Plenary Session I
Thursday, October 20, 8:45 – 9:25 a.m., Washington
The Next Stage for Early Intervention: Transdiagosic, Personalized, Universal
Patrick McGorry, MD, Ph.D
Orygen, the National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, University of Melbourne, Parkville, Australia
Chair: Peter B. Jones, University of Cambridge, Cambridge, UK
Co-Chair: Angelo Barbato, Mario Negri Institute, Milan, Italy
More than a quarter of a century ago the aspirational goal of early intervention in psychotic disorders emerged as a reality for patients and families. Guided by an international wave of research and inspired by new clinical service models with optimistic, stigma-free cultures of care, the idea transformed thinking within a psychiatry which was struggling to modernise and catch up with the rest of health care. Much progress has occurred culminating in studies such as the RAISE project in the USA which have opened the gateway for national reform.Yet progress is piecemeal and comprehensive upscaling has not yet occurred to enable every person with psychotic illness is to receive timely, personalised and sustained clinical care and reach their full potential. The success of the EI paradigm in psychosis however indicates the need for this principle to be extended to the full diagnostic spectrum. EI has universal value in health care and the fluidity of our syndromal approach to diagnosis both cross-sectionally and longtitudinaly means that we cannot focus too narrowly. The clinical staging model may enable us to translate the principles of early intervention to a wide range of mental disorders.
This obviously means a progressive and substantial increase in spending in mental health care and a major redesign of the way mental health care is delivered within our mainstream health systems. We need new cultures of care appropriate to early intervention and mental health care. We can no longer be expected to merely fit in to standard medical environments as if mental health care is exactly the same as physical health care. Outcomes can already be dramatically improved with existing knowledge for most people not only with psychotic illness but other potentially serious disorders. This will also save a great deal of taxpayers’ money.
Through more refined prediction strategies and definition of underlying mechanisms we can also move towards the holy grail of a more personalized approach to treatment. Rather than developing risk syndromes for a number of traditional disorders within our 19th century diagnostic silos we need to consider a pluripotential approach. The move to RDoC in the USA also supports this goal. Transdiagnostic research will be more feasible if we transform and rebuild systems of care to remove stigma and guarantee “soft entry”, investing heavily in a new youth oriented culture of care, through which very early access is possible at the sub threshold stage, stepwise expertise is progressively available and functional recovery is the goal. All these things are achievable if we combine the power of the evidence-based paradigm with greater confidence, tenacity and much more intensive and professional advocacy in partnership with every single member of the general public.
Plenary Session II
Thursday, October 20, 9:25 – 10:05 a.m., Washington
Feasibility, Effectiveness, Predictors and Moderators of Outcome of a Multi-Element Psychosocial Intervention for First-Episode Psychosis in “Real World” Community Care. Results From the Cluster Randomized Controlled GET UP PIANO Trial in a Catchment Area of 10 Million Inhabitants
Section of Psychiatry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy
Chair: Maximilian Birchwood, Mental Health and Wellbeing, Warwick Medical School, Coventry, UK
Co-Chair: Antonio Preti, University of Cagliari, Sardinia, Italy
Background. Integrated multi-element psychosocial interventions for first-episode psychosis (FEP) patients may benefit from studies performed in real world setting and in epidemiologically representative samples to facilitate translation of findings to clinical practice and decision making.
Methods. We performed a cluster-randomized controlled trial, comparing an integrated multi-element psychosocial intervention, comprising cognitive behavioral therapy, family intervention, and case management, with treatment as usual (TAU) for 1 year incident FEP patients in 117 community mental health centers (CMHCs) in a large area of northern Italy (10 million inhabitants), treated for 9 months after the first contact with services The randomized units (clusters) were the CMHCs, and the units of observation the patients (and, when available, their family members). Feasibility and effectiveness was tested, together with predictors and moderators of outcome. A subset of demographic and baseline clinical variables were selected a priori, on clinical grounds or derived from the literature, as potential predictors or moderators of outcomes at 9 months. These included gender, age at first-contact, citizenship (Italian/non-Italian), educational level, duration of untreated psychosis (DUP), type of psychosis (affective/non-affective), pre-morbid functioning and insight into illness. Statistical analyses were conducted using an intention-to-treat (ITT) approach. Outcomes were analyzed separately in mixed-effects random regression models.
