People living with epilepsy (PWE) experience higher rates of depression compared with the general population. Depression in PWE is associated with increased seizure burden and reduced quality of life. We aimed to examine clinical and demographic correlates of depression severity using the nine-item Patient Health Questionnaire in PWE experiencing negative health events in the past 6 months.

1. (a) To assess how depressive severity correlated with seizure frequency;

2. (b) To examine how outcomes such as quality of life are influenced by depressive severity;

3. (c) To investigate how demographic factors affect depressive severity.

Depressive severity was defined as a score of 0–9 for no depression to mild symptoms (NMD), 10–19 for moderate depression (MOD) and 20–27 for severe depression. Continuous variables were analysed using the Kruskal–Wallis equality-of-populations rank test, and categorical variables were compared using Fisher’s exact test. Baseline data were taken from Sequential, Multiple Assignment Randomized Trial no. NCT04705441.

The sample of 159 participants had a mean age of 39.46 years (s.d., 12.15), with the majority (n = 131, 82.4%) identifying as White. A total of 48% (n = 76) of participants met the criteria for NMD, 41% (n = 65) met those for MOD and 11% (n = 18) met those for severe depression. The severe depression group had significantly more seizures in the past 30 days, as well as greater perceived stigma, lower social support and lower quality of life, compared with the other groups. Race was found to correlate with depressive severity in NMD and MOD versus the severe depression group.

Among adults with epilepsy, depressive severity was positively correlated with seizure frequency and stigma and negatively correlated with quality of life, social support and overall functioning. These results highlight the importance of routine screening for depression, and of providing management of these symptoms in comprehensive epilepsy care.

Motor functional neurological disorder (FND) is a common illness associated with significant functional impairment. There are no effective pharmacotherapies, and despite the early promise of physiotherapy studies, many suffer disabling symptoms in the long term. There is a theoretical rationale for combining psychedelics with physiotherapy; however, the potential benefit of this approach and optimal treatment model remains unexplored. Here, we present the protocol for the first study investigating the tolerability, feasibility, and potential efficacy of two distinct treatment regimens of psilocybin-assisted physiotherapy for refractory motor FND: a moderate dose that incorporates movement tasks during the acute drug effects versus a standard dose alone.

Twenty-four participants with refractory motor FND will be randomised in a 1:1 ratio to either (1) psilocybin 15mg, with movement tasks conducted during the acute drug effects; or (2) psilocybin 25mg alone. All participants will receive two sessions of FND-specific physiotherapy pre-dosing, six sessions of physiotherapy post-dosing, and undergo follow-up visits one week and four weeks following their final physiotherapy session. A battery of outcome measures will be completed as scheduled, assessing tolerability, feasibility, motor FND symptom severity, psychiatric and physical symptoms, quality of life, treatment expectations, intensity of the acute drug effects, personality, motor function, force-matching performance, resting-state and task-based brain imaging, and subjective experiences of the study treatment.

These findings will assist the design of an adequately powered randomised controlled trial in this cohort. The findings may also inform the feasibility of psychedelic treatment in related functional and neuropsychiatric disorders.

Achieving a first pass recanalization (FPR) improves clinical outcomes in patients with basilar artery strokes, but its association with initial infarct burden is unknown. We aimed to study the benefits of FPR for basilar artery strokes by initial infarct burden using the Posterior Circulation Alberta Stroke Program Early CT score (pc-ASPECTS).

We retrospectively analyzed the prospective multicentric Endovascular Treatment of Ischemic Stroke registry and included 194 patients diagnosed with an acute basilar artery occlusion who were treated with thrombectomy. Our primary outcome was a modified Rankin Scale (mRS) of 0–3 at 90 days, and our secondary outcomes were an mRS of 4–6 and mortality. We compared the 90-day clinical outcomes of achieving an FPR versus multiple thrombectomy passes based on patients’ initial infarct size on pretreatment MRI: small (pc-ASPECTS = 9–10), medium (pc-ASPECTS = 6–8) and large (pc-ASPECTS <6).

Patients with a medium or large infarct size had significantly better outcomes (mRS 0–3 at 3 months) if FPR was achieved than if multiple passes were required (RR = 1.61, 95% CI: 1.16, 2.24; p-value = 0.005; and RR = 3.41, 95% CI: 1.54–7.57; p-value = 0.003, respectively). No similar difference was seen among patients with small infarcts. Achieving an FPR was also associated with a significantly lower mortality risk among patients with a moderate infarct size (RR = 0.36, 95% CI: 0.17–0.79; p-value = 0.010) but not with those with small or large infarcts.

Achieving an FPR significantly improves clinical outcomes in acute stroke patients with basilar artery occlusions undergoing thrombectomy when their infarcts are medium or large. Ongoing research to develop surgical techniques to achieve FPR is crucial to improving patients’ prognoses.

