS: The sample included 7,350 White American and 1,786 Black American children (ages 9-10) from the Adolescent Brain Cognitive Development Study (public data release 2.0). Structural MRI data, parent and child self-reports of adversity-related measures, and U.S. Census neighborhood data were used to investigate the relationship between racial disparities in adversity exposure and race-related differences in brain structure. RESULTS: Black children experienced more traumatic events, family conflict, and material hardship on average compared with White children, and their parents or caregivers had lower educational attainment, lower income, and more unemployment…

One in three adults with major depressive disorder (MDD) do not experience clinically significant improvement after multiple sequential courses of antidepressants and have treatment-resistant depression (TRD). The presence of TRD contributes to the morbidity and excess mortality associated with MDD and has been linked to significantly increased health care expenses. In the absence of a consensus definition of TRD, this report takes a broad approach by considering inadequate response to one or more courses of antidepressants and focuses on atypical antipsychotics that are approved by the U.S. Food and Drug Administration for treatment of depression (aripiprazole, brexpiprazole, cariprazine, extended-release quetiapine, and olanzapine-fluoxetine combination). While multiple acute-phase studies have demonstrated the efficacy of these medications in improving depressive symptoms, clinically meaningful improvement (i.e., remission) remains limited, with significant concerns about side effects (including weight gain, metabolic dysfunction, extrapyramidal symptoms, and tardive dyskinesia),…

The fields of psychiatry and mental health are increasingly recognizing the importance of social determinants of health (SDOH) and their impact on mental health outcomes. In this overview, the authors discuss the recent research, from the past 5 years, on advances made in SDOH work. SDOH frameworks and theories have expanded to include more social conditions, from traumas associated with immigration to psychosocial and community strengths, that impact mental health and well-being. Research has consistently shown the pervasive deleterious impacts of inequitable social conditions (e.g., food insecurity, housing instability) on minoritized populations' physical and mental health. Social systems of oppression (e.g., racism, minoritization) have also been shown to confer higher risk for psychiatric and mental disorders. The COVID-19 pandemic illuminated the inequitable impact of the social determinants of health outcomes. More efforts have been made in recent years to intervene on the social determinants through interventions at the individual, community, and policy levels, which have…

Alcohol is regularly consumed throughout most of the world, including by nearly half the U.S. population age 12 or older. Heavy drinking, which is also common, contributes to multiple adverse medical, psychiatric, and social outcomes and more than 140,000 deaths annually in the United States. It is the major risk factor for alcohol use disorder (AUD), whose current U.S. prevalence is 11%. However, AUD is undertreated, with less than 15% of individuals with a lifetime diagnosis receiving any treatment. Risk of AUD is nearly equally genetic and environmental. AUD is responsive to psychosocial treatments, including cognitive-behavioral therapy and motivational enhancement therapy. Alcohol affects multiple neurotransmitter systems, and thus pharmacotherapy for AUD is also effective. The three medications approved in the United States to treat AUD-disulfiram, naltrexone (oral and long-acting injectable formulations), and acamprosate-are underprescribed, despite being considered first-line treatments in clinical practice guidelines. Two medications not approved for treating AUD,…