In psychosis, higher TNF-α levels have been associated with increased gray matter volume (GMV) of the left thalamus, while higher CRP levels were associated with increased volume of the left putamen. In depression, higher levels of IL-6 were associated with lower GMV in the hippocampus and higher levels of CRP with lower GMV in the prefrontal cortex. Several mechanisms may be involved in the association between immune dysregulation and structural brain alterations, potentially stemming from genetic and environmental risks (eg, substance misuse and stress). This evidence concerns the gene CRP and major depressive disorder.