Psychiatric symptoms in multiple sclerosis: a biological perspective on synaptic and network dysfunction

Psychiatric symptoms frequently occur in multiple sclerosis (MS), presenting with a complex phenomenology that encompasses a large clinical spectrum from clear-cut psychiatric disorders up to isolated psychopathological manifestations. Despite their relevant impact on the overall disease burden, such clinical features are often misdiagnosed, receive suboptimal treatment and are not systematically evaluated in the quantification of disease activity. The development of psychiatric symptoms in MS underpins a complex pathogenesis involving both emotional reactions to a disabling disease and structural multifocal central nervous system damage. Here, we review MS psychopathological manifestations under a biological perspective, highlighting the pathogenic relevance of synaptic and neural network dysfunction. Evidence obtained from human and experimental disease models suggests that MS-related psychiatric phenomenology is part of a disconnection syndrome due to diffuse inflammatory and neurodegenerative brain damage.

Automated summary

Psychiatric symptoms in multiple sclerosis (MS) are diverse, ranging from clear-cut psychiatric disorders to isolated psychopathological manifestations. These clinical features often go misdiagnosed, receive suboptimal treatment, and are not adequately assessed in disease activity quantification. Pathogenesis of psychiatric symptoms in MS involves emotional reactions to the disability caused by the disease as well as structural damage in the central nervous system. Biological perspective reveals that MS-related psychiatric manifestations are associated with synaptic and neural network dysfunction due to diffuse brain damage from inflammation and neurodegeneration.