Towards Precision Medicine in Psychosis: Benefits and Challenges of Multimodal Multicenter Studies-PSYSCAN: Translating Neuroimaging Findings From Research into Clinical Practice.

Tognin S, van Hell HH, Merritt K, Winter-van Rossum I, Bossong MG, Kempton MJ, Modinos G, Fusar-Poli P, Mechelli A, Dazzan P, Maat A, De Haan L, Crespo-Facorro B, Glenthøj B, Lawrie SM, McDonald C, Gruber O, van Amelsvoort T, Arango C, Kircher T, Nelson B, Galderisi S, Bressan R, Kwon JS, Weiser M, Mizrahi R, Sachs G, Maatz A, Kahn R, McGuire P; PSYSCAN Consortium

In the last 2 decades, several neuroimaging studies investigated brain abnormalities associated with the early stages of psychosis in the hope that these could aid the prediction of onset and clinical outcome. Despite advancements in the field, neuroimaging has yet to deliver. This is in part explained by the use of univariate analytical techniques, small samples and lack of statistical power, lack of external validation of potential biomarkers, and lack of integration of nonimaging measures (eg, genetic, clinical, cognitive data). PSYSCAN is an international, longitudinal, multicenter study on the early stages of psychosis which uses machine learning techniques to analyze imaging, clinical, cognitive, and biological data with the aim of facilitating the prediction of psychosis onset and outcome. In this article, we provide an overview of the PSYSCAN protocol and we discuss benefits and methodological challenges of large multicenter studies that employ neuroimaging measures.

Schizophr Bull. 2019 Aug 19. pii: sbz067. doi: 10.1093/schbul/sbz067

Basic Self-Disturbances Related to Reduced Anterior Cingulate Volume in Subjects at Ultra-High Risk for Psychosis.

Bonoldi I, Allen P, Madeira L, Tognin S, Bossong MG, Azis M1, Samson C, Quinn B, Calem M, Valmaggia L, Modinos G, Stone J, Perez J, Howes O, Politi P, Kempton MJ, Fusar-Poli P, McGuire P.

Introduction: Alterations of the “pre-reflective” sense of first-person perspective (e.g., of the “basic self”) are characteristic features of schizophrenic spectrum disorders and are significantly present in the prodromal phase of psychosis and in subjects at ultra-high risk for psychosis (UHR). Studies in healthy controls suggest that neurobiological substrate of the basic self involves cortical midline structures, such as the anterior and posterior cingulate cortices. Neuroimaging studies have identified neuroanatomical cortical midline structure abnormalities in schizophrenic spectrum disorders. Objectives: i) To compare basic self-disturbances levels in UHR subjects and controls and ii) to assess the relationship between basic self-disturbances and alterations in cortical midline structures volume in UHR subjects. Methods: Thirty-one UHR subjects (27 antipsychotic-naïve) and 16 healthy controls were assessed using the 57-item semistructured Examination of Anomalous Self-Experiences (EASE) interview. All subjects were scanned using magnetic resonance imaging (MRI) at 3 T, and gray matter volume was measured in a priori defined regions of interest (ROIs) in the cortical midline structures. Results: EASE scores were much higher in UHR subjects than controls (p < 0.001). The UHR group had smaller anterior cingulate volume than controls (p = 0.037). There were no structural brain imaging alterations between UHR individuals with or without self-disturbances. Within the UHR sample, the subgroup with higher EASE scores had smaller anterior cingulate volumes than UHR subjects with lower EASE scores and controls (p = 0.018). In the total sample, anterior cingulate volume was inversely correlated with the EASE score (R = 0.52, p < 0.016). Conclusions: Basic self-disturbances in UHR subjects appear to be related to reductions in anterior cingulate volume

Front Psychiatry. 2019 May 10;10:254. doi: 10.3389/fpsyt.2019.00254.

Gender differences of patients at-risk for psychosis regarding symptomatology, drug use, comorbidity and functioning – Results from the EU-GEI study.

Menghini-Müller S, Studerus E, Ittig S, Heitz U, Egloff L, Andreou C, Valmaggia LR, Kempton MJ, van der Gaag M, de Haan L, Nelson B, Barrantes-Vidal N, Nordentoft M, Ruhrmann S, Sachs G, Rutten BP, Os JV, Riecher-Rössler A; EU-GEI High Risk Study Group, McGuire P, Valmaggia LR, Kempton MJ, Calem M, Tognin S, Modinos G15, de Haan L17, van der Gaag M18, Velthorst E19, Kraan TC20, van Dam DS21, Burger N22, Nelson B, McGorry P, Amminger GP, Pantelis C, Politis A, Goodall J, Riecher-Rössler A, Borgwardt S, Rapp C, Ittig S, Studerus E, Smieskova R, Bressan R, Gadelha A, Brietzke E, Asevedo G, Asevedo E, Zugman A, Barrantes-Vidal N, Domínguez-Martínez T, Racioppi A, Cristóbal-Narváez P, Kwapil TR, Monsonet M, Kazes M, Daban C, Bourgin J, Gay O, Mam-Lam-Fook C, Krebs MO, Nordholm D, Randers L, Krakauer K, Glenthøj L, Glenthøj B, Nordentoft M, Ruhrmann S, Gebhard D, Arnhold J, Klosterkötter J, Sachs G, Lasser I, Winklbaur B, Delespaul PA, Rutten BP, van Os J

