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Background The Mental Capacity Act 2005 of England and Wales is a ground-breaking piece of legislation with reach into healthcare, social care and legal settings. Professionals have needed to develop skills to assess mental capacity and handle malign influence, but it is unclear how assessments are implemented in real world settings. Our previously reported survey found professionals juggling competing resources in complex systems, often struggling to stay up to date with law. The current follow-up study uses one-to-one interviews of professionals to characterise in detail six areas of uncertainty faced when assessing mental capacity, whilst suggesting ways to make improvements. Methods Forty-four healthcare, social care and legal professionals were interviewed, using a semi-structured topic guide. Transcripts were analysed using framework analysis: a qualitative technique built to investigate healthcare policy. Results Our topic guide generated 21 themes. In relation to the six areas of uncertainty: 1) Many participants stressed the importance of capturing a holistic view, adding that their own profession was best-placed for this - although a medical diagnosis was often needed. 2) The presumption of capacity was a laudable aim, though not always easy to operationalise and occasionally being open to abuse. 3) There was cautious interest in psychometric testing, providing a cognitive context for decisions. 4) Undue influence was infrequent, but remained under-emphasised in training. 5) Multi-professional assessments were common, despite doubts about fitting these within local resources and the law. 6) Remote assessment was generally acceptable, if inadequate for identifying coercion. Conclusions Practical constraints and competing demands were reported by professionals working within real world systems. Assessment processes must be versatile, equally applicable in routine and emergency settings, across diverse decisional types, for both generalist and specialist assessors, and able to handle coercion. Recognising these challenges will guide development of best practices in assessment and associated policy.

Summary: 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 with Parkinson's disease, we aimed to characterise the association between specific psychiatric comorbidities and subsequent prognosis and neurological outcomes: cognitive impairment, death, disability, disease progression, falls or fractures and care home admission. Methods: We searched MEDLINE, Embase, PsycINFO and AMED up to 13th November 2023 for longitudinal observational studies which measured disease outcomes in people with Parkinson's disease, with and without specific psychiatric comorbidities, and a minimum of two authors extracted summary data. Studies of individuals with other parkinsonian conditions and those with outcome measures that had high overlap with psychiatric symptoms were excluded to ensure face validity. For each exposure-outcome pair, a random-effects meta-analysis was conducted based on standardised mean difference, using adjusted effect sizes–where available–in preference to unadjusted effect sizes. Study quality was assessed using the Newcastle–Ottawa Scale. Between-study heterogeneity was assessed using the I2 statistic and publication bias was assessed using funnel plots. PROSPERO Study registration number: CRD42022373072. Findings: There were 55 eligible studies for inclusion in meta-analysis (n = 165,828). Data on participants’ sex was available for 164,514, of whom 99,182 (60.3%) were male and 65,460 (39.7%) female. Study quality was mostly high (84%). Significant positive associations were found between psychosis and cognitive impairment (standardised mean difference [SMD] 0.44, [95% confidence interval [CI] 0.23–0.66], I2 30.9), psychosis and disease progression (SMD 0.46, [95% CI 0.12–0.80], I2 70.3%), depression and cognitive impairment (SMD 0.37 [95% CI 0.10–0.65], I2 27.1%), depression and disease progression (SMD 0.46 [95% CI 0.18–0.74], I2 52.2), depression and disability (SMD 0.42 [95% CI 0.25–0.60], I2 7.9%), and apathy and cognitive impairment (SMD 0.60 [95% CI 0.02–1.19], I2 27.9%). Between-study heterogeneity was moderately high. Interpretation: Psychosis, depression, and apathy in Parkinson's disease are all associated with at least one adverse outcome, including cognitive impairment, disease progression and disability. Whether this relationship is causal is not clear, but the mechanisms underlying these associations require exploration. Clinicians should consider these psychiatric comorbidities to be markers of a poorer prognosis in people with Parkinson's disease. Future studies should investigate the underlying mechanisms and which treatments for these comorbidities may affect Parkinson's disease outcomes. Funding: Wellcome Trust, UK National Institute for Health Research (NIHR), National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at University College London Hospitals NHS Foundation Trust, National Brain Appeal.

