Benjamin Ian Perry

The association between first-episode psychosis and abnormal glycaemic control: systematic review and meta-analysis

BACKGROUND Schizophrenia might share intrinsic inflammatory disease pathways with type 2 diabetes. We aimed to assess whether first-episode psychosis, which could be described as developing schizophrenia, is associated with prediabetic markers, or developing diabetes, to determine whether intrinsic disease links could cause the disorders to develop in unison. We hypothesised that biochemical measures of prediabetic states would be more common in antipsychotic naive patients with first-episode psychosis than in healthy matched controls. METHODS For this systematic review and meta-analysis, using PRISMA criteria, we searched Embase, MEDLINE, PsycINFO, Web of Science, and Google Scholar for clinical studies published between database inception and Jan 6, 2016. We assessed case-control studies with biochemical assessment of prediabetic states in patients with first-episode psychosis alongside matched controls. We sought data at the summary estimate level. Several measurements were used to test for prediabetes, including fasting plasma glucose, insulin resistance (measured by the Homeostatic Model Assessment), and impaired glucose tolerance. We calculated standardised mean differences for each outcome. We used the inverse variance method, for which the weight given to each study was the inverse of the variance of the effect estimate. For dichotomous outcomes, we entered the number of events and number in each group into RevMan 5.3 and used the Mantel-Haenszel method to pool studies. FINDINGS We identified 1436 studies, of which 12 were included in final analysis, including 1137 participants. Pooled analyses found first-episode psychosis to be related to insulin resistance (mean difference 0·30 [95% CI 0·18 to 0·42]), impaired glucose tolerance (mean difference 1·31 [0·37 to 2·25]), and the number of patients with impaired glucose tolerance (odds ratio 5·44 [2·63 to 11·27]), but not fasting plasma glucose (mean difference 0·03 mmol/L [-0·04 to 0·09]). INTERPRETATION Our findings suggest a potential link between prediabetic markers, in particular impaired glucose tolerance and insulin resistance, and first-episode psychosis. However, we cannot establish causality, and the studies contributing to this review were at some risk of bias. Nevertheless, the findings might help to explain the increased prevalence of type 2 diabetes in patients with schizophrenia and could have implications for the management of patients with schizophrenia. FUNDING None.

Are neurocognitive factors associated with repetition of self-harm? A systematic review

Background: Prediction of self‐harm is limited clinically. Early identification of individuals likely to repeat self‐harm could improve outcomes and reduce suicide risk. Various neurocognitive deficits have been found in people who self‐harm, but the ability of these to predict repetition has yet to be established Aims: Identify neurocognitive factors that may predict repetition of self‐harm. Methods: Systematic narrative review of English language publications assessing neurocognitive functioning and self‐harm repetition, searching multiple databases from inception to March 2015. Quality of studies was appraised. A narrative synthesis was performed. Results: 7026 unique records were identified, and 169 full‐texts assessed. 15 unique studies provided data. No imaging studies could be included. Most studies assessed cognitive control or problem solving, but neither factor was consistently associated with repetition. However, specific tasks may show promise. Two studies in adolescents suggest that value‐based decision‐making impairments could be predictive of repetition. There were too few results for memory to draw specific conclusions. Conclusions: Selected studies suggest promise for particular neurocognitive factors and specific cognitive tasks in terms of repetition of self‐harm. HIGHLIGHTSWe conducted a systematic review of all studies examining neurocognition and repeat self‐harm.15 studies were included in the review.Decision‐making studies showed an association; most problem‐solving studies failed to show this.Findings were inconclusive for other factors (cognitive control, memory, emotional‐processing).Future research should consider focussing on promising areas and using neuroimaging.

