Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.

In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.

The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).

Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.

Lesbian, gay, and bisexual (LGB) individuals are more than twice as likely to experience anxiety and depression compared with heterosexuals. Minority stress theory posits that stigma and discrimination contribute to chronic stress, potentially affecting clinical treatment. We compared psychological therapy outcomes between LGB and heterosexual patients by gender.

Retrospective cohort data were obtained from seven NHS talking therapy services in London, from April 2013 to December 2023. Of 100,389 patients, 94,239 reported sexual orientation, 7,422 identifying as LGB. The primary outcome was reliable recovery from anxiety and depression. Secondary outcomes were reliable improvement, depression and anxiety severity, therapy attrition, and engagement. Analyses were stratified by gender and employed multilevel regression models, adjusting for sociodemographic and clinical covariates.

After adjustment, gay men had higher odds of reliable recovery (OR: 1.23, 95% CI: 1.13–1.34) and reliable improvement (OR: 1.16, 95% CI: 1.06–1.28) than heterosexual men, with lower attrition (OR: 0.88, 95% CI: 0.80–0.97) and greater reductions in depression (MD: 0.51, 95% CI: 0.28–0.74) and anxiety (MD: 0.45, 95% CI: 0.25–0.65). Bisexual men (OR: 0.67, 95% CI: 0.54–0.83) and bisexual women (OR: 0.84, 95% CI: 0.77–0.93) had lower attrition than heterosexuals. Lesbian and bisexual women, and bisexual men, attended slightly more sessions (MD: 0.02–0.03, 95% CI: 0.01–0.04) than heterosexual patients. No other differences were observed.

Despite significant mental health burdens and stressors, LGB individuals had similar, if not marginally better, outcomes and engagement with psychological therapy compared with heterosexual patients.

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric condition that frequently originates in early development and is associated with a variety of functional impairments. Despite a large functional neuroimaging literature on ADHD, our understanding of the neural basis of this disorder remains limited, and existing primary studies on the topic include somewhat divergent results.

The present meta-analysis aims to advance our understanding of the neural basis of ADHD by identifying the most statistically robust patterns of abnormal neural activation throughout the whole-brain in individuals diagnosed with ADHD compared to age-matched healthy controls.

We conducted a meta-analysis of task-based functional magnetic resonance imaging (fMRI) activation studies of ADHD. This included, according to PRISMA guidelines, a comprehensive PubMed search and predetermined inclusion criteria as well as two independent coding teams who evaluated studies and included all task-based, whole-brain, fMRI activation studies that compared participants diagnosed with ADHD to age-matched healthy controls. We then performed multilevel kernel density analysis (MKDA) a well-established, whole-brain, voxelwise approach that quantitatively combines existing primary fMRI studies, with ensemble thresholding (p<0.05-0.0001) and multiple comparisons correction.

Participants diagnosed with ADHD (N=1,550), relative to age-matched healthy controls (N=1,340), exhibited statistically significant (p<0.05-0.0001; FWE-corrected) patterns of abnormal activation in multiple brains of the cerebral cortex and basal ganglia across a variety of cognitive control tasks.

This study advances our understanding of the neural basis of ADHD and may aid in the development of new brain-based clinical interventions as well as diagnostic tools and treatment matching protocols for patients with ADHD. Future studies should also investigate the similarities and differences in neural signatures between ADHD and other highly comorbid psychiatric disorders.

None Declared

To test the hypothesis that exposure to peer self-harm induces adolescents’ urges to self-harm and that this is influenced by individual suggestibility.

We recruited 97 UK-based adults aged 18–25 years with a recent history of self-harm, measuring baseline suggestibility (Resistance to Peer Influence; RPI) and perceived ability to control urges to self-harm (using an adapted item from the Self-Efficacy to Resist Suicidal Action scale; SEASA) before and after two self-harm vignettes featuring named peers from the participant’s social network (to simulate exposure to peer non-suicidal self-harm) and after a wash-out exposure. We used paired t-tests to compare mean SEASA scores pre- and post-exposure, and linear regression to test for an association between RPI and change in SEASA scores pre- and post-exposure.