Abstract Depersonalisation disorder (DPD) is a psychopathological condition characterised by a feeling of detachment from one's own body and surrounding, and it is understood as emerging from the downregulation of interoceptive afferents. However, the precise mechanisms that drive this ‘interoceptive silencing’ are yet to be clarified. Here we present a computational and neurobiologically plausible model of DPD within the active inference framework. Specifically, we describe DPD as arising from disrupted interoceptive processing at higher levels of the cortical hierarchy where the interoceptive and exteroceptive streams are integrated. We simulated the behaviour of an agent subjected to a situation of high interoceptive activation despite the absence of a perceivable threat in the external environment. The simulation showed how a similar condition, if perceived as inescapable, would result in a downregulation of interoceptive signals, whilst leaving the exteroceptive ones unaffected. Such interoceptive silencing would force the agent to over-rely on exteroceptive information and would ultimately lead to the DPD phenomenology. Finally, our simulation shows that repeated exposure to similar situations over time will lead the agent to increasingly disengage from bodily responses even in the face of a less triggering situation, explaining how a single episode of depersonalization can lead to chronic DPD.

Summary: 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 psychiatric cause, conventionally defined. Methods: In this systematic review and meta-analysis of diagnostic test accuracy (PROSPERO CRD42021239027), Medline, EMBASE, PsycInfo, and AMED were searched from inception to May 11, 2022 for articles published in peer-reviewed journals that reported EEG findings in catatonia of a medical or psychiatric origin and were reported in English, French, or Italian. Eligible study types were clinical trials, cohort studies, case–control studies, cross-sectional studies, case series, and case reports. The reference standard was the final clinical diagnosis. Data extraction was conducted using individual patient-level data, where available, by two authors. We prespecified two types of studies to overcome the limitations anticipated in the data: larger studies (n ≥ 5), which were suitable for formal meta-analytic methods but generally lacked detailed information about participants, and smaller studies (n

BackgroundThe 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 and prognosis; and to describe the phenomenology of catatonia, particularly with reference to fear.MethodsA retrospective descriptive cross-sectional study was conducted using the electronic healthcare records of a large secondary mental health trust in London, United Kingdom. Patients with catatonia were identified in a previous study by screening records using natural language processing followed by manual validation. The presence of items of the Bush-Francis Catatonia Screening Instrument was coded by the investigators. The presence of psychomotor alternation was assessed by examining the frequency of stupor and excitement in the same episode. A cluster analysis and principal component analysis were conducted on catatonic signs. Principal components were tested for their associations with demographic and clinical variables. Where text was available on the phenomenology of catatonia, this was coded by two authors in an iterative process to develop a classification of the subjective experience of catatonia.ResultsSearching healthcare records provided 1,456 validated diagnoses of catatonia across a wide range of demographic groups, diagnoses and treatment settings. The median number of catatonic signs was 3 (IQR 2–5) and the most commonly reported signs were mutism, immobility/stupor and withdrawal. Stupor was present in 925 patients, of whom 105 (11.4%) also exhibited excitement. Out of 196 patients with excitement, 105 (53.6%) also had immobility/stupor. Cluster analysis produced two clusters consisting of negative and positive clinical features. From principal component analysis, three components were derived, which may be termed parakinetic, hypokinetic and withdrawal. The parakinetic component was associated with women, neurodevelopmental disorders and longer admission duration; the hypokinetic component was associated with catatonia relapse; the withdrawal component was associated with men and mood disorders. 68 patients had phenomenological data, including 49 contemporaneous and 24 retrospective accounts. 35% of these expressed fear, but a majority (72%) gave a meaningful narrative explanation for the catatonia, which consisted of hallucinations, delusions of several different types and apparently non-psychotic rationales.ConclusionThe clinical signs of catatonia can be considered as parakinetic, hypokinetic and withdrawal components. These components are associated with diagnostic and prognostic variables. Fear appears in a large minority of patients with catatonia, but narrative explanations are varied and possibly more common.

