Ernst Strüngmann Forum

Impetus for this topic came from Peter Uhlhaas and Stephen Wood, who formulated the original proposal. Joining them on the on the program advisory committee were Andrew Chanen, Matcheri Keshavan, and Andreas Meyer-Lindenberg. From July 29 to August 3, 2018, participants gathered in Frankfurt for this 28th Forum to explore the nature of emergent psychopathology underlying causal factors and mechanisms and to develop a framework for prevention and early intervention in youth mental health.

This volume synthesizes the resulting discourse and is comprised of two types of contributions. Background papers, written before the Forum, address key aspects of the overall theme. These chapters have been peer reviewed and subsequently revised. In addition, Chapters 3, 6, 9, and 13 provide an overview of the working groups and expose diverging opinions as well as areas where future attention is needed.

An endeavor of this kind creates its own unique group dynamics and puts demands on everyone who participates. Each invitee played an active role and for their efforts, I am grateful to all. A special word of thanks goes to the program advisory committee, to the authors and reviewers of the background papers, as well as to the moderators of the individual working groups (Alyson Yung, Stephen Wood, Matcheri Keshavan, and Andrew Chanen). Importantly, the rapporteurs of the working groups (Jai Shah, Urvakhsh Meherwan Mehta, Christopher Davey, and John Torous) deserve special recognition, for to draft a report during the Forum and finalize it in the months thereafter is no simple matter. Finally, I extend my appreciation to Peter Uhlhaas and Stephen Wood, whose commitment was essential to this 28th Ernst Strüngmann Forum.

The Ernst Strüngmann Forum is reliant on institutional stability. The generous support of the Ernst Strüngmann Foundation, established by Dr. Andreas and Dr. Thomas Strüngmann in honor of their father, enables the Ernst Strüngmann Forum to pursue its work in the service of science. In addition, the following valuable partnerships are gratefully acknowledged: the Scientific Advisory Board, which ensures the scientific independence of the Forum; the Deutsche Forschungsgemeinschaft, for its supplemental financial support; and the Frankfurt Institute for Advanced Studies, which shares its intellectual setting with the Forum.

Long-held views are never easy to put aside. Yet, when the limits to our knowledge begin to appear and the resulting gaps are identified, the act of formulating strategies to move past this point becomes a most invigorating activity. On behalf of everyone involved, I hope this volume will spur further action to address the myriad issues being faced in youth mental health.

Nicholas B. Allen, Mario Alvarez-Jimenez, G. Paul Amminger, Shelli Avenevoli, Hannah F. Behrendt, Tolulope Bella-Awusah, Maximus Berger, Byron K. Y. Bitanihirwe, Drew Blasco, John D. Cahill, Joanne S. Carpenter, Andrew M. Chanen, Eric Y. H. Chen, Shane D. Colombo, Christoph U. Correll, Christopher G. Davey, Kim Q. Do, Damien A. Fair, Helen L. Fisher, Sophia Frangou, John Gleeson, Robert K. Heinssen, Ian B. Hickie, Frank Iorfino,Matcheri S. Keshavan, Kerstin Konrad, Phuong Thao D. Le, Francis Lee, Leslie D. Leve, Sarah A. Lieff, Cindy H. Liu, Beatriz Luna, Patrick D. McGorry, Urvakhsh Meherwan Mehta, Andreas Meyer-Lindenberg, Shreya V. Nallur, Cristopher Niell, Merete Nordentoft, Dost Öngür, George C. Patton, Tomáš Paus, Ulrich Reininghaus, Bernalyn Ruiz, Fred Sabb, Akira Sawa, Michael Schoenbaum, Gunter Schumann, Elizabeth M. Scott, Jai Shah, Vinod H. Srihari, Ezra Susser, John Torous, Peter J. Uhlhaas, Swapna K. Verma, T. Wilson Woo, Stephen J. Wood, Lawrence H. Yang, Alison R. Yung

Abstract

Progress in science is frequently achieved when challenges are made to the dominant mode of thinking and novel paradigms begin to emerge, providing new frameworks to organize data and conduct empirical inquiry. To examine current thinking in the areas of youth mental health, this 28th Ernst Strüngmann Forum was convened to scrutinize early intervention and treatment for emerging mental disorders during youth. The multifaceted contributions in this volume argue that current approaches to research and intervention need to shift away from adulthood and focus on the predominant onset period for mental ill-health: youth, the period between 15–24 years of age. Wide-ranging implications emerged for diagnosis, treatment, and research. This chapter provides background to the topics addressed at this 28th Ernst Strüngmann Forum and highlights future prospects for a youth mental health paradigm.

