LOCUS-MENTAL - Locus-Coeruleus Norepinephrine functioning as a predictor of childhood mental health

• Applicant: Dr. Nico Bast
• Subject Area: Personality Psychology, Clinical and Medical Psychology, Methodology ; Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 548343771

Mental Health Disorders (MHD) describe suffering by altered cognition, emotion, and behavior. MHD remain a leading cause of the global burden of diseases. Most MHD diagnoses have an onset in the childhood and lead to a lifetime of psychopathology. Recently, the locus coeruleus – norepinephrine system (LC-NE) has been established as a modulator of sensory processing that translates endocrine stress responses to neurophysiological excitability. We propose LC-NE functioning as a developmental mechanism that underlies early dispositional risks for MHD and explains a differential susceptibility to childhood adverse experiences. LC-NE functioning is conceptualized as a biomarker that shapes psychopathology across diagnostic labels. LOCUS-MENTAL will put this to the test in a transdiagnostic, developmental, and dimensional approach. We will assess LC-NE functioning in preschoolers as a predictor of a later psychopathology and stress regulation. We will utilize pupillometry as a feasible neuroimaging technique to quantify LC-NE functioning in our outpatient clinic for early detection. This will be implemented in an accelerated longitudinal design to reveal prospective effects. In cross-lagged panel models, we will quantify the relationship of LC-NE functioning, transdiagnostic psychopathology, and childhood adversity. LC-NE functioning is further characterized as a neurophysiological mechanism of early dispositional risks by concurrent pupillometry and electroencephalography, while LC-NE functioning in stress regulation is explored by combined pupillometry and analyzing hair cortisol levels and salivary cortisol after a social stress test. LOCUS-MENTAL ultimately aims to generate an objective tool of risk prediction based on pupillometric markers that informs an early and targeted prevention of lifetime psychopathology.

• DFG Programme: Independent Junior Research Groups