Abstract
Behavioral interventions including exercise, stress management, patient education, psychotherapy and multidisciplinary neurorehabilitation in general are receiving increasing recognition in multiple sclerosis (MS) clinical practice and research. Most scientific evaluations of these approaches have focused on psychosocial outcome measures such as quality of life, fatigue or depression. However, it is becoming increasingly clear that neuropsychiatric symptoms of MS are at least partially mediated by biological processes such as inflammation, neuroendocrine dysfunction or regional brain damage. Thus, successful treatment of these symptoms with behavioral approaches could potentially also affect the underlying biology. Rigidly designed scientific studies are needed to explore the potential of such interventions to affect MS pathology and biological pathways linked to psychological and neuropsychiatric symptoms of MS. Such studies need to carefully select outcome measures on the behavioral level that are likely to be influenced by the specific intervention strategy and should include biomarkers with evidence for an association with the outcome parameter in question. In this overview, we illustrate how biological and psychological outcome parameters can be combined to evaluate behavioral interventions. We focus on two areas of interest as potential targets for behavioral interventions: depression and fatigue.