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[FG] Sterzer Philipp

Projects & Collaborations

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EEG resting-state connectivity and psychosis: Dopaminergic influences

Research Project  | 5 Project Members

The dopamine hypothesis has proven to be the most enduring neurobiological model of psychosis, and all currently licensed antipsychotic drugs are dopamine antagonists. Although the pharmacological actions of antipsychotics have been extensively investigated, research into how these translate into their effects on symptoms is relatively new. The present project focuses on the relationships between medication-induced changes in dopaminergic activity and brain connectivity, disturbances of which are considered to be a core neurophysiological characteristic of psychotic disorders. It uses electroencephalography (EEG) to assess how dopaminergic agents affect the fast dynamics of brain networks, drawing upon two complementary lines of research: a drug challenge study, and a longitudinal patient study. Method: The project consists of two parts: a drug-challenge study in healthy individuals (Project A), and a longitudinal study with medication-naïve patients with psychotic disorders before and after antipsychotic treatment (Project B). -Participants: Project A includes single-dose administration of a dopaminergic agonist (L-dopa 100 mg), a dopaminergic antagonist (haloperidol 2 mg) and placebo to 60 healthy subjects within a randomized, double-blind, cross-over design. Project B will investigate 40 medication-naïve patients with psychotic disorders before and after 8-10 weeks of antipsychotic medication treatment. -Measures of interest: Analyses will be performed based on 10-min, eyes-closed, resting-state 64-channel EEG data. Three different measures of interest will be assessed: (1) lagged phase coherence (multivariate interaction method) and (2) orthogonalized power envelope correlation at the level of brain electrical sources in the theta and gamma frequency band; and (3) resting-state EEG microstates as a measure of global brain connectivity. -Statistical analyses: In Project A, regressors will be defined for linear and quadratic substance contrasts; in Project B, differences between pre-and post-treatment will be assessed. For measures (1) and (2), a cluster-based permutation method (network-based statistic) will be used for analyses. Microstate parameters (3) will be subjected to repeated-measures ANOVAs with microstate class as a within-subject factor. Expected value of the project: The project aims to fill a significant knowledge gap regarding the mechanisms of action of antipsychotic drugs. Beyond their theoretical value in understanding the pathophysiology of psychosis, results are expected to be valuable in informing use-inspired research, especially given the growing interest in non-invasive neuromodulation techniques for the treatment of neuropsychiatric disorders.

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Improving the Detection of Depression in Early Intervention Settings: A Transdiagnostic Approach (IDEAS)

Research Project  | 1 Project Members

Major depression is one of the most frequent mental disorders. Especially severe and chronic forms of depression are often characterized by an early onset in adolescence. However, early detection and intervention services have so far focused mostly on psychosis, while largely neglecting other mental health problems including depression. As it has become more apparent that emerging mental disorders do not present as clearly diagnosable syndromes in youth and young adults, new transdiagnostic models have been proposed to capture the fluctuating symptoms of these subthreshold states. A broader, multidimensional and transdiagnostic at-risk mental state has been proposed to reduce the risk of missing out on patients in need, a majority of whom develop major depression later in life. Therefore, IDEAS aims at investigating the clinical trajectories of young people seeking help at early intervention services with a focus on the predictability of the future development of depressive disorders. The project will assess the clinical risk for depression from a transdiagnostic perspective by conducting a longitudinal, multidimensional clinical assessment on the help-seeking population at the early intervention services of UPK Basel. Furthermore, the project will establish the online assessment of mechanism-based behavioural markers for the discrimination between depression and psychosis risk, and will evaluate their prospective feasibility and accuracy for the diagnostic discrimination and prediction of clinical trajectories. The results of this study will pave the way for the future development of new targeted interventions for young people at risk for depression.