Glyn Lewis

• PhD FRCPsych
• Professor at University College London

Objective To investigate the associations between neonatal unit admission (NNU) and subsequent emotional and behavioural difficulties during childhood and adolescence. Design Longitudinal general population cohort study. Setting The Millennium Cohort Study: nationally representative UK-based cohort. Participants All children with exposure, outco...

Background Age-related hearing loss and mild cognitive impairment (MCI) independently increase dementia risk. The Ageing and Cognitive Health Evaluation in Elders randomised controlled trial (RCT) found hearing aids reduce cognitive decline in high-risk older adults with poor hearing. Methods This pilot RCT in London memory clinics randomised peop...

Encephalitis lethargica, an epidemic neurological illness, typically involved a severe sleep disorder and progressive parkinsonism. A century later, our understanding relies on seminal descriptions, more recent historical research and the study of small numbers of possible sporadic cases. Theories around infection, environmental toxins, catatonia a...

Background. Research on mortality and admissions for physical health problems across eating disorder diagnoses in representative settings is scarce but necessary to understand clinical needs of this population. Inequalities in these health outcomes across a range of socio-demographic characteristics have rarely been investigated.Aims. We investigat...

Aims Irritability is a common symptom in children and adolescents, often resulting in referral to mental health services and is associated with depression. Depression in adolescents and adults at familial risk of, and with depression, is associated with reduced risk-taking on the Cambridge Gambling Task (CGT) particularly when the chance of winning...

Aims Irritability is common and easily identified in childhood. It is transdiagnostic and a common reason for referral to mental health services. Irritability which does not decrease during early childhood is associated with adolescent depression. We hypothesised that irritability would be associated with increased risk-taking overall but reduced r...

Aims Conduct disorder carries significant individual and societal repercussions. Despite heightened risk-taking and challenges in adapting to changing probabilities of choice outcomes being linked to maladaptive behaviours such as conduct disorder, no study to date has examined the association behind childhood decision-making and adolescent conduct...

Aims The prevalence of emotional problems, such as depressive and anxiety disorders, increases sharply during adolescence. There is evidence for familial clustering of mental health problems during early childhood and adulthood, however no studies have investigated whether adolescent mental health problems cluster within families. This study tests...

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from...

Background Early detection could reduce the duration of untreated psychosis. GPs are a vital part of the psychosis care pathway, but find it difficult to detect the early features. An accurate risk prediction tool, P Risk, was developed to detect these. Aim To externally validate P Risk. Design and setting This retrospective cohort study used a v...

Importance There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration. Objective To determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practit...

Background Seclusion is a restrictive practice that many healthcare services are trying to reduce. Previous studies have sought to identify predictors of seclusion initiation, but few have investigated factors associated with adverse outcomes after seclusion termination. AimsTo assess the factors that predict an adverse outcome within 24 h of seclu...

Purpose Psychotic like experiences (PLEs) are relatively common during adolescence and associated with a range of negative outcomes. There is evidence that sexual minorities are at increased risk of mental health problems including depression, anxiety, self-harm and suicidality. However, no study has investigated the association between sexual orie...

Purpose Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepr...

Background Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. Method...

Depression is a leading cause of disability in high- and middle-income countries and is of increasing relative burden in low-income countries. The Global Burden of Disease study illustrates how depression is increasing as a proportion of all the disabilities resulting from illness. This is because we know how to prevent other major causes of disabi...

Background Guidelines on the management of depression recommend that practitioners use patient-reported outcome measures for the follow-up monitoring of symptoms, but there is a lack of evidence of benefit in terms of patient outcomes. Objective To test using the Patient Health Questionnaire-9 questionnaire as a patient-reported outcome measure fo...

Background Outcome monitoring of depression treatment is recommended but there is a lack of evidence on patient benefit in primary care. Aim To test monitoring depression using the Patient Health Questionnaire (PHQ-9) with patient feedback. Design and setting An open cluster-randomised controlled trial was undertaken in 141 group practices. Meth...

Background The burden of psychiatric symptoms in Parkinson's disease includes depression, anxiety, apathy, psychosis, and impulse control disorders. However, the relationship between psychiatric comorbidities and subsequent prognosis and neurological outcomes is not yet well understood. In this systematic review and meta-analysis, in individuals wi...

Purpose There are discrepancies in mental health treatment outcomes between ethnic groups, which may differ between genders. NHS Talking Therapies for anxiety and depression provide evidence-based psychological therapies for common mental disorders. This study examines the intersection between ethnicity and gender as factors associated with psychol...

Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n...

Background New treatments are needed for people with treatment-resistant depression (TRD), who do not benefit from anti-depressants and many of whom do not recover fully with psychological treatments. The Community Navigator programme was co-produced with service users and practitioners. It is a novel social intervention which aims to reduce loneli...

Background It is unclear whether young people who attend higher education are at increased risk of common mental disorders, compared with those who do not attend. We aimed to investigate whether higher education attendance was associated with increased symptoms of common mental disorders (depression and anxiety) in young people before, during and a...

Background This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long–term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression. Me...

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual data from 13 clinical studies o...

Background Cognitive behavioural therapy (CBT) is an effective treatment for depression. Self-directed online CBT interventions have made CBT more accessible at a lower cost. However, adherence is often poor and, in the absence of therapist support, effects are modest and short-term. Delivering CBT online using instant messaging is clinically and c...

Purpose Psychotic experiences are relatively common during adolescence and associated with a range of negative outcomes. There is evidence that sexual minorities are at increased risk of mental health problems including depression, anxiety, self-harm and suicidality. However, no study has investigated the association between sexual orientation and...

Background: The role of alcohol use in the development of depression is unclear. We aimed to investigate whether alcohol dependence, but not high frequency or quantity of consumption, during adolescence increased the risk of depression in young adulthood. Methods: In this prospective cohort study, we included adolescents who were born to women r...

Objective: To investigate longitudinal associations between changes in early childhood irritability, and depressive symptoms and self-harm at 14 years. Method: We used data from 7,225 children in a UK-based general population birth-cohort. Childhood irritability was measured at 3, 5 and 7 years using four items from two questionnaires (Children'...

The British Association for Psychopharmacology developed an evidence-based consensus guideline on the management of catatonia. A group of international experts from a wide range of disciplines was assembled. Evidence was gathered from existing systematic reviews and the primary literature. Recommendations were made on the basis of this evidence and...

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for de- pression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether reinforcement learning processes mediate the treatment effects of SSRIs. Reinforcement learning pr...

Background: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. Metho...

Objectives We are not aware of a simple and short structured measure that retrospectively assesses time to relapse for depression. We developed the retrospective Clinical Interview Schedule Revised (rCIS-R) to assess depression relapse in the previous 12 weeks, for use in a clinical trial of maintenance antidepressant treatment. We assessed test-re...

Background: Catatonia is a neuropsychiatric syndrome associated with both psychiatric disorders and medical conditions. Understanding of the pathophysiology of catatonia remains limited, and the role of the environment is unclear. Although seasonal variations have been shown for many of the disorders underlying catatonia, the seasonality of this s...

Background: Antidepressants have been proposed to act via their influence on emotional processing. We investigated the effect of discontinuing maintenance antidepressant treatment on positive and negative self-referential recall and the association between self-referential recall and risk of relapse. Methods: The ANTLER trial was a large (N = 47...

Background: Catatonia is a psychomotor syndrome that has a wide range of aetiologies. Determining whether catatonia is due to a medical or psychiatric cause is important for directing treatment but is clinically challenging. We aimed to ascertain the performance of the electroencephalogram (EEG) in determining whether catatonia has a medical or psy...

Objective The presence of two or more chronic diseases results in worse clinical outcomes than expected by a simple combination of diseases. This synergistic effect is expected to be higher when combined with some conditions, depending on the number and severity of diseases. Multimorbidity is a relatively new term, with the first fundamental defini...

Background Cognitive Behavioural Therapy for psychosis (CBTp) has an established evidence base and is recommended by clinical guidelines to be offered during the acute phases of psychosis. However, few research studies have examined the efficacy of CBTp interventions specifically adapted for the acute mental health inpatient context with most resea...

Catatonia is a neuropsychiatric disorder characterised by altered movement, speech, and behaviour. Clozapine is an established therapy for treatment-resistant schizophrenia, but its role in catatonia has not been systematically examined. In this systematic review, we aimed to assess the evidence for clozapine as a treatment for catatonia. Full text...

Background An accurate risk prediction algorithm could improve psychosis outcomes by reducing duration of untreated psychosis. Objective To develop and validate a risk prediction model for psychosis, for use by family doctors, using linked electronic health records. Methods A prospective prediction study. Records from family practices were used b...

