title: Cortical grey matter volume reduction in people with schizophrenia is associated with neuro-inflammation.
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.
authors.affiliation: Schizophrenia Research Institute, Randwick, NSW, Australia.|Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Schizophrenia Research Institute, Randwick, NSW, Australia.|Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: V S
authors.initials: VS
authors.lastname: Catts
authors.affiliation: Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Sheedy
authors.affiliation: Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: T
authors.initials: T
authors.lastname: McCrossin
authors.affiliation: Discipline of Pathology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kril
authors.affiliation: Schizophrenia Research Institute, Randwick, NSW, Australia.|Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW, Australia.|School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Shannon Weickert
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy; D002540:Cerebral Cortex / Q000473:pathology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000502:physiology; D017397:Prefrontal Cortex / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D012559:Schizophrenia / Q000235:genetics / Q000473:pathology*; D013223:Statistics as Topic
chemical_list: D016207:Cytokines; D012333:RNA, Messenger