Abstract Background Patients continue to suffer from medically unexplained symptoms otherwise referred to as persistent physical symptoms (PPS). General practitioners (GPs) play a key role in the management of PPS and require further training. Patients are often frustrated with the care they receive. This study aims to assess the acceptability of an ‘integrated GP care’ approach which consists of offering self-help materials to patients with PPS and offering their GPs training on how to utilise cognitive behavioural skills within their consultations, as well as assessing the feasibility of conducting a future trial in primary care to evaluate its benefit. Methods A feasibility cluster randomised controlled trial was conducted in primary care, South London, UK. GP practices (clusters) were randomly allocated to ‘integrated GP care plus treatment as usual’ or ‘treatment as usual’. Patients with PPS were recruited from participating GP practices before randomisation. Feasibility parameters, process variables and potential outcome measures were collected at pre-randomisation and at 12- and 24-weeks post-randomisation at cluster and individual participant level. Results Two thousand nine hundred seventy-eight patients were identified from 18 GP practices. Out of the 424 patients who responded with interest in the study, 164 fully met the eligibility criteria. One hundred sixty-one patients provided baseline data before cluster randomisation and therefore were able to participate in the study. Most feasibility parameters indicated that the intervention was acceptable and a future trial feasible. 50 GPs from 8 GP practices (randomised to intervention) attended the offer of training and provided positive feedback. Scores in GP knowledge and confidence increased post-training. Follow-up rate of patients at 24 weeks was 87%. However estimated effect sizes on potential clinical outcomes were small. Conclusions It was feasible to identify and recruit patients with PPS. Retention rates of participants up to 24 weeks were high. A wide range of health services were used. The intervention was relatively low cost and low risk. This complex intervention should be further developed to improve patients’/GPs’ utilisation of audio/visual and training resources before proceeding to a full trial evaluation. Trial registration NCT02444520 (ClinicalTrials.gov).

Abstract Background Although insight in schizophrenia spectrum disorders (SSD) has been associated with positive outcomes, the effect size of previous treatments on insight has been relatively small to date. The metacognitive basis of insight suggests that metacognitive training (MCT) may improve insight and clinical outcomes in SSD, although this remains to be established. Methods This single-center, assessor-blind, parallel-group, randomised clinical trial (RCT) aims to investigate the efficacy of MCT for improving insight (primary outcome), including clinical and cognitive insight, which will be measured by the Schedule for Assessment of Insight (Expanded version) (SAI-E) and the Beck Cognitive Scale (BCIS), respectively, in (at least) n = 126 outpatients with SSD at three points in time: i) at baseline (T0); ii) after treatment (T1) and iii) at 1-year follow-up (T2). SSD patients receiving MCT and controls attending a non-intervention support group will be compared on insight level changes and several clinical and cognitive secondary outcomes at T1 and T2, whilst adjusting for baseline data. Ecological momentary assessment (EMA) will be piloted to assess functioning in a subsample of participants. Discussion To the best of our knowledge, this will be the first RCT testing the effect of group MCT on multiple insight dimensions (as primary outcome) in a sample of unselected patients with SSD, including several secondary outcomes of clinical relevance, namely symptom severity, functioning, which will also be evaluated with EMA, hospitalizations and suicidal behaviour. Trial registration ClinicalTrials.gov: NCT04104347. Date of registration: 26/09/2019 (Retrospectively registered).

Background: The Mental Capacity Act (2005) of England and Wales described in statute a test to determine whether a person lacked the “mental capacity” to make a particular decision. No large-scale survey has explored experiences of capacity assessment across professional groups. Methods: We administered an opportunistic self-report questionnaire survey of professionals who undertake capacity assessments in England and Wales (n= 611). Topics of interest included; how often and where capacity assessment took place, self-ratings of competency and challenges experienced in assessment, use of psychological testing and concerns about undue influence. We analysed the quantitative responses using a mixed-methods approach using regression methods for the quantitative ratings and a thematic analysis for qualitative data. Results: Our sample included 307/611 (50.2%), social workers, 89/611 (14.6%) psychiatrists, 62/611 (10.1%) nurses, 46/611 (7.5%) clinical psychologists, 30/611 (4.9%) doctors from other medical specialties, 12/611 (2.0%) speech and language therapists and 8/611 (1.3%) solicitors. 53% of these professionals undertook more than 25 capacity assessments per year, with psychiatrists, social workers and nurses undertaking them the most frequently. Most professionals reported high self-ratings of confidence in their assessment skills, although non-psychiatrist doctors rated themselves significantly lower than other groups (p< .005). Most professionals (77.1%) were at least moderately concerned about undue influence, with people with dementia and learning disabilities and older adults considered to be the most at risk. Qualitative themes for challenges in capacity assessment included inter-disciplinary working, complicated presentations and relational issues such as interpersonal influence. Requests for support mainly focused on practical issues. Conclusions: Most professionals feel confident in their ability to assess capacity but note substantial challenges around practical and relational issues. Undue influence is a particularly common concern amongst professionals when working with service users with dementia and learning disabilities which public services and policy makers need to be mindful of.

