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.

Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls.

We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables.

FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123–2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368–0.997 and OR = 0.646, CI 0.457–0.913 respectively) and JTC bias (OR = 0.625, CI 0.422–0.925 and OR = 0.602, CI 0.460–0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297–2.578, FRP deficits (OR = 1.393, CI 1.031–1.882, and JTC (OR = 1.661, CI 1.271–2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups.

Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.

Maternal vitamin-D and omega-3 fatty acid (DHA) deficiencies during pregnancy have previously been associated with offspring neurodevelopmental traits. However, observational study designs cannot distinguish causal effects from confounding.

First, we conducted Mendelian randomisation (MR) using genetic instruments for vitamin-D and DHA identified in independent genome-wide association studies (GWAS). Outcomes were (1) GWAS for traits related to autism and ADHD, generated in the Norwegian mother, father, and child cohort study (MoBa) from 3 to 8 years, (2) autism and ADHD diagnoses. Second, we used mother–father–child trio-MR in MoBa (1) to test causal effects through maternal nutrient levels, (2) to test effects of child nutrient levels, and (3) as a paternal negative control.

Associations between higher maternal vitamin-D levels on lower ADHD related traits at age 5 did not remain after controlling for familial genetic predisposition using trio-MR. Furthermore, we did not find evidence for causal maternal effects of vitamin-D/DHA levels on other offspring traits or diagnoses. In the reverse direction, there was evidence for a causal effect of autism genetic predisposition on lower vitamin-D levels and of ADHD genetic predisposition on lower DHA levels.

Triangulating across study designs, we did not find evidence for maternal effects. We add to a growing body of evidence that suggests that previous observational associations are likely biased by genetic confounding. Consequently, maternal supplementation is unlikely to influence these offspring neurodevelopmental traits. Notably, genetic predisposition to ADHD and autism was associated with lower DHA and vitamin-D levels respectively, suggesting previous associations might have been due to reverse causation.

Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.

Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.

Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.

We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.

The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).

The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

In persons with severe psychiatric disorders, distinct neurocognitive profiles hold differential associations to positive, negative and disorganized symptom dimensions of psychosis. These patterns portend specific functional outcomes, treatment efficacy, and prognoses. Similar associations have not been established in multimorbid samples in which persons present with a complex array of psychiatric symptoms. The objective of this study was to (1) establish neurocognitive profiles in a multimorbid, marginalized sample and (2) investigate their pattern(s) of association with psychiatric symptom dimensions and psychosocial outcomes.

Participants (n=370; Mage = 45 years; 74% male) were precariously housed, substance-using adults with multimorbidity, recruited from Single-Room Occupancy hotels and a community court within the Downtown Eastside of Vancouver, BC, Canada. Data were collected as part of a longitudinal examination consisting of annual, bi-annual, and monthly neurocognitive, psychosocial, and psychiatric assessments. Neurocognitive scores were combined into five cognitive domains (Attentional Control [AC]; Processing Speed [PS]; Fluid Reasoning [Problem Solving and Reversal Learning; Gf]; Encoding and Retrieval [ER]; and Decision Making [DM]) and submitted to a latent profile analysis. The resulting profiles capturing neurocognition were validated on sociodemographic and clinical variables. Finally, the profiles were compared across previously validated, population-distinct factors derived from the Positive and Negative Syndrome Scale (PANSS), as well as on measures of psychosocial functioning.

An optimal goodness-of-fit was reached for a three-profile model (BLRT=127.86, p=.01). Profile 1 (n=207, 55.9%) showed stronger neurocognition (all p<.05), with a within-profile strength in Gf (p<.001). With the exception of ER, Profile 2 (n=109, 29.5%) exhibited inferior neurocognition across all indicators compared to Profile 1 (all p <.05); yet showed a relative, within-profile strength in Gf (p < .01). Profile 3 (n=54, 14.6%) generally displayed comparable impairments to Profile 2. Additionally, their performance on Gf was remarkably low compared to Profiles 1 and 2 (p<.001). Psychiatrically, compared to Profile 1, Profile 2 exhibited more positive/disorganized symptoms and general psychopathology, as well as higher total PANSS (all p <.05), whereas Profile 3 showed the poorest insight/awareness (p<.01). Profiles 2 and 3 had lower levels of adaptive functioning and work productivity compared to Profile 1 (all p<.01).

Three neurocognitive profiles were detected in a sample of precariously housed adults with multimorbidity: one profile of comparatively higher neurocognitive capacity, with less symptoms of psychosis and better psychosocial functioning; a second profile of comparatively poorer neurocognition and psychosocial functioning, with more symptoms of psychosis; and a third profile with a severe deficit in fluid reasoning and poor insight and awareness. Given their poor insight, the third profile may be comprised of particularly vulnerable persons at greater risk of unmet healthcare needs. Interventions to improve these individuals' understanding of their personal health risks might facilitate their capacity to access services. Conversely, individuals from Profile 2 may benefit from outreach programs focusing on medication access and adherence to address their symptoms of psychosis. In sum, our findings suggest that the confluence of neurocognition and psychiatric symptoms may implicate unique treatment approaches and outcomes in precariously-housed persons with multimorbid conditions.

