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.

A common assumption to maximise cognitive training outcomes is that training tasks should be adaptive, with difficulty adjusted to the individual’s performance. This has only been tested once in adults (von Bastian & Eschen, 2016). We aimed to examine children’s outcomes of working memory training using adaptive, self-select and stepwise approaches to setting the difficulty of training tasks compared to an active control condition.

In a randomised controlled trial (ACTRN 12621000990820), children in Grades 2-5 (7 to 11 years) were allocated to one of four conditions: adaptive working memory training, self-select working memory training, stepwise working memory training, or active control. An experimental intervention embedded in Minecraft was developed for teachers to deliver in the classroom over two weeks (10 x 20-minute sessions). The working memory training comprised two training tasks with processing demands similar to daily activities: backward span with digits and following instructions with objects. The control condition comprised creative building tasks. As part of a larger protocol, children completed at baseline and immediately post-intervention working memory measures similar to the training activities (primary outcome): backward span digits and letters versions, following instructions objects and letters versions. Primary analyses were intention-to-treat. Secondary analyses included only children who completed 10 sessions.

Of 204 children recruited into the study, 203 were randomised, with 95% retention at post-intervention. 76% of children completed all 10 training sessions. Comparisons between each working memory training condition and the active control on working memory measures were non-significant (f 2 = 0.00), with one exception. Children in the self-select condition on average performed 1-point better than the controls on the following instructions objects measure (p = .02, f2 = 0.03). A pattern emerged that the self-select condition performed better on most measures.

We found little evidence that an adaptive approach to setting the difficulty of training tasks maximises training outcomes for children. Findings suggest that working memory outcomes following training are limited and are not modulated by the approach to setting the difficulty of training tasks. This is consistent with findings from von Bastian & Eschen (2016), who also observed that the self-select condition (and not the adaptive condition) showed a slightly larger change in working memory performance following training than the control. It is helpful for clinicians to be aware that adaptive working memory training programs might not be superior in improving children’s working memory, and the benefits of programs are limited.

Neonates and infants who undergo congenital cardiac surgery frequently have difficulty with feeding. The factors that predispose these patients to require a gastrostomy tube have not been well defined. We aimed to report the incidence and describe hospital outcomes and characteristics in neonates and infants undergoing congenital cardiac surgery who required gastrostomy tube placement.

A retrospective review was performed on patients undergoing congenital cardiac surgery between October 2015 and December 2020. Patients were identified by International Classification of Diseases 10th Revision codes, utilising the performance improvement database Vizient® Clinical Data Base, and stratified by age at admission: neonates (<1 month) and infants (1–12 months). Outcomes were compared and comparative analysis performed between admissions with and without gastrostomy tube placement.

There were 11,793 admissions, 3519 (29.8%) neonates and 8274 (70.2%) infants. We found an increased incidence of gastrostomy tube placement in neonates as compared to infants following congenital cardiac surgery (23.1% versus 6%, p = <0.001). Outcomes in neonates and infants were similar with increased length of stay and cost in those requiring a gastrostomy tube. Gastrostomy tube placement was noted to be more likely in neonates and infants with upper airway anomalies, congenital abnormalities, hospital infections, and genetic abnormalities.

Age at hospitalisation for congenital cardiac surgery is a definable risk factor for gastrostomy tube requirement. Additional factors contribute to gastrostomy tube placement and should be used when counselling families regarding the potential requirement of a gastrostomy tube.

Children born very preterm (VP) are susceptible to a range of cognitive impairments, yet the effects of VP birth on long-term, episodic, and prospective memory remains unclear. This study examined episodic and prospective memory functioning in children born VP compared with their term-born counterparts at 13 years.

VP (n = 81: born <30 weeks’ gestation) and term (n = 26) groups were aged between 12 and 14 years. Children completed: (i) standardized verbal and visuospatial episodic memory tests; and (ii) an experimental time- and event-based prospective memory test that included short-term (within assessment session) and long-term (up to 1-week post-session) tasks. Parents completed a questionnaire assessing memory functions in everyday life.

The VP group performed worse on all measures of verbal and visuospatial episodic memory than the term group. While there were no group differences in event-based or long-term prospective memory, the VP group performed worse on time-based and short-term prospective memory tasks than term-born counterparts. Parents of children born VP reported more everyday memory difficulties than parents of children born at term, with parent-ratings indicating significantly elevated rates of everyday memory challenges in children born VP.

Children born VP warrant long-term surveillance, as challenges associated with VP birth include memory difficulties at 13 years. This study highlights the need for greater research and clinical attention into childhood functional memory outcomes.

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.

Vitamin A (VA) deficiency, more common in low- and middle-income countries (LMIC) secondary to malnutrition, is associated with increased morbidity and mortality. The prevalence and impact of VA deficiency in high-income countries (HIC) where chronic conditions may predispose is less well understood.

Interpretation of serum retinol may be affected by inflammation, so C-reactive protein (CRP) levels were sought. Binary logistic regression and generalised estimating equations were performed to review the relationship between CRP and VA.

We examined the scale of low and deficient VA status in our tertiary University Teaching Hospital (HIC).

Patients undergoing serum retinol concentrations 2012–2016 were identified from laboratory records, and records examined.

Totally, 628 assays were requested, with eighty-two patients VA low (0·7–0·99 Umol/l) or deficient (<0·7 Umol/l). Sixteen patients were symptomatic (fifteen deficient), predominantly visual. Only one symptomatic patient’s VA deficiency was secondary to poor intake. Other symptomatic patients had chronic illnesses resulting in malabsorption. The incidence of a low VA level increases significantly with a raised CRP.

The majority of patients tested either were replete or likely to have abnormal VA levels due to concomitant inflammation. A minority of patients had signs and symptoms of VA deficiency and was a cause of significant morbidity, but aetiology differs from LMIC, overwhelmingly malabsorption, most commonly secondary to surgery or hepatobiliary disease. A correlation between inflammation and low VA levels exists, which raises the possibility that requesting a VA level in an asymptomatic patient with active inflammation may be of questionable benefit.

It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.

Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.

The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.

Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.

Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.

We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.

16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).

PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.