Cognitive impairment is a significant, yet often overlooked, non-motor symptom of Parkinson’s disease, and a strong predictor of quality of life for those affected. Despite the availability of both pharmacological and non-pharmacological treatment options for Parkinson’s disease, their efficacy for the cognitive symptoms of the disease specifically is unclear, as no ‘gold standard’ treatment strategy for cognitive impairment in the disease has yet emerged. Further, a comparative understanding of the efficacy of each of these treatment options is severely lacking.

This systematic review aims to critically evaluate the efficacy of non-pharmacological interventions for the treatment of cognitive impairment in Parkinson’s disease.

A comprehensive systematic search will be conducted to identify studies involving participants clinically diagnosed with Parkinson’s disease that assess non-pharmacological interventions targeting cognitive impairment. If feasible, results will be synthesised using meta-analysis; otherwise, narrative synthesis will be used.

This is a protocol for a systematic review that is yet to be conducted.

The findings from this review will provide critical insight into the efficacy of non-pharmacological treatment options for cognitive impairment in Parkinson’s disease, which may help to influence clinical recommendations for the treatment of cognitive impairment in Parkinson’s disease and highlight existing gaps in the literature.

Negative symptoms in schizophrenia, particularly motivational deficits, pose significant challenges to treatment and recovery. Despite their profound impact on functional outcomes, these symptoms remain poorly understood and inadequately addressed by current interventions.

The CHANSS (Characterising Negative Symptoms in Schizophrenia) study aims to dissect the cognitive mechanisms underlying motivational impairments by focusing on three interconnected domains: executive cognition, motivational cognition and meta-cognition.

This large, international, cross-sectional study recruits a heterogeneous sample of patients across illness stages – from first-episode psychosis to treatment-resistant schizophrenia – and uses a comprehensive cognitive battery, clinical scales, self-report measures and computerised cognitive tasks. Four novel tasks assess key processes in motivated behaviour: option generation, reward-based decision-making, risk sensitivity and performance self-evaluation. By incorporating control for secondary influences like depression, psychosis, sedation and illness chronicity, the study seeks to identify distinct cognitive and behavioural subtypes within motivational dysfunction.

CHANSS tests the hypothesis that specific patient profiles exhibit predominant impairments in one or more cognitive domains, which may differentially affect goal-directed behaviour. The study’s design allows exploration of hierarchical relationships between cognitive processes, such as how neurocognitive deficits may cascade to impair motivation and self-evaluation.

Ultimately, CHANSS aims to advance mechanistic understanding of motivational deficits in schizophrenia and pave the way for personalised, targeted interventions. Its findings may inform future clinical trials and contribute to a shift away from one-size-fits-all approaches towards more effective, stratified treatment strategies in schizophrenia.

Research indicates that treatment outcomes are poorer for people with long-term physical health conditions (LTCs) in Talking Therapies services (formerly known as Improving Access to Psychological Therapies). However, the impact of having an LTC on attendance at assessment and treatment appointments within Talking Therapies remains unclear. Internet-enabled therapies may be one way to overcome barriers to treatment engagement in Talking Therapies. However, their effect on engagement and the influence of LTC status on receipt of internet-enabled therapies is unknown.

To explore the association between LTC status and assessment attendance, treatment engagement and internet-enabled therapy receipt within Talking Therapies services, and whether receipt of internet-enabled treatment bolsters engagement.

We used anonymous patient-level data from two inner London Talking Therapies services during January to December 2022 (n = 17 095 referrals). Binary logistic regression models were constructed to compare differences between LTC and non-LTC groups on (a) assessment attendance, (b) engagement and (c) internet-enabled therapy receipt. In our regression models, we controlled for key clinical and demographic covariates.

There were no differences between patients with or without an LTC in assessment attendance or treatment engagement, after controlling for covariates. Across the whole sample, receiving internet-enabled treatment increased engagement. People with an LTC were less likely to receive an internet-enabled treatment.

Having an LTC does not negatively affect assessment attendance and engagement with talking therapies. However, receiving an internet-enabled treatment bolstered engagement in our regression models. People with an LTC were less likely to receive internet-enabled treatment.

In-person, therapist-supported interventions targeting emotion regulation have been shown to improve the mental health of adolescents. Increasingly, self-directed digital interventions (e.g. mobile apps) are being developed as a cost-effective, scalable solution to widen access to support. However, evidence of the acceptability and feasibility of these interventions has yet to be synthesised.

