Inflammatory subgroups of schizophrenia and their association with brain structure: A semi-supervised machine learning examination of heterogeneity.

OBJECTIVE: Immune system dysfunction is hypothesised to contribute to structural brain changes through aberrant synaptic pruning in schizophrenia. However, evidence is mixed and there is a lack of evidence of inflammation and its effect on grey matter volume (GMV) in patients. We hypothesised that inflammatory subgroups can be identified and that the subgroups will show distinct neuroanatomical and neurocognitive profiles. METHODS: The total sample consisted of 1067 participants (chronic patients with schizophrenia n = 467 and healthy controls (HCs) n = 600) from the Australia Schizophrenia Research Bank (ASRB) dataset, together with 218 recent-onset patients with schizophrenia from the external Benefit of Minocycline on Negative Symptoms of Psychosis: Extent and Mechanism (BeneMin) dataset. HYDRA (HeterogeneitY through DiscRiminant Analysis) was used to separate schizophrenia from HC and define disease-related subgroups based on inflammatory markers. Voxel-based morphometry and inferential statistics were used to explore GMV alterations and neurocognitive deficits in these subgroups. RESULTS: An optimal clustering solution revealed five main schizophrenia groups separable from HC: Low Inflammation, Elevated CRP, Elevated IL-6/IL-8, Elevated IFN-γ, and Elevated IL-10 with an adjusted Rand index of 0.573. When compared with the healthy controls, the IL-6/IL-8 cluster showed the most widespread, including the anterior cingulate, GMV reduction. The IFN-γ inflammation cluster showed the least GMV reduction and impairment of cognitive performance. The CRP and the Low Inflammation clusters dominated in the younger external dataset. CONCLUSIONS: Inflammation in schizophrenia may not be merely a case of low vs high, but rather there are pluripotent, heterogeneous mechanisms at play which could be reliably identified based on accessible, peripheral measures. This could inform the successful development of targeted interventions.

Transdiagnostic structural neuroimaging features in depression and psychosis: A systematic review.

BACKGROUND: Previous research suggests that there may be similarities in structural brain changes seen in patients with depression and psychosis compared to healthy controls. However, there is yet no systematic review collating studies comparing structural brain changes in depression and psychosis. Establishing shared and specific neuroanatomical features could aid the investigation of underlying biological processes. AIMS: To identify structural neuroimaging similarities and differences between patients with depression and psychosis. METHOD: We searched PubMed, PsychInfo, Embase, NICE Evidence, Medline and the Cochrane Library were searched from inception to 30/06/2021 using relevant subject headings (controlled vocabularies) and search syntax. Papers were assessed for quality using the Newcastle-Ottawa Scale. RESULTS: Five-hundred and twenty papers were retrieved, seven met inclusion criteria. In narrative collation of results, grey matter volume (GMV) reductions were found in the medial frontal gyrus (MFG), hippocampus and left-sided posterior subgenual prefrontal cortex in both psychosis and depression. GMV reductions affected more brain regions in psychosis, including in the insula and thalamus. White matter volume (WMV) decline was found in both depression and psychosis. Reduced fractional anisotropy (FA) was more commonly seen in depression. CONCLUSIONS: Our results suggest potential transdiagnostic patterns of GMV and WMV reductions in areas including the MFG, hippocampus, and left-sided posterior subgenual prefrontal cortex. These could be investigated as a future biomarker of transdiagnostic signature across mental illnesses. However, due to the limited number and poor quality of studies future research in large samples and harmonised imaging data is first needed.