Abstract
Cortical grey matter volume deficits and neuro-inflammation exist in patients with schizophrenia, although it is not clear whether elevated cytokines contribute to the cortical volume reduction. We quantified cortical and regional brain volumes in fixed postmortem brains from people with schizophrenia and matched controls using stereology. Interleukin (IL)-6, IL-1β, IL-8 and SERPINA3 messenger RNAs (mRNAs) were quantified in the contralateral fresh frozen orbitofrontal cortex. We found a small, but significant reduction in cortical grey matter (1.3% F(1,85)=4.478, P=0.037) and superior frontal gyrus (6.5% F(1,80)=5.700, P=0.019) volumes in individuals with schizophrenia compared with controls. Significantly reduced cortical grey matter (9.2% F(1,24)=8.272, P=0.008) and superior frontal gyrus (13.9% F(1,20)=5.374, P=0.031) volumes were found in cases with schizophrenia and ‘high inflammation' status relative to schizophrenia cases with ‘low inflammation' status in the prefrontal cortex. The expression of inflammatory mRNAs in the orbitofrontal cortex was significantly correlated with those in dorsolateral prefrontal cortex (all r>0.417, all P<0.022), except for IL-8. Moreover, average daily and lifetime antipsychotic intake negatively correlated with cortical grey matter and superior frontal gyrus volumes (all r<−0.362, all P<0.05). The results suggest that the reduction in cortical grey matter volume in people with schizophrenia is exaggerated in those who have high expression of inflammatory cytokines. Further, antipsychotic medication intake does not appear to ameliorate the reduction in brain volume.
Highlights
Neuroimaging studies indicate that many individuals with schizophrenia have reduced cortical brain volumes,[1,2,3] it is debated whether this is due to a pathological process[4] or medication effects.[5]
In our recent clinical magnetic resonance imaging (MRI) study, we suggested that increased expression of peripheral blood cytokines is associated with Broca’s area volume reduction,[6] leading us to speculate that neuro-inflammation within the brain tissue may contribute to cortical volume reduction
We focused on the prefrontal cortex (PFC), because we and others have documented evidence of neuro-inflammation in this region,[14,15,16] and we were seeking to determine whether inflammatory status relates to brain volume in the regions proximal to where neuro-inflammation was identified in tissue
Summary
Neuroimaging studies indicate that many individuals with schizophrenia have reduced cortical brain volumes,[1,2,3] it is debated whether this is due to a pathological process[4] or medication effects.[5]. No direct volume measurements of postmortem brain tissue from people with schizophrenia were included, perhaps because only a small number of such studies exist.[7,8,9,10,11] the previous studies suggest that volume reduction is evident in brains from people with schizophrenia after death, it is not clear to what extent it relates to neuro-inflammation
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