2023 Congress Recordings

y eldest brother Donald was diagnosed in 1968 with schizophrenia. I was three years old. Over the course of the next thirteen years, five of my older brothers were diagnosed on the spectrum of Serious Mental Illness. My story is that of a sibling, a victim, a survivor, and now, an advocate and thriver.

My therapeutic journey began at age 18 when I took myself to the local mental health center while in college at University of Colorado in Boulder. Thinking I was delusional, the therapist did not believe my story. Dr. Nancy Gary, a family friend of my parents and a child psychologist, introduced me to Dr. Louise Silvern, a psychology professor specializing in childhood trauma. I spent the next
25 years in her care battling chronic PTSD.

The impact on me, as an unaffected sibling, has required a lifelong unraveling. Therapy taught me to feel safe with negative feelings, to identify past emotion as part of my past. This hard work gave
me permission to have joy and gave me the tools to overcome survivor guilt. Experiencing my brothers, one after another, succumb to the terror and confusion of psychosis is traumatizing to a child. It left me with the chronic and overwhelming fear I was next. I spent my youth not expressing anger or sadness as I attributed these emotions to being “mentally ill”. I grew a mask of wishful perfection to try and hide any flaws, any cracks in my armor.

Without the guidance, expertise, compassion, and empathy from this remarkably skilled therapist, I would not have found a way out of the darkness, the ruminating, and the effects of trauma.
The resilience I developed to overcome this tremendous adversity was found in a little therapy room at the University of Colorado psychology department.

Our plenary speaker is Dr. Deidre M. Anglin, Professor of Psychology at The City College and Graduate Center, City University of New York. She will provide a critical overview of the relationship between racialized identity, sociocultural factors underlying risk for psychosis, and ethnoracial disparities in schizophrenia. Her lecture will explore how racial discrimination and related social determinants may increase the risk for psychotic experiences. Dr. Anglin examines growing evidence from multiple sources (e.g., nontreatment seeking, nationally representative, clinical high-risk, and first-episode psychosis samples) that demonstrate how social, and environmental factors may increase the risk for psychosis outcomes among ethnoracial minoritized populations. Dr. Anglin uses qualitative examples from a Photovoice study with young people with first-episode psychosis to illustrate how social and cultural isolation in neighborhoods and experiences of racial discrimination can serve as triggers for vulnerable Black youths.

From the Speaker:

While there is a documented history of over- and mis-diagnosis of schizophrenia in Black people in the U.S., there is also increasing evidence that racial discrimination and related social determinants may increase risk for psychotic experiences in Black and Latinx populations—experiences that may or may not lead to a clinical psychotic disorder, but that contribute to mental morbidity.  This lecture will provide a critical overview of the role of structural racism in shaping social determinants of psychosis risk and outcomes and ethnoracial disparities in these outcomes. In addition, this lecture examines accumulating evidence from non-treatment seeking, nationally representative, clinical high risk, and first episode psychosis samples that demonstrates aspects of the social environment are associated with increased vulnerability for psychosis outcomes among ethnoracial minoritized populations. Qualitative examples from a Photovoice study with Black young people with first episode psychosis will be used to illustrate how social and cultural isolation in neighborhoods and racial discriminatory experiences can be triggering for vulnerable youth. Community and family supports identified through this study and suggestions for enhancing coordinated specialty care services for Black youth will also be highlighted.

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In almost all societies, persons with enduring severe mental health problems are particularly subject to discrimination and social exclusion. The adoption of the United Nations Convention on Rights of Persons with Disabilities (CRPD) in 2006 has created a paradigm shift in our approach to addressing this problem from seeing such persons as objects of charity to holders of rights, as passive recipients of care to active partners in managing their lives. While the CRPD ensrhines a number of existing rights into international law, the challenge is to ensure the realization of these rights for persons with enduring and severe mental illness  in almost all countries. These barriers are at the societal level but also at the level of health services and attitudes of health professionals. In particular, the realization of these rights requires a fundamental paradigm shift in the way services are funded and provided for persons with enduring and severe mental illness. All too often, societal attitudes are shaped by the way services are designed (for example a reliance on institutional and coercive care) and attitudes of mental health professionals (eg. attitudes towards risk and dangerousness). Communities also use these service organization and health professional attitudes to justify their social exclusion.

These ideas and possible solutions that can be applied even in resource poor settings will be discussed in my talk.

Psychosis spectrum disorders are characterized by significant clinical and neurobiological heterogeneity. Current diagnostic criteria and psychopharmacological strategies do not take this heterogeneity into account, instead clinicians are relegated to make 'one size fits all' diagnoses and provide treatments based on trial-and-error. There is an urgent need to develop clinically relevant biomarkers that aid in dissecting clinical heterogeneity and treatment decisions with the ultimate goal to improve patient care and clinical outcomes for patients how suffer from this complex neuropsychiatric syndrome.