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Abstract

This chapter reviews a clinical staging framework that was developed for youth-onset anxiety, mood, and psychotic disorders. Used for over a decade in early intervention services in Australia, a more restricted version of this framework has been used internationally for specific diagnostic groupings, most notably among youth with psychotic or bipolar disorders. The validity of these different clinical staging frameworks is being assessed within longitudinal cohort, concurrent neurobiological, and specific intervention studies. Preliminary evidence suggests that (a) varying stages of illness are associated with predicted differences in a range of objectively measured neuropsychological, circadian, and structural brain imaging measures; (b) while earlier stages are considered subthreshold disorders from a diagnostic perspective, they are associated with significant reductions in educational, employment, and social participation as well as substantial comorbidity and suicidal thoughts and behaviors; and (c) as predicted by the Sydney model, earlier (subthreshold) stages of illness progress at lower rates to more severe (full-threshold), recurrent, or persistent disorders. Importantly, since approximately 15–30% of young people classified as “attenuated” (subthreshold) syndromes progress to more severe (full-threshold) disorders, this particular group is the most obvious focus for early clinical intervention and secondary prevention trials. The chapter concludes with a discussion of major issues that need to be pursued in future research.

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Abstract

This chapter articulates a framework for bringing together developmentally contextualized mental and physiological processes to guide the characterization, staging, and interventions necessary in treating mental health disorders in youth. This framework spans from population-level risk identification to individual-level clinical care, drawing on knowledge about developmentally informed trajectories and clinical systems. At a fundamental level, it necessitates appreciating the influence of both inherited and acquired factors on brain specialization and the setting of trajectories during periods of plasticity and risk, all of which delineate adult trajectories in multiple dimensions. More pragmatically, it requires us to track a range of salient mental/physiological systems during a dynamic developmental period that includes both vulnerability and risk, to contemplate their utility in identifying enriched groups that might benefit from further individual-level assessment in clinical or community settings, and to translate findings into planning prevention and intervention programs and to informing clinical decision making.

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Abstract

This chapter explores the ways in which developmental science can shed light on salient issues within developmental epidemiology and intervention science. The highly replicated pattern of typical age of onset for different classes of mental disorders suggests that these epidemiological patterns might be a result of periods of development when certain processes are highly plastic and more sensitive to environmental input (i.e., sensitive periods). Understanding the particular adaptive goals of each stage of development can thus reveal mechanisms associated with the characteristic forms of vulnerability during each life phase. Puberty appears to be a salient example of a developmental process associated with a sensitive period for social learning as well as with the emergence of a range of mental disorders that are particularly associated with social cognitive symptoms (e.g., depressive disorders). Developmental science also has implications for precision intervention. Developmental moderation of intervention effectiveness is commonly observed, but a mechanistic understanding of the processes that underlie these effects has received relatively little research attention. Although the integration of insights from developmental science into our approaches to understanding and treating mental disorders across the life span is just emerging, the prospects for greater understanding and more effective interventions appear to be promising.

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Abstract

This chapter provides a comprehensive overview of the impact of social context factors, conceptualized as both risk and resilience factors, on the emergence of youth (age 15–24 years) mental health problems. The influences of cultural background (i.e., individualism vs. collectivism) and recent societal developments (e.g., digital media use) are explored, as are innovative technological advances which may aid reliable measurement of such factors in future studies. It critically discusses the concept of a second sensitive period for social experiences to impact youth development starting in adolescence (age 10–19 years). It is argued that goals in social development may undergo systematic shifts across the life span and that social experiences in each developmental phase are interdependent insofar as their effects cascade into successive periods. To further understanding and improve treatment of youth psychopathology, conceptual models need to be broadened to include multiple, interdependent sensitive periods of social development. The timing of social experiences may play a central role in the efficacy of different types of interventions.

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Abstract

Vulnerability for the development of major mental health conditions during the transition from adolescence to adulthood is highly influenced by social and cultural contexts, yet our understanding of the way these contexts interact with individual differences (such as genetic variation) to generate or moderate psychopathology is limited. Such contextual interactions are likely to be nonlinear, bidirectional, and potentially age sensitive, requiring complex modeling to disentangle the most significant factors that contribute to the onset of mental illness in youth. Combined with known transcultural variation in these contexts (and psychopathology itself), there is a critical need to better understand the general applicability of models of youth mental health if we are to develop appropriate interventions. This chapter identifies gaps in current understanding in terms of how an individual’s interaction with the environment shapes the risks and vulnerabilities to develop major mental disorders, or their behavioral precursors, thus resulting in functional impairments and increasing the high global burden of disease.

