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2022 Congress Recordings

Keynote Session

Students with Psychosis

Presenter
Cecilia McGough 

 

Abstract

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.

Plenary Sessions

Translating New Developments in Neurobiology to Effective Intervention in Schizophrenia Research; Towards Precision Psychiatry

Presenter
Kim Do

 

Abstract

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.

Can We Improve Long-Term Outcomes of Psychotic Disorders through Early intervention?

Presenter
Eric YH Chen

 

Abstract

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.

Agency in Cultural Context: Making 'Sense' of Psychosis

Presenter
Nev Jones

 

Abstract

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.

Schizophrenia Research in Brazil — from Lemons to Caipirinha 

Presenter
Rodrigo Bressan

 

Abstract

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.

Optimal Psychosis Care for Women

Presenter
Iris Sommer

 

Abstract

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: Looking Back to Look Forward

Presenter
Nina Schooler

 

Abstract

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?

New Ways of Seeing the World - Lessons from the Study of Psychosis in Understudied Populations

Presenter
Oye Gureje

 

Abstract

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.

Workshop

Evolving Concepts of Schizophrenia: Time to Revisit Its Name?

Chair
Matcheri Keshavan

Co-Chair
Rajiv Tandon

Discussant
Rajiv Tandon

Presenters
Henry Nasrallah
Raquelle Mesholam-Gately
Jim van Os
Elyn Saks 

Abstract

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.

SIRS Early Career Award Workshop 2022: What Can We Learn From Our Rising Stars?

Chair
Susan Rossell

Co-Chair
Eric Tan

Presenters
Yulia Zaytseva 
Alessandro Pigoni
Eric Tan

Abstract

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.

SIRS Expert Classes: A Bright Future for ECRs in Schizophrenia Research

Chair
Gemma Modinos

Co-Chair
Sebastian Walther

Presenters
Robin Murray
Kim Do 
Raquel Gur 
Anthony Grace 
Cynthia Shannon Weickert 
Andreas Meyer-Lindenberg 

Abstract

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.

SIRS Workshop on Women in SCIENCE: Hurdles and Achievements

Chair
Elisabetta C. del Re

Co-Chair
Mary Cannon

Discussant
Dolores Malaspina

Moderator
Diane Gooding

Presenters
Susana Ochoa
Ana Pinheiro 
Gamze Erzin 
Jun Miyata 
Kia Crittenden-Ward 
Joanne Kenney

Abstract

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.

Symposia

Cognitive Decline in Schizophrenia: Origins, Life course, and Mechanisms

Chair
Abraham Reichenberg

Co-Chair
Katherine Jonas

Discussant
Mark Weiser

Presenters
Katherine Jonas
Abraham Reichenberg
Miruna Barbu
Oliver Howes

Abstract

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. 1 2022 Congress of the Schizophrenia International Research Society 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 Impact of Cannabis Use on the Characteristics and Incidence of Psychosis

Chair
Joni Lee Pow

Co-Chair
Robin Murray

Discussant
Mark Weiser

Presenters
Joni Lee Pow
Carsten Hjorthøj
Diego Quattrone
Robin Murray

Abstract

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 1 2022 Congress of the Schizophrenia International Research Society 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 and Psychopathological, Cognitive and Functional Outcomes in Psychosis, Exploring Potential Mechanisms

Chair
Luis Alameda

Co-Chair
Monica Aas

Discussant
Richard Bentall

Presenters
Monica Aas
Luis Alameda
Lucia Sideli
Giulia Trotta

Abstract

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 1 2022 Congress of the Schizophrenia International Research Society 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.

Vulnerability to Early-Life Insults as a Risk Factor for Psychiatric Disorders: Developmental Trajectories and Long-Term Consequences

Chair
Ulrike Weber-Stadlbauer

Co-Chair
Marco Andrea Riva

Discussant
Marco Andrea Riva

Presenters
Anthony Grace
Ulrike Weber-Stadlbauer
Marco Andrea Riva
Annamaria Cattaneo

Abstract

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 1 2022 Congress of the Schizophrenia International Research Society 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.

Worldwide Long-Term Outcomes after a First Episode Psychosis - Taking a Look at the Later Stages of Illness among Patients Treated in Modern Mental Health Services from Different Sites All over the World

Chair
Merete Nordentoft

Co-Chair
Marie Starzer

Discussant
Katherine Jonas

Presenters
Helene Gjervig Hansen
Olesya Ajnakina
Susan Cotton
Eric YH Chen

Abstract

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 1 2022 Congress of the Schizophrenia International Research Society 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.

Psychosis Prediction 2.0: Increasing Capacity for Psychosis Prevention Using a “High Risk Systems” Approach

Chair
Ian Kelleher

Co-Chair
Moriyama Tais Silveira

Discussant
Maria Jalbrzikowski

Presenters
Koen Bolhuis
Ian Kelleher
Ulla Lång
David Gyllenberg

Abstract

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 1 2022 Congress of the Schizophrenia International Research Society 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.

Complement Pathway Dysregulation in Schizophrenia; From Mechanisms to a Potential Target for Novel Therapies

Chair
David Cotter

Co-Chair
Emily Severance

Discussant
David Cotter

Presenters
Rachel Sager
Sophie Laye
David Mongan
Emily Severance

Abstract

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) 1 2022 Congress of the Schizophrenia International Research Society 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.

Cannabis and Psychosis: Where are we at? 

Chair
Marta Di Forti

Co-Chair
Isabelle Austin-Zimmerman

Discussant
Marta Di Forti

Moderator
Diane Gooding

Presenters
Isabelle Austin-Zimmerman
Laura Ferraro
Paolo Marino
Deepak D’Souza

Abstract

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 1 2022 Congress of the Schizophrenia International Research Society 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.

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