Neural mechanisms of delusions: towards a transnoslogical model

• Applicant: Professor Dr. Robert Christian Wolf
• Subject Area: Biological Psychiatry
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 449168024

Delusions are core symptoms of psychotic disorders. Despite their outstanding clinical relevance, it is very surprising to witness a dearth of research devoted to neural mechanisms of delusion formation and delusional content. In patients with full-blown schizophrenia (SZ), neural correlates of delusions are very difficult to study because of the often phasic nature and heterogeneous content of such symptoms, and because a plethora of other symptoms can substantially introduce bias that has to be carefully controlled, such as co-ocurrent hallucinations, negative symptoms or cognitive deficits. Delusional disorder (DD), a psychotic disorder that is characterized by a single and enduring delusional symptom in the absence of other SZ-defining clinical features, could serve as a “single-symptom” model disease for the in-vivo investigation of neural abnormalities that underlie the delusional belief and content. The major goals of this project are 1. To determine whether different delusional content in DD, paranoid or somatic, is related to distinct neural features in terms of brain structure, tract integrity and intrinsic neural network function. 2. To delineate common neural patterns underlying delusions across diagnostic categories within the SZ-spectrum. Clinical, behavioral and multimodal neuroimaging data (high-resolution magnetic resonance imaging [MRI], diffusion-weighted MRI and resting-state functional MRI) together with advanced uni- and multivariate statistical data analysis techniques will be employed. Fifty patients with DD (paranoid or somatic delusional content, n=25, respectively), 50 patients with SZ with persistent delusions (paranoid or somatic content) and 50 healthy controls will be examined cross-sectionally. The following hypotheses will be tested: 1. DD patients presenting with somatic vs. paranoid content will significantly differ in distinct neural features in terms of brain volume, white matter tract integrity, and neural system connectivity. 2. Compared to patients with SZ presenting with persistent somatic or non-somatic delusional content, neural deficits will not significantly differ between diagnostic categories, suggesting common transnosological neural features. Taken together, this collaborative project seeks, for the first time, to comprehensively characterize delusion-specific neural signatures within the SZ-spectrum. Insights gained from this project are of transdiagnostic relevance, as much as they can be expanded to dimensional models of delusion formation. Given the poor clinical response to conventional treatment modalities in patients with DD and in individuals with SZ presenting with enduring delusional symptoms, this project will seek to determine potential neural targets that may inform novel treatment strategies for persistent delusions, particularly non-invasive neurostimulation.

• DFG Programme: Research Grants
• International Connection: Russia
• Partner Organisation: Russian Foundation for Basic Research, until 3/2022
• Cooperation Partner: Professor Dr. Anatoly Boleslavovich Smulevich, until 3/2022