Background: Several cross-sectional studies report brain structure differences between healthy volunteers and subjects at genetic or clinical high risk of developing schizophrenia. However, longitudinal studies are important to determine whether altered trajectories of brain development precede psychosis onset.Methods: We conducted a systematic review to determine if brain trajectories differ between (i) those with psychotic experiences (PE), genetic (GHR) or clinical high risk (CHR), compared to healthy volunteers, and (ii) those who transition to psychosis compared to those who do not.Results: Thirty-eight studies measured gray matter and 18 studies measured white matter in 2,473 high risk subjects and 990 healthy volunteers. GHR, CHR, and PE subjects show an accelerated decline in gray matter primarily in temporal, and also frontal, cingulate and parietal cortex. In those who remain symptomatic or transition to psychosis, gray matter loss is more pronounced in these brain regions. White matter volume and fractional anisotropy, which typically increase until early adulthood, did not change or reduced in high risk subjects in the cingulum, thalamic radiation, cerebellum, retrolenticular part of internal capsule, and hippocampal–thalamic tracts. In those who transitioned, white matter volume and fractional anisotropy reduced over time in the inferior and superior fronto-occipital fasciculus, corpus callosum, anterior limb of the internal capsule, superior corona radiate, and calcarine cortex.Conclusion: High risk subjects show deficits in white matter maturation and an accelerated decline in gray matter. Gray matter loss is more pronounced in those who transition to psychosis, but may normalize by early adulthood in remitters.

Functional neurological disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart – leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed using “rule-in” examination signs. The parallel use of scientific tools to bridge brain structure - function relationships has helped refine an integrated biopsychosocial framework through which to conceptualize FND. In particular, a growing number of quality neuroimaging studies using a variety of methodologies have shed light on the emerging pathophysiology of FND. This renewed scientific interest has occurred in parallel with enhanced interdisciplinary collaborations, as illustrated by new care models combining psychological and physical therapies and the creation of a new multidisciplinary FND society supporting knowledge dissemination in the field. Within this context, this article summarizes the output of the first International FND Neuroimaging Workgroup meeting, held virtually, on June 17th, 2020 to appraise the state of neuroimaging research in the field and to catalyze large-scale collaborations. We first briefly summarize neural circuit models of FND, and then detail the research approaches used to date in FND within core content areas: cohort characterization; control group considerations; task-based functional neuroimaging; resting-state networks; structural neuroimaging; biomarkers of symptom severity and risk of illness; and predictors of treatment response and prognosis. Lastly, we outline a neuroimaging-focused research agenda to elucidate the pathophysiology of FND and aid the development of novel biologically and psychologically-informed treatments.

The 2005 Mental Capacity Act of England and Wales provides a description in statute law of a test determining if a person lacks “mental capacity” to take a particular decision and describes how the “best interests” of such a person should be determined. The Act established a new Court of Protection (CoP) to hear cases related to the Act and to rule on disputes over mental capacity. The court gathers a range of evidence, including reports from clinicians and experts. Human rights organisations and others have raised concerns about the nature of assessments for incapacity, including the role of brain investigations and psychometric tests.Aim: Describe use and interpretation of structured measures of psychological and brain function in CoP cases, to facilitate standardisation and improvement of practices, both in the courtroom and in non-legal settings.Method: Quantitative review of case law using all CoP judgments published until 2019. The judgments (n = 408) were read to generate a subset referring to structured testing (n = 50). These were then examined in detail to extract the nature of the measurements, circumstances of their use and features of interpretation by the court.Results: The 408 judgments contained 146 references to structured measurement of psychological or brain function, spread over 50 cases. 120/146 (82.2%) referred to “impairment of mind or brain,” with this being part of assessment for incapacity in 58/146 (39.7%). Measurement referred on 25/146 (17.1%) occasions to “functional decision-making abilities.” Structured measures were used most commonly by psychiatrists and psychologists. Psychological measurements comprised 66.4% of measures. Neuroimaging and electrophysiology were presented for diagnostic purposes only. A small number of behavioural measures were used for people with disorders of consciousness. When assessing incapacity, IQ and the Mini-Mental-State Examination were the commonest measures. A standardised measure of mental capacity itself was employed just once. Judges rarely integrated measurements in their capacity determinations.Conclusion: Structured testing of brain and psychological function is used in limited ways in the Court of Protection. Whilst there are challenges in creating measures of capacity, we highlight an opportunity for the neuroscience community to improve objectivity in assessment, inside and outside the courtroom.

