TY - JOUR
T1 - Inflammatory subgroups of schizophrenia and their association with brain structure
T2 - A semi-supervised machine learning examination of heterogeneity
AU - Alexandros Lalousis, Paris
AU - Schmaal, Lianne
AU - Wood, Stephen J
AU - L E P Reniers, Renate
AU - Cropley, Vanessa L
AU - Watson, Andrew
AU - Pantelis, Christos
AU - Suckling, John
AU - Barnes, Nicholas M
AU - Pariante, Carmine
AU - Jones, Peter B
AU - Joyce, Eileen
AU - Barnes, Thomas R E
AU - Lawrie, Stephen M
AU - Husain, Nusrat
AU - Dazzan, Paola
AU - Deakin, Bill
AU - Shannon Weickert, Cynthia
AU - Upthegrove, Rachel
N1 - Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
Funding Information:
We thank Roxanne Cadiz and Dr. Hayley North in for excellent research assistance and expertise in preforming the cytokine and hsCRP assays.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/10
Y1 - 2023/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85165952259&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2023.06.023
DO - 10.1016/j.bbi.2023.06.023
M3 - Article
C2 - 37423513
SN - 0889-1591
VL - 113
SP - 166
EP - 175
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -