Forecasting prognostic trajectories with mismatch negativity in early psychosis

Abstract Background Prognostic heterogeneity in early psychosis patients yields significant difficulties in determining the degree and duration of early intervention; this heterogeneity highlights the need for prognostic biomarkers. Although mismatch negativity (MMN) has been widely studied across early phases of psychotic disorders, its potential as a common prognostic biomarker in early periods, such as clinical high risk (CHR) for psychosis and first-episode psychosis (FEP), has not been fully studied. Methods A total of 104 FEP patients, 102 CHR individuals, and 107 healthy controls (HCs) participated in baseline MMN recording. Clinical outcomes were assessed; 17 FEP patients were treatment resistant, 73 FEP patients were nonresistant, 56 CHR individuals were nonremitters (15 transitioned to a psychotic disorder), and 22 CHR subjects were remitters. Baseline MMN amplitudes were compared across clinical outcome groups and tested for utility prognostic biomarkers using binary logistic regression. Results MMN amplitudes were greatest in HCs, intermediate in CHR subjects, and smallest in FEP patients. In the clinical outcome groups, MMN amplitudes were reduced from the baseline in both FEP and CHR patients with poor prognostic trajectories. Reduced baseline MMN amplitudes were a significant predictor of later treatment resistance in FEP patients [Exp(β) = 2.100, 95% confidence interval (CI) 1.104–3.993, p = 0.024] and nonremission in CHR individuals [Exp(β) = 1.898, 95% CI 1.065–3.374, p = 0.030]. Conclusions These findings suggest that MMN could be used as a common prognostic biomarker across early psychosis periods, which will aid clinical decisions for early intervention.

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Impulsivity in early psychosis: A complex link with violent behaviour and a target for intervention

European Psychiatry ◽

10.1016/j.eurpsy.2017.12.003 ◽

2018 ◽

Vol 49 ◽

pp. 30-36 ◽

Cited By ~ 11

Author(s):

V. Moulin ◽

P. Golay ◽

J. Palix ◽

P.S. Baumann ◽

M-M. Gholamrezaeec ◽

...

Keyword(s):

Substance Abuse ◽

Early Intervention ◽

Psychotic Disorders ◽

Interaction Analysis ◽

Early Psychosis ◽

First Episode ◽

Positive Symptoms ◽

Violent Behaviour ◽

Increased Risk ◽

Early Intervention In Psychosis

AbstractBackgroundViolent behaviour (VB) occurs in first episode of schizophrenia and can have devastating impact both on victims and patients themselves. A better knowledge of the underlying mechanisms of VB may pave the way to preventive treatments.Objectives1) To explore the nature of the link between impulsivity and VB in early psychosis (EP) patients; 2) To explore the interactions between impulsivity and substance abuse, insight, and positive symptoms, the main dynamic risk factors of VB described to date.Design and methodsPost hoc analysis of data acquired in the frame of a 36-months EP cohort study. A total of 265 EP patients, aged 18 to 35, treated at TIPP (Treatment and early Intervention in Psychosis Program), at the Department of Psychiatry in Lausanne, Switzerland, were included in the study. Logistic regression analyzes were performed as well as mediation analysis and interaction analysisResultsOur data suggest that impulsivity is a predictor of VB when analyzed independently and as part of a multi-factorial model. Impulsivity continues to differentiate violent patients from non-violent ones at the end of the program. In addition, the relationship between impulsivity and VB is not mediated by substance abuse. Finally, the effect of impulsivity on the probability of VB is potentiated by the interaction of different levels of insight and positive symptoms.ConclusionsEarly intervention strategies in psychotic disorders should include evaluation of impulsivity considering it is linked to increased risk of VB and may respond to treatment.

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Special Issue: Psychosis from early intervention to treatment resistance

Irish Journal of Psychological Medicine ◽

10.1017/ipm.2019.40 ◽

2019 ◽

Vol 36 (4) ◽

pp. 239-241 ◽

Cited By ~ 1

Author(s):

C. McDonald ◽

D.R. Cotter

Keyword(s):

Early Intervention ◽

Clinical Research ◽

Social Stress ◽

Psychotic Disorders ◽

Management Strategies ◽

Treatment Resistance ◽

Research Network ◽

First Episode ◽

Special Issue ◽

Health Service Provision

Psychotic disorders are central to mental health service provision and a common theme of academic research programmes in Ireland, which explore the neurobiological and psychosocial risk factors underpinning the development and progression of these illnesses. While we await the discovery of novel pharmacological treatment targets for psychotic disorders, it is important to employ our existing management strategies to optimal effect. In this special issue on psychosis, a selection of clinical research studies and reviews from Irish researchers, and often of Irish populations, are brought together which span the trajectory of psychotic illness from early intervention to treatment resistance. The topics include the characteristics and course of first episode psychosis cohorts, real-world evaluation of early intervention services, management strategies for treatment resistant schizophrenia and neurobiological research into social stress. The current editorial provides an overview of these papers and highlights the initial steps of the Irish Psychosis Research Network towards developing an integrated clinical research network focusing on the treatment and research into psychotic disorders.

