2022 Congress Recordings

Students are fed up with the current public perception of psychosis. In this keynote, Founder and Executive Director Cecilia McGough of the nonprofit Students With Psychosis is joined by their colleagues to voice the student-led lived experience perspective and the nonprofit's origins, current activity, and future goals. Students With Psychosis is a 501(c)(3) nonprofit that empowers student leaders and advocates worldwide through community building and collaboration. Students With Psychosis provides over 160+ hours monthly of virtual programming at no cost to their student leaders and advocates with at least five hours facilitated each day and opportunities to get more involved. Students With Psychosis envisions a world where no student or advocate living with psychosis worldwide goes without community and access to education. Students With Psychosis values (1) the lived experience perspective in leadership positions, (2) both the accurate and respectful representation of people living with psychosis, (3) community, workplace, and educational environments to not only be supportive but also empowering to people living with psychosis, (4) a person's worth is not determined by grades or degree level, and (5)shared decision making in treatment options. Students With Psychosis does not promote any particular treatment option. Students With Psychosis aims to expand mental health/brain health advocacy at the college level to ensure psychosis representation, including a global perspective. Too often is psychosis left out of the mental health/brain health conversation on college campuses, and our narrative is also often limited, excluding intersectional community members. The nonprofit's primary objectives include (1) growing and connecting their virtual and in-person programs, (2) organizing outreach initiatives, and (3) founding in-person college clubs/affiliates/hubs.

Dr Kim Do will discuss a translational program aimed at early detection and intervention in schizophrenia. It requires mechanism-based biomarkers that capture neural circuitry dysfunction, allowing better patient stratification, personalization of treatment and monitoring of disease progression. She will show how interaction of genes and environment risk factors during neurodevelopment converge on a hub consisting of neuroinflammation, NMDA receptor hypofunction, dysregulation of mitochondria, dopamine, and redox balance, inducing oxidative stress and reinforcing each other in a damaging feedforward mechanism. This affects parvalbumin interneurons (PVI), including their associated gamma synchronization, and impacts myelination, thus leading to structural and functional alterations of local microcircuits and long-range connections, essential for cognitive, affective and social functioning. Animal models showed that additional insults at peripuberty, but not in adults, lead to PVI impairments that persist until adulthood. NAC application, only when it is followed by an environmental enrichment, leads to normalization of adult PVI (Dwir &al 2021). Reverse translation allowed mechanism-based stratification of patients towards early detection and novel treatments. The potential therapeutic effect of the antioxidant N-acetyl cysteine (NAC) observed in models was tested in patients with chronic schizophrenia, and improved negative symptoms, NMDA and related potentials in EEG. In early psychosis patients, NAC improved cognition (Conus &al 2018), as well as structural (Klauser &al 2018), and functional connectivity (Mullier &al 2019). Two blood exosomal markers, elevated miR137 and decreased COX6A2, allow to characterize the oxidative status of PVI mitochondria and to correlate it with a reduction of ASSR gamma EEG oscillations and with worse psychopathological status, neurocognitive performance, and global and social functioning (Khadimallah &al 2021). This stratification would allow the specific selection of patients for treatments targeting brain mitochondria dysregulation, and the investigation of the clinical and functional efficiency of future clinical trials.

Early intervention (EI) has increasingly been recognized as an established clinical paradigm. Studies of sustained long-term outcome requires appropriate contextualization to appreciate. We review these issues with data from a population-based program in Hong Kong. EI involved three interacting components: early detection, phase-specific intervention, and indicated prevention. EI programs also enhance other mental health programs in the population (a ripple effect involving the sharing of knowledge, paradigm, and human resources). Based on a series of outcome studies in Hong Kong, EI has resulted in a shortening of DUP for the adult patients but not youth patients. The multi-disciplinary EI team improved functioning and reduced hospitalization. Beyond the direct program effects, there are sustained long-term effects for up to 10 years. In addition, there was a significant and sustained reduction in suicide. These data supported the critical period hypothesis: better outcome in the initial years of the disorder can be sustained after the patients have exited to generic service, for a period of up to 10 years. This is despite there being concurrent improvement in generic services (partly as a result of the ripple effect). This reinforced the role of EI programs in leading continuous cycles of quality improvements. Accordingly, we explored opportunities where further outcome improvements could be targeted. Maintenance therapy after first episode psychosis is a complex area under intense investigations. Data from our cohort suggest that for first episode patients with a good post-episode outcome (no residual psychosis, no early relapse) continuation of maintenance for up to year 3 leads to a sustained good outcome in 10 years. Those who stopped maintenance between year 2 and year 3 ended up with a less favourable outcome comparable with those that did not have the most favourable initial outcome. Fine-tuning maintenance strategy to individual circumstances and needs. Another important areas of opportunity is in improving outcome through cognitive function enhancement. Our studies showed that mind-body exercise (Yoga) as well as aerobic exercise could significantly improve attention and memory, with corresponding brain changes. To enhance the establishment of exercise habits. It has been shown that a motivational coaching program can be a useful augmentation to exercise intervention programs. Our data showed that EI paradigm can improve long-term outcome of psychosis patients which are sustained beyond the period of intervention. This highlights the importance of timely intervention and securing the best possible outcome during the critical period. Early psychosis programs produce ripple effects on generic services which may complicate long term outcome comparison. EI service are well positioned to lead continuous cycles of outcome improvements for psychotic disorders.

As anthropologists and qualitative researchers have long argued, the phenomenology of psychosis varies in many ways across distinct historical and cultural contexts. Nevertheless, the full ramifications of these diverse forms and experiences, and the systems of understanding in which they are embedded, arguably remain deeply under-theorized in the context of clinical and services research, perhaps particularly when it comes to investigations of the many and complex reasons why clients ultimately disengage from (or never truly engage with) psychosis services. Zooming out from these narrower clinical contexts, the presentation will also take up the question of the relationship between meaning-making, available cultural scripts and identities, and long-term healing and community integration. Throughout, the presenter will draw on sustained research, clinical and activist engagement with service users/experiencers in diverse cultural contexts; work, in turn, inspired and animated by long-term personal and family experiences of psychosis.

Psychosis can be examined through the evolution of psychotic experiences in time, and unraveling these dynamics may provide insights for innovative interventions. Data about the trajectory of psychosis experiences during neurodevelopment from the Brazilian High-Risk Cohort Study for Psychiatric Disorders, in which 2,241 individuals aged 6–14 years were followed for the last 12 years will be presented. Subjects provided self-ratings of 20 psychotic experiences using the Community Assessment of Psychic Experiences (CAPE). A trained psychologist conducted an interview to validate reported experiences and to rate the presence of attenuated psychosis symptoms and affective flattening. In parallel, parents provided information about child mental health to an independent interviewer. General Psyhopatology, such as P-factor and structural and functional brain maturation during the adolescence will be presented as well as the emotional and social environment. When searching for optimal moments to intervene, valuable insights may come from examining analogous phenomena. Increasing familiarity with dimensional psychopathology dynamics, brain maturation and environmental aspects is expected to fine-tune treatment. We illustrate how time-driven interventions can be used for controlled interference in clinical settings. In orbital mechanics, the Oberth effect poses that an aircraft gains more kinetic energy when accelerating at the nearest point to a central body, where potential is lowest and speed is highest. These properties are used to spiral out of Earth’s orbit for satellites. An intuitive example can be observed in the playground swing. In order to optimize efforts, adults push the seat synchronizing it with the natural motion of the pendulum when going down-and-forward. This manoeuvre uses gravitational forces to maximize kinetic energy and make transitions to orbits of larger amplitudes. Using a similar timewise rationale to fine-tune psychosocial and drug interventions may be crucial to prevention and treatment efficacy. Examining the dynamics of psychotic states, general psychopathology, social emotional environment and brain maturation markers during neurodevelopment can give us insightful new ways to help people with mental disorders. Specifically, one may synchronize interventions with standard and deviant trajectories.

