Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.

In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.

The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).

Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

We compare the Emory 10-item, 4-choice Rey Complex Figure (CF) Recognition task with the Meyers and Lange (M&L) 24-item yes/no CF Recognition task in a large cohort of healthy research participants and in patients with heterogeneous movement disorder diagnoses. While both tasks assess CF recognition, they differ in key aspects including the saliency of target and distractor responses, self-selection versus forced-choice formats, and the length of the item sets.

There were 1056 participants from the Emory Healthy Brain Study (EHBS; average MoCA = 26.8, SD = 2.4) and 223 movement disorder patients undergoing neuropsychological evaluation (average MoCA = 24.3, SD = 4.0).

Both recognition tasks differentiated between healthy and clinical groups; however, the Emory task demonstrated a larger effect size (Cohen’s d = 1.02) compared to the M&L task (Cohen’s d = 0.79). d-prime scoring of M&L recognition showed comparable group discrimination (Cohen’s d = 0.81). Unidimensional two-parameter logistic item response theory analysis revealed that many M&L items had low discrimination values and extreme difficulty parameters, which contributed to the task’s reduced sensitivity, particularly at lower cognitive proficiency levels relevant to clinical diagnosis. Dimensionality analyses indicated the influence of response sets as a potential contributor to poor item performance.

Emory CF Recognition task demonstrates superior psychometric properties and greater sensitivity to cognitive impairment compared to the M&L task. Its ability to more precisely measure lower levels of cognitive functioning, along with its brevity, suggests it may be more effective for diagnostic use, especially in clinical populations with cognitive decline.

Rapid molecular diagnostics, such as the BIOFIRE® Blood Culture Identification 2 (BCID2) panel, have improved the time to pathogen identification in bloodstream infections. However, accurate interpretation and antimicrobial optimization require Infectious Disease (ID) expertise, which may not always be readily available. GPT-powered chatbots could support antimicrobial stewardship programs (ASPs) by assisting non-specialist providers in BCID2 result interpretation and treatment recommendations. This study evaluates the performance of a GPT-4 chatbot compared to ASP prospective audit and feedback interventions.

This prospective observational study assessed 43 consecutive real-world cases of bacteremia at a 399-bed VA Medical Center from January to May 2024. The GPT-chatbot utilized “chain-of-thought” prompting and external knowledge integration to generate recommendations. Two independent ID physicians evaluated chatbot and ASP recommendations across four domains: BCID2 interpretation, source control, antibiotic therapy, and additional diagnostic workup. The primary endpoint was the combined rate of harmful or inadequate recommendations. Secondary endpoints assessed the rate of harmful or inadequate responses for each domain.

The chatbot had a significantly higher rate of harmful or inadequate recommendations (13%) compared to ASP (4%, p = 0.047). The most significant discrepancy was observed in the domain of antibiotic therapy, where harmful recommendations occurred in up to 10% (p <0.05) of chatbot evaluations. The chatbot performed well in BCID2 interpretation (100% accuracy) but provided more inadequate responses in source control consideration (10% vs. 2% for ASP, p = 0.022).

GPT-powered chatbots show potential for supporting antimicrobial stewardship but should only complement, not replace, human expertise in infectious disease management.

Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) can treat suicidal symptoms; however, the effects of rTMS on suicidal ideation (SI) in late-life depression (LLD) have not been well-characterized, particularly with theta burst stimulation (TBS).

Data were analyzed from 84 older adults with depression from the FOUR-D trial (ClinicalTrials.gov identifier: NCT02998580), who received either bilateral standard rTMS or bilateral TBS targeting the dorsolateral prefrontal cortex. The primary outcome was change in the Beck Scale for Suicide Ideation (SSI). The secondary outcome was remission of SI. Demographic, cognitive, and clinical characteristics that may moderate the effects of rTMS or TBS on SI were explored.