To identify existing evidence on the benefits, acceptability and feasibility of self-directed digital interventions that target emotion regulation in adolescents (aged 11–18 years).

A Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-guided systematic review was conducted to identify studies published from 1 January 2010 to 13 November 2024 investigating self-directed digital emotion regulation interventions for adolescents. A total of ten electronic databases were searched (e.g. PsycInfo). Data on the effects, and perceived acceptability, of the interventions were extracted, with results narratively synthesised. Methodological quality was assessed using the Effective Public Health Practice Project Quality Assessment tool.

Six out of 9049 studies met the eligibility criteria and included preliminary evidence on self-directed digital interventions that target emotion regulation, in a pooled sample of 1271 adolescents. All interventions identified were brief (most <1 month) and included different components to target emotion regulation (e.g. mindfulness, mood monitoring). Most interventions demonstrated benefits for emotion regulation and were acceptable for use by an adolescent population.

Although the evidence base was small, the included studies demonstrate preliminary evidence of the benefits and acceptability of self-directed, digital interventions for emotion regulation in adolescents. Future research should focus on approaches beyond mindfulness, including components to target the related skills required to access emotion regulation strategies (e.g. emotional awareness) and use them flexibly.

Previous studies have found substantial costs to be associated with depression and insomnia (as separate entities).

To estimate healthcare service use and costs associated with insomnia in Australian adults experiencing subthreshold depression or major depressive disorder (MDD).

Healthcare service use and productivity loss were extracted from the cross-sectional 2020–2022 National Survey of Mental Health and Wellbeing data. Insomnia and depression were assessed using questions aligned with DSM-IV criteria. Weighted two-part models were used to calculate average annual costs (presented as 2021–2022 Australian dollars).

The analytical sample meeting subthreshold depression or MDD criteria consisted of 1331 adults (aged 40.5 ± 16.1 years; 59% female; insomnia prevalence: 84%). Healthcare service use and healthcare costs between individuals with insomnia and those without insomnia were similar in the MDD group. For subthreshold depression, healthcare costs were significantly higher for those with insomnia compared with those without insomnia (Δ = A$990, 95% CI: 234 to 1747), but healthcare resource use was not significantly different. Productivity loss among employed people and reduced employment were much greater (although the difference did not reach statistical significance) in adults with insomnia compared with those without insomnia.

Healthcare resource use among adults with depression was similar in those with and without insomnia. However, higher healthcare costs associated with insomnia were observed in adults with subthreshold depression. Further studies are encouraged to understand the nature of the increased healthcare cost associated with insomnia in individuals with subthreshold depression and to optimise healthcare service use in people with comorbid depression and insomnia.

Pupils in alternative education provision, known as ‘Educated in Other Than At School’ (EOTAS) in Wales, UK, are among the most vulnerable learners and who, for reasons such as mental health or behavioural challenges, do not attend a mainstream or special school.

We compared self-harm, neurodevelopmental disorders and mental health conditions between EOTAS pupils and controls with similar characteristics, before and after being in EOTAS provision.

This population-based electronic cohort study included pupils in Wales aged 7–18 years, from the academic years 2010–11 to 2018–19. We linked data from Education Wales to primary and secondary healthcare records within the Secure Anonymised Information Linkage (SAIL) Databank. Individuals included in the EOTAS data-set were identified as cases. Controls were pseudo-randomly selected based on equivalent age and academic year distribution.

This study included 8056 pupils in EOTAS and 224 247 controls. Higher levels of deprivation, childhood maltreatment, self-harm, neurodevelopmental disorders and mental health conditions before EOTAS entry were linked to higher odds of being in EOTAS. Pupils in EOTAS provision had increased incidence of self-harm, neurodevelopmental disorders and mental health conditions, from 1 year after entering EOTAS provision up to 24 years of age, than pupils with similar characteristics not in EOTAS provision.

While EOTAS provision plays an important role, our findings indicate that it is not sufficient on its own to meet pupils’ social, emotional, behavioural and mental health needs. Additional support and better integration with health and social services are required.

Adolescence marks a critical transition period, with significant mental health challenges including anxiety and depression symptoms that affect long-term happiness. There has been a lack of research exploring the factors mediating adolescent happiness.

To investigate the mediating effects of anxiety and depression on adolescent happiness, as well as the contributions of sociodemographic factors.

