International Congress on Schizophrenia Research Concurrent Symposia Presentations S7 5.3 ENDOPHENOTYPES GUIDE PSYCHOSIS NEUROBIOLOGY FORMULATIONS Carol Tamminga* ,1 , Brett Clementz 2 , Matcheri Keshavan 3 , Elliot Gershon 4 , Godfrey Pearlson 5 , and Elena Ivleva 1 1 The University of Texas Southwestern Medical Center; 2 University of Georgia; 3 BIDMC/Harvard Medical School; 4 University of Chicago; 5 Yale University, Background: Conventional diagnoses arguably have not been successful at organizing psychiatric conditions into disease constructs with clear patho- physiology and etiology. Moreover, research has shown that conventional diagnoses are poorly characterized, if at all, by discrete functional brain biomarkers or biomarker composites. Methods: The Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP) recruited a large group of probands with psychotic conditions, their family members, and healthy controls (N > 2300) to carry out deep phenotyping across 5 sites in the United States. Results: In the BSNIP1 study, none of the biomarkers sampled (>50 dis- tinct endophenotypes) fell discretely onto any of the phenomenologically defned conventional diagnoses. Alternatively, using the endophenotypes to create homogeneous, neurobiologically distinct proband groups resulted in units we called Biotypes, each with distinctive neurobiological charac- teristics, which tempted further biological formulations. The analyses of additional biomarkers garnered support for biomarker-based classifca- tion (potentially the Biotype formulation) for psychosis research. The pro- bands show nearly the same levels of psychosis across the three Biotypes (1–3), while profoundly high negative symptoms are clustered in Biotype 1. Biotypes 1 and 2 differ in basal EEG power, with B-1 showing low and B-2 showing high basal EEG characteristics. The lifetime rates of Axis I and II psychosis in relatives distinguishes the Biotype groups (highest in B-I, lowest in B-3) as does the frequency of adolescent cannabis use (high- est in B-3). Biotype was a signifcant predictor of gray matter change in the psychosis group, while conventional diagnosis was not based on step- wise regression analysis. Relatives of the Biotypes show the same, but less extreme, pattern of deviations on each of the biomarkers and on the bio- marker composites as do the probands, indicating familiality. Conclusion: These early analyses of disease group characteristics based on endophenotypes lead us to suggest “proof-of-principal” demonstration of the value of neurobiologically based endophenotype groups, groups with indicate Irv Gottesman’s generativity in psychosis research. Whether or not these endophenotype-defned groups lead to genes, to distinct molecu- lar markers and onto distinct treatments, will be a defnitive test of their usefulness. 5.4 FROM PHENOMICS TO GENOMICS: THE ENDOPHENOTYPE BRIDGE Raquel Gur*, Monica Calkins, David Roalf, and Ruben Gur University of Pennsylvania Background: Most data sets currently included in genomic analyses of schizophrenia are comprised of case–control design that focuses on diag- nostic categorization on those who meet diagnostic criteria for schizophre- nia and of healthy participants. A hallmark of schizophrenia is impaired cognitive functioning. The goal of the study was to examine cognitive endo- phenotypes in 3 large-scale consortia that differ in recruitment and assess the pattern of neurocognitive performance across consortia. Methods: The 3 consortia were family based with different sampling strat- egies. The Multiplex Investigation of Multigenerational families (MGI) included Caucasian families with at least 2 frst-degree relatives with schizophrenia spectrum disorders. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) included African American families—affected sibling pairs, TRIOs, or multiplex. The Consortium on the Genetics of Schizophrenia (COGS) included families with a proband, unaffected sibling and both parents (COGS-1) as well as a case–control design (COGS-2). The Penn computerized neurocognitive battery (CNB), based on tasks administered in functional neuroimag- ing, was administered across consortia. The CNB measures performance accuracy and response time in several domains including: Executive Functions, Episodic Memory, Complex Cognition, Social Cognition and Sensori-Speed. Results: Across consortia, probands with schizophrenia showed a simi- lar pattern of neurocognitive defcits in performance accuracy and speed implicating frontotemporal impairment. Notably, family members mani- fested mild impairment, intermediate between probands and controls. The neurocognitive parameters were heritable and met established criteria for endophenotypes. Conclusion: Quantitative neurocognitive measures are endophenotypes that can be administered in large-scale consortia and integrated in genomic analyses. Such efforts can advance the understanding of the neurobiology of schizophrenia and be evaluated in treatment studies. 6. WHAT DO PSYCHOTIC SYMPTOMS IN CHILDHOOD MEAN FOR NEURODEVELOPMENT AND ADULT MENTAL HEALTH OUTCOMES? Ian Kelleher Royal College of Surgeons in Ireland Overall Abstract: Research over the past 15 years has shown that psychotic symptoms are relatively prevalent in both the clinic and the community, outside the context of psychotic disorders. Epidemiological studies have shown that 8%–17% of children and 5%–7% of adults report these symp- toms, which, in the general population, are often referred to as “psychotic experiences.” Although initially conceptualized as an epidemiological com- plement to the clinic-based “ultra high risk” approach to psychosis, more recent research has demonstrated that psychotic experiences occur across the full spectrum of mental disorders. An important question, then, is, what does it mean when an individual reports psychotic experiences/symptoms outside the context of a psychotic disorder? This symposium will bring together researchers from Australia, Europe, and the United States to look at this question from multiple perspectives, including associations with clinical/disorder outcomes, functional outcomes, cognitive outcomes, and structural and functional brain development outcomes. James Scott will talk about an Australian cohort study of community-based 14-year-olds, followed up at both 21 years and at 30–33 years. This talk will look at the relationship between hallucinations in adolescence and mental illness outcomes in adulthood, demonstrating that hallucinatory experi- ences in youth predict increased risk of psychotic disorders, substance use disorders, and suicide attempt as well poor outcomes in terms of education, employment, and quality-of-life measures. Agna Bartels will talk about a Dutch cohort study of 7- to 8-year-olds, followed up 5 years and 11 years later. This talk will look not only at the persistence rate of psychotic experiences from early childhood into early adulthood but also the relationship between persistence of psychotic experiences and risk of measures of both psychopathology and trauma as well as exploring a novel network approach to understanding psychotic experiences. Ian Kelleher will discuss a Swedish cohort study of community-based 15-year-olds, followed up 3 years later at age 18. This talk will delve into different subtypes of psychotic experiences—visual and auditory hallucina- tions and different delusional beliefs—and whether these specifc symptom subtypes differentially predicted poor mental health outcomes, including suicidal behavior and substance use disorders. Daniel Wolf will discuss the Philadelphia Neurodevelopmental Cohort, the largest neuroimaging study to date of a community sample with psychotic Downloaded from https://academic.oup.com/schizophreniabulletin/article-abstract/43/suppl_1/S7/3075358 by guest on 08 June 2020