Identifying people with potentially undiagnosed dementia with Lewy bodies using natural language processing.

Natural language processing (NLP) can expand the utility of clinical records data in dementia research. We deployed NLP algorithms to detect core features of dementia with Lewy bodies (DLB) and applied those to a large database of patients diagnosed with dementia in Alzheimer's disease (AD) or DLB. Of 14,329 patients identified, 4.

Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study.

Reinforcement learning is a fundamental aspect of adaptive behaviour, since it involves the acquisition and updating of associations between actions and their outcomes based on the rewarding or punishing consequences. Acute experimental manipulations of serotonin have provided compelling evidence for its role in reinforcement learning. However, it remains unknown how more chronic manipulation of serotonin, which holds greater clinical relevance, affects reinforcement learning and the underlying neural mechanisms.

Hippocampal perineuronal net degradation identifies prefrontal and striatal circuits involved in schizophrenia-like changes in marmosets.

In schizophrenia, anterior hippocampus (aHipp) overactivity is associated with orbitofrontal cortex (OFC) dysfunction, but the contribution to symptomatology is unknown. In rodents, degradation of the hippocampal perineuronal net (PNN) replicates this overactivity, but uncertainty over rodent/human prefrontal homology limits translation to humans. Here, we test the hypothesis that aHipp PNN degradation in a species with a human-like prefrontal cortex, the marmoset, alters aHipp-striatal and aHipp-OFC circuitry.

Network analysis of functional disabilities and their association with mental well-being in children and adolescents: multi-country study across low- and middle-income countries.

Background: To develop effective mental health interventions for children and adolescents, it is essential to understand the intricate link between functional disability and mental well-being in this group.

Aims: To explore the network connections between various aspects of functional disability and mental well-being in young people with disabilities.

Method: We analysed data from the Multiple Indicator Cluster Surveys in 47 low- and middle-income countries, tracking progress towards health-related sustainable development goals.

Deconstructing Delay Discounting in Human Cocaine Addiction Using Computational Modeling and Neuroimaging.

Background: A preference for sooner-smaller over later-larger rewards, known as delay discounting, is a candidate transdiagnostic marker of waiting impulsivity and a research domain criterion. While abnormal discounting rates have been associated with many psychiatric diagnoses and abnormal brain structure, the underlying neuropsychological processes remain largely unknown. Here, we deconstruct delay discounting into choice and rate processes by testing different computational models and investigate their associations with white matter tracts.

Atomoxetine Reduces Decisional Impulsivity in Human Cocaine Addiction.

Background: Impulsivity is a well-known determinant of maladaptive behavior in cocaine use disorder (CUD), but there are currently no effective strategies for managing excessive impulsivity. Growing evidence from preclinical and clinical studies suggests that atomoxetine, a selective noradrenaline reuptake inhibitor, is effective in improving impulse control in both healthy individuals and individuals with neuropsychiatric conditions.

Methods: We investigated the effects of atomoxetine on decisional impulsivity in patients with CUD.

Associations between rural/urban status, duration of untreated psychosis and mode of onset of psychosis: a mental health electronic clinical records analysis in the East of England, UK.

Purpose: The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis.

Methods: We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015.

Temporal trends in population attributable fractions of modifiable risk factors for dementia: a time-series study of the English Longitudinal Study of Ageing (2004-2019).

Background: Interest in modifiable risk factors (MRFs) for dementia is high, given the personal, social, and economic impact of the disorder, especially in ageing societies such as the United Kingdom. Exploring the population attributable fraction (PAF) of dementia attributable to MRFs and how this may have changed over time remains unclear. Unravelling the temporal dynamics of MRFs is crucial for informing the development of evidence-based and effective public health policies.

Predicting patients with dementia most at risk of needing psychiatric in-patient or enhanced community care using routinely collected clinical data: retrospective multi-site cohort study.

Background: Dementia is a common and progressive condition whose prevalence is growing worldwide. It is challenging for healthcare systems to provide continuity in clinical services for all patients from diagnosis to death.

Aims: To test whether individuals who are most likely to need enhanced care later in the disease course can be identified at the point of diagnosis, thus allowing the targeted intervention.

The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study.

Background: A significant proportion of people with clozapine-treated schizophrenia develop 'checking' compulsions, a phenomenon yet to be understood.

Aims: To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive-compulsive symptoms (OCS).

Method: Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking.

5-HT 2A and 5-HT 2C receptor antagonism differentially modulate reinforcement learning and cognitive flexibility: behavioural and computational evidence.

Rationale: Cognitive flexibility, the ability to adapt behaviour in response to a changing environment, is disrupted in several neuropsychiatric disorders, including obsessive-compulsive disorder and major depressive disorder. Evidence suggests that flexibility, which can be operationalised using reversal learning tasks, is modulated by serotonergic transmission. However, how exactly flexible behaviour and associated reinforcement learning (RL) processes are modulated by 5-HT action on specific receptors is unknown.

Perseveration and Shifting in Obsessive-Compulsive Disorder as a Function of Uncertainty, Punishment, and Serotonergic Medication.

Background: The nature of cognitive flexibility deficits in obsessive-compulsive disorder (OCD), which historically have been tested with probabilistic reversal learning tasks, remains elusive. Here, a novel deterministic reversal task and inclusion of unmedicated patients in the study sample illuminated the role of fixed versus uncertain rules/contingencies and of serotonergic medication. Additionally, our understanding of probabilistic reversal was enhanced through theoretical computational modeling of cognitive flexibility in OCD.

