Inflammation and viral infection as disease modifiers in schizophrenia

Abstract

Numerous studies have now implicated a role for inflammation in schizophrenia. However, many aspects surrounding this aspect of the disease are still controversial. This controversy has been driven by conflicting evidence on the role of both pro-and anti-inflammatory factors and by often contentious findings concerning cytokine and immune cell profiles in the central nervous system and periphery. Current evidence supports the point that interleukin-6 is elevated in CSF, but does not support activation of microglia, resident macrophage-like cells in the brain. Furthermore, the mechanisms involving transit of the peripheral immune system factors across the blood brain barrier to central parenchyma have still not been completely elucidated. This process appears to involve perivascular macrophages and accompanying dendritic cells retained in the parenchyma by the chemokine and cytokine composition of the surrounding milieu. In addition, a number of studies have shown that this can be modulated by infection with viruses such as herpes simplex virus type I which may disrupt antigen presentation in the perivascular space, with long-lasting consequences. In this review article, we discuss the role of inflammation and viral infection as potential disease modifiers in schizophrenia. The primary viral hit may occur in the fetus in utero, transforming the immune response regulatory T-cells or the virus may secondarily remain latent in immune cells or neurons and modify further immune responses in the developing individual. It is hoped that unraveling this pathway further and solidifying our understanding of the pathophysiological mechanisms involved will pave the way for future studies aimed at identification and implementation of new biomarkers and drug targets. This may facilitate the development of more effective personalized therapies for individuals suffering with schizophrenia.

Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

“…Currently, functional changes in the CNS are prominent in LC symptomatology. The role of microglial activation linked to viral infections in the development of mild neuroinflammation (neuroparainflammation) is undeniable, not only in the pathogenesis of neurodegenerative diseases and accelerated brain aging [ 201 , 202 , 203 ] but also in canonical neuropsychiatric diseases such as schizophrenia and depression [ 204 , 205 , 206 ]. Moreover, the molecular mechanisms of cellular and tissue proinflammatory stress manifest not only in pathologies but also support many physiological processes of the CNS.…”

Bartonella species bacteremia in association with adult psychosis

“…Psychosis constitutes a severely demoralizing illness for the patient, creates numerous emotional and medical management challenges for family members and physicians, and contributes to a substantial economic burden for society (1,2). An increasing number of studies supports a role for chronic inflammation in various neurological conditions, including studies that have focused on patients with schizophrenia and psychosis (3)(4)(5). In a study involving 638,213 Swedish men, high erythrocyte sedimentation rate, a global indicator of inflammation, was associated with increased risk for schizophrenia and decreased risk for other nonaffective psychoses in adulthood (6).…”