Longitudinal cortical thinning in antipsychotic-naïve first episode psychosis
Poster No:
423
Submission Type:
Abstract Submission
Authors:
Sidhant Chopra1, Alexander Holmes2, Ashlea Segal3, Xihan Zhang3, Shona Francey4, Brian O'donoghue4, Vanessa Cropley5, Barnaby Nelson4, Jessica Graham4, Lara Baldwin4, Hok Pan Yuen4, Kelly Allott4, Mario Alvarez-Jimenez4, Susy Harrigan4, Avram Holmes4, Christos Pantelis4, Stephen Wood6, Patrick McGorry4, Alex Fornito7
Institutions:
1Orygen, Preston, Victoria, 2University of Oxford, Oxford, Oxfordshire, 3Yale University, New Haven, CT, 4Orygen, Melbourne, Victoria, 5Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia, 6University of Melbourne, Parkville, Victoria, 7Monash University, Clayton, Victoria
First Author:
Co-Author(s):
Introduction:
Changes in cortical thickness are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis[1]. Moreover, numerous longitudinal studies suggest that anatomical deficits can progress with illness duration[2-4]. A major unresolved question in the field is whether these changes are driven by the underlying illness or represent effects of antipsychotic medication. The only way to experimentally disentangle illness and medication effects on the human brain is through a randomised placebo-controlled MRI study of antipsychotic medications in patients.
Methods:
We report findings from a triple-blind randomised placebo-controlled MRI study where 62 antipsychotic-naïve people with first episode psychosis (FEP) received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. A healthy control group (n=27) was also recruited. Anatomical T1-weighed scans were collected at baseline, 3-months and 12-months. Cortex-wide linear mixed effects models were used to examine illness- and antipsychotic-related changes in cortical thickness and surface area. We also examined whether cortical changes were enriched within canonical functional and cytoarchitectonic networks, normative receptor/transporter densities measured in vivo via PET imaging [5], and normative transcript-defined cell densities measured ex vivo [6].
Results:
We found widespread cortical thinning over 12 months (p<.05 FDR; Fig1A) in people with FEP receiving placebo compared to healthy controls, primarily in frontal, cingulate, and occipital areas. No significant thinning was detected in antipsychotic-treated people with FEP, or any changes in surface area or at 3 months post baseline (Fig1B-D). Thinning in the placebo group spatially aligned with normative distributions of GABA-A/BZ, 5HT-1B, 5HT-2A, and H3 receptors (.17 < r < .28; p<.05 FDR; Fig2A). Koniocortical areas defined using the von Economo and Koskinas atlas [7,8] were relatively protected from cortical thinning (p<.05 FDR; Fig2D). No significant associations were detected between cortical thinning and symptom or functional changes.
·Fig1. Illness related cortical thinning over the first 1 year of illness cannot be attributed to antipsychotic medications.
·Fig2. Illness related cortical thinning is spatially correlated with the distribution of multiple neurotransmitter systems, and primary sensory regions are relatively protected from thinning.
Conclusions:
In this sample, we previously reported a decline in basal ganglia volume over 3 months in people with FEP receiving placebo compared to healthy controls, which was ameliorated in those receiving antipsychotics [4]. Here we extended this finding to the cortex to show widespread cortical thinning over 12 months in people with FEP receiving placebo compared to healthy controls, with no such difference detected in those receiving antipsychotics. These findings are consistent with the view that cortical thinning is an illness-related phenomenon in FEP that is not necessarily caused by antipsychotic medications, at least during the first year of treatment. Moreover, our results suggest that antipsychotics may ameliorate or prevent illness-related cortical thinning. Highlighting potential molecular and cellular vulnerabilities, the observed thinning was spatially associated with neurotransmitter receptor distributions with primary sensory cortices relatively preserved.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Physiology, Metabolism and Neurotransmission:
Pharmacology and Neurotransmission 2
Keywords:
Pharmacotherapy
Psychiatric
Psychiatric Disorders
Schizophrenia
1|2Indicates the priority used for review
Abstract Information
By submitting your proposal, you grant permission for the Organization for Human Brain Mapping (OHBM) to distribute your work in any format, including video, audio print and electronic text through OHBM OnDemand, social media channels, the OHBM website, or other electronic publications and media.
The Open Science Special Interest Group (OSSIG) is introducing a reproducibility challenge for OHBM 2025. This new initiative aims to enhance the reproducibility of scientific results and foster collaborations between labs. Teams will consist of a “source” party and a “reproducing” party, and will be evaluated on the success of their replication, the openness of the source work, and additional deliverables. Click here for more information. Propose your OHBM abstract(s) as source work for future OHBM meetings by selecting one of the following options:
Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.
Please indicate which methods were used in your research:
For human MRI, what field strength scanner do you use?
Which processing packages did you use for your study?
Provide references using APA citation style.
2 van Haren, N. E. M. Changes in Cortical Thickness During the Course of Illness in Schizophrenia. Archives of General Psychiatry 68, 871, doi:10.1001/archgenpsychiatry.2011.88 (2011).
3 Vita, A., De Peri, L., Deste, G. & Sacchetti, E. Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies. Translational Psychiatry 2, e190-e190, doi:10.1038/tp.2012.116 (2012).
4 Chopra, S. et al. Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study. Neuropsychopharmacology 46, 1494-1501 (2021).
5 Markello, R. D. et al. Neuromaps: structural and functional interpretation of brain maps. Nature Methods 19, 1472-1479 (2022).
6 Zhang, X.-H. et al. The cell-type underpinnings of the human functional cortical connectome. Nature Neuroscience, 1-11 (2024).
7 Scholtens, L. H., de Reus, M. A., de Lange, S. C., Schmidt, R. & van den Heuvel, M. P. An MRI Von Economo – Koskinas atlas. NeuroImage 170, 249-256, doi:https://doi.org/10.1016/j.neuroimage.2016.12.069 (2018).
8 von Economo, C. F. & Koskinas, G. N. Die cytoarchitektonik der hirnrinde des erwachsenen menschen. (J. Springer, 1925).