Dysglycaemia, inflammation and psychosis : findings from the UK ALSPAC birth cohort

Abstract Background Psychosis is associated with both dysglycaemia and low-grade inflammation, but population-based studies investigating the interplay between these factors are scarce. Aims (1) To explore the direction of association between markers of dysglycaemia, inflammation and psychotic experiences (PEs); and (2) To explore whether dysglycaemia moderates and/or mediates the association between inflammation and PEs. Method Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were modeled using logistic and linear regression to examine cross-sectional and longitudinal associations between markers of dysglycaemia (ages 9 and 18), interleukin-6 (IL-6) (age 9), and PEs (ages 12 and 18). We tested for an interaction between dysglycaemia and IL-6 on risk of PEs at age 18, and tested whether dysglycaemia mediated the relationship between IL-6 and PEs. Results Based on 2627 participants, at age 18, insulin resistance (IR) was associated with PEs (adjusted OR = 2.32; 95% CI, 1.37–3.97). IR was associated with IL-6 both cross-sectionally and longitudinally. Interaction analyses under a multiplicative model showed that IR moderated the association between IL-6 at age 9 and PEs at age 18 (adjusted OR for interaction term = 2.18; 95% C.I., 1.06–4.49). Mediation analysis did not support a model of IR mediating the relationship between IL-6 and PEs. Implications IR is associated with PEs in young people even before the onset of clinical psychosis. Metabolic alterations may interact with childhood inflammation to increase risk of PEs. The findings have implications for clinical practice and future research.

30.1 IMMUNE PATHOGENESIS OF PSYCHOSIS: THE CHALLENGE OF CO-MORBIDITY

Abstract Background The immune pathogenesis story of schizophrenia is gathering momentum, with increasing evidence from genetic, circulating biomarker and neuropathological studies. New treatment approaches are being trialled. However immune dysfunction is not unique to schizophrenia, and circulating proinflammatory biomarkers identified in schizophrenia have also been identified in bipolar disorder and major depressive disorders. Similarly, in recent times there has been an increasing recognition of commonality across categorical diagnoses at a symptom level; as RDoC criteria acknowledge. For example, depressive symptoms are common in schizophrenia, hallucinations and delusional beliefs common in mood disorders and anhedonia a cross diagnostic challenge Methods This presentation will include data of altered circulating pro-inflammatory markers from recently completed meta-analysis in first episode psychosis, established schizophrenia and bipolar disorder, highlighting the potential pluripotent inflammation pathway to mental disorders and outline a circulating cytokine profile at the onset and development of mental disorder as related to symptom specific profiles. Results Data on circulating inflammatory makers as related to symptom profiles cross-sectional and longitudinally will also be presented from the recently concluded NIHR funded BeneMin (The Benefits of Minocycline on negative symptoms in early phase psychosis) study. Discussion Future research should recognise co-morbidity, adopt a dimensional approach, or investigate symptom specific biomarkers at early stages of illness with numbers large enough to explore an immune specific clinical profile. This knowledge is essential in the developing story of inflammation and psychosis with the most potential in decades to translate into tailored effective treatment options.

Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses

Background A reliable biomarker signature for bipolar disorder sensitive to illness phase would be of considerable clinical benefit. Among circulating blood-derived markers there has been a significant amount of research into inflammatory markers, neurotrophins and oxidative stress markers. Aims To synthesise and interpret existing evidence of inflammatory markers, neurotrophins and oxidative stress markers in bipolar disorder focusing on the mood phase of illness. Method Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a systematic review was conducted for studies investigating peripheral biomarkers in bipolar disorder compared with healthy controls. We searched Medline, Embase, PsycINFO, SciELO and Web of Science, and separated studies by bipolar mood phase (mania, depression and euthymia). Extracted data on each biomarker in separate mood phases were synthesised using random-effects model meta-analyses. Results In total, 53 studies were included, comprising 2467 cases and 2360 controls. Fourteen biomarkers were identified from meta-analyses of three or more studies. No biomarker differentiated mood phase in bipolar disorder individually. Biomarker meta-analyses suggest a combination of high-sensitivity C-reactive protein/interleukin-6, brain derived neurotrophic factor/tumour necrosis factor (TNF)-α and soluble TNF-α receptor 1 can differentiate specific mood phase in bipolar disorder. Several other biomarkers of interest were identified. Conclusions Combining biomarker results could differentiate individuals with bipolar disorder from healthy controls and indicate a specific mood-phase signature. Future research should seek to test these combinations of biomarkers in longitudinal studies. Declaration of interest None.

First-episode psychosis and abnormal glycaemic control – Authors' reply

We thank Karin Fehsel and Stefan Loffler for their thought-provoking summary of the possible role of protein kinase B (Akt) in predisposing people with first-episode psychosis to dysglycaemia, which they consider a potential explanation for the findings of our meta-analysis.1 We found that markers of prediabetes were more common in patients with first-episode psychosis than in healthy matched controls. As they rightly state, we were unable to show causality in our findings, which were observational. However, we did present our own possible explanation; that the two disorders might share intrinsic inflammatory disease links.