Here we show that neuroimaging data captured using different imaging modalities (structural, functional, neurometabolic) contain clinically relevant information, both in the context of predicting treatment response and in dissecting clinical heterogeneity, albeit at the group-level. To make further progress towards precision medicine, it is important to move beyond the group-level, where interindividual differences are considered noise, and instead capture this variability in context of the normal range.

We use normative modeling (“brain growth charting”), a statistical technique that allows characterization of neurobiological disease signatures at the individual level. Data our team has collected in a large group of antipsychotic medication-naive first-episode patients shows that normative modeling allows to capture inter-individual heterogeneity in neurobiological disease signatures in psychosis spectrum disorder patients. We also demonstrate, for the first time, that region level structural brain volume deviations from the reference range in key dopaminergic brain regions are better predictors of subsequent clinical response to antipsychotic treatment compared to raw volume measures.

This holds great promise for progress in precision medicine in psychiatry, where group-level studies have failed to derive definitive maps of brain pathology in psychosis spectrum disorders.

Global recognition for the crucial role of meaningful and authentic involvement of people with lived experience in the mental health and social development sectors has gained momentum. People with lived experience are being acknowledged as integral partners in the fields of research, policy reform, service development and delivery, project implementation and monitoring and evaluation. In research, people with lived experience, both academic and non-academic, are able to contribute lived experience expertise throughout all project phases, not merely be seen as subjects of research. In my presentation I will speak about the benefits of including people with lived experience in research, the existing obstacles and the principles and key strategic elements to meaningfully and authentically involve academic/ non-academic lived experience partners.

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.

The prevalence of diabetes is increased 2-3 fold in people with severe mental illness (schizophrenia and bipolar disorder). Diabetes affects approximately 12% of people receiving antipsychotics. The consequences of diabetes in someone with severe mental illness are more severe with higher rates of microvascular and macrovascular complications, acute metabolic dysregulation and diabetes-related deaths.

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.

Converging lines of evidence strongly implicate aberrant neurodevelopment in the etiology of schizophrenia and other neuropsychiatric disorders. Specifically, prenatal and early life insults during critical periods of brain development and maturation are associated with the subsequent emergence of psychopathology, albeit with potentially differential developmental trajectories for males and females. A deeper understanding of the complex neurobiological mechanisms leading to psychopathology and impaired cognition is a prerequisite for individual risk stratification, early intervention, and identification of new treatment strategies. In this symposium we will explore how early risk factors influence neurodevelopment from converging lines of research including epidemiological, clinical and preclinical research. Dr Cecilie Lemvigh will present findings from a nation-wide danish register study examining how multiple early factors influence disease risk and age of illness onset in males and females with a psychotic disorder. She will relate the register data to data from clinical cohorts of child-, adolescents, and adult patients with first-episode psychosis with detailed psychopathology and cognition. MD Julie Rosenberg will present clinical data from a large prospective birth cohort of 700 mother-child pairs followed from pregnancy (The COPSYCH Study). The data show that maternal low-grade inflammation in pregnant mothers increase the risk of psychopathology in the child at age 10. Ongoing analyses relate these findings to the children’s’ white matter integrity. Dr Vernon will present data from human induced pluripotent stem cell models that provide evidence for cell specific effects of IL-6 and IFN-y on human neurons and microglia that recapitulate cellular and molecular phenotypes associated with neurodevelopmental disorders. Finally, Dr Elisa Guma will present preclinical data examining the effects of early or late gestational exposure to maternal immune activation on mouse neurodevelopment across the lifespan. These data highlight the differential effects due to gestational timing of exposure on trajectories of brain development for neuroanatomy, behaviour, and transcription.

Advances in our understanding of schizophrenia have highlighted its complexity across diagnosis, treatment, and outcome. The notion that it is a unitary diagnostic entity mediated by a single mechanism has been set aside. It has been suggested that schizophrenia may better be conceptualized as a syndrome and, as such, differs one individual to the next. Numerous shifts in research capture these changes in thinking e.g., trans-diagnosis, clinical staging and subtyping, novel research targets. This symposium examines these shifts from various perspectives. For example, the complexity of schizophrenia's clinical presentation is now mirrored by the complexity of proposed underlying pathophysiological mechanisms, calling for strategies that can assist in establishing groups that are biologically and pharmacologically meaningful. At the same time, new lines of research are identifying risk factors that warrant further research and possible inclusion as we strive to isolate those that influence risk, course, and outcome. A focus on early intervention has been embraced as part of schizophrenia research for the better part of 4 decades now, and research on this topic has grown exponentially. What have we learned and what are the challenges going forward? In a similar fashion, antipsychotic treatment resistance was identified soon after the introduction of chlorpromazine but as a diagnostic entity it really emerged in the 1980's in the form of 'treatment resistant schizophrenia', paralleling clozapine's reintroduction. Once again, what have we learned what issues stand out as relevant to work in this area? Summarizing, the symposium and each of its presentations seek to provide an update on topics relevant to clinical diagnosis and treatment, as well as strategies to advance the field going forward.