There was a statistically significant change in the total SSI score over time [χ2(7) = 136.018, p < 0.001], with no difference between the two treatment groups. Remission of SI was 55.8% in the standard rTMS group and 53.7% in the TBS group. In the standard rTMS group, there was no difference in remission of SI between males and females, whereas remission was higher in females in the TBS group (χ2(1) =6.87, p = 0.009). There was a significant correlation between time to remission of SI and RCI z-score for D-KEFS inhibition/switching [rs = −0.389, p = 0.012].

Both bilateral rTMS and bilateral TBS were effective in reducing SI in LLD. There may be sex differences in response to TBS, with females having more favorable response in reducing SI. There may be an association between improvement in cognitive flexibility and inhibition and reduction of SI.

Older adults with treatment-resistant depression (TRD) benefit more from treatment augmentation than switching. It is useful to identify moderators that influence these treatment strategies for personalised medicine.

Our objective was to test whether age, executive dysfunction, comorbid medical burden, comorbid anxiety or the number of previous adequate antidepressant trials could moderate the superiority of augmentation over switching. A significant moderator would influence the differential effect of augmentation versus switching on treatment outcomes.

We performed a preplanned moderation analysis of data from the Optimizing Outcomes of Treatment-Resistant Depression in Older Adults (OPTIMUM) randomised controlled trial (N = 742). Participants were 60 years old or older with TRD. Participants were either (a) randomised to antidepressant augmentation with aripiprazole (2.5–15 mg), bupropion (150–450 mg) or lithium (target serum drug level 0.6 mmol/L) or (b) switched to bupropion (150–450 mg) or nortriptyline (target serum drug level 80–120 ng/mL). Treatment duration was 10 weeks. The two main outcomes of this analysis were (a) symptom improvement, defined as change in Montgomery–Asberg Depression Rating Scale (MADRS) scores from baseline to week 10 and (b) remission, defined as MADRS score of 10 or less at week 10.

Of the 742 participants, 480 were randomised to augmentation and 262 to switching. The number of adequate previous antidepressant trials was a significant moderator of depression symptom improvement (b = −1.6, t = −2.1, P = 0.033, 95% CI [−3.0, −0.1], where b is the coefficient of the relationship (i.e. effect size), and t is the t-statistic for that coefficient associated with the P-value). The effect was similar across all augmentation strategies. No other putative moderators were significant.

Augmenting was superior to switching antidepressants only in older patients with fewer than three previous antidepressant trials. This suggests that other intervention strategies should be considered following three or more trials.

Cortical excitability has been proposed as a novel neurophysiological marker of neurodegeneration in Alzheimer’s dementia (AD). However, the link between cortical excitability and structural changes in AD is not well understood.

To assess the relationship between cortical excitability and motor cortex thickness in AD.

In 62 participants with AD (38 females, mean ± SD age = 74.6 ± 8.0) and 47 healthy control (HC) individuals (26 females, mean ± SD age = 71.0 ± 7.9), transcranial magnetic stimulation resting motor threshold (rMT) was determined, and T1-weighted MRI scans were obtained. Skull-to-cortex distance was obtained manually for each participant using MNI coordinates of the motor cortex (x = −40, y = −20, z = 52).

The mean skull-to-cortex distances did not differ significantly between participants with AD (22.9 ± 4.3 mm) and HC (21.7 ± 4.3 mm). Participants with AD had lower motor cortex thickness than healthy individuals (t(92) = −4.4, p = <0.001) and lower rMT (i.e., higher excitability) than HC (t(107) = −2.0, p = 0.045). In the combined sample, rMT was correlated positively with motor cortex thickness (r = 0.2, df = 92, p = 0.036); however, this association did not remain significant after controlling for age, sex and diagnosis.

Patients with AD have decreased cortical thickness in the motor cortex and higher motor cortex excitability. This suggests that cortical excitability may be a marker of neurodegeneration in AD.

It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.

To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.

Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.

IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).

Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.

Mood and anxiety disorders co-occur and share symptoms, treatments and genetic risk, but it is unclear whether combining them into a single phenotype would better capture genetic variation. The contribution of common genetic variation to these disorders has been investigated using a range of measures; however, the differences in their ability to capture variation remain unclear, while the impact of rare variation is mostly unexplored.

We aimed to explore the contributions of common genetic variation and copy number variations associated with risk of psychiatric morbidity (P-CNVs) to different measures of internalising disorders.

We investigated eight definitions of mood and anxiety disorder, and a combined internalising disorder, derived from self-report questionnaires, diagnostic assessments and electronic healthcare records (EHRs). Association of these definitions with polygenic risk scores (PRSs) of major depressive disorder and anxiety disorder, as well as presence of a P-CNV, was assessed.

The effect sizes of both PRSs and P-CNVs were similar for mood and anxiety disorder. Compared to mood and anxiety disorder, internalising disorder resulted in higher prediction accuracy for PRSs, and increased significance of associations with P-CNVs for most definitions. Comparison across the eight definitions showed that PRSs had higher prediction accuracy and effect sizes for stricter definitions, whereas P-CNVs were more strongly associated with EHR- and self-report-based definitions.

Future studies may benefit from using a combined internalising disorder phenotype, and may need to consider that different phenotype definitions may be more informative depending on whether common or rare variation is studied.

Disaster response plans play a major role in mitigating the impact of climate-related disasters on community food access. This study examined existing disaster response plans in 5 US locations that experienced the costliest hurricanes since 2017 (states: Florida, Texas, Louisiana; territories: Puerto Rico, US Virgin Islands) to assess how existing disaster response plans and response efforts address food-related issues across 4 key domains: availability, accessibility, agency, and acceptability.

A content analysis of disaster response plans was conducted. Disaster response plans were complemented by a review of gray literature and media sources examining the post-hurricane aftermaths. Disaster plans were coded using a deductive analysis approach guided by the Disaster Food Security Framework.

The analysis revealed significant disparities in planning and resources between territories and states. Findings highlight political and structural drivers of disparities in food access, particularly in US territories. State-mandated procedures resulted in a consistent level of effectiveness in their food distribution strategies.

These disparities underscore the need for targeted policy reforms and enhanced federal support to ensure equitable food security during disasters.

Opioid use disorder (OUD) is a devastating condition with frequent suicidality, contributing to overdose deaths. Theta burst stimulation (TBS) to the dorsolateral prefrontal cortex (DLPFC) is used to treat major depressive disorder (MDD) and is effective in treating suicidal ideation. We piloted a randomized, double-blind, sham-controlled trial of bilateral rTMS for patients with OUD and MDD experiencing suicidality.

Sequential bilateral TBS was delivered guided by structural neuroimaging: continuous TBS to the right then intermittent TBS to the left DLPFC, daily (20 treatments). The primary objective was to determine the feasibility of this population. The primary clinical outcome was the scale for suicidal ideation (SSI), secondary outcomes included depressive symptoms and opioid cue-induced craving. ClinicalTrials.gov: NCT04785456.

Eighty-seven individuals were pre-screened. The most common reasons for ineligibility included being unreachable by the study team, difficulty with scheduling/travel requirements, and medical/psychiatric instability. Six participants (5:1 M:F) were enrolled (3/arm), four had a fentanyl use history; two completed per protocol (1/arm). Of the participants with follow-up data, SSI scores decreased in 2/3 in the sham arm and 2/2 in the active arm; depression and opioid craving scores decreased in all participants.

We present the first data piloting a structural neuroimaging-guided, multi-session rTMS treatment course in outpatients with suicidality and OUD in the current North American context. Recruitment and retention were the main challenges given the highly unstable medical and psychosocial context of this patient population. Future trials should consider a suitable environment to improve the feasibility of delivering this treatment.