Precariously housed individuals are exposed to multiple adverse factors negatively impacting neurocognitive functioning. Additionally, this population is subjected to poor life outcomes, such as impaired psychosocial functioning. Neurocognitive functioning plays an important role in psychosocial functioning and may be especially critical for precariously housed individuals who face numerous barriers in their daily lives. However, few studies have explicitly examined the cognitive determinants of functional outcomes in this population. Cognitive intraindividual variability (IIV) involves the study of within-person differences in neurocognitive functioning and has been used as marker of frontal system pathology. Increased IIV has been associated with worse cognitive performance, cognitive decline, and poorer everyday functioning. Hence, IIV may add to the predictive utility of commonly used neuropsychological measures and may serve as an emergent predictor of poor outcomes in at-risk populations. The objective of the current study was to examine IIV as a unique index of the neurocognitive contributions to functional outcomes within a large sample of precariously housed individuals. It was hypothesized that greater IIV would be associated with poorer current (i.e., baseline) and long-term (i.e., up to 12 years) psychosocial functioning.

Four hundred and thirty-seven adults were recruited from single-room occupancy hotels located in the Downtown Eastside of Vancouver, Canada (Mage = 44 years, 78% male) between November 2008 and November 2021. Baseline neurocognitive functioning was assessed at study enrolment. Scores from the Social and Occupational Functioning Assessment Scale (SOFAS), the Role Functioning Scale (RFS), the physical component score (PCS) and the mental component score (MCS) of the 36-Item Short Form Survey Instrument were obtained at participants’ baseline assessments and at their last available follow-up assessment to represent baseline and long-term psychosocial functioning, respectively. Using an established formula, an index of IIV was derived using a battery of standardized tests that broadly assessed verbal learning and memory, sustained attention, mental flexibility, and cognitive control. A series of multiple linear regressions were conducted to predict baseline and long-term social and role functioning (average across SOFAS and RFS scores), and PCS and MCS scores from IIV. In each of the models, we also included common predictors of functioning, including a global cognitive composite score, age, and years of education.

The IIV index and the global composite score did not explain a significant proportion of the variance in baseline and long-term social and role functioning (p > .05). However, IIV was a significant predictor of baseline (B = -3.84, p = .021) and long-term (B = -3.58, p = .037) PCS scores, but not MCS scores (p > .05). The global composite score did not predict baseline or long-term PCS scores.

IIV significantly predicted baseline and long-term physical functioning, but not mental functioning or social and role functioning, suggesting that IIV may be a sensitive marker for limitations in everyday functioning due to physical health problems in precariously housed individuals. Critically, the present study is the first to show that IIV may be a useful index for predicting poor long-term health-related outcomes in this population compared to traditional neuropsychological measures.

To describe antimicrobial therapy used for multidrug-resistant (MDR) Acinetobacter spp. bacteremia in Veterans and impacts on mortality.

This was a retrospective cohort study of hospitalized Veterans Affairs patients from 2012 to 2018 with a positive MDR Acinetobacter spp. blood culture who received antimicrobial treatment 2 days prior to through 5 days after the culture date. Only the first culture per patient was used. The association between treatment and patient characteristics was assessed using bivariate analyses. Multivariable logistic regression models examined the relationship between antibiotic regimen and in-hospital, 30-day, and 1-year mortality. Generalized linear models were used to assess cost outcomes.

MDR Acinetobacter spp. was identified in 184 patients. Most cultures identified were Acinetobacter baumannii (90%), 3% were Acinetobacter lwoffii, and 7% were other Acinetobacter species. Penicillins—β-lactamase inhibitor combinations (51.1%) and carbapenems (51.6%)—were the most prescribed antibiotics. In unadjusted analysis, extended spectrum cephalosporins and penicillins—β-lactamase inhibitor combinations—were associated with a decreased odds of 30-day mortality but were insignificant after adjustment (adjusted odds ratio (aOR) = 0.47, 95% CI, 0.21–1.05, aOR = 0.75, 95% CI, 0.37–1.53). There was no association between combination therapy vs monotherapy and 30-day mortality (aOR = 1.55, 95% CI, 0.72–3.32).

In hospitalized Veterans with MDR Acinetobacter spp., none of the treatments were shown to be associated with in-hospital, 30-day, and 1-year mortality. Combination therapy was not associated with decreased mortality for MDR Acinetobacter spp. bacteremia.

Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.

In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.

Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.

Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.