Treatment of psychosis in Parkinson’s disease (PD) is challenging; pharmacological options are limited, with clozapine considered most effective. The risk of agranulocytosis restricts the use of clozapine, but, where this occurs, cautious re-challenge with granulocyte stimulating factor can be successful. We present a unique case of a patient who developed early-onset PD on a background of antecedent treatment-resistant schizophrenia, who had been treated effectively with clozapine for over 15 years with no adverse events. However, during a hospital admission intended to optimise her Parkinsonian medications, she developed persistent neutropenia necessitating clozapine discontinuation. Numerous attempts to re-challenge with clozapine failed until augmentation with lithium and G-CSF was trialled. Two doses of G-CSF led to a sustained increase in the neutrophil count, allowing the continuation of clozapine therapy in the 1 year of follow up. This illustrates the potential for G-CSF to be used to facilitate clozapine use in a patient population not described previously. Neutrophil augmentation allowed the sustained continuation of this effective therapy, treating her psychotic symptoms without detriment to her movement disorder. We suggest that G-CSF might be considered as a treatment option in other cases where clozapine-associated neutropenia obstructs its use.

Neuroimaging offers a valuable insight into human brain development by allowing in vivo assessment of structure, connectivity and function. Multimodal neuroimaging data have been obtained as part of three sub-studies within the Avon Longitudinal Study of Parents and Children, a prospective multigenerational pregnancy and birth cohort based in the United Kingdom. Brain imaging data were acquired when offspring were between 18 and 24 years of age, and included acquisition of structural, functional and magnetization transfer magnetic resonance, diffusion tensor, and magnetoencephalography imaging. This resource provides a unique opportunity to combine neuroimaging data with extensive phenotypic and genotypic measures from participants, their mothers, and fathers.

Background: Recovery has become a priority in schizophrenia spectrum disorders (SSDs). This study aimed to investigate predictors of objective—general functioning and disability—and subjective—quality of life (QoL)—measures of functional outcomes in SSD. Methods: Sample: n = 77 SSD outpatients (age 18–64, IQ > 70) participating in a randomised controlled trial. Baseline data were used to build three multivariable linear regression models on: (i) general functioning—General Assessment of Functioning (GAF); (ii) disability—the World Health Organization Disability Assessment Schedule (WHODAS-2.0); and (iii) QoL—Satisfaction Life Domains Scale (SLDS). Results: Young age and being employed (R2 change = 0.211; p = 0.001), late adolescence premorbid adjustment (R2 change = 0.049; p = 0.0050), negative symptoms and disorganization (R2 change = 0.087; p = 0.025) and Theory of Mind (R2 change = 0.066, p = 0.053) predicted general functioning. Previous suicidal behaviour (R2 change = 0.068; p = 0.023) and negative and depressive symptoms (R2 change = 0.167; p = 0.001) were linked with disability. Previous suicidal behaviour (R2 change = 0.070, p = 0.026), depressive symptoms (R2 change = 0.157; p < 0.001) and illness recognition (R2 change = 0.046, p = 0.044) predicted QoL. Conclusions: Negative, disorganization and depressive symptoms, older age, unemployment, poor premorbid adjustment, previous suicide attempts and illness awareness appear to underlie a poor global functional outcome in SSD. Achieving recovery in SSD appears to require both symptomatic remission (e.g., through antipsychotics) and measures to improve mastery and relieve low mood.

Longitudinal studies offer a unique window into developmental change. Yet, most of what we know about the pathophysiology of psychiatric disorders is based on cross-sectional work. Here, we highlight the importance of adopting a longitudinal approach in order to make progress towards identifying the neurobiological mechanisms of social anxiety disorder (SAD). Using examples, we illustrate how longitudinal data can uniquely inform SAD etiology and timing of interventions. The brain’s inherently adaptive quality requires that we model risk correlates of disorders as dynamic in their expression. Developmental theories regarding timing of environmental events, cascading effects and (mal)adaptations of the developing brain will be crucial components of comprehensive, integrative models of SAD. We close by discussing analytical considerations when working with longitudinal, developmental data. Keywords: Social anxiety, Development, Longitudinal imaging, Adolescence, fMRI, Psychopathology

