Converging evidence indicates the importance of prenatal life to subsequent risk for psychopathology across the lifespan, suggesting that potential intervention during this period of heightened brain plasticity may also have enduring protective effects. We describe a novel experimental approach, the "learning" birth cohort, that couples observational and interventional methods over multiple investigation cycles, wherein high-throughput data collected in each wave are canvassed to discover, develop, and implement new interventions in subsequent waves. As illustrated, we can harness both family- and population-level data to effect iterative changes in the prenatal environment, with the goal of improved neurodevelopmental outcomes.

Disaster-related prenatal maternal stress, whether due to natural or human-made crises, can have profound effects on offspring health and development. This narrative review synthesizes research findings on the epigenetic mechanisms through which prenatal maternal stress influences long-term offspring health outcomes. Focusing primarily on DNA methylation, we examine how exposure to stress during gestation alters the epigenetic profile and may contribute to mental, cognitive, and physical health vulnerabilities. Studies were categorized based on disaster type, including time-limited events such as hurricanes, floods, and earthquakes, and stressors like the COVID-19 pandemic and famine. Key findings highlight the timing of exposure, sex-specific epigenetic effects, and the potential for epigenetic markers to mediate stress-induced health outcomes. While considerable progress has been made, our review emphasizes the need for further research on how epigenetics may mediate mental health outcomes and the development of interventions that target these molecular mechanisms.

Patients presenting with treatment-resistant depression (TRD) often have complex medical comorbidities that can limit the use of new and novel treatments. Transcranial magnetic stimulation (TMS) is FDA-approved and, overall, has a low adverse side-effect profile. Consensus guidelines, however, are broad and lack specificity around managing individual patient risk. Therefore, individual clinicians must make significant determinations about candidacy and risk management in medically complex patient presentations. This case report details a 49-year-old male with a 10-year history of major depressive disorder with significant medical comorbidity (chronic pain, post-thyroidectomy hypocalcemia secondary to hypoparathyroidism, and basal ganglia calcifications). We illustrate how interdisciplinary care coordination can allow for safe and effective use of TMS in a medically complex patient with severe TRD. This case highlights the importance of personalized treatment planning to expand access to neuromodulation.

Though Asian Americans (AAs) are the fastest growing racially minoritized group in the United States, their mental health care needs have not received adequate attention. AAs are less likely to seek mental health care than other minoritized groups. When they do, they often present more acutely, a trend exacerbated by events amidst the COVID-19 pandemic. During the pandemic, AAs experienced increased discrimination and anti-Asian hate crimes that still persist today. One in five AAs who has encountered racism has suffered psychological and emotional effects as a result. Recent studies have shown an increased risk of depression associated with anti-Asian crime rates. Although the psychological toll of COVID-19-related racism has led to increased prevalence of overall mental health symptoms, the likelihood that AAs seek care still remains low. This column highlights the specific challenges faced by AAs and the critical need for culturally responsive mental health initiatives and resources to better serve the unique needs of this community.

Functional neurologic disorder (FND) is an underrecognized but important cause of acute neurological presentations in the postpartum period, particularly among culturally diverse patient populations. We present the case of a female Nepali immigrant (G5P3023 [fifth pregnancy, three term births, zero preterm births, two pregnancies that ended before 20 weeks, three living children]) in her late 30s with no prior medical or psychiatric history. She developed sudden neurological deficits on postoperative Day 0 following an uncomplicated Cesarean delivery. Approximately 11 hours after delivery, the patient became dizzy, pale, and diaphoretic, then developed right-upper and bilateral-lower extremity paralysis with impaired eye and mouth opening. A code stroke was initiated. Extensive workup (including computed tomography head, computed tomography angiography head/neck, and magnetic resonance imaging brain) was unremarkable. Neurological deficits resolved within hours after ammonia inhalant stimulation. The patient was ultimately diagnosed with postpartum FND. This case highlights key diagnostic and management challenges in distinguishing FND from stroke, catatonia, and dissociative states in medically complex postpartum patients. It also underscores the importance of trauma-informed, culturally sensitive approaches to diagnosis and care. Our discussion explores the limited but evolving literature on postpartum FND-potentially inclusive of sensory-motor mismatch, loss of agency, hormonal shifts, and psychosocial stressors-while also exploring strategies for culturally grounded psychoeducation. Clinicians must vigilantly watch for functional presentations postpartum to avoid unnecessary interventions and promote holistic recovery. Cross-disciplinary collaboration among psychiatry, neurology, and obstetrics is essential for optimal care.

The pathophysiology of depressive disorder (DD) has been linked to the inflammatory process, and neutrophil-to-lymphocyte ratio (NLR) is considered a marker of systemic inflammation. Increasing research suggests a potential correlation between NLR and DD onset and prognosis. Current literature, however, presents conflicting results, highlighting a need for further investigation. A systematic literature search was performed in PubMed, Embase, Web of Science, and the Cochrane Library, from inception to September 4, 2024, to identify studies evaluating the relationship between NLR and DD. The primary outcomes pointed to DD prevalence and suicide risk in individuals with DD. Sensitivity and subgroup analyses were conducted to explore the heterogeneity and robustness of results. Meta-analyses were executed using STATA 15.0 and Review Manager 5.4.1. A total of 37 studies comprising 88,019 participants were included. Categorical analyses showed that high NLR was significantly associated with presence of DD (odds ratio [OR]: 1.57, 95% confidence interval [CI]: 1.28, 1.93). Continuous analyses revealed elevated NLR levels in individuals diagnosed with DD (standardized mean difference [SMD]: 0.73, 95% CI: 0.51, 0.94). Furthermore, increased NLR was associated with heightened suicide risk among those with DD (categorical outcome OR: 1.56, 95% CI: 1.26, 1.94; continuous outcome SMD: 0.42, 95% CI: 0.23, 0.61). Elevated NLR is associated with higher prevalence of DD and increased suicide risk in this patient population. NLR may serve as a promising biomarker for diagnosing and assessing individuals with DD.

Developmental psychopathology frameworks view development as a dynamic process that integrates multiple systems, clarifying how psychopathology develops and who develops it. High-risk study designs, such as those investigating progressive changes in youth with familial psychopathological histories, are one developmental research strategy. While much research focuses on clinical symptoms after they emerge, this approach hinders our understanding of when and how clinical symptoms and psychopathology develop and identification of risk factors, neural mechanisms, and clinical correlates. We review the critical value and advantages of using high-risk designs and developmental psychopathology frameworks to understand the emergence of affective psychopathology. We focus on anhedonia, a transdiagnostic affective symptom-defined as diminished experiences of pleasure-which emerges during adolescence, and occurs prior to onset of disorders like depression. We review the phenomenology, behavior, and neural mechanisms of anhedonia. Then we discuss the symptom from a developmental psychopathology perspective, outlining the advantages and disadvantages of using high-risk designs. From there, we synthesize the literature and conclude with clinical implications and considerations for future directions. These approaches are critical for understanding mental health, particularly affective psychopathology, and deserve more attention in the field.