Towards a 'systems'-level understanding of the nervous system and its disorders

It is becoming clear that nervous system development and adult functioning are highly coupled with other physiological systems. Accordingly, neurological and psychiatric disorders are increasingly being associated with a range of systemic comorbidities including, most prominently, impairments in immunological and bioenergetic parameters as well as in the gut microbiome. Here, we discuss various aspects of the dynamic crosstalk between these systems that underlies nervous system development, homeostasis, and plasticity. We believe a better definition of this underappreciated systems physiology will yield important insights into how nervous system diseases with systemic comorbidities arise and potentially identify novel diagnostic and therapeutic strategies.