Abstract Background People with psychosis have a reduced life expectancy of 10–20 years, largely due to cardiovascular disease. This trial aimed to determine the effectiveness of a modular health promotion intervention (IMPaCT Therapy) in improving health and reducing cardiovascular risk in psychosis. Methods A multicentre, two arm, parallel cluster RCT was conducted across five UK mental health NHS trusts. Community care coordinators (CC) were randomly assigned to training and supervision in delivering IMPaCT Therapy or treatment as usual (TAU) to current patients with psychosis (cluster). The primary outcome was the physical and mental health subscales of the Short form-36 (SF-36) questionnaire. Results Of 104 care coordinators recruited, 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) randomised to TAU. Of 406 patients, 318 (78%) and 301 (74%) attended 12- and 15-month follow-up respectively. IMPaCT therapy showed no significant effect on the physical or mental health component SF-36 scores versus TAU at 12 or 15 months. No effect was observed for cardiovascular risk indicators, except for HDL cholesterol, which improved more with IMPACT therapy than TAU (Treatment effect (95% CI); 0.085 (0.007 to 0.16); p = 0.034). The 22% of patients who received >180 min of IMPACT Therapy in addition to usual care achieved a greater reduction in waist circumference than did controls, which was clinically significant. Conclusion Training and supervising community care coordinators to use IMPaCT therapy in patients with psychosis is insufficient to significantly improve physical or mental health quality of life. The search for effective, pragmatic interventions deliverable in health care services continues. Trial registration The trial was retrospectively registered with ISRCTN registry on 23/4/2010 at ISRCTN58667926 ; recruitment started on 01/03/2010 with first randomization on 09.08.2010 ISRCTN58667926 .

Abstract Background Little is known about patients with a first episode of psychosis (FEP) who had first presented to prodromal services with an “at risk mental state” (ARMS) before making the transition to psychosis. We set out to identify the proportion of patients with a FEP who had first presented to prodromal services in the ARMS state, and to compare these FEP patients with FEP patients who did not have prior contact with prodromal services. Methods In this study information on 338 patients aged ≤37 years who presented to mental health services between 2010 and 2012 with a FEP was examined. The data on pathways to care, clinical and socio-demographic characteristics were extracted from the Biomedical Research Council Case Register for the South London and Maudsley NHS Trust. Results Over 2 years, 14 (4.1% of n = 338) young adults presented with FEP and had been seen previously by the prodromal services. These ARMS patients were more likely to enter their pathway to psychiatric care via referral from General Practice, be born in the UK and to have had an insidious mode of illness onset than FEP patients without prior contact with the prodromal services. Conclusions In the current pathways to care configuration, prodromal services are likely to prevent only a few at-risk individuals from transitioning to psychosis even if effective preventative treatments become available.

Background: Grey matter (GM) abnormalities are robust features of schizophrenia and of people at ultra high-risk for psychosis. However the extent to which neuroanatomical alterations are evident in non-clinical subjects with isolated psychotic experiences is less clear. Methods: Individuals (mean age 20 years) with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified from a population-based cohort. All underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI, to characterise GM macrostructure, microstructure and myelination respectively. Differences in quantitative GM structure were assessed using voxel-based morphometry (VBM). Binary and ordinal models of PEs were tested. Correlations between socioeconomic and other risk factors for psychosis with cortical GM measures were also computed. Results: GM volume in the left supra-marginal gyrus was reduced in individuals with PEs relative to those with no PEs. The greater the severity of PEs, the greater the reduction in T1 relaxation rate (R1) across left temporoparietal and right pre-frontal cortices. In these regions, R1 was positively correlated with maternal education and inversely correlated with general psychopathology. Conclusions: PEs in non-clinical subjects were associated with regional reductions in grey-matter volume reduction and T1 relaxation rate. The alterations in T1 relaxation rate were also linked to the level of general psychopathology. Follow up of these subjects should clarify whether these alterations predict the later development of an ultra high-risk state or a psychotic disorder.

An amendment to this paper has been published and can be accessed via the original article.

Suicidal thinking, self-harm and suicidal acts are common, although determining their precise prevalence is complex. Epidemiological work has identified a number of associated demographic and clinical factors, though, with the exception of past acts of self-harm, these are non-specific and weak future predictors. There is a critical need shift focus from managing ‘suicidality-by-proxy’ through general mental health treatments, to better understand the neuropsychology and neurophysiology of such behaviour to guide targeted interventions. The model of the cognitive control of emotion (MCCE) offers such a paradigm, with an underlying pan-diagnostic pathophysiology of a hypoactive prefrontal cortex failing to suitably inhibit an overactive threat-responding limbic system. The result is a phenotype – from any number of causative gene-environment interactions – primed to impulsively self-harm. We argue that such neural dysconnectivity is open to potential therapeutic modification from repetitive transcranial magnetic stimulation (rTMS). The current evidence base for this is undoubtedly extremely limited, but the societal and clinical burden self-harm and suicide pose warrants such investigation.