Antipsychotic drugs remain the first-line pharmacological treatment for schizophrenia and other psychoses. However, approximately 30% of people do not respond to two (or more) trials of these drugs, and another 30% of those who initially responded subsequently experience symptom relapse even during assured maintenance treatment with long-acting antipsychotics. This second group has been particularly neglected by research so far, although antipsychotic loss of effectiveness over time has emerged as a key issue for people with lived experience of psychosis taking long-term treatment. We urgently need to characterise the mechanisms underlying both early and late lack of response to antipsychotics. Characterizing these mechanisms can inform the etiopathogenesis of schizophrenia, and provide a basis for personalized treatments, stratification in clinical trials and pharmacological testing. Chaired by P. Dazzan (London, UK) and A. Vernon (London, UK) this symposium will present clinical and pre-clinical evidence on neuromorphological, physiological and cellular biomarkers of early and late lack of response to antipsychotic drugs. P. Dazzan will discuss the relationship between brain
morphology and response to antipsychotics. R. Upthegrove (Birmingham, UK) will introduce evidence on novel approaches to investigating the relevance of peripheral inflammatory markers, brain structure and targeted treatments. This will be extended by I. Khadimallah (Lausanne, Switzerland), with new data on mechanistic response biomarkers reflecting oxidative stress and mitochondrial dysfunction in treatment-resistant patients in early phase of psychosis (TRS). She will highlight the critical role of NMDAR co-agonists pathways in TRS patients and their interaction with mitochondrial deficits, which together may represent potential biomarkers based on central mechanisms of cognitive impairment in these patients. In the fourth presentation, D. Amato (Cincinnati, USA) will offer a reverse-translational perspective, showing preclinical data demonstrating cellular and molecular mechanisms of primary and acquired antipsychotic treatment resistance. Finally, J. Kane (New York, USA) will lead the discussion on how these findings can inform future research to advance our understanding of early and late response to antipsychotic medications. 

Elucidating the neurobiological and psychological mechanisms, which promote resilience against schizophrenia, promises to provide novel pathways toward improved treatment and prevention strategies. Resilience is a dynamic process facilitating adjustments to potentially disabling stressors. Nevertheless, there is clear evidence that resilience factors, which increase resilience capacity, can be genetically determined. Resilience and resilience factors are orthogonal to illness vulnerability and risk factors respectively. Thus, the resilience paradigm constitutes a complementary approach to traditional risk-centered strategies by aiming to induce or enhance these protective mechanisms, which can buffer against central pathophysiological processes underlying schizophrenia. To this end current research focuses on high-risk individuals who do not develop schizophrenia. In addition to people at clinical high risk (CHR) risk this includes cohorts at elevated genetic risk. The former group can illuminate factors protecting against a conversion to full blown illness. The latter group can help identify genetic resilience factors, which can facilitate the search for resilience mechanisms that have evolved naturally in the general population. This symposium will highlight current finding based on these approaches including data from genetics, neuroimaging, psychopathology, and psychotherapeutic interventions. Dr. J. Hess will discuss successful attempts at elucidating the genetic architecture of schizophrenia resilience, which have discovered common genetic variants that offset the inherited risk for schizophrenia among resilient unaffected individuals. These findings resulted in the derivation and subsequent refinement of a multivariate measure of genetic resilience in the form of a polygenic resilience score. Dr. R. Bittner will present neuroimaging data, which indicate that heritable mediators of resilience to schizophrenia exert their protective effect partly through cortical neuroplastic alterations with
the strongest impact in the fusiform gyrus. This indicates that schizophrenia resilience emerges partly from the strengthening of neural circuits crucial for the disambiguation of social and non-social visual information. These findings also imply an important role for neuroplasticity in promoting schizophrenia resilience. Dr. K. Cadenhead will present data from the NAPLS 3 study of CHR individuals demonstrating that prosocial involvement and resilient personality traits comprising empathy, psychological maturity and self-directedness are more common in people who did not convert to psychosis. Enhancing these resilience factors through targeted psychotherapeutic interventions might therefore not only have a positive impact on symptom severity and functional outcome but also reduce the rate of conversion to psychosis. Dr. D. Holt will present data demonstrating the beneficial effects of a brief resilience-enhancing behavioral intervention in college students. This intervention led to significant reductions in subclinical psychopathology including depression, anxiety, and psychotic experiences as well as improvements in resilience-related factors including emotion regulation. Furthermore, fMRI data revealed a significance increase in fronto-hippocampal connectivity, which was associated with a comparable decrease in PEs. This effect was fully mediated by improvements in emotion regulations. Together, these findings illustrate how findings from resilience research can be leveraged to develop novel strategies for improved risk prediction, illness prevention as well as treatment.