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Abstract

The journey from youth to adulthood involves a dynamic neurodevelopmental agenda which governs a series of intricate molecular and cellular events in the brain that ultimately affect the maturation of neural circuitry and cognitive properties. These neurobiological changes confer the ability to transition from parental guidance or guardianship to self-sufficiency. Adolescence represents an important inflection point on this journey: each person’s unique experience during this distinct neurodevelopmental period is linked to positive and negative gradients of mental health as well as to vulnerability to mental illness. Despite significant technical achievements and advances in neuroscience, gaps still remain in our understanding and knowledge of the mechanisms that guide brain development and their relevance to the onset of psychiatric disease in youth. To contextualize the emergence of psychopathology in youth, this chapter outlines the neurobiological mechanisms underlying the development and maturation of neural circuitry in the brain during this critical period of life. Emphasis is placed on examining neural circuitry reorganization in response to physiological and pathological influences in relation to the emergence of developmental psychopathology. Controversial and open questions are discussed regarding developmental psychopathology in relation to youth. Unsolved problems, knowledge gaps, and the neurobiologically inspired notion of preventing psychopathology during this delicate period of neurodevelopment are also addressed.

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Abstract

For many years it was believed that the fundamental properties of the brain were sculpted mainly in utero and in the early postnatal years, but data from a range of disciplines have forced a reassessment of this notion. The transition from childhood to adulthood, especially the critical period of adolescence, involves a profound reorganization of both architecture and functionality of large-scale networks, which is likely to constitute a vulnerability for emerging psychopathologies and opportunities for intervention.

For youth (15–24 yr) and, in particular, adolescents (10–19 yr), dramatic changes occur (physically and behaviorally) during this critical period of development. Although most teenagers successfully navigate the transition from dependence on a caregiver to being a self-sufficient member of society, adolescence is also a time of increasing incidence of several classes of psychiatric illness, including psychosis, mood disorders, and substance abuse. The pathophysiology of these disorders is increasingly understood as arising from aberrations in the maturational changes that normally occur in the adolescent brain. This chapter reviews the neurobiological changes that occur during adolescence and discuss their possible relationship to the emergence of psychopathology.

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Abstract

Given the disease burden of mental health in youth, the development of age-appropriate treatments and effective prevention strategies needs to be prioritized. This, however, requires a better understanding of how and why mental disorders emerge. The clustering of the onset of mental disorders in youth suggests that there may be identifiable underlying brain circuit changes during this period, and that examination of normal and abnormal circuit development can improve our understanding of emerging mental disorders. This chapter synthesizes evidence related to multiscale changes in large-scale networks that occur during youth and highlights their relevance to emerging psychopathology. The impact of environmental risk factors is explored and strategies for future research proposed.

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Abstract

Extant interventions and services for young people with mental ill-health and their families have significant limitations, including poor access to services, relapse prevention, social recovery, research translation, and family support as well as limited effectiveness and significant adverse events of pharmacological interventions. Based on research literature and the authors’ work in the field, this chapter reviews three avenues for progress: novel digital, family, and transdiagnostic biomarker-guided interventions.

Main findings and conclusions: Despite their potential and consistent evidence supporting their effectiveness, digital interventions have not been integrated into youth mental health services. Integration of digital interventions into mainstream services is likely to create a new paradigm, driven by ongoing innovation and rapid evaluation and clinical implementation. Family interventions need to move away from a narrow focus on psychotic disorders, patient symptoms, and relapse to include overlooked populations, transdiagnostic processes, family burden, and the mental and physical health of families. Finally, transdiagnostic prevention and treatment of severe psychiatric disorders is a promising avenue for reducing the burden, mortality gap, and adverse effects of current medications. Supplementation of n3PUFA via fish oil is proposed as a prototype of a transdiagnostic, benign, biomarker-guided intervention.

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Abstract

Whereas identification of a “clinical high-risk state for psychosis” (CHR-P) marks a groundbreaking global advance in the treatment of youth with potential subthreshold psychotic symptoms, controversies regarding the CHR-P exist. This chapter explores three sets of challenges: validity of the CHR-P diagnosis, stigma and ethical concerns, and challenges in implementing CHR-P identification measures globally.

