Pharmacological treatment patterns for bipolar disorder have changed during recent years, but for better or worse?

To investigate the comparative real-world effectiveness of antipsychotics and mood stabilisers in bipolar disorder.

Register-based cohort study including all Finnish residents aged 16–65 with a diagnosis of bipolar disorder from in-patient care, specialised out-patient care, sickness absence and disability pensions registers between 1996 and 2018, with a mean follow-up of 9.3 years (s.d. = 6.4). Antipsychotic and mood stabiliser use was modelled using the PRE2DUP method and risk for hospital admission for psychiatric and non-psychiatric reasons when using versus not using medications was estimated using within-individual Cox models.

Among 60 045 individuals (56.4% female; mean age 41.7 years, s.d. = 15.8), the five medications associated with lowest risk of psychiatric admissions were olanzapine long-acting injection (LAI) (aHR = 0.54, 95% CI 0.37–0.80), haloperidol LAI (aHR = 0.62, 0.47–0.81), zuclopenthixol LAI (aHR = 0.66, 95% CI 0.52–0.85), lithium (aHR = 0.74, 95% CI 0.71–0.76) and clozapine (aHR = 0.75, 95% CI 0.64–0.87). Only ziprasidone (aHR = 1.26, 95% CI 1.07–1.49) was associated with a statistically higher risk. For non-psychiatric (somatic) admissions, only lithium (aHR = 0.77, 95% CI 0.74–0.81) and carbamazepine (aHR = 0.91, 95% CI 0.85–0.97) were associated with significantly reduced risk, whereas pregabalin, gabapentin and several oral antipsychotics, including quetiapine, were associated with an increased risk. Results for a subcohort of first-episode patients (26 395 individuals, 54.9% female; mean age 38.2 years, s.d. = 13.0) were in line with those of the total cohort.

Lithium and certain LAI antipsychotics were associated with lowest risks of psychiatric admission. Lithium was the only treatment associated with decreased risk of both psychiatric and somatic admissions.

Evidence suggests a familial coaggregation of major psychiatric disorders, including schizophrenia, bipolar disorder, major depression (MDD), autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Those disorders are further related to suicide and accidental death. However, whether death by suicide may coaggregate with accidental death and major psychiatric disorders within families remains unclear.

To clarify the familial coaggregation of deaths by suicide with accidental death and five major psychiatric disorders.

Using a database linked to the entire Taiwanese population, 68 214 first-degree relatives of individuals who died by suicide between 2003 and 2017 and 272 856 age- and gender-matched controls were assessed for the risks of death by suicide, accidental death and major psychiatric disorders.

A Poisson regression model showed that the first-degree relatives of individuals who died by suicide were more likely to die by suicide (relative risk RR = 4.61, 95% CI 4.02–5.29) or accident (RR = 1.62, 95% CI 1.43–1.84) or to be diagnosed with schizophrenia (RR = 1.53, 95% CI 1.40–1.66), bipolar disorder (RR = 1.99, 95% CI 1.83–2.16), MDD (RR = 1.98, 95% CI 1.89–2.08) or ADHD (RR = 1.34, 95% CI 1.24–1.44).

Our findings identified a familial coaggregation of death by suicide with accidental death, schizophrenia, major affective disorders and ADHD. Further studies would be required to elucidate the pathological mechanisms underlying this coaggregation.

It is well-known that childhood attention-deficit hyperactivity disorder (ADHD) is associated with later adverse mental health and social outcomes. Patient-based studies suggest that ADHD may be associated with later cardiovascular disease (CVD) but the focus of preventive interventions is unclear. It is unknown whether ADHD leads to established cardiovascular risk factors because so few cohort studies measure ADHD and also follow up to an age where CVD risk is evident.

To examine associations between childhood ADHD problems and directly measured CVD risk factors at ages 44/45 years in a UK population-based cohort study (National Child Development Study) of individuals born in 1958.