Results. A total of 444 patients completed the 9 month assessments. The integrated multi-element psychosocial intervention proved to be superior to TAU in terms of reduction of overall symptom severity, greater improvements of global functioning, emotional well-being, and subjective burden of delusions. Higher education, shorter DUP, better premorbid adjustment and insight into illness predicted better outcomes regardless of treatment. Age at first contact with the CMHC proved to be the only moderator of treatment outcome: TAU intervention proved to be ineffective in subjects aged 35 years and above, while the experimental treatment was more beneficial in all ages, and thus proved to be more generalisable
Conclusions. This study, performed in the largest catchment area ever tested in FEP treatment, supports feasibility and effectiveness of early interventions for psychosis also when provided by dedicated Teams based in generalist mental health services and gives information on which patients benefit more from the experimental intervention.
The identification of age at first contact as the only moderator of treatment outcome suggests that the GET UP multi-element psychosocial intervention is beneficial to a broad array of FEP patients treated within routine community mental health services.
Plenary Session III
Thursday, October 20, 10:30 – 11:15 a.m., Washington
RAISE 2.0 – Establishing a National Early Psychosis Intervention Network in the U.S.
Division of Services and Intervention Research, National Institute of Mental Health, Rockwell, Maryland, USA
Chair: Patrick McGorry, MD, Ph.D, Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, University of Melbourne, Parkville, Australia
Co-Chair: Merete Nordentoft, Mental Health Services in the Capital Region of Denmark, University of Copenhagen, Denmark
Background: Historically, early intervention services (EIS) for psychosis in the United States were rarely found outside academic research centers. In 2008 the National Institute of Mental Health (NIMH) launched the Recovery After an Initial Schizophrenia Episode (RAISE) initiative to test the feasibility and effectiveness of team-based, multi-component treatment for first episode psychosis (FEP). RAISE was designed to accelerate uptake of FEP research findings in community clinics, with the goal of implementing EIS across the U.S.
Methods: RAISE featured close partnerships between NIMH, FEP researchers, and government healthcare agencies. Comparative effectiveness and implementation research results were applied over time to inform FEP policy choices, and were translated into practical tools for initiating early intervention programs. A national network was established among researchers, clinicians, service users, and advocates to promote EIS best practices.
Results: RAISE results influenced federal and state agencies’ support of broad implementation of EIS. To date, 32 states (64%) plan to initiate or expand early intervention programs for FEP, a 16-fold increase over the number of states with such plans before RAISE. Over 100 EIS teams will operate in the U.S. by 2018.
Conclusion: The rapid expansion of EIS clinics makes possible a nationwide platform for delivering, studying, and refining evidence-based care for persons with FEP. Moving forward, NIMH will establish the Early Psychosis Intervention Network (EPINET). This national learning healthcare system will promote effective, high-quality services for FEP service users, encourage continuous improvement and innovation in practice, and leverage data collected during routine care to facilitate scientific investigation.
Plenary Session IV
Friday, October 21, 8:30 – 9:15 a.m., Washington
Familial High Risk Studies – Why Are They Still Relevant? The Danish High Risk and Resilience Study – Status, Results and Perspectives
Anne A.E. Thorup
Institute of Clinical Medicine, Faculty Health and Medical Science, University of Copenhagen, Denmark
Chair: Larry J. Seidman, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA
Co-Chair: Philippe Conus, DP-CHUV, Lausanne University, Lausanne Switzerland
Background: For decades familial high-risk studies have informed us about genetic and environmental risk factors for schizophrenia and recently also bipolar disorder. Familial high-risk studies are important and relevant and may represent a possible shortcut to learning more about early markers of illness, mental vulnerability and resilience.
Method: The Danish High Risk and Resilience Study – VIA 7 is a prospective cohort study of 522 7-year old children, 202 of them born to at least one parent diagnosed with schizophrenia in the Danish registries, 120 of them born to a least one parent diagnosed with bipolar disorder and 200 of them born to parents without any of these diagnoses. A comprehensive battery has been used combining assessments from several domains for both parents and children.
Results: Results show that children born to parents with schizophrenia or bipolar disorder score higher on the CBCL than controls, indicating early mental problems. Further there are marked differences between the three groups concerning psychopathology, neuro-cognition, motor functioning, language development and home environment.
Discussion: Results from the first assessment in VIA 7 indicate that many children and families have unmet needs and problems. Perspectives are two-fold: we aim to follow the cohort and conduct a new assessment before puberty (at age 11). Simultaneously, we are evolving an early, integrated, specialized and family based intervention, called VIA Family, to prevent or ameliorate development of severe mental illness in individuals born to parents with chizophrenia or bipolar disorder.