Because of the complexity of Alzheimer’s Disease (AD) clinical presentations across bio-psycho-social domains of functioning, data-reduction approaches, such as latent profile analysis (LPA), can be useful for studying profiles rather than individual symptoms. Previous LPA research has resulted in more precise characterization and understanding of patients, better clarity regarding the probability and rate of disease progression, and an empirical approach to identifying those who might benefit most from early intervention. Whereas previous LPA research has revealed useful cognitive, neuropsychiatric, or functional subtypes of patients with AD, no study has identified patient profiles that span the domains of health and functioning and that also include motor and sensory functioning.

LPA was conducted with data from the Advancing Reliable Measurement in Alzheimer’s Disease and cognitive Aging study. Participants were 209 older adults with amnestic mild cognitive impairment (aMCI) or mild dementia of the Alzheimer’s type (DAT). LPA indicator variables were from the NIH Toolbox® and included cognitive, emotional, social, motor, and sensory domains of functioning.

The data were best modeled with a 4-profile solution. The latent profiles were most differentiated by indices of social and emotional functioning and least differentiated by motor and sensory function.

These multi-domain patient profiles support and extend previous findings on single-domain profiles and highlight the importance of social and emotional factors for understanding patient experiences of aMCI/DAT. Future research should investigate these profiles further to better understand risk and resilience factors, the stability of these profiles over time, and responses to intervention.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Antipsychotics are primarily indicated for psychotic disorders. There is increasing concern regarding their potential overuse for other conditions.

To examine the change in the number of community prescriptions and corresponding costs for antipsychotics per head of population over 25 years (1998–2022) in England.

The data for 1998–2022 were obtained from two separate resources from the OpenPrescribing database: from 1998 to 2016 from their long-term trends data-set; and for 2017–2022 from the monthly medication prescribing data. The relevant British National Formulary subcategories 4.2.1 ‘antipsychotic drugs’ and 4.2.2 ‘antipsychotic depot injections’ were selected. The annual differences in prescriptions and the mean average annual increase were calculated. Scatter plots to visualise the yearly trend and Spearman testing to assess the strength of the correlations were done. The total annual costs of these medications were calculated for this time period.

The annual mean increase in the number of prescriptions was 287 548 in raw numbers and 4.27 per 1000 population. There is a statistically significant and strong positive relationship between time and the prescriptions of antipsychotics per 1000 population (Spearman correlation coefficient 0.995, P ≤ 0.001). This increasing trend is driven by the increase in oral antipsychotic drug prescriptions over time (Spearman correlation coefficient 0.995, P ≤ 0.001). Antipsychotic drug costs increased until 2011, reduced until 2016 and rose again during 2020–2022.

This analysis suggests a worrying increasing trend in antipsychotic medication prescribing. Potential causal factors include off-licence use. Clinical practice and research implications are discussed.

Ketamine exerts potent but transient antidepressant effects in treatment-resistant depression (TRD). Combinations of ketamine and psychotherapy have attracted interest, but no trial has investigated a psychedelic model of ketamine–psychotherapy for TRD to our knowledge.

This secondary analysis of a randomised clinical trial (RCT) explores the therapeutic effects and experiential mechanisms of the Montreal Model of ketamine–psychotherapy for TRD, with or without music.

A two-centre, single-blinded, RCT conducted in Montreal, Canada, between January 2021 and August 2022 (NCT04701866). Participants received ketamine–psychotherapy for TRD – six subanaesthetic infusions over 4 weeks and psychological support – with either music or matched non-music support during ketamine doses, as per random group assignments. The primary therapeutic outcome was the Montgomery–Åsberg Depression Rating Scale, assessed by blinded raters. Psychedelic-like experiences, evaluated by the Mystical Experience Questionnaire and Emotional Breakthrough Inventory, and their session-by-session relationships with depression were explored with multilevel, time-lagged covariate models with autoregressive residuals.

Thirty-two participants with severe and highly comorbid TRD, including high rates of personality disorder and suicidality, received 181 ketamine infusions. Therapeutic outcomes and psychedelic experiences did not differ between music (n = 15) and non-music (n = 17) interventions. Both groups experienced significant reductions in clinician-rated and self-reported depression (d = 1.2 and d = 0.87, respectively; p < 0.001), anxiety (d = 0.8, p < 0.001) and suicidality (d = 0.4, p < 0.05) at 4 weeks, fully maintained at 8-week follow-up. Ketamine experiences were highly emotional and mystical. Converging analyses supported mystical-like ketamine experiences as mechanisms of its antidepressant effects.

This trial found large and notably sustained benefits of ketamine–psychotherapy for severe TRD, with or without music, and psychedelic experiences of comparable intensity to those observed with psilocybin. Mystical-like experiences may particularly contribute to ketamine’s immediate and persistent psychiatric benefits.