When first diagnosed, women with a schizophrenia-spectrum disorder (SSD) have a better clinical profile than men. Several factors account for this benefit, amongst these is the higher level of estrogens, which ameliorate negative and cognitive deficits. Unfortunately, women with SSD progress to the same state as men within the first years of living with SSD. They need just as many rehospitalisations and their chance for full recovery is only 12.9% (against 12.1% for men). There are benefits to be gained across different areas in the care offered to women with psychosis. An important point for improvement is the early detection of female-specific signs of a first episode of psychosis, to shorten the duration of untreated psychosis, with prompt access to early intervention services. Early intervention programs are mostly tailored to the specific needs of men and could provide more attention to women's sexual health, any history of trauma and need fo relation management and child care. Antipsychotics require dosing and prescription tailored to the female physiology that consider hormonal life phases such as menopause. Given the inhibiting effects of estrogens on the CYP1A2 enzyme and the lower renal clearance in women, serum levels of many antipsychotics easily become high in women. Side-effects are indeed much more common in women than in men. Special attention should be paid to prolactin, as high levels will reduce estrogen production, which negatively impacts mental, somatic and sexual health. Switching to prolactin-sparing medications or adding aripiprazole can be beneficial. Menopause has many consequences and often deteriorates the clinical course. Hormonal replacement therapy should be considered for postmenopausal women. We recently replicated the beneficial effects of raloxifene, a selective estrogen receptor modulator, which improved negative symptoms and cognitive functioning in women but not in men. In sum, women need different psychosis care than men. By providing female-specific care, women with schizophrenia-spectrum disorders can live up to their full potential.

Treatment for first episode psychosis (FEP) has been of interest and a challenge since the earliest studies of neuroleptic antipsychotics. The general guiding hypothesis animating these studies is that initial or early treatment is more effective than treatment later in the illness course. Such studies can also assess biomarkers and other characteristics that are freer of the confounding effects of exposure to medications and the influences of life course and environmental factors. And finally, the idea of a degenerative course in psychosis, particularly non-affective psychosis provides impetus for such research. This presentation will follow my personal history to illuminate the course of treatment research in FEP. The studies span 60 years; most were conducted in the United States and reflects its health care environment. The NIMH nine-hospital study of phenothiazines in schizophrenia (1964) compared three phenothiazines to a placebo. It began as a first-episode study; recruitment challenges expanded inclusion criteria to acute symptom exacerbation. The next, the Pittsburgh first episode study (1998) was a biomarker study of FEP with embedded psychosocial and antipsychotic treatments. An international relapse prevention study compared the second-generation antipsychotic (SGA) risperidone to first generation haloperidol (2006). A study of initial treatment compared SGAs; olanzapine and risperidone (2006). Long-acting risperidone was compared to any oral antipsychotic in adherence and relapse prevention (2012). Long-acting aripiprazole was compared to any anti-psychotic in a prevention of hospitalization study (2020). These studies generally focused on medications and were randomized clinical trials (RCTs). Some of these medication RCTs included psychosocial intervention platforms for all trial participants. Given an increasing recognition that successful outcomes require more than medication, an important focus in 21st century FEP studies has been comparison of interventions that include psychosocial and medication components to treatment as usual. In the US these are currently called Coordinated Specialty Care (CSC); across the world the term used is Early Intervention Services (EIS). The RAISE-ETP study represents that focus (2015) for me. Study designs, implementation strategies and statistical methods have changed over time. Some studies have been double blind; others open treatment with blinded/masked assessors. Dose ranges of medications studied varied. Study length range was six weeks to over two years. Outcomes varied; they include symptoms, relapse, adherence, hospitalization and community functioning. Based on these experiences and the work of many others, three questions for future FEP RCTs will be considered. What treatments should be evaluated? How should trials be designed? What outcomes should be assessed and how?

Psychotic disorders are a major cause of disease burden globally, with impact on individual sufferers, their families, and societies. Despite their huge public health importance, there is still so much we do not know about these disorders. Variations in rate of occurrence and what social and other contextual factors may be undergirding them, lay understanding of the disorders and its possible influence on how affected persons and their families make sense of their situation, help-seeking behavior and how differences in the pattern of care may affect outcomes, are a few of currently existing gaps in knowledge. On the other hand, what we currently know these disorders has been provided mainly by researchers working in the global North. Understudied populations in different parts of the work, particularly those in the global South, may provide opportunities for filling current gaps in knowledge and, perhaps, provide leads that may raise new vistas of enquiry. In this lecture, an insight is provided to some of the possibilities for such expansion in knowledge. Drawing on studies examining lay views of psychosis, especially of schizophrenia, the prototypical psychotic disorder, onset and course of psychosis, treatment approaches and how they affect outcomes, the lecture will seek to highlight how the findings from such studies may help provide new ways to address the burden of psychotic disorders in different populations.

Schizophrenia, (“split mind” in Greek) is a confusing term coined by Eugene Bleuler over a century ago to the disease earlier called dementia praecox by Emil Kraepelin. There has been a recent and growing interest to change the name of this illness for several reasons. First, this term has been stigmatized and associated with terms such as insanity, hopelessness, and violence. Second, uncertainty about what the core aspects of this syndrome are, and its enormous heterogeneity have even led to views that the term schizophrenia should be abandoned altogether. Third, several countries such as Japan, South Korea and Taiwan have already implemented alternative names for this entity designed primarily in an effort to reduce stigma, and a groundswell of stake-holder support is emerging for a name change in the US and Europe. Renaming will avoid use of the term schizophrenia as an adjective or metaphor, may increase help seeking and may reduce stigma and discrimination. However, renaming the illness requires serious consideration of what it represents conceptually. Any effort to change the name of a major disorder requires considerable Introspection and debate about the nature of the illness. Is it a syndrome, disease, simply a deviation or a spectrum of diverse disorders? What is the core feature of this entity: is it cognitive dysfunction, reality distortion, a self disorder, or a combination of all those? In this symposium we will discuss the currently fuzzy conceptual underpinnings of the entity we call schizophrenia, and critically evaluate the various models in light of accumulating scientific knowledge. Once the concept of SZ is revised and accepted by the international 1 2022 Congress of the Schizophrenia International Research Society community, then the name of schizophrenia can be “re invented” to reflect the core features of the syndrome. The symposium will be interactive, and will engage the audience in a constructive discussion and generating potential areas of consensus.

Since its inception SIRS has been dedicated to supporting the continued development of early career researchers and clinicians. The Awards program has supported 100s of applicants, many of which have gone on to have established and decorated careers. The aim of this current workshop is to hear from three awardees. The awardees will speak about their careers, their goals and the benefit that the SIRS Early Career Award had on their career. We will hear about their journey to becoming a successful schizophrenia researcher. Our speakers have been selected across the last 10 years of awardees from 2014 Dr Yuliya Zaytseva (Czech Republic), 2018 Dr Eric Tan (Australia), to most recently, 2020 Dr Alessandro Pigoni (Italy). This workshop is recommended for all, but especially for those at the inception of their careers who may want to get some useful tips to assist with their journey.