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Suicide Prevention in First Episode Psychosis: The Development of a Randomised Controlled Trial of Cognitive Therapy for Acutely Suicidal Patients With Early Psychosis

Australian & New Zealand Journal of Psychiatry ◽

10.1046/j.1440-1614.2003.01209.x ◽

2003 ◽

Vol 37 (4) ◽

pp. 414-420 ◽

Cited By ~ 94

Author(s):

P.J.R. Power ◽

R.J. Bell ◽

R. Mills ◽

T. Herrman-Doig ◽

M. Davern ◽

...

Keyword(s):

Early Intervention ◽

Treatment Group ◽

Young People ◽

Controlled Trial ◽

First Episode Psychosis ◽

Early Psychosis ◽

First Episode ◽

Episode Psychosis ◽

Randomised Controlled ◽

Suicidal Patients

Background: Young people with early psychosis are at particularly high risk of suicide. However, there is evidence that early intervention can reduce this risk. Despite these advances, first episode psychosis patients attending these new services still remain at risk. To address this concern, a program called LifeSPAN was established within the Early Psychosis Prevention and Intervention Centre (EPPIC). The program developed and evaluated a number of suicide prevention strategies within EPPIC and included a cognitively oriented therapy (LifeSPAN therapy) for acutely suicidal patients with psychosis. We describe the development of these interventions in this paper. Method: Clinical audit and surveys provided an indication of the prevalence of suicidality among first episode psychosis patients attending EPPIC. Second, staff focus groups and surveys identified gaps in service provision for suicidal young people attending the service. Third, a suicide risk monitoring system was introduced to identify those at highest risk. Finally, patients so identified were referred to and offered LifeSPAN therapy whose effectiveness was evaluated in a randomised controlled trial. Results: Fifty-six suicidal patients with first episode psychosis were randomly assigned to standard clinical care or standard care plus LifeSPAN therapy. Forty-two patients completed the intervention. Clinical ratings and measures of suicidality and risk were assessed before, immediately after the intervention, and 6 months later. Benefits were noted in the treatment group on indirect measures of suicidality, e.g., hopelessness. The treatment group showed a greater average improvement (though not significant) on a measure of suicide ideation. Conclusions: Early intervention in psychosis for young people reduces the risk of suicide. Augmenting early intervention with a suicide preventative therapy may further reduce this risk.

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Loneliness in early psychosis: A qualitative study exploring the views of mental health practitioners in early intervention services

10.21203/rs.3.rs-45913/v1 ◽

2020 ◽

Author(s):

Theodora Stefanidou ◽

Jingyi Wang ◽

Nicola Morant ◽

Brynmor Lloyd-Evans ◽

Sonia Johnson

Keyword(s):

Mental Health ◽

Early Intervention ◽

Public Health Problem ◽

Early Psychosis ◽

Mental Health Practitioners ◽

First Episode ◽

Physical And Mental Health ◽

Early Intervention Services ◽

Health Practitioners ◽

Intervention Services

Abstract Background: Loneliness is an important public health problem with established adverse effects on physical and mental health. Although, people with psychosis often experience high levels of loneliness, relatively little is known about the relationship between loneliness and early psychosis. Potential interventions to address loneliness might be easier to implement early in the illness when social networks and social skills may be more intact than at a later stage. We investigated the views of mental health practitioners about the context and causes of loneliness in people with early psychosis, and about potential interventions.Methods: Semi-structured face-to-face interviews were conducted with mental health practitioners (n=20). Participants were purposively recruited from four early intervention services for first-episode psychosis in the UK. Interviews were transcribed verbatim and thematic analysis was conducted.Results: Participants believed that the majority of service users with early psychosis experience feelings of loneliness. They often saw socially isolated and disconnected clients and believed them to be lonely, but rarely discussed loneliness explicitly in clinical interactions. A combination of symptoms, stigma and negative sense of self were believed to underpin loneliness. Participants could not identify any specific current interventions delivered by their services for tackling loneliness, but thought some routinely provided interventions, including social groups and psychological treatments, could be helpful. They favoured making a wider range of loneliness interventions available and believed that community agencies beyond mental health services should be involved to make these effective and feasible to deliver. They suggested social participation interventions without an explicit mental health focus as potentially promising and valued a co-produced approach to intervention development. Conclusions: This study suggests that loneliness is not routinely discussed in early intervention services, and a targeted strategy for tackling it is lacking. Co-produced, individualised community approaches, and interventions that target symptoms, stigma and negative self-schemas might be beneficial in alleviating loneliness for people with early psychosis. Empirical research is needed to develop and test such interventions.

