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 severely affects the outcome of people with psychotic disorders, yet there is a lack of treatments. To address this, in 2019 the National Health Service (NHS) Cannabis Clinic for Psychosis (CCP) was developed to support adults suffering from psychosis to reduce and/or stop their cannabis use.

Examine outcome data from the first 46 individuals to complete the CCP's intervention.

The sample (N = 46) consisted of adults (aged ≥ 18) with psychosis under the care of the South London and Maudsley NHS Foundation Trust, referred to the CCP between January 2020 and February 2023, who completed their intervention by September 2023. Clinical and functional measures were collected before (T0) and after (T1) the CCP intervention (one-to-one sessions and peer group attendance). Primary outcomes were changes in the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) score and pattern of cannabis use. Secondary outcomes included T0–T1 changes in measures of delusions, paranoia, depression, anxiety and functioning.

A reduction in the mean CUDIT-R score was observed between T0 (mean difference = 17.10, 95% CI = 15.54–18.67) and T1, with 73.91% of participants achieving abstinence and 26.09% reducing the frequency and potency of their use. Significant improvements in all clinical and functional outcomes were observed, with 90.70% being in work or education at T1 compared with 8.70% at T0. The variance in CUDIT-R scores explained between 34 and 64% of the variance in our secondary measures.

The CCP intervention is a feasible strategy to support cannabis use cessation/reduction and improve clinical and functional outcomes of people with psychotic disorders.

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.

Translational science (TS) teams develop and conduct translational research. Academic TS teams can be categorized under three constituency groups: trainees and faculty, clinical research professionals (CRP), and community partners. Our study objectives were to define individual and team competencies of these three constituency groups during their career life course and determine relative importance and the level of mastery of each of the competencies needed at different stages of their life course.

Each group was composed of experts for their constituency group. We applied individual and team competencies in TS teams by Lotrecchiano et al. (2020) as a starting point for structured expert discussions following a modified Delphi approach that we adapted based on the emergent needs and insights per constituency group.

The degree of relevance and level of mastery for individual and team competencies varies for trainees and faculty members across the career life course based on opportunities provided and relative importance at that career stage. However, CRPs enter TS teams at various career stages with fundamental, skilled, or advanced levels of smart skills that may or may not be contextual to their role. Community partners equally possess and develop competencies in a non-linear and contextual fashion that are required to facilitate constructive, bi-directional collaboration with other members of TS teams.

Team science competencies across the career life course do not develop linearly among different constituency groups and require an adaptive framework to enhance TS team effectiveness.

Cognitive dysfunction is prominent in homeless and precariously housed persons, and memory dysfunction is the most pervasive domain. The presence of multimorbid physical and mental illness suggests that several underlying mechanisms of memory impairment may be at play. The serial position phenomenon describes the tendency to best recall the beginning (primacy effect) and last (recency effect) words on a supra-span wordlist. Recency recall engages executive and working-memory systems, whereas primacy recall depends on long-term memory. This study investigates memory dysfunction in a homeless and precariously housed sample by identifying and characterizing unique subtypes of serial position profiles on a test of verbal memory.

Data were used from a 20-year study of homeless and precariously housed adults recruited from an impoverished neighbourhood in Vancouver, Canada. Participants were sub-grouped according to their serial position profile on the Hopkins Verbal Learning Test-Revised using a latent profile analysis (LPA; n = 411). Paired samples t-tests were conducted to determine differences in percent recall from each word-list region within classes. Linear regression analyses were used to examine between-class differences in mean serial position scores and other cognitive measures (memory, attention, processing speed, cognitive control). Covariates included age, sex, and education.

LPA identified two profiles characterized by (1) reduced primacy relative to recency (RP; n = 150); and (2) reduced recency relative to primacy (RR; n = 261). Pairwise comparisons within the RP class showed that recency was better than primacy (p < .001, d = .66) and middle recall (p < .001, d = .52), with no difference between primacy and middle recall (p = .68, d = .04). All pairwise comparisons differed within the RR class (primacy > middle recall: p < .001, d = 1.85; primacy > recency recall: p < .001, d = 1.32; middle > recency recall: p < .05, d = .132). The RP class had worse performance on measures of total immediate (ß = .47, p < .001) and delayed verbal recall (ß = .32, p < .001); processing speed (ß = .20, p < .001); and cognitive control (ß = .22, p < .001). The RR class made more repetition errors (ß = .25, p < .001).

These findings support substantial heterogeneity in memory functioning in homeless and precariously housed individuals. The RP profile was characterized by poorer cognitive functioning across several domains, which suggests multiple contributions to memory impairment, including dysfunction of long-term memory circuitry. The RR profile with their higher number of repetition errors, may experience difficulties with self-monitoring in verbal learning. Subsequent studies will explore the neurobiological underpinnings of these subgroups to further characterize profiles and identify targets for cognitive intervention.

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.