In the past year, the SIRS Membership Committee launched the SIRS EXPERT Classes, a series of exclusive virtual events for SIRS members who are early-career researchers (ECR). The overarching aim of the EXPERT Classes is to support the career development of ECRs in schizophrenia. The topics for each Class have covered some of the most important concerns at this career stage, and were based on questions submitted to the Mentoring panel discussion at SIRS 2021. EXPERT Classes have provided a unique platform for ECRs to access and interact with eminent scientists in the SIRS community as role models. This series has represented an exceptional space for networking, mentoring and inspiration for SIRS ECRs, and has covered a series of topics critical for career development, delivered by leading figures in our field, including a clinical and a basic scientist. Topics have included “Finding your own path”, where Robin Murray & Kim Do provided advice on research careers and the transition to independence. The second session covered “Academia and family life”, where Raquel Gur & Tony Grace offered their views and guidance on work-life balance and combining a researcher’s career with caring responsibilities. The third session focused on “Researcher Mobility”, with Andreas Meyer-Lindenberg & Cynthia Shannon Weickert sharing their views and advice on advantages and challenges for working in different labs and locations. This fourth session will take a workshop format, as a summary session where the 6 experts are brought together in one room for a panel discussion and a direct, stimulating interaction with ECRs. This will be a unique opportunity for attendees to personally engage in an active conversation with the Experts, to ask questions and receive mentoring relevant to concerns and aspirations at this important career stage.

One of the major goals of SIRS, since its inception, has been to strive for increasing diversity and for achieving sex equality in academia and neuroscience, with a focus on schizophrenia research and to that end has established a Diversity Task Force as a key committee. This workshop is run by the Diversity Task Force with input from the Education Committee.There is concerning data from many academic institutions indicating a higher percentage of female researchers at early and mid career levels but a sharp drop at senior career level. This is sometimes referred to as the “leaky pipeline”. In this workshop we will examine this issue to see whether it applies to women in academic positions in neuroscience, psychiatry and psychology. We will present data from different countries and then hear from some countries who have introduced initiatives to tackle this problem. We will then host a wide ranging discussion and end with suggestions on how we as SIRS members can help bring about change. The workshop is inspired by a paper recently published by several SIRS members in Psychiatry research [A snapshot of female representation in twelve academic psychiatry institutions around the world” Kenney J, Ochoa S,.....del Re EC, Psychiatry Research, (2022) ] and follows on from a workshop held at the SIRS virtual conference in 2021. This workshop is recommended to all striving for diversity and equality.

This symposium will look at new research on the origins and course of the neurocognitive impairment in schizophrenia across the lifespan by going beyond cross-sectional description of group averages. Specifically, the four speakers will focus on core questions around (1) course, (2) familial vs. disease specific, and (3) potential biological mechanisms and biomarkers of cognitive decline. Dr. Katherine Jonas will present new data charting the trajectory of IQ from age 5 to 76 in schizophrenia and other psychotic disorders. Data are from the Suffolk County Mental Health Project, in which premorbid IQ scores were extracted from school and medical records, and post-onset IQ scores were based on testing at 6-month, 24-month, 20-year, and 25-year follow-ups. The study identified three phases of cognitive change, with evidence for premorbid decline in schizophrenia, and accelerated cognitive decline in late adulthood in all psychotic disorders. Dr. Avi Reichenberg will focus on the origins of the cognitive impairment in schizophrenia, examining the hypothesis that the early cognitive impairment in schizophrenia reflects a decrement from the expected familial level of cognitive functioning. Building on unique multi-generation information from the Israeli Conscripts Cohort and linking cognitive test scores to psychiatric hospitalization data on father-offspring pairs showed progressively increasing cognitive impairment across generations: Fathers of future schizophrenia patients had a cognitive impairment when they were teenagers. The cognitive impairment in the offspring was greater than that in their respective fathers when the fathers were at the same age. Low paternal IQ was associated with increasing risk for schizophrenia in the offspring. Dr. Heather Whalley will present work investigating the impact of parent-offspring deviation in cognitive ability on psychopathology in a general population sample. Prior studies have defined deviation in intelligence in reference to population norms. However, given the high heritability of intelligence, the degree of parent-offspring deviation in intelligence may provide a more personalized, possibly more sensitive, measure of the association between cognition and psychopathology. Using cognitive data from the Generation Scotland (N=23,000) study, a large community-based sample of parents and offspring, we show that that parent-offspring cognitive deviation was significantly associated with schizotypal symptoms, but not measures of mood-related symptoms. Comparisons with general cognition will also be discussed. Finally, Dr. Oliver Howes will focus on the mechanism underlying cognitive impairments in schizophrenia. He will present new multi-modal imaging PET and fMRI data of synaptic terminal density and neural activity during cognitive tasks in patients with schizophrenia across the course of the disorder from first episode to chronic schizophrenia. These data provide in vivo evidence for lower synaptic terminal density in schizophrenia, and that the normal relationship between synaptic terminal density and neural activity during cognitive processing is disrupted in schizophrenia, and that this is potentially linked to glutamate synaptic loss. This provides a potential mechanism to explain cognitive impairments in schizophrenia. The four presentations of this symposium will offer new insights into the neurocognitive impairment in schizophrenia, and an up-to-date summary of what we know and need to know. Discussant Dr. David Glahn will summarize the findings for the audience and highlight future directions.

The legal status of cannabis is changing in many countries with resultant increase in the use and potency of cannabis. Although most users enjoy their use and come to no harm, a minority develop dependence or psychiatric disorders. The evidence that cannabis use is a contributory cause of psychosis is now incontrovertible. However, it is not clear just how important cannabis use is in contributing to psychosis, and whether it is sufficient to have an impact on the incidence and nature of psychosis. This symposium will address these questions. Dr Joni Lee Pow will present results from the INTREPID II study. Variation in the incidence of psychosis, and the extent of cannabis exposure, was examined across India, Trinidad and Nigeria. The incidence was higher in Trinidad, as was cannabis use. One hypothesis is that more frequent use of cannabis may be contributing to a) higher rates of psychotic disorder in the Trinidad sample, b) higher rates amongst males compared to females in Trinidad and c) higher rates amongst  Afro-Trinidadians compared to Indo Trinidadians. Higher cannabis exposure may also explain variation in the presence of affective symptomatology and age of onset of psychosis between and within sites. Dr Diego Quattrone will present results from a unique study in which the incidence of schizophrenia, was tracked from the 1964 to 2012 in South-East London. Findings show a threefold rise in the incidence of schizophrenia with the increase particularly marked in latter years. Over the same time, the proportion of patients reported to be smoking cannabis rose from 5% to over 50% with use of high potency cannabis especially common in the latter years. Dr Carsten Hjorthøj will synthesize a range of studies, utilizing the unselected nationwide Danish registers to show how the incidence of cannabis-induced psychosis has increased over time, and so contemporaneously has the incidence of schizophrenia with comorbid cannabis use disorder. This presentation will demonstrate that cannabis-induced psychosis has important implications for the understanding of the association between cannabis and schizophrenia, possibly reflecting a cannabis-related subtype of schizophrenia. Sir Robin Murray will present data from a Canadian-based study with Dr Russ Callaghan examining the associations between recreational cannabis legalization (October 17, 2018) and weekly emergency department (ED) presentation counts of cannabis-induced psychosis and schizophrenia and related conditions where presentations for cannabis-induced psychosis doubled between April 2015 and December 2019. Evidence from the above-mentioned countries show the relationship between cannabis use and the frequency of various psychotic disorders. Cannabis is an important modifiable risk factor for schizophrenia. Reduction in use and potency would have population-level benefits in terms of greatly reduced incidence of schizophrenia. Current trends towards increased use suggest a likely further increase in incidence.