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O1.3. BACK TO THE FUTURE: PREDICTING POPULATION NEED FOR PSYCHOSIS CARE BASED ON THE EPIDEMIOLOGY OF PSYCHOTIC DISORDERS IN ENGLAND, AN APPLIED BAYESIAN METHODOLOGY

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa028.002 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S1-S2

Author(s):

Keltie McDonald ◽

Tao Ding ◽

Rebecca Dliwayo ◽

David Osborn ◽

Pia Wohland ◽

...

Keyword(s):

Mental Health ◽

Early Intervention ◽

Small Area ◽

Psychotic Disorders ◽

Population Projections ◽

First Episode ◽

Evidence Based ◽

Psychosis Risk ◽

Small Area Level ◽

Early Intervention In Psychosis

Abstract Background Providing timely, adequate and appropriately-resourced care to people experiencing their first episode of psychosis needs to be informed by evidence-based models of future need in the population. We sought to develop a validated prediction model of need for provision of early intervention in psychosis [EIP] services at the small area level in England up to 2025, based on current epidemiological evidence and demographic projections of the at-risk population. Methods We developed a Bayesian population-level prediction tool. First, we obtained small area incidence data on first episode psychoses, aged 16–64 years, from three major empirical studies of psychosis risk (ÆSOP, ELFEP and SEPEA). Second, we identified suitable prior information from the published literature on variation in psychosis risk by age, sex, ethnicity, deprivation and cannabis use. Third, we combined this empirical data with prior beliefs in six Bayesian Poisson regression models to obtain a full characterisation of the underlying uncertainty in the form of suitable posterior distributions for the relative risks for different permutations of covariate data. Fourth, model coefficients were applied to population projections for 2017 to predict the expected incidence of psychotic disorders, aggregated to Commissioning Group [CCG] and national levels. Fifth, we compared these predictions to observed national FEP data from the NHS Mental Health Services Data Set in 2017 to establish the most valid model. Sixth, we used the best-fitting model to predict three nested indicators of need for psychosis care: (i) total annual referrals to early intervention in psychosis [EIP] for “suspected” FEP (ii) total annual cases accepted onto EIP service caseloads, and (iii) total annual new cases of probable FEP in England up until 2025, using small area population projections. Results A model with an age-sex interaction, ethnicity, small area-level deprivation, social fragmentation and regional cannabis use provided best internal and apparent validity, predicting 8112 (95% Credible Interval 7623 to 8597) individuals with FEP in England in 2017, compared with 8038 observed cases (difference: n=74; 0.94%). Apparent validity was acceptable at CCG level, and by sex and ethnicity, although we observed greater-than-expected need before 35 years old. Predicted new referrals, caseloads and probable incidences of FEP rose over the forecast period by 6.2% to 25,782, 23,187 and 9,541 new cases in 2025, respectively. Discussion Our translational epidemiological tool provides an accurate, validated method to inform planners, commissioners and providers about future population need for psychosis care at different stages of the referral pathway, based on individual and small area level determinants of need. Such tools can be used to underpin evidence-based decision-making in public mental health and resource allocation in mental health systems.

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Familial and socioeconomic contributions to premorbid functioning in psychosis: Impact on age at onset and treatment response

European Psychiatry ◽

10.1192/j.eurpsy.2020.41 ◽

2020 ◽

Vol 63 (1) ◽

Author(s):

Alex Hatzimanolis ◽

Pentagiotissa Stefanatou ◽

Emmanouil Kattoulas ◽

Irene Ralli ◽

Stefanos Dimitrakopoulos ◽

...