Background Neuropsychiatric presentations of monkeypox (MPX) infection have not been well characterised, despite evidence of nervous system involvement associated with the related smallpox infection. Methods In this pre-registered (PROSPERO ID 336649) systematic review and meta-analysis, we searched MEDLINE, EMBASE, PsycINFO, AMED and the preprint...

The study Duffy L, Clarke CS, Lewis G, et al. Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT. Health Technol Assess 2021;25:69. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/almost-half-people-long-term-antidepressants-stop-without-relapse/

Background The external clinical manifestations (psychopathology) and internal subjective experience (phenomenology) of catatonia are of clinical importance but have received little attention. This study aimed to use a large dataset to describe the clinical signs of catatonia; to assess whether these signs are associated with underlying diagnosis a...

Depression is highly recurrent, even following successful pharmacological and/or psychological intervention. We aimed to develop clinical prediction models to inform adults with recurrent depression choosing between antidepressant medication (ADM) maintenance or switching to mindfulness-based cognitive therapy (MBCT). Using previously published dat...

Objective: Catatonia is a debilitating psychomotor disorder. Previous neuroimaging studies have used small samples with inconsistent results. The authors aimed to describe the structural neuroradiological abnormalities in clinical magnetic resonance imaging (MRI) brain scans of patients with catatonia, comparing them with scans of psychiatric inpa...

Background Adolescents in low-resource urban settings in Brazil are often exposed to high levels of trauma that can result in post-traumatic stress disorder (PTSD). However, preliminary evidence indicates that PTSD tends to be under-reported in Brazilian health services, despite the high prevalence of trauma. Additionally, little is known about the...

Background Antipsychotic medication can reduce psychotic symptoms and risk of relapse in people with schizophrenia and related disorders, but it is not always effective and adverse effects can be significant. We know little of patients’ views about continuing or discontinuing antipsychotic treatment. Aims To explore the views of people with schizo...

Importance: Socioeconomic factors are associated with the prevalence of depression, but their associations with prognosis are unknown. Understanding this association would aid in the clinical management of depression. Objective: To determine whether employment status, financial strain, housing status, and educational attainment inform prognosis...

Background Eating disorders are stigmatised. Little is known about whether stigma has decreased over time and which groups hold more stigmatising beliefs. Aims To explore whether stigma towards eating disorders has changed between 1998 and 2008 and whether it varies by sociodemographic characteristics. Method We used the Office for National Stati...

Background: Subgrouping methods have the potential to support treatment decision making for patients with depression. Such approaches have not been used to study the continued course of depression or likelihood of relapse following treatment. Method: Data from individual participants of seven randomised controlled trials were analysed. Latent pr...

Objective : To investigate associations between major life events and prognosis independent of treatment type: 1) after adjusting for clinical prognostic factors and socio-demographics; 2) among patients with depressive episodes at least six-months long; and 3) patients with a first life-time depressive episode. Methods : Six RCTs of adults seekin...

Background Psychotic experiences emerge from abnormalities in perception and belief formation, and occur more commonly in those experiencing childhood trauma. Yet, which precise aspects of belief formation are atypical in psychosis is not well understood. We used a computational modelling approach to characterise belief-updating in young adults in...

Background Age‐related hearing loss is an independent and potent risk factor for dementia. There is observational evidence that hearing aid use may mitigate deterioration in cognitive performance and could prevent dementia, but experimental evidence is lacking. A trial on whether treating hearing loss reduces the risk of dementia may not be feasibl...

Background Depression is a common mental health condition with considerable negative impact on health and well-being. Although antidepressants are recommended as first-line treatment, there is limited evidence regarding the cost effectiveness of long-term maintenance antidepressants for preventing relapse.Objectives Our objective was to calculate t...

Background Catatonia, a severe neuropsychiatric syndrome, has few studies of sufficient scale to clarify its epidemiology or pathophysiology. We aimed to characterise demographic associations, peripheral inflammatory markers and outcome of catatonia. Methods Electronic healthcare records were searched for validated clinical diagnoses of catatonia....

Background There has been a steady increase in the number of primary care patients receiving long-term maintenance antidepressant treatment, despite limited evidence of a benefit of this treatment beyond 8 months. Objective The ANTidepressants to prevent reLapse in dEpRession (ANTLER) trial investigated the clinical effectiveness and cost-effectiv...