Childhood trauma (CT) experiences such as severe forms of abuse and neglect are associated with a psychotic disorder. However, the impact of CT does not stop at the level of the risk of developing the condition but is also associated with a variety of harmful clinical (depressive, negative, and positive symptoms of psychosis), neurocognitive and functional outcomes. However, the mechanism and moderating factors linking CT to such outcomes are poorly understood. Furthermore, although a variety of psychopathological mechanisms have been suggested as possible mediators between CT and psychosis (including dissociation, mood related symptoms of negative biases about the self and the world), little is known about potential nonclinical mediators, such a cannabis use, that can be targeted via therapeutic interventions, thus potentially reduce the harmful effects of CT. In the current symposia novel data from large epidemiological studies and meta-analyses will be presented exploring the relationship between CT and a variety of symptoms dimensions in psychosis, cognitive deficits, and functional outcomes. In addition, new insights into how cannabis use can mediate the effect of CT on psychosis will be presented. Possible mechanisms and potential therapeutic interventions will be discussed. The first speaker will explore the interplay between CT and schizophrenia-polygenic risk on the psychopathological profile of people with a first-episode psychosis (FEP) from the EU-GEI study consisting of 384 patients. The second speaker will present new meta-analytical data from 41 studies, comprised of 1,1403 people with psychosis demonstrating an association between CT and functional outcomes at different stages of the disease, and secondly, novel data on neurocognitive and social cognition as putative mediating factors between CT and poorer function over time. The third speaker with further explore the question of the link between CT, examining the differential effect of childhood abuse or neglect, and educational attainment and Intellectual Quotient (IQ), in a sample of 829 patients with a first-episode of psychosis (FEP) and 1,283 community controls from 16 EU-GEI The last speaker will talk about how cannabis use, in various forms and at different times, can mediate the link between various CT experiences and psychosis. This question will be addressed in a sample of 853 patients with a first-episode psychosis (FEP) and 1,174 controls as part of the EU-GEI study.

Exposure to early-life insults is an important environmental risk factor for psychiatric and neurological disorders with neurodevelopmental components, such as schizophrenia and autism. When occurring during sensitive periods of brain development, environmental stressors have the potential to change the offspring’s neurodevelopmental trajectories and increase the risk to develop psychiatric and neurological disorders later in life. Despite the increasing evidence from both clinical and preclinical research for significant health consequences of early-life insults, it is important to note that the long-term outcomes are variable and heterogenous. The underlying developmental factors that are determining vulnerability or resilience, however, remain largely unknown. Yet, a further understanding of the developmental trajectories and molecular underpinnings that determine vulnerability and resilience is of critical importance for the development of alternative, more targeted treatment and preventive approaches, as demanded for personalized medicine. Against this background, our multidisciplinary symposium will bring together the expertise of key opinion leaders working on distinct aspects in this area of research and comprise novel findings from animal models and clinical cohorts across different early-life insults: Prof. Anthony Grace (University of Pittsburgh) will discuss how early life stress affects susceptibility to major psychiatric disorders in rat models, that is dependent on the timing of stress. Specifically, lesions of the prelimbic PFC, which regulates stress responses, makes rats more vulnerable for schizophrenia, depression and anxiety as adults. Stress administered prepubertally causes a precocious maturation of the amygdala-prelimbic PFC projection. He discusses how preadolescent stress-induced precocious maturation of amygdala-PFC plasticity is enabling early adaptation to stress with the consequence of increased vulnerability to pathology in adults. Dr. Ulrike Weber-Stadlbauer (University of Zurich) will present data on vulnerability towards maternal immune activation in isogenic mice and show how adult offspring can be stratified into resilient and susceptible subgroups based on behavioral, molecular or neuroanatomical signatures. She will also discuss that an early-onset of behavioral deficits can predict the dissociation into resilience and susceptibility in adulthood, with potential implications for preventive treatment approaches. Prof. Marco A. Riva (University of Milan) will show how exposure to prenatal stress in rodents produces short and long-lasting changes on brain function. He will specifically focus on adolescence as a critical time window for the manifestation of a fully blown phenotype, but also for developing new approaches aimed at minimizing the pathologic consequences of early in life stress exposure. Dr. Annamaria Cattaneo (IRCCS Fatebenefratelli Institute, University of Milan) will show biological blood transcriptomic signatures mapping patients with schizophrenia and with a childhood trauma history and the role of miRNAs in mediating the effect of early stress on the underlying biology. Together with the discussant (Tertia Purves-Tyson, Neuroscience Research Australia), the expert panel of speakers will discuss how these findings can advance the understanding of mechanisms involved in vulnerability towards early-life insults and the potential towards the identification of novel, more targeted strategies for preventive and therapeutic interventions.

Historically, a diagnosis of schizophrenia was perceived as a severe chronic disease with progressive worsening. Fortunately, the WHO multicentre studies initiated in the late 1960’s has made it clear that people with schizophrenia can experience symptomatic improvements and regain a degree of social and occupational functioning. Because of this, it is now widely recognized that psychotic disorders are heterogenous with diverse clinical presentation and prognosis. However, the WHO lead studies included individuals from the pre-neuroleptic era with various stages of illness and large differences in health care systems. It is therefore questionable to what degree these investigations can be used to draw conclusion regarding the treatment outcomes of patients today. Over the past two decades early specialised interventions have been proven effective on short-term outcomes in patients after a first episode psychosis. Still, there is a lack of knowledge on the longterm outcomes among patients treated in modern mental health services. In addition, few studies from large representative cohorts have been able to conduct longitudinal analyses of outcomes. This symposium will give a unique opportunity to gain new knowledge on the longitudinal treatment outcomes in the later stages of illness when patients are entering mid- to late- adulthood. We will present data on illness outcomes including physical health and mortality among patients treated in modern mental health services from different parts of the world. We will reflect on treatment standards twenty years ago and examine the clinical symptoms as well as functional outcomes into the second and third decades of illness. Furthermore, due to the diverse cultural setting of the symposium panelists we have the opportunity to discuss transcultural differences and sociocultural influences on the treatment outcomes of schizophrenia on a global scale. Prof. Merete Nordentoft is the cofounder of the OPUS trial and has supervised the reassessment of the OPUS cohort through 20 years and she will be chairing this symposium together with Co-chair Dr. Marie Starzer. Dr Thara Rangaswamy will present interesting findings from her 35 year follow up of 90 FEP patients in Chennai , India. This will include cultural factors such as marriage, employment etc. New data from a Danish 20-year follow-up of a large FEP cohort of 578 persons, a part of the OPUS Trial, will be presented and discussed by Dr. Helene Gjervig Hansen The EPICC study has longitudinal data on 723 FEP persons in Australia over 20 years and Prof. Sue Cotton will among others discuss findings on physical health and mortality. Dr Eric Chen who has been leading the development of the Early Detection and Intervention Services (EASY) in Hong Kong since 2001 will present data from their work on long-term outcomes in a modern Chinese setting. Dr. Katherine Jonas who has been working on the Suffolk County Mental Health Project from USA has conducted assessments of a cohort with psychotic disorders for over 20 years will lead the discussion on changing patterns in the course and outcome of schizophrenia.

