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.

To examine associations between executive function (EF) domains (attentional control, information processing, cognitive flexibility, and goal setting) and math computation performance at 7 and 13 years in children born very preterm (VP; <30 weeks' gestation), and secondly, to investigate the associations of 7-year EF with change in math performance from 7 to 13 years.

In the prospective, longitudinal Victorian Infant Brain Studies (VIBeS) cohort of children born VP, assessment of EF and math performance was undertaken at 7 (n = 187) and 13 years (n = 174). Univariable and multivariable regression models (including all domains of EF) were used to examine associations between EF domains at both timepoints with math performance, as well as associations between EF at 7 years with change in math from 7 to 13 years.

At 7 and 13 years, all EF domains were positively associated with concurrent math performance, with multivariable models finding information processing, cognitive flexibility and goal setting independently contributed to math performance at both ages. All EF domains were positively associated with improvement in math performance from 7 to 13 years, with multivariable models finding that goal setting contributed unique variance to improvement in math over this period.

This study provides evidence for a strong, consistent association between EF and math performance in children born VP and emphasizes the importance of goal setting capacity for later improvement in math performance.

For infants born in the contemporary era of neonatal care, little is known about adult mental health outcomes of extremely preterm birth (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g). This study aimed to compare attention deficit hyperactivity disorder (ADHD), anxiety, mood, and substance use disorder prevalence in young adults born EP/ELBW and normal birthweight (NBW; >2499 g) controls, and to compare change in prevalence of mental health symptoms and disorders from 18 to 25 years.

Participants were a prospective geographical cohort of 297 consecutive survivors born EP/ELBW during 1991–1992 and 260 NBW controls. At age 25 years, 174 EP/ELBW and 139 NBW participants completed the Adult ADHD Rating Scale, Structured Clinical Interview for DSM-IV Disorders, Beck Anxiety Inventory, and Center for Epidemiologic Studies Depression Scale-Revised. Data from follow-up at 18 years were also utilized. Multiple imputation was used to account for attrition.

Mental health outcomes at 25 years were similar between groups: prevalence rates were ADHD 7% v. 5%; anxiety 32% v. 27%; mood 38% v. 35%; substance use 12% v. 14% in the EP/ELBW and NBW groups, respectively. In both groups, ADHD declined between 18 and 25 years [odds ratio (OR) per year = 0.87, 95% confidence interval (CI) 0.79–0.95], and generalized anxiety disorder and major depressive episode became more common (OR 1.22, 95% CI 1.10–1.35 per year; OR 1.20, 95% CI 1.10–1.30 respectively).

This contemporary EP/ELBW cohort has comparable young adult mental health outcomes to controls, and similar patterns of change in mental health from late adolescence.

Positive affect and anhedonia are important but challenging targets for mental health treatments. Previous research indicates the potential of a computerised cognitive training paradigm involving generation of positive mental imagery, termed positive mental imagery training (PMIT), to increase positive affect and reduce anhedonia.

Our main aim was to investigate the feasibility of PMIT as a positive affect-focused, transdiagnostic adjunct to treatment as usual for patients in in-patient mental health settings.

We ran an open feasibility, randomised controlled trial with three parallel arms: treatment as usual; treatment as usual plus PMIT; and treatment as usual plus an active comparator, cognitive control training. Fifty-seven patients from two different in-patient mental health treatment clinics in Germany were randomised in a 1:1:1 ratio. PMIT and cognitive control training comprised an introductory session followed by eight 15-min training sessions over 2 weeks. Clinical outcomes such as positive affect (primary outcome measure) and anhedonia were assessed at pre- and post-training, and at a further 2-week follow-up.

Adherence was good and attrition was low. The patterns of results for the outcome data were not consistent with a specific effect of PMIT on positive affect, but were more consistent with a specific effect on anhedonia.

The results indicate feasibility and potential promise of a larger efficacy trial investigating PMIT as a treatment adjunct in in-patient mental health settings. Limitations include lack of researcher blinding, small sample size and lack of pre-specified feasibility outcomes. Anhedonia may be a more suitable primary outcome for a future larger trial.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Children born very preterm (VP) display altered growth in corticolimbic structures compared with full-term peers. Given the association between the cortiocolimbic system and anxiety, this study aimed to compare developmental trajectories of corticolimbic regions in VP children with and without anxiety diagnosis at 13 years.

MRI data from 124 VP children were used to calculate whole brain and corticolimbic region volumes at term-equivalent age (TEA), 7 and 13 years. The presence of an anxiety disorder was assessed at 13 years using a structured clinical interview.

VP children who met criteria for an anxiety disorder at 13 years (n = 16) displayed altered trajectories for intracranial volume (ICV, p < 0.0001), total brain volume (TBV, p = 0.029), the right amygdala (p = 0.0009) and left hippocampus (p = 0.029) compared with VP children without anxiety (n = 108), with trends in the right hippocampus (p = 0.062) and left medial orbitofrontal cortex (p = 0.079). Altered trajectories predominantly reflected slower growth in early childhood (0–7 years) for ICV (β = −0.461, p = 0.020), TBV (β = −0.503, p = 0.021), left (β = −0.518, p = 0.020) and right hippocampi (β = −0.469, p = 0.020) and left medial orbitofrontal cortex (β = −0.761, p = 0.020) and did not persist after adjusting for TBV and social risk.

Region- and time-specific alterations in the development of the corticolimbic system in children born VP may help to explain an increase in anxiety disorders observed in this population.

To identify attention profiles at 7 and 13 years, and transitions in attention profiles over time in children born very preterm (VP; <30 weeks’ gestation) and full term (FT), and examine predictors of attention profiles and transitions.

Participants were 167 VP and 60 FT children, evaluated on profiles across five attention domains (selective, shifting and divided attention, processing speed, and behavioral attention) at 7 and 13 years using latent profile analyses. Transitions in profiles were assessed with contingency tables. For VP children, biological and social risk factors were tested as predictors with a multinomial logistic regression.

At 7 and 13 years, three distinct profiles of attentional functioning were identified. VP children were 2–3 times more likely to show poorer attention profiles compared with FT children. Transition patterns between 7 and 13 years were stable average, stable low, improving, and declining attention. VP children were two times less likely to have a stable average attention pattern and three times more likely to have stable low or improving attention patterns compared with FT children. Groups did not differ in declining attention patterns. For VP children, brain abnormalities on neonatal MRI and greater social risk at 7 years predicted stable low or changing attention patterns over time.

VP children show greater variability in attention profiles and transition patterns than FT children, with almost half of the VP children showing adverse attention patterns over time. Early brain pathology and social environment are markers for attentional functioning.