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.

The impact of chronic pain and opioid use on cognitive decline and mild cognitive impairment (MCI) is unclear. We investigated these associations in early older adulthood, considering different definitions of chronic pain.

Men in the Vietnam Era Twin Study of Aging (VETSA; n = 1,042) underwent cognitive testing and medical history interviews at average ages 56, 62, and 68. Chronic pain was defined using pain intensity and interference ratings from the SF-36 over 2 or 3 waves (categorized as mild versus moderate-to-severe). Opioid use was determined by self-reported medication use. Amnestic and non-amnestic MCI were assessed using the Jak-Bondi approach. Mixed models and Cox proportional hazards models were used to assess associations of pain and opioid use with cognitive decline and risk for MCI.

Moderate-to-severe, but not mild, chronic pain intensity (β = −.10) and interference (β = −.23) were associated with greater declines in executive function. Moderate-to-severe chronic pain intensity (HR = 1.75) and interference (HR = 3.31) were associated with a higher risk of non-amnestic MCI. Opioid use was associated with a faster decline in verbal fluency (β = −.18) and a higher risk of amnestic MCI (HR = 1.99). There were no significant interactions between chronic pain and opioid use on cognitive decline or MCI risk (all p-values > .05).

Moderate-to-severe chronic pain intensity and interference related to executive function decline and greater risk of non-amnestic MCI; while opioid use related to verbal fluency decline and greater risk of amnestic MCI. Lowering chronic pain severity while reducing opioid exposure may help clinicians mitigate later cognitive decline and dementia risk.

Antibiotics overuse leads to bacterial resistance. The biomarker procalcitonin rises with bacterial pneumonias and remains normal in viral respiratory tract infections. Its use can distinguish between these etiologies and thus guide antibiotics use. We aimed to quantify the effect of procalcitonin use on clinical decision-making.

A retrospective study, spanning a year at a tertiary care center, where 348 patients hospitalized with aspiration pneumonia and 824 with non-aspiration pneumonia were evaluated with regards to procalcitonin use, the length of stay (LOS) and antibiotics prescribing practices. Descriptive statistics and univariate analyses were applied to the ensemble data. Subsets of cases were manually reviewed and analyzed with descriptive statistics. P < 0.05 indicated statistical significance.

21% of both the aspiration and non-aspiration pneumonia cases had procalcitonin checked. In the ensemble analyses, a check of procalcitonin was more likely to happen in prolonged hospitalizations with aspiration pneumonia. The LOS was statistically the same regardless of procalcitonin results (elevated or normal) for both the aspiration and non-aspiration pneumonia cohorts. The overall use of antibiotics was not affected by the procalcitonin results. After excluding two extreme outliers, the per-person antibiotics cost was not affected by the procalcitonin results. Detailed chart reviews of 33 cases revealed that for the vast majority, the procalcitonin results were not used by clinicians to guide the duration of antibiotics use.

Despite its promise as a biomarker for antibiotics stewardship, procalcitonin results appeared to not be utilized by clinicians as a decision-making tool in the management of pneumonia.

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.