There has been extensive research over the past two decades on psychosis prediction. This is important because successful prediction of psychosis opens up the possibility of psychosis prevention. Prediction research to date has largely focused on symptomatic risk for psychosis, based on the presence of subclinical psychotic symptoms or full-threshold but brief psychotic symptoms. Structured interviews, including the Comprehensive Assessment of At Risk Mental States (CAARMS) and Structured Interview for Psychosis Risk Syndromes (SIPS) have been developed to help identify individuals with an increased psychosis risk, termed an At Risk Mental State (also called Clinical/Ultra High Risk). A major challenge for the field is that recent research has suggested that the At Risk Mental State approach identifies only a small proportion of the total number of individuals at risk of psychosis in the population. Additional approaches to identifying individuals at risk of psychosis are needed to complement the At Risk Mental State approach if we are to realise the potential of psychosis prediction and, ultimately, psychosis prevention. This symposium will explore new approaches to identifying psychosis risk. As opposed to the Clinical/Ultra High Risk focus on identifying symptoms that indicate elevated psychosis risk, this symposium will focus on identifying systems that indicate elevated psychosis risk. This symposium will explore four different “systems” associated with psychosis risk and look at how we can leverage the risk that is naturally concentrated in these systems to help identify more young people at risk of psychosis. Dr Kelleher will discuss inpatient admissions to Child and Adolescent Mental Health (CAMHS) units as a high risk system for psychosis. Looking at a total birth cohort born in 1987, they found that, of all individuals who had been admitted to a CAMHS inpatient unit during childhood, 20% were diagnosed with a psychotic disorder by age 28 years. The median time to diagnosis of psychosis in this cohort from the time of initial inpatient admission was more than 6 years, highlighting a large window of opportunity for preventive interventions. Dr Kääriälä will discuss “out of home care” (being placed in the care of the State) as a risk system for early onset (<18 years old) psychosis and bipolar disorder. Looking at 3,254 young people placed in out of home care, they found that more than 5% of this group were diagnosed with an early onset psychotic or bipolar disorder by age 18 years (RR for diagnosis: 12.8, 95%CI 10.5–15.5). What is more, children in out of home care accounted for >40% of all psychosis and bipolar disorder diagnoses up to age 18 years. Ms Lång will discuss non-normative school progress (failing to progress to upper secondary school with same age peers) as a risk system for psychosis. They found that this group had more than double the risk of psychosis and bipolar disorder of peers who had typical school progression over a 10-year follow up. Dr Bolhuis will discuss hospital Emergency Departments as a risk system for psychosis, bipolar, and depressive disorders – specifically, Emergency Department presentations for self-harm. In a large Swedish population sample, they found that 50% of individuals who had presented to the Emergency Department with self-harm went on to ultimately receive a diagnosis of psychosis, bipolar disorder or major depressive disorder in secondary/specialist mental health services. Dr Jalbrzikowski will summarise the key findings and discuss how a “High Risk Systems” approach might play an important role in the early detection and prediction of psychosis and other serious mental illness in the future.

The complement pathway is implicated in schizophrenia by a strong genetic association involving the complement component 4 (C4) gene, postmortem evidence of dysregulated C4 RNA expression in schizophrenia, and blood studies. These latter studies have demonstrated dysregulated complement proteins preceding first reports of psychotic experiences, in association with transition from the clinical high risk (CHR) to psychotic disorder (PD), and in association with first episode psychosis and antipsychotic drug response. Several studies analyzing complement pathway-specific activity have indicated increased complement activation in schizophrenia patients, although not all studies have yielded consistent findings. In animal models, overexpression of C4A revealed reduced cortical synapse density, increased microglial engulfment of synapses, as well as behavior. These findings are consistent with evidence for altered synaptic regulation in schizophrenia and may provide a mechanism whereby complement pathway dysregulation impacts on synaptic and brain function leading to schizophrenia. Modulation of the complement pathway may offer novel therapeutic opportunities both in schizophrenia and among those in the CHR. Recent evidence suggests that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) contribute to the regulation of complement pathway. In the current symposium we bring together speakers for the first time who will address the potential roles of the complement pathway in schizophrenia from these different perspectives. Cynthia Shannon Weickert studied cortical complement RNA and protein in the developing human prefrontal cortex from 2 months to 25 years and showed that activation of the complement cascade occurs between 1 and 5 years but that in the adolescent brain complement activators are low, and inhibitors are high. Based on this she hypothesizes that an upregulation of C4 associated with the C4 CNV could lead to increased complement activity in the adolescent brain when reduced activity is the normal. Sophie Laye focusses on synaptic function and plasticity and how omega-3 polyunsaturated fatty acids (PUFAs) impacts on this through complement function. Using an animal model she shows that early life n-3 PUFA deficiency leads to enhanced microglial mediated phagocytosis of synapses and demonstrates that this effect is mediated by the complement system. David Mongan presents data which demonstrates dysregulated plasma complement pathway proteins at age 11 preceding later psychotic experiences and among those in the CHR who transition to PD. He also presents showing that raised n-3 PUFAs in childhood reduces risk of later PD and proposes that modulation of synaptic pruning by n-3 PUFAs may underpin this relationship. Emily Severance discusses how many known risk factors for schizophrenia, including inflammatory conditions, act as triggers for complement activation. In studies of an animal model of inflammatory bowel disease she demonstrates increases in many complement components in the blood, and in schizophrenia demonstrates that C4 levels are increased among subjects exposed to pathogens. She concludes that the complement system unites multiple risk factors for schizophrenia and that screening tools involving the complement pathway should be considered among those at risk of psychotic illness. Oliver Schubert, discussant, will bring these strands together. Overall our symposium explores the relationship of complement pathway to psychosis risk and the mechanisms, involving synaptic pruning, by which the pathway may mediate its effects. Potential therapeutic and preventative effects of the modulation of the complement pathway in schizophrenia will be discussed.

While epidemiological evidence consistently support a causal association between heavy cannabis use and psychosis phenotypes, recent genetic studies have disputed the direction and the causal nature of this association. The recent large Genome-Wide Association Studies (GWAS) of cannabis initiation, cannabis use disorder and schizophrenia have allowed to explore the genetic overlap between these phenotypes. Polygenic risk scores for schizophrenia (SZ PRS) seem to explain a small, but significant, proportion of the variance in cannabis use initiation and in CUD but Mendelian Randomisation studies have yet failed to clarify the direction of causality between cannabis use and schizophrenia. Indeed, many questions remain unanswered about the impact of cannabis use on mental health. The work we propose to present combines the analyses of genetic, cognitive, behavioural and physiological data to add important and novel evidence to the effect of cannabis use on mental health and beyond. Dr Isabelle Austin-Zimmer will start presenting data from the EUGEI multisite study and from the UKBiobank. Using the data available from the latest Schizophrenia Psychiatric Genomic Consortium her work aims to investigate a) the role of SZ PRS in predicting cannabis use and pattern of use in a European general population sample and replicate it in the UKBiobank b) the combined and independent effect of SZ PRS and heavy cannabis use on risk for psychotic disorder in both dataset. These analyses will be carried out using the latest bioinformatic tools to allow the inclusion of participants from diverse ethnic background, to produce results that represent the diversity of the world population. Dr Laura Ferraro, using a two-step Cluster Analysis of the premorbid adjustment and current IQ data available in the EUGEI study, will show three main patterns of changes in cognitive function. Participants with first episode psychosis (FEP), who present with a deteriorating pattern before psychosis onset, have the lowest SZ PRS but they are more likely to have started using cannabis in early adolescence and to have used high potency types. This novel findings suggest that in some individuals the cognitive deterioration observed before psychosis onset, is not pre-determined by SCZ genes but could be prevented informing about the risk of early and high potency cannabis use. Dr Paolo Marino will present novel data from a comprehensive systematic review on the association of violent events with cannabis use. This study aims to expand our understanding of the impact that cannabis use has on society beyond its association with risk of psychosis. Indeed, the combined pooled effect showed a doubling in the probability of being an offender in cannabis user from the general population and even greater among cannabis users with a psychiatric disorder. Cannabis use was also associated, to a lesser extent, with an increased probability of being a victim of violence. Professor Cyril D’Souza will conclude with a unique longitudinal behavioural, cognitive and electro-physiological characterization of patients with FEP with exposure to cannabis compared to FEP with no cannabis exposure. These novel findings will contribute to understand the biological mechanism and changes that underlie the effect of cannabis use on risk of psychosis and beyond. Thus, at a time when cannabis is becoming legal in many countries across the world, the work we propose to present can further support the importance of public education programs that inform about the wider impact of cannabis use at an individual and societal level.