Computational modelling of reinforcement learning and functional neuroimaging of probabilistic reversal for dissociating compulsive behaviours in gambling and cocaine use disorders.

Background: Individuals with cocaine use disorder or gambling disorder demonstrate impairments in cognitive flexibility: the ability to adapt to changes in the environment. Flexibility is commonly assessed in a laboratory setting using probabilistic reversal learning, which involves reinforcement learning, the process by which feedback from the environment is used to adjust behavior.

Aims: It is poorly understood whether impairments in flexibility differ between individuals with cocaine use and gambling disorders, and how this is instantiated by the brain.

Comparable roles for serotonin in rats and humans for computations underlying flexible decision-making.

Serotonin is critical for adapting behavior flexibly to meet changing environmental demands. Cognitive flexibility is important for successful attainment of goals, as well as for social interactions, and is frequently impaired in neuropsychiatric disorders, including obsessive-compulsive disorder. However, a unifying mechanistic framework accounting for the role of serotonin in behavioral flexibility has remained elusive.

Trends in Gender and Racial/Ethnic Disparities in Physical Disability and Social Support Among U.S. Older Adults With Cognitive Impairment Living Alone, 2000-2018.

Background And Objectives: Informal care is the primary source of support for older adults with cognitive impairment, yet is less available to those who live alone. We examined trends in the prevalence of physical disability and social support among older adults with cognitive impairment living alone in the United States.

Research Design And Methods: We analyzed 10 waves of data from the U.

Mortality rates and proximal causes of death in patients with Lewy body dementia versus Alzheimer's disease: A longitudinal study using secondary care mental health records.

Background: Previous studies have shown reduced survival in Lewy body dementia (LBD) compared to Alzheimer's disease (AD), but the reasons for this are not known. We identified cause of death categories accounting for the reduced survival in LBD.

Methods: We linked cohorts of patients with dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and AD, with proximal cause of death data.

De-identified Bayesian personal identity matching for privacy-preserving record linkage despite errors: development and validation.

Background: Epidemiological research may require linkage of information from multiple organizations. This can bring two problems: (1) the information governance desirability of linkage without sharing direct identifiers, and (2) a requirement to link databases without a common person-unique identifier.

Methods: We develop a Bayesian matching technique to solve both.

Predicting treatment resistance from first-episode psychosis using routinely collected clinical information.

Around a quarter of people who experience a first episode of psychosis (FEP) will develop treatment-resistant schizophrenia (TRS), but there are currently no established clinically useful methods to predict this from baseline. We aimed to explore the predictive potential for clozapine use as a proxy for TRS of routinely collected, objective biomedical predictors at FEP onset, and to externally validate the model in a separate clinical sample of people with FEP. We developed and externally validated a forced-entry logistic regression risk prediction Model fOr cloZApine tReaTment, or MOZART, to predict up to 8-year risk of clozapine use from FEP using routinely recorded information including age, sex, ethnicity, triglycerides, alkaline phosphatase levels, and lymphocyte counts.

Economic evaluation of interventions for treatment-resistant depression: A systematic review.

Background: The extraordinarily high prevalence of treatment-resistant depression (TRD), coupled with its high economic burden to both healthcare systems and society, underscore how critical it is that resources are managed optimally to address the significant challenge it presents.

Objective: To review the literature on economic evaluation in TRD systematically, with the aim of informing future studies by identifying key challenges specific to the area, and highlighting good practices.

Methods: A systematic literature search across seven electronic databases was conducted to identify both within-trial and model-based economic evaluations in TRD.

Risk Factors for Longer-Term Mortality in Discharged Patients with Dementia and SARS-CoV-2 Infection: A Matched Case-Control Study.

Background: Persisting symptoms and increased mortality after SARS-CoV-2 infection has been described in COVID-19 survivors.

Objective: We examined longer-term mortality in patients with dementia and SARS-CoV-2 infection.

Methods: A retrospective matched case-control study of 165 patients with dementia who survived an acute hospital admission with COVID-19 infection, and 1325 patients with dementia who survived a hospital admission but without SARS-CoV-2 infection.

Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomised study.

Several studies of the effects on cognition of selective serotonin reuptake inhibitors (SSRI), administered either acutely or sub-chronically in healthy volunteers, have found changes in learning and reinforcement outcomes. In contrast, to our knowledge, there have been no studies of chronic effects of escitalopram on cognition in healthy volunteers. This is important in view of its clinical use in major depressive disorder (MDD) and obsessive-compulsive disorder (OCD).

Longitudinal effect of clozapine-associated sedation on motivation in schizophrenia: naturalistic longitudinal study.

Negative symptoms of schizophrenia manifest as reduced motivation and pleasure (MAP) and impaired emotional expressivity (EXP). These can occur as primary phenomena, but have also been suggested to occur secondary to other clinical factors, including antipsychotic-induced sedation. However, this relationship has not been established formally.

Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study.

Background: Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality than Alzheimer's disease (AD). The reasons for this are unclear, but antidementia drugs (including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit people with DLB and might improve outcomes. We investigated whether AChEIs and/or memantine were associated with reduced hospital admissions and mortality.

Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans.

Background: The non-selective serotonin 2A (5-HT) receptor agonist lysergic acid diethylamide (LSD) holds promise as a treatment for some psychiatric disorders. Psychedelic drugs such as LSD have been suggested to have therapeutic actions through their effects on learning. The behavioural effects of LSD in humans, however, remain incompletely understood.