Childhood ADHD problems were defined by elevated ratings on both the parent Rutter A scale and a teacher-rated questionnaire at age 7 years. Outcomes were known cardiovascular risk factors (blood pressure, lipid measurements, body mass index and smoking) at the age 44/45 biomedical assessment.

Of the 8016 individuals assessed both during childhood and at the biomedical assessment 3.0% were categorised as having childhood ADHD problems. ADHD problems were associated with higher body mass index (B = 0.92 kg/m2, s.d. = 0.27–1.56), systolic (3.5 mmHg, s.d. = 1.4–5.6) and diastolic (2.2 mmHg, s.d. = 0.8–3.6) blood pressure, triglyceride levels (0.24 mol/l, s.d. = 0.02–0.46) and being a current smoker (odds ratio OR = 1.6, s.d. = 1.2–2.1) but not with LDL cholesterol.

Childhood ADHD problems predicted multiple cardiovascular risk factors by mid-life. These findings, when taken together with previously observed associations with cardiovascular disease in registries, suggest that individuals with ADHD could benefit from cardiovascular risk monitoring, given these risk factors are modifiable with timely intervention.

Cannabis has been associated with poorer mental health, but little is known of the effect of synthetic cannabinoids or cannabidiol (often referred to as CBD).

To investigate associations of cannabis, synthetic cannabinoids and cannabidiol with mental health in adolescence.

We conducted a cross-sectional analysis with 13- to 14-year-old adolescents across England and Wales in 2019–2020. Multilevel logistic regression was used to examine the association of lifetime use of cannabis, synthetic cannabinoids and cannabidiol with self-reported symptoms of probable depression, anxiety, conduct disorder and auditory hallucinations.

Of the 6672 adolescents who participated, 5.2% reported using of cannabis, 1.9% reported using cannabidiol and 0.6% reported using synthetic cannabinoids. After correction for multiple testing, adolescents who had used these substances were significantly more likely to report a probable depressive, anxiety or conduct disorder, as well as auditory hallucinations, than those who had not. Adjustment for socioeconomic disadvantage had little effect on associations, but weekly tobacco use resulted in marked attenuation of associations. The association of cannabis use with probable anxiety and depressive disorders was weaker in those who reported using cannabidiol than those who did not. There was little evidence of an interaction between synthetic cannabinoids and cannabidiol.

To our knowledge, this study provides the first general population evidence that synthetic cannabinoids and cannabidiol are associated with probable mental health disorders in adolescence. These associations require replication, ideally with prospective cohorts and stronger study designs.

Neurocognitive deficits are a core feature of psychosis and depression. Despite commonalities in cognitive alterations, it remains unclear if and how the cognitive deficits in patients at clinical high risk for psychosis (CHR) and those with recent-onset psychosis (ROP) are distinct from those seen in recent-onset depression (ROD).

This study was carried out within the European project ‘Personalized Prognostic Tools for Early Psychosis Management’, and aimed to characterise the cognitive profiles of patients with psychosis or depression.

We examined cognitive profiles for patients with ROP (n = 105), patients with ROD (n = 123), patients at CHR (n = 116) and healthy controls (n = 372) across seven sites in five European countries. Confirmatory factor analysis identified four cognitive factors independent of gender, education and site: speed of processing, attention and working memory, verbal learning and spatial learning.

Patients with ROP performed worse than healthy controls in all four domains (P < 0.001), whereas performance of patients with ROD was not affected (P > 0.05). Patients at CHR performed worse than healthy controls in speed of processing (P = 0.001) and spatial learning (P = 0.003), but better than patients with ROP across all cognitive domains (all P ≤ 0.01). CHR and ROD groups did not significantly differ in any cognitive domain. These findings were independent of comorbid depressive symptoms, substance consumption and illness duration.

These results show that neurocognitive abilities are affected in CHR and ROP, whereas ROD seems spared. Although our findings may support the notion that those at CHR have a specific vulnerability to psychosis, future studies investigating broader transdiagnostic risk cohorts in longitudinal designs are needed.