Background: Gender differences in symptomatology in chronic schizophrenia and first episode psychosis patients have often been reported. However, little is known about gender differences in those at risk of psychotic disorders. This study investigated gender differences in symptomatology, drug use, comorbidity (i.e. substance use, affective and anxiety disorders) and global functioning in patients with an at-risk mental state (ARMS) for psychosis. Methods: The sample consisted of 336 ARMS patients (159 women) from the prodromal work package of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI; 11 centers). Clinical symptoms, drug use, comorbidity and functioning were assessed at first presentation to an early detection center using structured interviews. Results: In unadjusted analyses, men were found to have significantly higher rates of negative symptoms and current cannabis use while women showed higher rates of general psychopathology and more often displayed comorbid affective and anxiety disorders. No gender differences were found for global functioning. The results generally did not change when corrected for possible cofounders (e.g. cannabis use). However, most differences did not withstand correction for multiple testing. Conclusions: Findings indicate that gender differences in symptomatology and comorbidity in ARMS are similar to those seen in overt psychosis and in healthy controls. However, observed differences are small and would only be reliably detected in studies with high statistical power. Moreover, such small effects would likely not be clinically meaningful.

Eur Psychiatry. 2019 Jun;59:52-59. doi: 10.1016/j.eurpsy.2019.04.007.

Differences Between Self-Reported Psychotic Experiences, Clinically Relevant Psychotic Experiences, and Attenuated Psychotic Symptoms in the General Population.

Moriyama TS, van Os J, Gadelha A, Pan PM, Salum GA, Manfro GG, Mari JJ, Miguel EC3,8, Rohde LA, Polanczyk GV, McGuire P, Bressan RA, Drukker M.

Purpose: Psychotic experiences in childhood (such as hearing voices or being suspicious) represent an important phenotype for early intervention. However, these experiences can be defined in several ways: self-reported psychotic experiences (SRPE) rely exclusively on the child’s report, clinically validated psychotic experiences (CRPE) are based on clinical assessment, and attenuated psychotic symptoms (APS) represents a categorization to do with clinical relevance in relation to severity. Very few studies have investigated how these distinctions impact clinical and other domains. The present study aims to compare SRPE, CRPE, and APS among children and adolescents. Methods: This study is part of the Brazilian High-Risk Cohort Study for Psychiatric Disorders, in which 2,241 individuals aged 6-14 years provided self-ratings of 20 psychotic experiences using the Community Assessment of Psychic Experiences (CAPE). A trained psychologist conducted an interview to validate or reject reported experiences and to rate the presence of APS and affective flattening. In parallel, parents provided information about child mental health to an independent interviewer. We tested the association of mutually exclusive categories of non-validated SRPE (nSRPE), clinically validated PE below the threshold for APS (nCRPE), and APS (nSRPE = 33%, nCRPE = 11%, APS = 6%), with parents’ information about the child’s positive attributes and levels of psychopathology and psychologist assessment of blunted affect. Results: Most associations were qualitatively similar, and there was a dose-response in the strength of associations across categories, such that APS > nCRPE > nSRPE. Experiences in all three categories were associated with female sex. nSRPE were associated with overall levels of psychopathology, but to a lesser degree than nCRPE and APS. APS and nCRPE were associated with less positive attributes, with APS more so than nCRPE. Only APS was associated with affective flattening. Conclusions: In children and adolescents, SRPE, CRPE, and APS all index liability for psychopathology, but as clinician rated relevance increases, associations get stronger and become evident across more domains.

Front Psychiatry. 2019 Oct 29;10:782. doi: 10.3389/fpsyt.2019.00782

The PSYSCAN project structure has been defined to maximize the participation of the consortium partners throughout the duration of the project. The geographical distribution of consortium partners and other participants are well balanced across the Europe Union, as visualized the figure below:

FEP Cohort

UHR Cohort

Due to Covid-19 restrictions, most of the in-person meetings were canceled. Our General Assembly meeting was held as an online meeting in July 2020. Despite the adverse circumstances, we would like to thank the huge effort from all centers

We have also continued holding our Executive Board meetings regularly. These meetings are an important opportunity for us to review the status of the project and discuss plans for publications and further dissemination of the project.