Plenary Session V
Friday, October 21, 9:15 – 10:00 a.m., Washington
New Approaches to Detection and Intervention for Social Recovery in Early Psychosis and At Risk Mental States
Professor of Clinical Psychology and Youth Mental Health, University of Sussex, UK
Chair: Jean Addington, Ph.D., University of Calgary, Alberta, Canada
Co-Chair: Anna Meneghelli, Ospedale Niguarda Ca’ Granda Milano, Italy
Extreme social avoidance and withdrawal is a key problem preventing recovery from early psychosis. It is also the key characteristic of those cases most at risk in youth mental health. The patterns of extreme inactivity in first episode psychosis associated with poor long term recovery frequently evolve from a longer term withdrawal strategy occurring premorbidly in context of complex chronic emotional and behavioural problems in childhood and adolescence. Such patterns of chronic behavioural inactivity are associated with long term poor symptomatic and social recovery across disorders. Low activity in first episode psychosis is associated with residual negative and positive symptoms, and persistent severe emotional disturbance. Low activity in risk mental state is associated with poor long term symptomatic and social course. Detection and intervention is needed. However, these cases present a problem to services as they are difficult to detect and engage and intervene. The young people most at risk may paradoxically be the most difficult to engage, and least likely to seek or respond to help, even though they may have severe ongoing problems. Specific strategies are required to detect and engage cases and to intervene. We have undertaken a program of research in this area. This includes two large randomised controlled trials: one in first episode psychosis (SUPEREDEN3); and one ongoing in at risk mental state (PRODIGY). These trials examine the efficacy of a specific social recovery form of cognitive behavioural intervention. The trials have been carried out in association with program of qualitative, and empirical screening and detection work in different populations. In this talk we provide an overview of the results of the trials and this research program.
Plenary Session VI
Friday, October 21, 10:30 – 11:15 a.m., Washington
Achievement and Future Perspectives for the Early Intervention in Psychoses
Mental Health Services in the Capital Region of Denmark, University of Copenhagen, Denmark
Chair: Eóin Killackey, Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, Parkville, Australia
Co-Chair: Young Chul Chung, Chonbuk National University Medical School, Jeonju, Korea
The early phase of psychosis is the most vulnerable phase with high risk of suicidal acts and social marginalisation. The evidence for the effectiveness of specialized assertive early intervention services is well established and the most recent findings will be presented. There are models for long term maintenance of the beneficial results, which have been tried out. Several countries have well established plan for implementation of EI services and for program fidelity measures. The core elements of content of early interventions services are team-based intensive case management and family involvement, but more specialized elements are being are being developed and tried out such as inclusion of new methods in CBT for psychotic and negative symptoms, neurocognitive and social cognitive training programs, interventions for comorbid substance abuse, supported employment and focus on physical health. Results of long term follow-up studies indicate that the prognosis of first episode psychosis is very diverse with the extremes represented by one group being well functioning and able to quit medication without relapse; and another group having a long term chronic course of illness with a need for support to maintain daily activities.
It has been demonstrated that CBT can reduce transition rates to psychosis in Ultra High Risk groups, but there are only few examples of implementation of treatment for this group. It will be of immense value to be able to intervene in risk groups identified in the premorbid phase, and there are few examples of ongoing trial for children of parent with schizophrenia and bipolar disorder.
Plenary Session VII
Saturday, October 22, 8:30 – 9:15 a.m., Washington
Tracking Clinical and Functional Outcomes in Young People with Emerging Anxiety, Mood or Psychotic Disorders
Ian B. Hickie
Brain & Mind Research Institute, University of Sydney, NSW, Australia
Chair: Jan Scott, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
Co-Chair: Davide Dettore, University of Florence, Italy
Background: Internationally, youth mental health services are being established to intervene earlier with young people with emerging anxiety, mood or psychotic disorders. The assumption is that earlier intervention will lead to improved clinical and functional outcomes.
Method: At the Brain & Mind Centre, in partnership with our local headspace centres, we have established a large, longitudinal study of young people presenting for care with emerging anxiety, mood or psychotic disorders. A strong emphasis is use of a clinical staging model, as well as tracking functional as well as clinical outcomes. Additional neuropsychological and neurobiological are collected in sub-samples.
Results: Baseline assessments on almost 7,000 subjects (57% female) provide detailed data on functional status (mean SOFAS score = 61.2), clinical stage at presentation (Stage 1a: 21%; Stage 1b: 54%, Stage 2 and above; 25%) and primary diagnosis (Anxiety: 20%; Depression: 38%; Bipolar: 6%; Psychotic: 6%, other behavioural and developmental: 18%). Longitudinal data – now extending up to 8 years from enrolment – indicate the extent to which demographic, functional and neuropsychological function at baseline assessment predict transition to later clinical stages and ongoing non-participation in education, employment and training.