People living with serious mental illnesses (SMI) have high rates of
cardiovascular morbidity and associated premature mortality. In recent years there has been considerable focus on cardiometabolic risk factors such as obesity, dysglycaemia and dyslipidaemia. However, less evidence exists on the relationships between a diagnosis of SMI and specific cardiac conditions, and on how having a psychotic illness may influence the management and outcomes of such conditions. Our session focuses on heart health and care in people with schizophrenia and psychotic disorders. Dr Christoffer Polcwiartek will present two retrospective cohort studies. One uses data from the Duke University Health System and he has replicated this in the Danish nationwide registries. The studies examine the characteristics, temporal trends, and clinical outlook of heart failure in people with serious mental illnesses, including all-cause mortality and trends for its management, including the use of medical therapies, implantable devices and surgical procedures. His work shows that heart failure affects people with SMI about seven years earlier than their peers, with equal access to advanced procedures. There is an increased risk of associated mortality in men with SMI than without (hazard ratio, 1.36 [95% CI, 1.17– 1.59]). Dina Farran will present her systematic review on the prevalence, management and outcomes of atrial fibrillation (AF) in people with SMI, which reports low rates of AF in people with SMI. She will present findings from two retrospective cohort studies examining anticoagulation (OAC) prescription trends in people with AF and co-morbid SMI. The first is in a general hospital, where people with SMI were less likely to receive OAC than their peers until 2019, when the difference was no longer significant. The second, in a mental health setting, saw that 61.5% of people with SMI and AF are not anti-coagulated. Substance dependency, and Activity of Daily Living scores on the Health of the Nation Outcome Scale were associated with the likelihood of OAC prescription. She will also describe the development and planned evaluation of our electronic Clinical Decision Support System to guide screening for OAC in mental health settings. Dr Kevin O’Gallagher will present findings from a new systematic review on the ‘treatment gap’ in coronary and cardiovascular disease (CVD) in patients with SMI. Importantly, he will summarise the work to date on the interactions between race, ethnicity, SMI and CVD which raises important points for research into intersectional vulnerabilities. He will also present early data from current
work on pathways to care in London ,UK for people with a diagnosis of SMI within highly protocolised primary angioplasty pathways. Prof Dan Siskind will present his new research on the relationship between clozapine and heartrate (HR). This shows a higher pulse rate in inpatients prescribed clozapine than those on other anti-psychotics (p<0.001); 30.2% of those on clozapine had a HR >100BPM, although there was no relationship with prolonged QT intervals. Among outpatients on clozapine, 61.1% had a HR>100BPM, while nearly 10% had rates of over 120BPM.
Our discussant, Prof Margaret Hahn is an expert in cardiometabolic risk and its management in people with psychosis and will bring the panel and attendees together to discuss and summarise the science presented. Overall, the presenters will provide evidence of the need for better detection and management of clozapine-related tachycardia, AF, coronary artery disease and heart failure in people with psychosis. 

Negative symptoms are a critical symptom dimension of schizophrenia, typically associated with reduced social and instrumental functioning. Negative symptoms are present early on in the disease process, are stable during chronic phases of illness and are difficult to treat. Negative symptoms are generally assessed using clinical rating scales; however, these rating scales have several inherent limitations that impact validity and efficacy for their use in clinical trials (e.g., PANSS, SANS, BNSS, CAINS). More recently, there have been increasing attempts to digitally phenotype negative symptoms using objective biobehavioral technologies, such as computerized analysis of speech and facial behaviors. These technologies have allowed to identify precise and intricate characteristics of negative symptoms that cannot be easily identified during clinical interviews, and may yield complex features of digitally characterized negative symptoms. Additionally, digital tools may have numerous potential benefits compared to traditional assessments: they are non-invasive, ecological, do not demand extra efforts, and provide continuous access which offers timely understandings of symptom and symptom changes. Current innovative digital approaches to assessment offer a unique opportunity to create predictive models of individual vulnerability based on the integration and interdependencies of symptoms
from diverse sources of information. Therefore, this panel will present clinically relevant digital technologies assessing negative symptoms and their relationship with clinical ratings as well their potential predictive power of illness development. The panel will also address reasons for the lack of convergence between digital technologies and clinical ratings, and further demonstrate how these digital technologies may enhance measurement of negative symptoms.