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BackgroundThe clinical high-risk for psychosis (CHR-P) paradigm was introduced to detect individuals at risk of developing psychosis and to establish preventive strategies. While current prediction of outcomes in the CHR-P state is based mostly on the clinical assessment of presenting features, several emerging biomarkers have been investigated in an attempt to stratify CHR-P individuals according to their individual trajectories and refine the diagnostic process. However, heterogeneity across subgroups is a key challenge that has limited the impact of the CHR-P prediction strategies, as the clinical validity of the current research is limited by a lack of external validation across sites and modalities. Despite these challenges, electroencephalography (EEG) biomarkers have been studied in this field and evidence suggests that EEG used in combination with clinical assessments may be a key measure for improving diagnostic and prognostic accuracy in the CHR-P state. The PSYSCAN EEG study is an international, multi-site, multimodal longitudinal project that aims to advance knowledge in this field.MethodsParticipants at 6 international sites take part in an EEG protocol including EEG recording, cognitive and clinical assessments. CHR-P participants will be followed up after 2 years and subcategorised depending on their illness progression regarding transition to psychosis. Differences will be sought between CHR-P individuals and healthy controls and between CHR-P individuals who transition and those who do not transition to psychosis using data driven computational analyses.DiscussionThis protocol addresses the challenges faced by previous studies of this kind to enable valid identification of predictive EEG biomarkers which will be combined with other biomarkers across sites to develop a prognostic tool in CHR-P. The PSYSCAN EEG study aims to pave the way for incorporating EEG biomarkers in the assessment of CHR-P individuals, to refine the diagnostic process and help to stratify CHR-P subjects according to risk of transition. This may improve our understanding of the CHR-P state and therefore aid the development of more personalized treatment strategies.

BackgroundNegative symptoms occur in individuals at ultrahigh risk (UHR) for psychosis. Although there is evidence that observer ratings of negative symptoms are associated with level of functioning, the predictive value of subjective experience in daily life for individuals at UHR has not been studied yet. ObjectiveThis study therefore aims to investigate the predictive value of momentary manifestations of negative symptoms for clinical outcomes in individuals at UHR. MethodsExperience sampling methodology was used to measure momentary manifestations of negative symptoms (blunted affective experience, lack of social drive, anhedonia, and social anhedonia) in the daily lives of 79 individuals at UHR. Clinical outcomes (level of functioning, illness severity, UHR status, and transition status) were assessed at baseline and at 1- and 2-year follow-ups. ResultsLack of social drive, operationalized as greater experienced pleasantness of being alone, was associated with poorer functioning at the 2-year follow-up (b=−4.62, P=.01). Higher levels of anhedonia were associated with poorer functioning at the 1-year follow-up (b=5.61, P=.02). Higher levels of social anhedonia were associated with poorer functioning (eg, disability subscale: b=6.36, P=.006) and greater illness severity (b=−0.38, P=.045) at the 1-year follow-up. In exploratory analyses, there was evidence that individuals with greater variability of positive affect (used as a measure of blunted affective experience) experienced a shorter time to remission from UHR status at follow-up (hazard ratio=4.93, P=.005). ConclusionsTargeting negative symptoms in individuals at UHR may help to predict clinical outcomes and may be a promising target for interventions in the early stages of psychosis.

Chronic psychosocial adversity induces vulnerability to mental illnesses. Animal studies demonstrate that this may be mediated by dopaminergic dysfunction. We therefore investigated whether long-term exposure to psychosocial adversity was associated with dopamine dysfunction and its relationship to psychological and physiological responses to acute stress. Using 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F]-DOPA) positron emission tomography (PET), we compared dopamine synthesis capacity in n = 17 human participants with high cumulative exposure to psychosocial adversity with n = 17 age- and sex-matched participants with low cumulative exposure. The PET scan took place 2 hr after the induction of acute psychosocial stress using the Montréal Imaging Stress Task to induce acute psychosocial stress. We found that dopamine synthesis correlated with subjective threat and physiological response to acute psychosocial stress in the low exposure group. Long-term exposure to psychosocial adversity was associated with dampened striatal dopaminergic function (p=0.03, d = 0.80) and that psychosocial adversity blunted physiological yet potentiated subjective responses to acute psychosocial stress. Future studies should investigate the roles of these changes in vulnerability to mental illnesses.

Background: Novel methods for measuring large-scale dynamic brain organisation are needed to provide new biomarkers of schizophrenia. Using a method for modelling dynamic modular organisation, previous evidence suggests higher ‘flexibility’ (switching between multilayer network communities) to be a feature of schizophrenia. Methods: The current study compared flexibility between 55 patients with schizophrenia and 72 controls (the COBRE Dataset). In addition, novel methods of ‘between resting state network synchronisation’ (BRSNS) and the probability of transition from one community to another were used to further describe group differences in dynamic community structure. Results: There was significantly higher schizophrenia group flexibility in cerebellar (F (1,124) = 9.33, p (FDR) = 0.017), subcortical (F (1,124) = 13.14, p (FDR) = 0.005), and fronto-parietal task control (F (1,124) = 7.19, p (FDR) = 0.033) resting state networks (RSNs), as well as in the left thalamus (MNI XYZ: -2, -13, 12; F(1, 124) = 17.1, p (FDR) < 0.001) and the right crus I (MNI XYZ: 35, -67, -34; F (1, 124) = 19.65, p (FDR) < 0.001). Flexibility in the left thalamus reflected transitions between communities covering default mode and sensory-somatomotor RSNs. BRSNS scores suggested altered dynamic inter-RSN modular configuration in schizophrenia. Discussion: This study suggests higher flexibility in a schizophrenia group at an RSN and node level and provides novel methods of exploring dynamic community structure. Mediation of group differences by mean time window correlation did however suggest flexibility to be no better as a schizophrenia biomarker than simpler measures and a range of methodological choices affected results. [ABSTRACT FROM AUTHOR]