Perceived ability to control urges to self-harm was significantly reduced following exposure to peer self-harm (t(96) = 4.02, p < 0.001, mean difference = 0.61; 95% CI = 0.31, 0.91), but was not significantly different from baseline after exposure to a wash-out. We found no association between suggestibility and change in urges to self-harm after exposure to peer self-harm.

Our findings support social influences on self-harm in a sample of young adults, regardless of their individual degree of suggestibility.

Delirium is characterised by an acute, fluctuating change in cognition, attention and awareness (Wilson et al. Nature Reviews 2020; 6). This presentation can make the diagnosis of delirium extremely challenging to clinicians (Gofton., Canadian Journal of neurological sciences. 2011; 38 673-680). It is commonly reported in hospitalised patients, particularly in those over the age of sixty five (NICE. Delirium: prevention, diagnosis and management. 2010).

Our aim is to identify which investigations and cognitive assessments are completed prior to a referral to the liaison psychiatry services in patients with symptoms of delirium.

Referrals (N = 6012) to the liaison psychiatry team at Croydon University Hospital made between April and September 2022 were screened. Search parameters used to identify referrals related to a potential diagnosis of delirium were selected by the authors. The terms used were confusion; delirium; agitation; aggression; cognitive decline or impairment; disorientation; challenging behaviour. Data was collected on the completion rates of investigations for delirium as advised by the NICE clinical knowledge summaries. Further data was gathered on neuroimaging (CT or MRI), cognitive assessment tools (MOCA/MMSE) and delirium screening tools (4AT/AMTS).

The study sample identified 114 referrals (61 males and 53 females), with 82% over 65 years at the time of referral. In 96% of referrals, U&E and CRP were performed. Sputum culture (1%), urine toxin screen (4%) and free T3/4 (8%) were the tests utilised the least. Neuroimaging was completed in 41% of referrals (see Graph 1 for a full breakdown of results).

A formal cognitive assessment or delirium screening tool was completed in 32% of referrals. The AMTS and 4AT tools were documented for 65% and 24% respectively. A total of 19 referrals explicitly stated the patient was suspected to have dementia. A delirium screening tool was documented in 47% of these cases however, a formal cognitive assessment was documented in only 5% of these patients.

Following psychiatric assessment 47% of referrals were confirmed as delirium.

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Our data highlights the low level completion of the NICE recommended delirium screen prior to referral to liaison psychiatry. The effective implementation of a delirium screen and cognitive assessment is paramount to reduce the number of inappropriate psychiatric referrals in hospital and helps to identify reversible organic causes of delirium. This in turn will ensure timely treatment of reversible causes of delirium and reduce the length of hospital admission.

None Declared

Lumateperone (LUMA) is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. An open-label study (Study 303) evaluated the safety and tolerability of LUMA in outpatients with stable schizophrenia who switched from previous antipsychotic (AP) treatment. This post hoc analysis of Study 303 investigated the safety and tolerability of LUMA stratified by previous AP in patients who switched to LUMA treatment for 6 weeks.

Adult outpatients (≥18 years) with stable schizophrenia were switched from previous AP to LUMA 42 mg once daily for 6 weeks followed by switching to another approved AP for 2 weeks follow-up. Post hoc analyses were stratified by most common previous AP: risperidone or paliperidone (RIS/PAL); quetiapine (QET); aripiprazole or brexpiprazole (ARI/BRE); olanzapine (OLA). Safety analyses included adverse events (AE), vital signs, and laboratory tests. Efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impressions-Severity (CGI-S) scale.

The safety population comprised 301 patients, of which 235 (78.1%) were previously treated with RIS/PAL (n=95), QET (n=60), ARI/BRE (n=43), or OLA (n=37). Rates of treatment-emergent AEs (TEAEs) while on LUMA were similar between previous AP groups (44.2%-55.8%). TEAEs with incidences of ≥5% in any AP group were dry mouth, somnolence, sedation, headache, diarrhea, cough, and insomnia. Most TEAEs were mild or moderate in severity for all groups. Rates of serious TEAEs were low and similar between groups (0%–7.0%).

