Implication of T Cell Exhaustion in Neuropsychiatric Disorders: Neuroimmunopathology and Treatment Strategies

T cell exhaustion denotes the progressive loss of T cell functions. The concept was initially defined in the context of infections. However, a large body of evidence stresses that T cell exhaustion plays a significant role in the tumour microenvironment. In the field of neuropsychiatry, the role of exhaustion mechanisms is somewhat understudied. Nevertheless, emerging evidence showed the role of T cell exhaustion in bipolar disorder (BD), schizophreniaSchizophrenia, and depression in the context of infections such as cytomegalovirus (CMV)Cytomegalovirus (CMV) and ToxoplasmaToxoplasma gondii, or childhood maltreatment. Research shows there may be a double-hit mechanism involving infection and neuropsychiatric diseases governing the exhaustion of the adaptive immune mechanisms. Overall, while there are interesting pieces of evidence surfacing in recent years, a strong neuroimmunopathological link between psychiatric disorders and exhaustion mechanisms is yet to be established, and more importantly there is a lack of studies attempting the therapeutic targeting of T cell exhaustion mechanisms which may deserve more attention. The present chapter introduces the basics of T cell exhaustion, discusses the role of exhaustion mechanisms in neuropsychiatric disorders in different contexts, and provides insights for possible directing of treatmentTreatment strategies targeting exhaustion mechanisms towards neuropsychiatric diseases.