Brick by Brick: Building a Transdiagnostic Understanding of Inflammation in Psychiatry

Inflammatory phenomena are found in many psychiatric disorders-notably, depression, schizophrenia, and posttraumatic stress disorder. Inflammation has been linked to severity and treatment resistance, and may both contribute to, and result from, the pathophysiology of some psychiatric illnesses. Emerging research suggests that inflammation may contribute to symptom domains of reward, motor processing, and threat reactivity across different psychiatric diagnoses. Reward-processing deficits contribute to motivational impairments in depression and schizophrenia, and motor-processing deficits contribute to psychomotor slowing in both depression and schizophrenia. A number of experimental models and clinical trials suggest that inflammation produces deficits in reward and motor processing through common pathways connecting the cortex and the striatum, which includes the nucleus accumbens, caudate nucleus, and putamen.The observed effects of inflammation on psychiatric disorders may cut across traditional conceptualizations of psychiatric diagnoses. Further study may lead to targeted immunomodulating treatments that address difficult-to-treat symptoms in a number of psychiatric disorders. In this review, we use a Research Domain Criteria framework to discuss proposed mechanisms for inflammation and its effects on the domains of reward processing, psychomotor slowing, and threat reactivity. We also discuss data that support contributing roles of metabolic dysregulation and sex differences on the behavioral outcomes of inflammation. Finally, we discuss ways that future studies can help disentangle this complex topic to yield fruitful results that will help advance the field of psychoneuroimmunology.