The experience of ‘felt presence’ (FP) in the absence of clear perceptual evidence has been described as a complex multimodal sensory experience that is both transdiagnostic and exists along a non-clinical and clinical continuum. FP occurs during periods of isolation, exposure to extreme elements, sleep paralysis, bereavement, religious experiences, anxiety, and psychosis. This symposium will unpack the multidimensional construct of FP within phenomenological, neurocognitive, social, and philosophical frameworks. Dr. Alderson-Day will present on two studies from Durham University’s Hearing the Voice project. First, a phenomenological survey of people experiencing early psychosis which showed a case rate of 52% for FP. Second, a comparison of FP across three online surveys, featuring the general population; people from spiritual groups; and people who engage in solo/endurance sports. These show that while FP overlaps with other hallucinations, it can occur as standalone hallucinatory experience. Many accounts of FP involve a distinct identity, sense of familiarity, and occurring on multiple occasions. Survey data shows that FP frequency is consistently associated with general hallucination-proneness but not dissociation or social imagery. These findings highlight a common thread to FP experiences across diverse samples and contexts, with implications for clinical practice. Dr. Rosen examined the interrelatedness of FP, self-disturbances (SD), and increased paranormal or magical ideation, mysticism, absorption, and enhanced imagery known as transliminality (TL). She also examined changes in sensory (visual, tactile, auditory, and olfactory) and perceptual experiences (sense of time, space, self-consciousness) during FP. Given that psychosis is associated with anomalous self-other processing and heightened absorption – implicating immersion in mental imagery– it is important to elucidate individual differences between FP, SD, and TL. Association and Network Analysis results show that as TL increased, all aspect of FP (frequency, distress, vividness) and SD increased. There were similar parallels between FP, increased TL, SD, and changes in the metaphysical construct of being, knowing, time, and space. Dr. Park examined two distinct types of bodily self-disturbance– felt presence (FP) and out-of-body experiences (OBE)– in relation to psychosis-risk, social isolation and resilience in the general population. FP and OBE involve spatial body imagery associated with the temporoparietal cortex, but differ with respect to the perceived self-location and the social context of the experience. Anxiety and stress were elevated in the FP and OBE groups but not depression. While the OBE group reported elevated trauma and lower resilience, the FP group reported increased spirituality. Co-occurrence of FP and OBE significantly increased psychosis-risk, but FP and OBE differentially shaped the key aspects of self-disturbances that may contribute to schizophrenia. Dr. Barnby will present on how generalised prior knowledge about social partners serves as a starting point for beliefs about others, and the unresolved question of whether we use similar mechanisms when interpreting FP as one generically learns about others. He examined formal mechanisms used to learn about social partners in the absence of immediate evidence, and how a frequent corollary of unusual experiences in clinical populations – paranoia – may bias this process. He will also present parallel work suggesting a common computational mechanism that ties together how we learn about others and learn about FP experiences.

The development of psychosis is complex. Psychotic disorders develop gradually over time with expressions of psychosis already present before onset of clinical illness. Psychotic experiences are subclinical experiences of psychotic symptoms such as hallucinations and delusions that can exist outside the context of a clinical disorder. When distressing or persistent, psychotic experiences index an increased risk for later psychotic disorder. Better understanding of the nature of such psychotic experiences, as well as of factors that increase the risk of persistence of such experiences, is crucial in developing better and timely interventions for psychosis. As psychotic disorders often emerge in young adulthood, this research is especially relevant in young people. The four presentations in the current symposium examine risk factors and the potential clinical impact of early psychosis expression in young people in different contexts. Dr. Koen Bolhuis will present data from the Generation R study encompassing of 3068 mother-offspring dyads. He found that maternal history of childhood adversity increases the risk of psychotic experiences in offspring through offspring exposure to childhood adversity. In other words, intergenerational transmission of adverse life events influences the etiology of psychosis vulnerability. This study highlights the need for a broad take on risk factors for psychotic symptoms by showing the importance of a familial-based approach. Dr. Salma Khaled will present results from her study on the relationship between stress reactivity and psychotic experiences, insomnia and depression-anxiety symptoms in a non-clinical sample of students in Qatar. She found direct associations between insomnia and depression-anxiety with psychotic experiences, but no direct association between psychotic experiences and perceived social stress. Possibly, social stress shares common pathways with psychotic experiences that are predominantly emotion-based. These results can have important implications for early detection and prevention of severe mental illness in non-clinical individuals in Qatar. Dr. Martin K. Rimvall will present secondary analyses from the Mind My Mind (MMM), a randomized controlled trial of a transdiagnostic cognitive behavioral therapy intervention encompassing 396 youths aged 6-17 years. The intervention was found effective in reducing the impact of common mental health problems. Results from the secondary analyses regarding psychotic experiences show that psychotic experiences at baseline did not moderate the positive effects of the treatment, providing evidence that psychotherapeutic interventions should be offered to help seeking youths, irrespective of the co-occurrence of psychotic experiences. Sara van der Tuin, PhD candidate, will present her work on dynamics between transdiagnostic symptoms in individuals in early clinical stages for psychosis from the Mapping Individual Routes of Risk and Resilience (Mirorr) study. She examined whether certain symptom dynamics are clinical stage specific (top-down) and, whether certain symptom dynamics can meaningfully cluster individuals (bottom-up). Theory-based subgroups distinguish between individuals based on psychotic severity while data-driven subgroups distinguish individuals based on overall psychopathological severity. The symposium will be chaired by Sara van der Tuin and co-chaired by dr. Johanna Wigman. Dr. Ian Kelleher will be discussant. Both Dr. Wigman and Dr. Kelleher are well-established researchers in the field of early psychosis.

The clinical high-risk (CHR-P) paradigm introduced more than 20 years ago has significantly advanced the understanding of emerging psychosis as well as provided a blueprint for pre-emptive psychiatry. Despite these facts, significant challenges in the field remain, one of which is that only a minority of patients who develop a first-episode of psychosis (FEP) are detected in specialised CHR-P clinics. This is because CHR-P criteria need to be established through semi-structured interviews administered by trained personnel in help-seeking populations. Accordingly, it is important to develop novel ways of identifying individuals who are at risk of psychosis but who are currently not detected within established clinical pathways. In the proposed symposium, we provide an overview of recent findings regarding the relevance of CHR-P pathways before a FEP as well as novel approaches for the detection of CHR-P participants. First, J. Shah (McGill University, Canada) will describe retrospective work in a catchment-based FEP population suggesting that only a minority of individuals seeking help for a FEP did not pass through an identifiable CHR-P phase. The distinction between these different psychopathologic pathways is important because the former (CHR-P) appears to have longer durations of untreated psychosis, poorer symptomatic and functional outcomes, and more emergency department visits and hospitalizations during the recommended two-years of FEP treatment. Second, P. Uhlhaas (University of Glasgow/Charite, Berlin, UK/Germany) will introduce an online screening platform for the detection of individuals meeting CHR-criteria in the community. Participants were invited via email, flyers, and posters to visit a website and n = 3500 completed the 16-item version of the prodromal questionnaire (PQ-16) and 9-item questionnaire for basic symptoms. Overall, 180 CHR-participants and 25 cases of FEP were detected. Receiver operating characteristic curve analysis revealed good to moderate sensitivity and specificity for predicting CHR-P status as assessed through clinical interviews (CAARMs, SPI-A) from online results. Third, S. Sullivan (University of Bristol, UK) will report on the development and validation of a risk prediction algorithm using linked primary care routine NHS consultation data. The risk prediction model development is based on 12 prodromal symptoms, age, gender and consultation frequency both overall and per symptom. Model development and internal validation will be carried out on a routine dataset of 300,000 primary care patients consulting for a non-psychotic mental health problem. External validation will be carried out in a separate UK primary care routine dataset. P. Fusar-Poli (King’s College, UK) will introduce an automated, transdiagnostic, and clinically-based individualised risk calculator that provides a powerful tool for supporting the early detection of CHR-individuals at scale by leveraging Electronic Health Records (EHRs). This risk calculator has been externally validated twice and is undergoing pilot testing for clinical implementation. Here, we present an approach for a prospective implementation of a real-time psychosis risk detection and alerting service in a real-world EHR system. This method leverages the CogStack platform which is an open-source, lightweight, and distributed information retrieval and text extraction system. This is the first ever study which has developed and implemented a similar detection and alerting system in clinical routine. The findings and their implications will be synthesized and critically appraised by the discussant, Prof A. Yung (University of Melbourne).