It critically analyzes the current knowledge regarding these challenges. Debates surrounding core validity of the CHR-P diagnosis include whether CHR-P is a distinct syndrome from other common mental disorders, decline of transition rates in studies over time, and the value of identifying an at-risk status when empirically validated treatments have not yet been developed. Ethical challenges include potential stigma of the CHR-P state, and the ethics of diagnosing an at-risk state that encompasses a period of adolescence and extends into youth. Challenges in implementing CHR-P interventions globally include questions of whether early mental health intervention shows sufficient economic return, and promotion of psychosis terms in cultural settings where such conceptions may be entirely novel. Addressing these controversies could facilitate adoption of the CHR-P identification into mental health-care systems globally, thus maximizing public health impact.

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Abstract

Can regional systems of care be designed to disseminate best practices and drive necessary research? This is a question of generic interest across health-care conditions, and literature from allied fields will be brought to bear here on how this can be done for youth mental health, with the example of early intervention services for psychotic disorders.

This chapter argues that (i) knowledge translation should be the organizing goal of such a system; (ii) population health can serve as a conceptual basis for reform, which will be facilitated by a shared vocabulary of “systems, networks, and pathways”; (iii) measuring value can guide inevitable trade-offs in regional allocation of resources; (iv) services should be designed to embrace complexity and avoid simplistic approaches to wicked problems; and (v) learning health systems are an optimal framework within which to design systems for knowledge translation.

The heterogeneous group of primary, non-affective, and chronic psychotic disorders that fall under the umbrella term schizophrenia will be used as a stand-in for the chronic mental illnesses of adulthood that typically onset in youth. While this focus has limitations, it should enable vigorous critique of the proposed design of systems of care: both for relevance to psychotic disorders as well as across the wide range of disorders affecting youth.

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Abstract

Mental ill-health poses the greatest threat worldwide to the survival, fulfillment, and productivity of young people. Implementation of prevention and early intervention services during adolescence and youth offers the best opportunity for health and productivity gains, as 75% of all mental and substance use disorders emerge before the age of 25 years. Our vision is that all young people will be better protected from the major risk factors that threaten their mental health and well-being so that they will be able to access freely, without stigma, mental health care that is as expert and evidence-based as possible—care that is continuously shaped by new research knowledge as well as perspectives and needs of young people, their families, and their communities.

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Abstract

Until recent decades, early intervention seemed like a Utopian ideal, hopelessly out of reach. One of the prerequisites for intervening early is the availability of effective treatment. However, even when effective treatments for the major mental disorders emerged in the 1950s, the weight of pessimism, neglect, and discrimination in the care of the mentally ill buried all realistic notions of intervening early to modify the course of serious mental illness. In the 1980s, research began to focus on first-episode psychosis to seek greater clarity of the underlying etiopathology. The long delays in accessing initial treatment became immediately apparent, as did the fact that the treatment needs of early-stage patients and their families were dramatically different from those with long-term chronic illness. The harm suffered by patients through these delays and the crudeness of standard care was exposed and demanded a new approach. The therapeutic value of hope was rediscovered, and the erroneous nature of the nineteenth-century belief of inevitable deterioration or degeneration, also captured in the 1980s phrase “doomed from the womb,” became clear. Short- to medium-range outcomes were improved and shown to be heterogeneous and malleable. The world of schizophrenia research was transformed, and several stages of illness, each with their own treatment needs, were defined, from the earliest clinical features to enduring chronic illness. This paradigm shift paved the way for the creation of a transdiagnostic model of clinical staging that was capable of catalyzing early intervention across other diagnostic landscapes and congruent reform of systems of mental health care. An international scientific movement emerged under the banner of the International Early Psychosis Association (IEPA) in 1997, and a new journal, Early Intervention in Psychiatry, was established in 2007 to sustain and extend the growth of knowledge in early intervention. With 75% of mental and substance use disorders emerging before the age of 25 years, this reform has focused especially on young people in transition to adult life, where the consequences of delayed and poor quality of care are greatest. Despite overwhelming logic, a compelling body of evidence, including cost-effectiveness data, reform, and investment, has been hampered by inertia, structural stigma, and a rearguard action, aimed at seeding doubt, by a small number of academic critics. The other major missing element is public engagement and mobilization in support of change. Reform is best informed by science, but it is in the end a sociopolitical process, and there are signs that this is becoming better understood. Early intervention provides a blueprint and launch pad to radically change the wider landscape of mental health care, to prioritize youth mental health, and to dissolve many of the barriers that have constrained progress for so long. This chapter captures the lessons learned and indicates avenues for further progress.

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