Keyword(s):

Treatment Response ◽

Social Functioning ◽

Early Adolescence ◽

Psychotic Disorders ◽

Age At Onset ◽

Familial Risk ◽

Treatment Resistance ◽

Joint Effect ◽

First Episode ◽

Environment Interaction

Abstract Background. Premorbid adjustment (PA) abnormalities in psychotic disorders are associated with an earlier age at onset (AAO) and unfavorable clinical outcomes, including treatment resistance. Prior family studies suggest that familial liability, likely reflecting increased genetic risk, and socioeconomic status (SES) contribute to premorbid maladjustment. However, their joint effect possibly indicating gene–environment interaction has not been evaluated. Methods. We examined whether family history of psychosis (FHP) and parental SES may predict PA and AAO in unrelated cases with first-episode psychosis (n = 108) and schizophrenia (n = 104). Premorbid academic and social functioning domains during childhood and early adolescence were retrospectively assessed. Regression analyses were performed to investigate main effects of FHP and parental SES, as well as their interaction. The relationships between PA, AAO, and response to antipsychotic medication were also explored. Results. Positive FHP associated with academic PA difficulties and importantly interacted with parental SES to moderate social PA during childhood (interaction p = 0.024). Positive FHP and parental SES did not predict differences in AAO. Nevertheless, an earlier AAO was observed among cases with worse social PA in childhood (β = −0.20; p = 0.005) and early adolescence (β = −0.19; p = 0.007). Further, confirming evidence emerged for an association between deficient childhood social PA and poor treatment response (p = 0.04). Conclusions. Familial risk for psychosis may interact with parental socioeconomic position influencing social PA in childhood. In addition, this study supports the link between social PA deviations, early psychosis onset, and treatment resistance, which highlights premorbid social functioning as a promising clinical indicator.

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The Role of Peripheral Inflammation in Clinical Outcome and Brain Imaging Abnormalities in Psychosis: A Systematic Review

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.612471 ◽

2021 ◽

Vol 12 ◽

Author(s):

Melisa Kose ◽

Carmine M. Pariante ◽

Paola Dazzan ◽

Valeria Mondelli

Keyword(s):

Systematic Review ◽

Clinical Outcome ◽

Inflammatory Markers ◽

Psychotic Disorders ◽

Treatment Resistance ◽

Hippocampal Volume ◽

Inflammatory Biomarkers ◽

Peripheral Inflammation ◽

Neuroimaging Data

Promising research investigating the association between inflammatory biomarkers and response to antipsychotic and/or adjunctive therapy, observed by improvement in psychiatric assessment, is emerging. Increased inflammation has been suggested to contribute to higher severity of symptoms/treatment resistance through the effects that this has on brain structure and function. The present systematic review aims to clarify the potential role of peripheral inflammatory markers as predictors of clinical outcomes and their association with neuroimaging markers in patients with psychosis. Systematic searches of the literature using the databases PsychInfo, OVID Medline, and Embase were conducted to collate studies investigating the association of inflammatory biomarkers with clinical outcome in patients with psychotic disorders and studies examining the relationships between inflammatory biomarkers and neuroimaging data. Seventeen studies on predictors of clinical outcome and 14 on associations between neuroimaging data and inflammatory biomarkers in psychosis were identified, and risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The main inflammatory markers associated with clinical outcome in psychosis were interleukin (IL)-6, IL-10, and C-reactive protein (CRP). High levels of CRP and IL-6 were associated with worse clinical outcome and deterioration of symptoms over time; in contrast, increased levels of IL-10 were associated with greater symptoms improvement. Smaller hippocampal volume and reduced cortical thickness were the main neuroimaging markers associated with increased peripheral inflammation. The heterogeneity across the studies (i.e., treatments strategies, duration) suggests that potential prediction power of inflammatory biomarkers could partially depend on the methodologies, supported by the overall NOS ratings of the studies. Future studies may need to consider whether a combination of these inflammatory and neuroimaging markers could further improve our ability of predicting clinical outcome in patients with psychosis.

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Cognitive markers of short-term clinical outcome in first-episode psychosis

The British Journal of Psychiatry ◽

10.1192/bjp.bp.107.040410 ◽

2008 ◽

Vol 193 (4) ◽

pp. 297-304 ◽

Cited By ~ 30

Author(s):

Michael Bodnar ◽

Ashok Malla ◽

Ridha Joober ◽

Martin Lepage

Keyword(s):