The rates of functional recovery from psychotic illness remains poor despite the provision of the state-of-art early interventions. Existing treatments predominantly focus on reducing delusions and hallucinations. Antipsychotics indeed reduce acute communication disturbances arising from thought/language disorder but have minimal effect on persistent language disturbances in psychosis. Paradoxically, persistent features such as negative symptoms, language disturbances and cognitive deficits that predict poor prognostic outcomes are made worse with existing therapies. Clinical trials focus on measuring only those symptoms that are likely to change; thus thought/language disorder has been a neglected area of therapeutic need. This is further compounded by the difficulties in recruiting a subject with language disturbances for interventional trials including psychotherapies, diminishing our ability to empirically evaluate the treatment effects on these core features of psychosis. We need to select and validate treatment targets in the thought/language domain, facilitate inclusion of patients with language deficits in ongoing trials and develop focussed remediation approaches to reduce key linguistic deficits that affect functional outcomes. We approach this by directly examining the effects of focussed neurochemical manipulations involving dopamine (antipsychotics/methamphetamine), serotonin (psychedelics/MDMA), neuropeptides (oxytocin) and glutamate (ketamine) on speech. • Drs. Sommer & de Boer highlight how dopaminergic treatments alter our utterances in a profound manner that enables us to identify the prescribed class of medications. This work focusses on the receptor-level specificity of linguistic readouts in schizophrenia and exposes the unmet therapeutic need in this area. • Using an extensive multi-domain linguistic analysis in healthy adults under acute pharmacological perturbations, Dr. Bedi will report that the serotonergic enhancement (MDMA) increases, but dopaminergic enhancement (methamphetamine) reduces prosocial concepts. Oxytocin, on the other hand, had effects limited to affect-related acoustic features. • Continuing with this ‘perturb-and-measure’ approach, Dr. Tagliazucchi will present the effects of 75mcg of intravenous LSD on speech markers. With its verbosity-enhancing but incoherence-inducing effects, the psychedelic LSD produces a mania-like effect on speech. • Drs. Stein & Kircher will discuss ketamine-related glutamatergic effects and present a network-level systems model of thought disorder. The insights from their transdiagnostic sample of >1000 patients will form the foundation for discussing the next priorities in the field. Dr. Corcoran will synthesize these neurochemical and circuit-level findings to discuss the utility of this knowledge for clinical trials. The overall goal of this symposium is to present key observations that generate tenable hypothesis for therapeutic progress in this area of unmet need.

The association between social disadvantage and psychosis has been identified across diverse cultural, social, and demographic contexts. Within this symposium, we will bring together data across the globe to illustrate disparities in health care and outcomes for underserved populations. We wish to demonstrate that these inequalities and complex contextual factors not only affect the individual’s predisposition for developing psychosis, but may also serve to drive enduring impairment. We make the case for change, and for services to adapt to the needs of these individuals whose illness is contextualised within disadvantaged social settings. First, data from an Australian ultra-high risk for psychosis (UHR) cohort (N=461) study will present evidence supporting a causal link between neighbourhood deprivation and identification of UHR individuals and transition to psychosis. The findings will provide support that Early Intervention Services (EIS) should be funded as per the expected incidence of psychotic disorders. Second, longitudinal cohort data from Swedish registers of 1.5m people living in Stockholm will provide evidence of an effect modification of parental region-of-origin on social capital and psychosis risk. Neighbourhood levels of personal trust – a form of bonding social capital – appears protective for those of Swedish and European descent but serves to increase risk for those of African and Middle Eastern and Sub-Saharan African descent. These patterns reveal the highly context-dependent nature of designing area-level intervention strategies to improve psychosis outcomes, and potentially unintended public health consequences. Next, long term recovery outcomes from a large UK EIS cohort (N=1027) of young people with first episode psychosis (FEP) will be presented. Here, we present evidence of disparities in a range of recovery outcomes for individuals with ethnic minority status at two years following discharge from EI services. Despite receiving gold standard EIS care, individuals of Black and Asian heritage showed less improvement in their long term social and clinical recovery, compared to their white counterparts. Social deprivation also contributed to the disparities in recovery outcomes. These findings highlight the need for improved service provision and targeted care to mitigate the effects of social deprivation on ethnic minority individuals following FEP. Finally, the concluding talk will provide a qualitative exploration of help seeking events prior to the receipt of early psychosis services, and barriers and facilitators to specialized services for psychosis in the U.S. Difficult and negative experiences on the path to specialized services can lead to extended duration of untreated psychosis and lack of engagement among service users and their families. Improving experiences and interactions with formal and informal sources within the community is imperative to reducing racial inequities in mental health. The findings presented here have the potential to provide much needed support on the pathway to and step down from specialized services for those from ethnically diverse backgrounds

The importance of philosophy for the future of psychiatry is unquestionable. Today, more than ever before, conceptual, philosophical and ethical questions are at the forefront of schizophrenia and psychosis research: What is psychosis? What is it like to be in the midst of a delusion? Do delusions have and give meaning? How does the social and environment context shape the experience of schizophrenia? A phenomenological approach that returns to the lived experience of the person with psychosis may suggest new ways to approach these fundamental questions, while also redressing power imbalances through the integration of different and equally valuable perspectives. As phenomenology leads psychiatry off the beaten track, this symposium engages with novel interdisciplinary work that emphasises rich and in-depth understandings of individual patients with psychosis and their worlds. The first presentation introduces a recent development in the field of phenomenological psychiatry: the integration of phenomenology and qualitative methods. The primary aim of this presentation is to introduce this methodological trend to provide the audience with helpful background for the following three presentations. The second presentation offers an example of a successful application of phenomenological approaches to the study of the lived experience of delusions in patients with a schizophrenia-spectrum diagnosis (Feyaerts et al., 2021). Implications of these phenomenological findings for psychosis research are far-reaching: they may shed light on current diagnostic discussions on the categorical or dimensional character of psychotic disorders, enliven current explanatory models of delusions, and inform the development of new person-centred therapeutic approaches. The third presentation draws on the results of the first systematic review of qualitative studies concerning the experience and meaning of delusions in psychosis (Ritunnano et al., in-progress). Rich and nuanced phenomenological data are discussed with a focus on three novel and yet unexplored dimensions of delusional experience: agency and selfhood, lived world and intersubjectivity, and meaning-making processes. These findings may not only assist with nosological and patho-aetiological issues but may also help redress power imbalances through the integration of different and equally valuable perspectives. In the fourth and final presentation, arguments for a contextual approach to the phenomenological and epidemiological investigation of schizophrenia are put forward, opening up new avenues for cross-disciplinary engagement. Several suggestions for modifying popular qualitative methods are discussed, which allow to expand the scope of phenomenological and epidemiological research and integrate extra-disciplinary findings. As schizophrenia is repositioned in the world, rather than within the narrow boundaries of the self, the contribution of social stigma and systemic discrimination to symptom development become clearer, with important implications for explanatory models of mental disorders.

