Anxiety in multiple sclerosis: Psychoneurobiological mechanisms, clinical importance, and relation to other stress-related neuropsychiatric syndromes

• Applicants: Professor Dr. Friedemann Paul; Dr. Martin Weygandt
• Subject Area: Biological Psychiatry ; Clinical Neurology; Neurosurgery and Neuroradiology ; Human Cognitive and Systems Neuroscience
• Term: from 2016 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 320333215

Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system leading to demyelination, axonal damage and neuronal degeneration. Besides key neurologic symptoms (e.g. visual, motor, or cognitive impairment), neuropsychiatric syndromes such as stress-disorders, depression and anxiety are among the most frequent comorbidities in MS. Recently, several studies have provided insights into the neurobiological mechanisms connecting stress and depression with MS. For example, based on our precursor project we could show that stress-induced brain activity is related to grey matter (GM) atrophy, and pyramidal and cognitive symptoms in MS. Other studies show that participation in a stress management program reduces the occurrence of new inflammatory brain lesions on cranial magnetic resonance imaging (MRI) and that psychotherapy for depression treatment can reduce proinflammatory cytokines and clinical disability measures in addition to depression in MS. The situation is completely different however with anxiety: Although epidemiological and clinical studies suggest that anxiety is of comparable importance for MS (i.e., high prevalence, close link to neurological symptoms and reduced quality of life), and although a large number of anxiety studies investigated biological mechanisms in persons without MS, nearly nothing is known about the neural foundations of anxiety in MS. This is surprising for two reasons. First, areas affected by GM atrophy in MS strongly overlap with key regions identified in non-MS studies on anxiety – which suggests a fundamental biological link between MS and anxiety. Second, non-MS biomarker studies revealed that activity in these areas is a suitable predictor for treatment success in anxiety disorders. Thus, a thorough investigation of these mechanisms might help in optimizing future strategies for anxiety treatment in MS. Due to these reasons, we propose an MS research project that intends to investigate neural foundations of three major mechanisms known to be involved in the development and maintenance of clinically relevant anxiety in persons without MS: Fear generalization, fear extinction, and processing of generic affective stimuli. This shall be done in anxious and not anxious persons with MS as well as in healthy participants with task-based functional MRI paradigms. This comprehensive research design will allow to investigate psychobiological mechanisms of anxiety in MS from a systems neuroscience perspective for the first time, to elucidate the association between functioning of these systems and MS neuropathology and symptoms, as well as to determine the commonalities and differences of these mechanisms relative to those of other neuropsychiatric syndromes.

• DFG Programme: Research Grants