Objectives We aimed to find the association of inflammation and respiratory failure with delirium in COVID-19 patients. We compare the inflammatory and arterial blood gas markers between patients with COVID-19 delirium and delirium in other medical disorders. Methods This cross-sectional study used the CHART-DEL, a validated research tool, to scre...

There is a sharp increase in depression in adolescence, but why this occurs is not well understood. We investigated how adolescents learn about social evaluation and whether learning is associated with depressive symptoms. In a cross-sectional school-based study, 598 adolescents (aged 11-15 years) completed a social evaluation learning task and the...

Background Psychotic experiences are reported by 5–10% of young people, although only a minority persist and develop into psychotic disorders. It is unclear what characteristics differentiate those with transient psychotic experiences from those with persistent psychotic experiences that are more likely to be of clinical relevance. Aims To investi...

There is a sharp increase in depression in adolescence, but why this occurs is not well understood. We investigated how adolescents learn about social evaluation and whether learning is associated with depressive symptoms. In a cross-sectional school-based study, 598 adolescents (aged 11-15 years) completed a social evaluation learning task and the...

Purpose Understanding long-term patterns of suicide methods can inform public health policy and prevention strategies. In Brazil, firearm-related policies may be one salient target for suicide prevention. This study describes trends in method-specific suicide at the national and state-levels in Brazil, with a particular focus on firearm-related sui...

Reprinted under Creative Commons CC-BY license.

BACKGROUND: Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting. METHODS: We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practi...

Ability‐grouping has been studied extensively in relation to children's academic, but not emotional and behavioral outcomes. The sample comprised 7259 U.K. children (50% male) with data on between‐class and within‐class ability‐grouping at age 7. Peer, emotional, hyperactivity, and conduct problems were measured at ages 7, 11, and 14 years. Childre...

Studies in post-mortem human brain tissue have associated major depressive disorder (MDD) with cortical transcriptomic changes, whose potential in vivo impact remains unexplored. To address this translational gap, we recently developed a transcriptome-based polygenic risk score (T-PRS) based on common functional variants capturing ‘depression-like’...

Background and Aims Having a negative cognitive style may lead someone to feel hopeless about his or her situation and be more likely to engage in coping-motivated drinking. We therefore aimed to investigate the association between cognitive style and drinking to cope. Design Prospective cohort study. Setting The former Avon Health Authority in S...

Background Antidepressants are a first line treatment for depression. However, only a third of individuals remit after the first treatment. Common genetic variation likely regulates, in part, antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic...

Objective Individuals with bulimia nervosa and binge eating disorder have greater cardiovascular morbidity than the general population. Longitudinal research on the association between binge eating and metabolic syndrome is limited. We tested the longitudinal association between binge eating and metabolic syndrome and its components in a large popu...

Importance People with anorexia nervosa often experience difficulties regulating their emotions. There is no longitudinal evidence as to whether these differences are already present in childhood or when they begin to emerge. Objective To investigate the association between emotion regulation trajectories from 3 to 7 years of age and symptoms of a...

Background : Older adults commonly experience depression and anxiety, yet are under-represented in psychological treatment services. There is uncertainty about the outcomes from psychological therapies for older adults relative to working-age adults. This study explored: pre-treatment differences between older and working-age patients with depressi...

Aims To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. Methods Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from thei...

Background Depression is commonly perceived as a single underlying disease with a number of potential treatment options. However, patients with major depression differ dramatically in their symptom presentation and comorbidities, e.g. with anxiety disorders. There are also large variations in treatment outcomes and associations of some anxiety como...

Background This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data. Methods Individual patient data from all six eligible randomised controlled trials were used to develop ( k = 3, n = 1722) and test ( k = 3, n = 918) nine models. Predictors inc...

Background Lithium is the most effective treatment in bipolar disorder. Its use is limited by concerns about risk of chronic kidney disease (CKD). We aimed to develop a model to predict risk of CKD following lithium treatment initiation, by identifying individuals with a high-risk trajectory of kidney function. Methods We used United Kingdom Clini...

Background This study aimed to investigate general factors associated with prognosis regardless of the type of treatment received, for adults with depression in primary care. Methods We searched Medline, Embase, PsycINFO and Cochrane Central (inception to 12/01/2020) for RCTs that included the most commonly used comprehensive measure of depressive...

Objective : Previous research on the minimal clinically important difference (MCID) for depression and anxiety is based on population averages. The present study aimed to identify the MCID across the spectrum of baseline severity. Study Design and Settings : The present analysis used secondary data from two randomised controlled trials for depress...