We recruited 392 adolescents. Anxiety symptoms, depression symptoms and happiness were assessed by the seven-item Generalized Anxiety Disorder scale, nine-item Patient Health Questionnaire and single-item happiness scale, respectively. Self-administered questionnaires were used to collect sociodemographic information.

Spearman correlation analysis showed significant negative correlations of happiness with anxiety (r = −0.37, P < 0.0001) and depression (r = −0.47, P < 0.0001). Positive predictors of happiness included quality of parents’ marriage (β = 0.12, P = 0.006), regular physical exercise (β = 0.13, P = 0.006) and regular diet (β = 0.10, P = 0.03). Mediation analysis indicated that depressive symptoms (estimate = 0.50, 95% CI: 0.25 to 0.80) and anxiety symptoms (estimate = 0.32, 95% CI: 0.12 to 0.57) partially mediated the relationship between regular exercise and happiness, whereas depressive symptoms completely mediated the relationship between anxiety symptoms and happiness (estimate = −0.14, 95% CI: −0.20 to −0.08).

The findings of this study highlight the intricate interplay of mental health issues, lifestyle factors and adolescent happiness and emphasise the need for comprehensive interventions focusing on enhancing physical activity and addressing psychological health to foster happiness among adolescents.

The dysconnection hypothesis of schizophrenia posits that widespread synaptic inefficiencies lead to altered macroscale brain connectivity, contributing to symptom severity and cognitive deficits in individuals with schizophrenia spectrum disorders (SSD). Emerging evidence suggests that physical exercise may help to ameliorate these connectivity abnormalities and associated clinical impairments.

This study investigated whether reductions in functional dysconnectivity following exercise therapy were associated with clinical improvements in individuals with SSD. In addition, it explored the genetic underpinnings of these changes using imaging transcriptomics.

Using data from the ESPRIT C3 trial, we analysed 23 SSD patients (seven female) undergoing aerobic exercise or flexibility, strengthening and balance training over 6 months. Functional dysconnectivity, assessed at baseline and post-intervention relative to a healthy reference sample (n = 200), was evaluated at the whole-brain, network and regional levels. Linear mixed effect models and voxel-wise Pearson’s correlations were used to assess exercise-induced changes and clinical relevance.

Functional dysconnectivity significantly decreased (d = −2.73, P < 0.001), and this decrease was primarily linked to enhanced oligodendrocyte-related gene expression. Reductions in the default-mode network were correlated with improved global functioning, whereas changes in insular regions were associated with symptom severity and functioning. Dysconnectivity reductions in somatomotor and frontoparietal networks were correlated with total symptom improvements, and changes in language-related regions (e.g. Broca’s area) were linked to cognitive benefits.

Our findings support the role of oligodendrocyte pathology in SSD and suggest that targeting dysconnectivity in the default-mode, salience and language networks may enhance global functioning, symptom severity and cognitive impairments.

Individuals with schizophrenia experience significantly higher rates of chronic physical health conditions, driving a 20-year reduction in life expectancy. Poor diet quality is a key modifiable risk factor; however, owing to side-effects of antipsychotic medication, cognitive challenges and food insecurity, standard dietary counselling may not be sufficient for this population group.

To evaluate the feasibility, acceptability and preliminary effectiveness of two dietary interventions – pre-prepared meals and meal kits – for individuals with schizophrenia.

The Schizophrenia, Nutrition and Choices in Kilojoules (SNaCK) study is a 12-week, three-arm, cross-over, randomised controlled trial. Eighteen participants aged 18–64 years diagnosed with schizophrenia or schizoaffective disorder will be recruited from community mental health services in Australia. Participants will be randomised to receive pre-prepared meals, meal kits or a supermarket voucher as a control, crossing-over at the end of weeks 4 and 8, so that all participants experience all three study arms. Primary outcomes include feasibility (recruitment rate and retention, number of days participants use pre-prepared meals or meal kits, adherence to meals as prescribed, difficulty in meal preparation and meal wastage) and acceptability (meal provision preference ranking and implementation) of the nutrition interventions. Secondary outcomes include the effects of the intervention on metabolic syndrome components, dietary intake, quality of life and food security measures.

Feasible, acceptable and effective dietary interventions for people with schizophrenia are urgently needed. Findings from this trial will inform future larger randomised controlled trials that have the potential to influence policy and improve health outcomes for this vulnerable population.