MMPs are a group of extracellular acting zinc-dependent proteases that are essential regulators of extracellular matrix, neuronal growth and plasticity. Specifically, they can remodel and control perineuronal nets (PNNs), the areas of condense extracellular matrix enveloping several specific subgroups of neurons, most notably parvalbumin interneurons (PVIs). MMP-9 is the largest, most complex, and best described MMP in the central nervous system. MMP-9 is expressed in the brain mostly in the hippocampus, choroid plexus (ChP), and the prefrontal cortex (PFC), and besides its role in neuronal growth and plasticity (through modulation of PNNs), it also plays a pivotal role in modulating central inflammatory response. Because of its role in PVI development, relationship with PNNs, and involvement in neuroinflammation, MMP-9 has recently attracted the attention of schizophrenia researchers. This symposium cuts across the disciplines of systems neuroscience, cellular and molecular neurobiology, clinical psychiatry and neuroimaging, to explore the mechanisms, in which MMP-9 is involved in the emergence of psychotic symptoms in schizophrenia. The first of our four presenters, Dr. Leszek Kaczmarek, Head of the Laboratory of Neurobiology, Nencki Institute, Warsaw, will introduce the MMP-9 function, its brain expression and its role in synaptic plasticity. His talk will also cover the newest developments in MMP-9 gene polymorphisms in schizophrenia. This talk will be followed by Dr. Wilson Woo, a founding Director of Laboratory of Cellular Neuropathology at McLean Hospital, Harvard Medical School, who will present his recent findings regarding MMP-9 gene expression, cellular and enzymatic activity in postmortem schizophrenia brain tissue, blood and CSF. These two talks from senior researchers will set up the stage for the last two presentations, given by talented, junior faculty members. First of those talks will be given by Dr. Johanna Seitz-Holland, Psychiatry Resident at Ludwig-Maximilians-University Munich Clinic for Psychiatry and Psychotherapy, and an Instructor at Psychiatry Neuroimaging Laboratory, Harvard Medical School, and will focus on the evidence of neuroimaging correlates of peripheral MMP-9 upregulation in schizophrenia. The last talk will be given by Dr. Daniella Dwir, Research Associate at the Center for Psychiatric Neuroscience, Department of Psychiatry Lausanne University Hospital. Daniella will present results of her translational research in animals and patients with schizophrenia investigating RAGE/MMP-9 neuroinflammation-redox mechanistic model, in the context of clinical and cognitive deficits. These presentations will be followed by an in-depth discussion (led by Dr. Daniel Umbricht, Associate Professor at University of Zurich and Distinguished Scientist at Roche) on the role of MMP-9 in psychosis psychopathology, its potential as diagnostic biomarker and treatment target. Altogether, this symposium is expected to stimulate discussions on the possible mechanistic basis of schizophrenia onset and thereby rational, neurobiologically-inspired, evidence-based treatment, early intervention and prevention approaches.

Psychotic disorders have a chronic intermittent course, with frequent and disabling relapses. Therapeutic interventions are often provided too late to change the course of this illness. Clinical symptom rating-scales have poor objectivity; their repeated use poses a high resource burden, they are often intrusive for patients and impractical for predicting therapeutic needs. We urgently need reproducible markers to track the illness course and enable wider implementation of early intervention at every stage of psychosis. The form and content of speech provide the primary diagnostic and prognostic information for psychosis. Our speech tracks our mental state; it remains the most accessible, remotely generated, inexpensively acquired, objectively recorded, and automatically analyzed digital health marker. Recently, several groups have reported clinically relevant predictive signals using computational linguistics in psychosis. There is an acute need for clinically validated, multilingual, repeated, patient-generated speech data in psychosis for large-scale sustainable deployment of speech in digital healthcare. Harmonizing acquisition is a critical step towards assembling such corpora. Recently we convened DISCOURSE in psychosis (https://discourseinpsychosis.org), a global network of interdisciplinary researchers focused on developing collaborative solutions to study the mechanisms underlying thought, language, and communication disturbances in psychosis. Our group currently includes 103 members from 28 sites and anticipates creating the first Psychosis Speechbank. We will build a shared corpus with linguistic, cultural, and socioeconomic diversity for communal usage from patients worldwide. We will provide an open data source for measurement comparisons, psycholinguistic applications, human/computer training, and sociological applications. This symposium proposal brings together four presenters from DISCOURSE, from 4 different continents, presenting recent data advancing basic and applied clinical research of psychosis. The four presentations will provide the opportunity to discuss results in the light of sociocultural diversity. The speakers will present cutting-edge progress that brings psycholinguistics, neurolinguistics, and computational linguistics together. The discussant, Lena Palaniyappan, will synthesize the presentations and highlight how the efforts towards data harmonization can tackle the challenges identified by the speakers. We will discuss translational opportunities for clinical benefit based on comparative research strategies (trans-diagnostic and interdisciplinary). The first presentation from Maria Francisca Alonso (Chile and Canadá) will discuss longitudinal clinical and linguistic follow-up since first-episode psychosis and how semantic similarities from one-minute picture description protocol correlate with symptomatic progression of psychosis in early stages. Following, Sunny Tang (USA) will provide data on the mechanistic investigation on the linguistics association of theory of mind and emotion recognition mixing several computational approaches since structural analysis based on graph theory, parts-of-speech, lexical characteristics, and coherence. Eric Tan (Australia) will present quantitative speech variable data in schizophrenia and discuss the diagnostic and clinical utility of speech assessment. To conclude, Alberto Parola (Denmark and Italy) will discuss vocal and prosodic atypicalities in schizophrenia, with a focus on generalizability, specifically addressing the question of whether previous findings and machine learning models generalize to new samples and languages.

Our understanding of subclinical psychotic experiences in young people from the general population has increased vastly over the past two decades. Psychotic experiences contribute to predictive models of later psychopathology over and above common mental health problems and disorders and are an important clinical marker of poorer functioning later in life, as well as both psychotic and non-psychotic mental disorders. This knowledge points to psychotic experiences as a promising target for early intervention and prevention of later severe mental health problems and disorders, yet studies of interventions directed at psychotic experiences in children and adolescents are lacking. This symposium which is chaired by Mary Cannon (RCSI University of Medicine and Health Sciences, Ireland) and Martin Rimvall (Child and Adolescent Mental Health Centre, Roskilde, Denmark) aims to explore potential avenues and target populations for early intervention efforts directed at psychotic experiences. Peter Jones (University of Cambridge, UK) will present data from a scoping review of published studies on interventions for psychotic experiences in young people showing that the evidence is sparse and further work needs to be done in this area. Colm Healy (RCSI University of Medicine and Health Sciences, Dublin) will present secondary data analyses on Irish data from the Saving and Empowering Young Lives in Europe study. He examined whether three community-based primary preventative measure for suicidality could reduce psychotic experiences in youth. He presents evidence that the selective intervention (ProfScreen) - which comprised questionnaire screening by a mental health professional with referral of at-risk youths - reduced the prevalence of psychotic experiences at 12 months, whereas the gatekeeper intervention and universal intervention did not. Maja Gregersen (Mental Health Center, Copenhagen, Denmark ) will present results from the Danish High Risk and Resilience Study of children of parents with schizophrenia spectrum disorder, bipolar disorders and control children who were assessed both at age 7 and age 11. Psychotic experiences already at age 7, particularly if recurrent, increased the risk of developing mental disorders over follow-up, indicating that interventions can be targeted in early childhood. PE at age 7 predicted mental disorders non-differentially across the three groups of children. Pia Jeppesen (University of Copenhagen, Denmark) will present data from Mind My Mind; a randomized controlled trial of a transdiagnostic cognitive-behavior therapy (Mind My Mind [MMM]) compared to management as usual (MAU) directed at youths aged 6-16 years with emotional and behavioral problems. The MMM was significantly superior to MAU in a wide range of clinically relevant measures of distress and functional impairments, and the findings add to the growing evidence for transdiagnostic need-based cognitive-behavior therapy for indicated prevention of common mental health problems and disorders. Consideration of these studies led by our Discussant, Jim van Os (Utrecht University Medical Centre, The Netherlands), will advance our understanding of the need for interventions for psychotic experiences, which young people to target and what type of interventions are likely to be effective.