Statistically significant (P<.05) decreases from baseline were observed in the OLA group that switched to LUMA in total cholesterol and low-density lipoprotein cholesterol with significant decreases thereafter on LUMA. Statistically significant decreases in prolactin levels were observed in both the RIS/PAL (P<.0001) and OLA (P<.05) groups. Patients switched from RIS/PAL to LUMA showed significant (P<.05) decreases for body mass index, waist circumference, and weight. At follow-up, 2 weeks after patients switched back from LUMA to another AP, none of the decreases in laboratory parameters or body morphology observed while on LUMA maintained significance.

Those switching from QET had significant improvements from baseline at Day 42 in PANSS Total score (mean change from baseline −3.47; 95% confidence interval [CI] −5.27, −1.68; P<.001) and CGI-S Total score (mean change from baseline −0.24; 95% CI, −0.38, −0.10; P<.01).

In outpatients with stable schizophrenia, LUMA 42 mg treatment was well tolerated in patients switching from a variety of previous APs. Patients switching from RIS/PAL or OLA to LUMA had significant improvements in cardiometabolic and prolactin parameters. These data further support the favorable safety, tolerability, and efficacy of LUMA in patients with schizophrenia.

Intra-Cellular Therapies, Inc.

There is substantial variation in patient symptoms following psychological therapy for depression and anxiety. However, reliance on endpoint outcomes ignores additional interindividual variation during therapy. Knowing a patient's likely symptom trajectories could guide clinical decisions. We aimed to identify latent classes of patients with similar symptom trajectories over the course of psychological therapy and explore associations between baseline variables and trajectory class.

Patients received high-intensity psychological treatment for common mental health problems at National Health Service Improving Access to Psychological Therapies services in South London (N = 16 258). To identify trajectories, we performed growth mixture modelling of depression and anxiety symptoms over 11 sessions. We then ran multinomial regressions to identify baseline variables associated with trajectory class membership.

Trajectories of depression and anxiety symptoms were highly similar and best modelled by four classes. Three classes started with moderate-severe symptoms and showed (1) no change, (2) gradual improvement, and (3) fast improvement. A final class (4) showed initially mild symptoms and minimal improvement. Within the moderate-severe baseline symptom classes, patients in the two showing improvement as opposed to no change tended not to be prescribed psychotropic medication or report a disability and were in employment. Patients showing fast improvement additionally reported lower baseline functional impairment on average.

Multiple trajectory classes of depression and anxiety symptoms were associated with baseline characteristics. Identifying the most likely trajectory for a patient at the start of treatment could inform decisions about the suitability and continuation of therapy, ultimately improving patient outcomes.

While studies from the start of the COVID-19 pandemic have described initial negative effects on mental health and exacerbating mental health inequalities, longer-term studies are only now emerging.

In total, 34 465 individuals in the UK completed online questionnaires and were re-contacted over the first 12 months of the pandemic. We used growth mixture modelling to identify trajectories of depression, anxiety and anhedonia symptoms using the 12-month data. We identified sociodemographic predictors of trajectory class membership using multinomial regression models.

Most participants had consistently low symptoms of depression or anxiety over the year of assessments (60%, 69% respectively), and a minority had consistently high symptoms (10%, 15%). We also identified participants who appeared to show improvements in symptoms as the pandemic progressed, and others who showed the opposite pattern, marked symptom worsening, until the second national lockdown. Unexpectedly, most participants showed stable low positive affect, indicating anhedonia, throughout the 12-month period. From regression analyses, younger age, reporting a previous mental health diagnosis, non-binary, or self-defined gender, and an unemployed or a student status were significantly associated with membership of the stable high symptom groups for depression and anxiety.

While most participants showed little change in their depression and anxiety symptoms across the first year of the pandemic, we highlight the divergent responses of subgroups of participants, who fared both better and worse around national lockdowns. We confirm that previously identified predictors of negative outcomes in the first months of the pandemic also predict negative outcomes over a 12-month period.