Clinical Outcome ◽

Verbal Memory ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

First Episode ◽

Short Term ◽

Cognitive Domains ◽

Good Outcome ◽

Poor Outcome ◽

Episode Psychosis

BackgroundOutcome from psychotic disorders is heterogeneous with poorer outcomes frequently identified too late to be influenced. Symptomatic ratings at 1 or more years following initiation of treatment have been related to cognition in firstepisode psychosis. However, the relationship between cognition and early outcome remains unclear.AimsTo determine whether specific cognitive domains could identify poor short-term outcome among individuals with first-episode psychosis.MethodOne hundred and fifty-one individuals with first-episode psychosis were divided into two groups based on 6-month clinical data after the initiation of treatment. Six cognitive domains were compared among 78 participants with poor outcomes, 73 with good outcomes and 31 healthy controls.ResultsLower performance on verbal memory (z-scores: poor outcome=–1.3 (s.d.=1.1); good outcome=–0.8 (s.d.=0.9); P=0.001) and working memory (poor outcome=–1.0 (s.d.=1.2); good outcome=–0.4 (s.d.=0.9); P=0.003) identified individuals with first-episode psychosis with a poor outcome after 6 months of treatment.ConclusionsThe early identification of those individuals with first-episode psychosis with a poor clinical outcome may encourage clinicians to pay special attention to them in the form of alternative pharmacological and psychological treatments for a more favourable outcome in the long term.

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Loneliness in early psychosis: a qualitative study exploring the views of mental health practitioners in early intervention services

BMC Psychiatry ◽

10.1186/s12888-021-03138-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Theodora Stefanidou ◽

Jingyi Wang ◽

Nicola Morant ◽

Brynmor Lloyd-Evans ◽

Sonia Johnson

Keyword(s):

Mental Health ◽

Early Intervention ◽

Public Health Problem ◽

Early Psychosis ◽

Mental Health Practitioners ◽

First Episode ◽

Physical And Mental Health ◽

Early Intervention Services ◽

Health Practitioners ◽

Intervention Services

Abstract Background Loneliness is an important public health problem with established adverse effects on physical and mental health. Although people with psychosis often experience high levels of loneliness, relatively little is known about the relationship between loneliness and early psychosis. Potential interventions to address loneliness might be easier to implement early in the illness when social networks and social skills may be more intact than at a later stage. We investigated the views of mental health practitioners about the context and causes of loneliness in people with early psychosis, and about potential interventions. Methods Semi-structured face-to-face interviews were conducted with mental health practitioners (n = 20). Participants were purposively recruited from four early intervention services for first-episode psychosis in the UK. Interviews were transcribed verbatim and thematic analysis was conducted. Results Participants believed that the majority of service users with early psychosis experience feelings of loneliness. They often saw socially isolated and disconnected clients and believed them to be lonely, but rarely discussed loneliness explicitly in clinical interactions. A combination of symptoms, stigma and negative sense of self were believed to underpin loneliness. Participants could not identify any specific current interventions delivered by their services for tackling loneliness, but thought some routinely provided interventions, including social groups and psychological treatments, could be helpful. They favoured making a wider range of loneliness interventions available and believed that community agencies beyond mental health services should be involved to make these effective and feasible to deliver. They suggested social participation interventions without an explicit mental health focus as potentially promising and valued a co-produced approach to intervention development. Conclusions This study suggests that loneliness is not routinely discussed in early intervention services, and a targeted strategy for tackling it is lacking. Co-produced, individualised community approaches, and interventions that target symptoms, stigma and negative self-schemas might be beneficial in alleviating loneliness for people with early psychosis. Empirical research is needed to develop and test such interventions.

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Early intervention and recovery for young people with early psychosis: consensus statement

The British Journal of Psychiatry ◽

10.1192/bjp.187.48.s116 ◽

2005 ◽

Vol 187 (S48) ◽

pp. s116-s119 ◽

Cited By ~ 160

Author(s):

J. Bertolote ◽

P. Mcgorry

Keyword(s):

Early Intervention ◽

Psychotic Disorders ◽

Consensus Statement ◽

Early Psychosis ◽

World Health ◽

Universal Principles ◽

Health Organization ◽

The Uk ◽

The Impact

SummaryInternational declarations that articulate core values, goals and standards have played an important role in enhancing the quality of care in a number of areas of medicine. This document attempts this task for early intervention in psychotic disorders. It was originally inspired by the St Vincents declaration on the care of diabetes and carefully developed by David Shiers and Jo Smith with support from the Initiative to Reduce the Impact of Schizophrenia, National Institute for Mental Health in England and Rethink, resulting in the UK-focused Newcastle Declaration. The World Health Organization and the International Early Psychosis Association then collaborated to produce an international version of the declaration, which articulates the universal principles of early intervention and tries to blend these with local capacities and cultural diversity.

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