Stress could increase delay discounting in subjects with bulimia nervosa and alcohol use disorder (AUD), meaning that the short-term benefits of coping through eating or drinking outweigh the long-term negative consequences. Therefore, this study explores differences in delay discounting between patients and healthy controls, the impact of stress on food and alcohol delay discounting and associated changes in brain activity.

A total of 102 female participants (AUD, 27; bulimia nervosa, 25; healthy controls, 50) underwent repeated functional magnetic resonance imaging scanning. Initially, all participants performed a monetary delay discounting task (DDT), followed by a food or alcohol DDT before and after stress induction. Specifically, those with bulimia nervosa completed a food DDT, those with AUD completed an alcohol DDT and healthy controls were randomly allocated to one or either DDT.

Participants with AUD, but not healthy controls, displayed a higher discounting of alcohol after stress. Healthy controls, but not those with bulimia nervosa, had nominally higher discounting rates of food following stress, although not significant following multiple testing correction. Participants with AUD displayed a lower activity of the right supplementary motor area while discounting alcohol after stress. Healthy controls showed a lower activity of the frontal cortex and a higher activity of the motor cortex while discounting food after stress, while those with bulimia nervosa displayed a higher activity of the occipital cortex.

The results suggest that, in subjects with AUD, stress induces neurobiological changes that cause them to prefer more immediately available alcohol. However, the results observed in participants with bulimia nervosa suggest a more complex relation between stress and food.

Nitrous oxide may possess antidepressant effects; however, limited data exist on repeated administrations and active placebo-controlled studies in treatment-resistant depression (TRD).

We aimed to test the feasibility of a randomised controlled trial examining a 4-week course of nitrous oxide or midazolam, an active placebo.

In this randomised, active, placebo-controlled pilot trial, 40 participants with TRD were assigned either a 1-h inhalation of 50% nitrous oxide plus intravenous saline (n = 20) or a 1-h inhalation of 50% oxygen plus intravenous midazolam (0.02 mg/kg, up to 2 mg; n = 20) once weekly, for 4 weeks. Feasibility was assessed by examining rates of recruitment, withdrawal, adherence, missing data and adverse events. The main measure of clinical efficacy was the change in depression severity (Montgomery–Åsberg Depression Rating Scale (MADRS)) score from baseline to day 42.

The recruitment rate was 22.3% (95% CI 16.9–29.0). Withdrawal rates were 10% (95% CI 2.8–30.1) in both groups and adherence rates were 100.0% (95% CI 82.4–100) in the nitrous oxide group and 94.4% (95% CI 74.2–99.0) in the placebo group. There were no missing primary clinical outcome data in either group (0.0%, 95% CI 0.0–17.6). MADRS score changed by −20.5% (95% CI −39.6 to −1.3) in the nitrous oxide group and −9.0% (95% CI −22.6 to 4.6) in the placebo group. Nearly all adverse events were mild to moderate and transient.

The findings support the feasibility and necessity of conducting a full-scale trial comparing nitrous oxide and midazolam in patients with TRD.

The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored.

To explore the clustering pattern of chronic PCNPS in a cohort of patients having their first COVID infection during the ‘Omicron wave’ and discover phenotypes of patients based on their symptoms’ patterns using a pre-registered protocol.

We assessed 1205 eligible subjects in Hong Kong using app-based questionnaires and cognitive tasks.

Partial network analysis of chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint–fatigue and anxiety–depression) and a minor headache–dizziness cluster, like our pre-Omicron cohort. Participants with high numbers of symptoms could be further grouped into two distinct phenotypes: a cognitive complaint–fatigue predominant phenotype and another with symptoms across multiple clusters. Multiple logistic regression showed that both phenotypes were predicted by the level of pre-infection deprivation (adjusted P-values of 0.025 and 0.0054, respectively). The severity of acute COVID (adjusted P = 0.023) and the number of pre-existing medical conditions predicted only the cognitive complaint–fatigue predominant phenotype (adjusted P = 0.003), and past suicidal ideas predicted only the symptoms across multiple clusters phenotype (adjusted P < 0.001). Pre-infection vaccination status did not predict either phenotype.

Our findings suggest that we should pursue a phenotype-driven approach with holistic biopsychosocial perspectives in disentangling the heterogeneity under the umbrella of chronic PCNPS. Management of patients complaining of chronic PCNPS should be stratified according to their phenotypes. Clinicians should recognise that depression and anxiety cannot explain all chronic post-COVID cognitive symptoms.