Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.

To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.

This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.

The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.

Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

Lithium has a narrow therapeutic index with a risk of toxicity and potential to increase morbidity and mortality, particularly in the elderly with co-morbid illness and polypharmacy. Lithium therapy and monitoring of lithium levels require precision and several guidelines have been issued including recommendations for strict control of lithium levels in the elderly population.

We evaluated the effect of implementation of a multifaceted management programme on the compliance with international practice standards for lithium monitoring in patients under the care of Psychiatry of Old Age (POA), Sligo Leitrim Mental Health Services in the North West of Ireland.

Results from a prior audit performed in February 2020 involving a cohort of 18 patients prescribed lithium under the care of POA were analysed and compared to accepted standards. The guideline used as the benchmark for compliance was the National Institute for Clinical Excellence (NICE) guidelines on the use and monitoring of lithium therapy, as published in 2014. Several deficits were found and therefore a designated Lithium Management Programme was established. A subsequent audit, performed using a simplified audit tool incorporating the NICE guidelines, delivered results which were directly compared to the initial findings and analysed to evaluate the effect of the implemented management programme.

In comparison with findings from 2020, there had been a significant improvement in most facets of lithium management and compliance to practice standards. Of particular note was the improvement of biochemical monitoring, side effect screening, polypharmacy surveillance, patient education and interdisciplinary communication.

The launch of a dedicated Lithium Management Programme with specific features aimed at identifying and addressing poor compliance with monitoring guidelines has led to improved adherence to accepted international practice standards. Our model provides a dynamic, multi-layered system which paves the way for better patient outcomes, timely access to care and furthering education for patients and staff members.

The role of APOE in Alzheimer’s disease and other dementias has been intensively investigated. However APOE in delirium has only recently been investigated in studies with small samples. There is evidence that APOE relates to delirium by one or more of the following pathophysiological mechanism: a) inhibition of inflammation in the CNS during acute illness, with release of inflammatory mediators, b) modification of inflammatory responses in an isoform-specific manner, c) by blocking both nicotine and acetylcholine receptors causing the anticholinergic effect which is assumed in delirium.

A meta-analysis of the published pooled data seems timely to establish any relationship between APOE and delirium, and to determine further direction of research in this topic.

To find out if there is any direct relationship between the APOE epsilon 4 and the occurrence of delirium.

Pubmed, MEDLINE, EBSCOhost and Google Scholar have been searched with the relevant keywords, and from the references of relevant papers. Nine papers were found which examined the relationship between APOE and delirium. Data were extracted from 8 of them and were pooled for meta-analysis using random effects with R software.

Data from 1762 participants showed no heterogeneity (Q=13.55, df:7, p=0.06). The possession of the APOE epsilon 4 allele has a small (OR:1.17, CI:0.77-1.80), non-significant (p=0.45) effect in the presence of delirium.

There is no association between APOE and the occurrence of delirium. Confirmation and clarification in larger studies could have important clinical implications for predicting prognosis and for treatment of delirium.

Studies of the association between blood BDNF levels and delirium are very few and have yielded mixed results.

To investigate the blood BDNF levels in the occurrence and recovery of delirium.

Prospective, longitudinal study. Participants were assessed twice weekly with MoCA, DRS-R98, APACHE-II. BDNF levels of the same were estimated with ELISA method. Delirium has been define as per DRS-98R (cut-off > 16) and recovery of delirium as at least two consequently assessments without delirium prior to discharge.

No differences in the levels of BDNF between those with delirium and those who never developed it. Excluding those who never developed delirium (n = 140), we analysed the effects of BDNF and the other variables on delirium resolution and recovery. Of the 58 remained with delirium in the subsequently observations (max = 8) some of them continue to be delirious until discharge or death (n = 39) while others recovered (n = 19). BDNF levels and MoCA scores were significantly associated with both delirium cases who became non-delirious (resolution) during the assessments and with overall recovery. BDNF (Wald χ2 = 11.652, df: 1 P = .001), for resolution. For recovery Wald χ2 = 7.155; df: 1, P = .007. No significant association was found for the other variables (APACHE-II, history of dementia, age or gender)

BDNF do not have a direct effect in the occurrence of delirium but for those delirious of whom the levels are increased during the hospitalisation they are more likely to recover from delirium.

The authors have not supplied their declaration of competing interest.

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.

Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.

Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?

Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.

The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models.

Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.

We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected).

These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4’s developmental role.