Neuroinflammatory Loop in Schizophrenia, Is There a Relationship with Symptoms or Cognition Decline?

Schizophrenia (SZ), a complex psychiatric disorder of neurodevelopment, is characterised by a range of symptoms, including hallucinations, delusions, social isolation and cognitive deterioration. One of the hypotheses that underlie SZ is related to inflammatory events which could be partly responsible for symptoms. However, it is unknown how inflammatory molecules can contribute to cognitive decline in SZ. This review summarises and exposes the possible contribution of the imbalance between pro-inflammatory and anti-inflammatory interleukins like IL-1beta, IL-4 and TNFalfa among others on cognitive impairment. We discuss how this inflammatory imbalance affects microglia and astrocytes inducing the disruption of the blood-brain barrier (BBB) in SZ, which could impact the prefrontal cortex or associative areas involved in executive functions such as planning and working tasks. We also highlight that inflammatory molecules generated by intestinal microbiota alterations, due to dysfunctional microbial colonisers or the use of some anti-psychotics, could impact the central nervous system. Finally, the question arises as to whether it is possible to modulate or correct the inflammatory imbalance that characterises SZ, and if an immunomodulatory strategy can be incorporated into conventional clinical treatments, either alone or in complement, to be applied in specific phases, such as prodromal or in the first-episode psychosis.