Discussion: Longitudinal data on a unique clinical cohort indicate the extent to which neuropsychological characteristics and functional status, rather than clinical diagnosis, predict transitions to later stages of illness and functional impairment. Interventions may need to focus on these features rather than specific clinical characteristics.
Plenary Session VIII
Saturday, October 22, 9:15 – 10:00 a.m., Washington
Time is of the Essence in Eating Disorders
Janet Treasure, Ph.D
FRCP FRCPsych, IOPPN Kings College London, UK
Chair: Masafumi Mizuno, Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan
Co-Chair: Paolo Fiori Nastro, Department of Neurology and Psychiatry, Sapienza University of Rome, Italy
A randomised trial in 1987 which compared family and individual relapse prevention following inpatient treatment for anorexia nervosa demonstrated the impact of the duration of untreated illness on both the overall outcome and the response to family treatment 1,2 . After three years anorexia nervosa becomes resistant to psychotherapy.3 Prolonged starvation has profound effects on both body and brain and cognitive, emotional and social functioning is disrupted. This sets up a web of maintaining factors that accumulate over time 4 . Early intervention taking into account other clinical factors such as age and severity is critical for the management of eating disorders5.
- Eisler I, Dare C, Russell GF, Szmukler G, le Grange D, Dodge E. Family and individual therapy in anorexia nervosa. A 5-year follow-up. Arch Gen Psychiatry 1997; 54(11): 1025-30.
- Russell GF, Szmukler GI, Dare C, Eisler I. An evaluation of family therapy in anorexia nervosa and bulimia nervosa. Arch Gen Psychiatry 1987; 44(12): 1047-56.
- Treasure J, Russell G. The case for early intervention in anorexia nervosa: theoretical exploration of maintaining factors. Br J Psychiatry 2011; 199(1): 5-7.
- Treasure J, Schmidt U. The cognitive-interpersonal maintenance model of anorexia nervosa revisited: a summary of the evidence for cognitive, socio-emotional and interpersonal predisposing and perpetuating factors. J Eat Disord 2013; 1: 13.
- Treasure J, Stein D, Maguire S. Has the time come for a staging model to map the course of eating disorders from high risk to severe enduring illness? An examination of the evidence. Early Interv Psychiatry 2015; 9(3): 173-84.
Plenary Session IX
Saturday, October 22, 10:30 – 11:15 a.m., Washington
Population Neuroscience: Observing to Change
Tomas Paus, M.D., Ph.D
Healthy Brain Network, Child Mind Institute, University of Toronto, Canada
Chair: Tyrone D. Cannon, Department of Psychology, Yale University, New Haven, CT, USA
Co-Chair: Matcheri Keshevan, M.D., Harvard Medical School, Massachusetts Mental Health Center, Boston, Massachusetts, USA
Population neuroscience endeavors to identify environmental and genetic factors that shape the function and structure of the human brain; it uses the tools and knowledge of genetics (and the “omics” sciences), epidemiology, and neuroscience1. By understanding the processes driving variations in brain function and structure across individuals, we will also be able to predict an individual’s risk of (or resilience against) developing a brain disorder. In the long term, the hope is that population neuroscience will lay the foundation for personalized preventive medicine and, in turn, reduce the burden associated with complex, chronic disorders of brain and body.
In this talk, I will introduce the basic concepts of population neuroscience and illustrate this approach using data collected in the Saguenay Youth Study2,3, the IMAGEN Study4 and ALSPAC5. I will talk about our recent work on polygenic risk score for schizophrenia, cannabis use and brain maturation6, as well as about the use of polygenic scores to investigate the influence of stress on the adolescent brain. I will close by outlining possible strategies for translating knowledge obtained by such observational sciences into stratified preventive strategies aimed at changing health behaviors and, in turn, preventing common disorders of the brain and body.
- Paus, T. Population Neuroscience, (Springer-Verlag, Berlin Heidelberg, 2013).
- Pausova, Z. et al. Genes, maternal smoking, and the offspring brain and body during adolescence: Design of the Saguenay youth study. Human Brain Mapping 28, 502-518 (2007).
- Paus, T. et al. Saguenay Youth Study: A multi-generational approach to studying virtual trajectories of the brain and cardio-metabolic health. Dev Cogn Neurosci (2014).
- Schumann, G. et al. The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology. Mol Psychiatry 15, 1128-39 (2010).
- Boyd, A. et al. Cohort Profile: the ‘children of the 90s’–the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol 42, 111-27 (2013).
- French, L. et al. Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence. JAMA Psychiatry (2015).