Exploring professionals’ understanding, interpretation and implementation of the ‘appropriate medical treatment test’ in the 2007 amendment of the Mental Health Act 1983

Background The appropriate medical treatment test (ATT), included in the Mental Health Act (MHA) (1983, as amended 2007), aims to ensure that detention only occurs when treatment with the purpose of alleviating a mental disorder is available. Aims As part of the Assessing the Impact of the Mental Health Act (AMEND) project, this qualitative study aimed to assess professionals’ understanding of the ATT, and its impact on clinical practice. Method Forty-one professionals from a variety of mental health subspecialties were interviewed. Interviews were coded related to project aims, and themes were generated in an inductive process. Results We found that clinicians are often wholly relied upon for the ATT. Considered treatment varied depending on the patient’s age rather than diagnosis. The ATT has had little impact on clinical practice. Conclusions Our findings suggest the need to review training and support for professionals involved in MHA assessments, with better-defined roles. This may enable professionals to implement the ATT as its designers intended. Declaration of interest None. Copyright and usage

Assessing the second-hand effects of a new no-smoking policy in an acute mental health trust

Aims and method To examine whether a new no-smoking policy in an in-patient mental health setting had any effects outside of smoking cessation. Our hypothesis stated that a forced smoking ban for in-patients may result in an increased susceptibility for clinical incidents, aggression and lower admission rates. All patients admitted to adult in-patient mental health services in Coventry and Warwickshire Partnership NHS Trust were included in the analysis. Data 6 months post-implementation of the smoking policy (1 July 2015 to 1 January 2016) were compared with the same period 1 year prior (1 July 2014 to 1 January 2015). Patient demographics, admission rates, ward occupancy, average lengths of stay, numbers of reported incidents and use of the Mental Health Act 1983 (MHA) were compared. Results We analysed 4223 admissions. We found a significantly increased number of admissions under the MHA (P = 0.007), a significantly greater number of reported smoking-related incidents (P < 0.001) and aggression-related incidents in the psychiatric intensive care unit (P < 0.001). However, we found no significant difference in capacity of in-patient wards (P = 0.39), admission length (P = 0.34) or total aggression-related incidents (P = 0.86). Clinical implications Although further comparisons over longer time periods are necessary, our results suggest that enforced smoking cessation on acutely unwell psychiatric patients admitted to the most restricted environments may have some negative effects. Nicotine replacement therapy should be offered to all patients to minimise the risk of clinical incident.

Prolactin monitoring in the acute psychiatry setting

Hyperprolactinaemia is a common side effect associated with psychotropic medication. Limited guidance on its monitoring and management results in inconsistency in practice due to individual clinical variability. A retrospective service evaluation study was conducted on all patients admitted to an acute psychiatric assessment unit in South Wales, United Kingdom, over one calendar year (n=524), to assess the prevalence and possible causes of hyperprolactinaemia, correlation with symptomatology and monitoring and management by clinicians. The prevalence of hyperprolactinaemia in this population (n=67, 13%) was higher than in the general population. The most common association was medication (n=39, 58%), particularly Risperidone (n=19). Illicit substance use (n=10, 15%), and physical conditions (n=12, 18%) may also have contributed. However, only 44 (66%) received follow-up for their hyperprolactinaemia. There was a statistically significant difference in the sample means of those that did receive follow-up and those who did not, suggesting a degree of bias in patients selected to receive follow-up. These findings suggest that hyperprolactinaemia is relatively common in patients with mental illness, and that comprehensive guidelines need to be established for the monitoring and management thereof.

A virtual reality: Technology′s impact on youth mental health

2016 will mark as the year when commercially available virtual reality headsets first become available across the world. This is set to be a landmark development and will revolutionize the way we interact with technology, which is already eating up more and more of our time, and is now inextricable from day-to-day life. Adolescents, at a critical stage in both physical and psychological development, are often the first to adopt advances in technology, and therefore also any associated impact on health. We discuss some of the current and important research on the positive and negative implications of technology on the mental health of children and adolescents, and briefly outline how future technological advances may further affect how we diagnose, monitor, and manage our young patients in the psychiatric clinic.