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Dynamic and progressive changes in thalamic functional connectivity over the first five years of psychosis

Molecular Psychiatry volume 27, pages 1177–1183 (2022)Cite this article

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Abstract

The early stage of psychosis (ESP) is a critical period where effective intervention has the most favorable impact on outcomes. Thalamic connectivity abnormalities have been consistently found in psychosis, and are associated with clinical symptoms and cognitive deficits. However, most studies consider ESP patients as a homogeneous population and fail to take the duration of illness into account. In this study, we aimed to capture the progression of thalamic connectivity changes over the first five years of psychosis. Resting-state functional MRI scans were collected from 156 ESP patients (44 with longitudinal data) and 82 healthy controls (24 with longitudinal data). We first performed a case-control analysis comparing thalamic connectivity with 13 networks in the cortex and cerebellum. Next, we modelled the shape (flat, linear, curvilinear) of thalamic connectivity trajectories by comparing flexible non-linear versus linear models. We then tested the significance of the duration of illness and diagnosis in trajectories that changed over time. Connectivity changed over the ESP period between the thalamus and default mode network (DMN) and fronto-parietal network (FPN) nodes in both the cortex and cerebellum. Three models followed a curvilinear trajectory (early increase followed by a subsequent decrease), while thalamo-cerebellar FPN connectivity followed a linear trajectory of steady reductions over time, indicating different rates of change. Finally, diagnosis significantly predicted thalamic connectivity. Thalamo-cortical and thalamo-cerebellar connectivity change in a dynamic fashion during the ESP period. A better understanding of these changes may provide insights into the compensatory and progressive changes in functional connectivity in the early stages of illness.

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Fig. 1: Study design and analysis pipeline.
Fig. 2: Results summarizing case-control analysis of thalamic connectivity by cortical/cerebellar networks.
Fig. 3: Results summarizing the 4 thalamic connectivity trajectories that changed over the ESP period.
Fig. 4: Results summarizing the effects of diagnosis specificity on thalamic connectivity trajectories that changed over the ESP period.

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Acknowledgements

This work was supported by the National Institute of Health/National Institute of Mental Health (R01MH116170 (ROB), R01MH117012 (KEL), P50MH115846 (DO), R01MH109687 (MHH)). This work was conducted with statistical support from Professor Garrett Fitzmaurice, Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health.

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Authors and Affiliations

  1. Schizophrenia and Bipolar Disorder Research Program, McLean Hospital, Belmont, MA, USA

    Shi Yu Chan, Roscoe O. Brady, Kathryn E. Lewandowski, Amy Higgins, Dost Öngür & Mei-Hua Hall

  2. Psychosis Neurobiology Laboratory, McLean Hospital, Belmont, MA, USA

    Shi Yu Chan, Amy Higgins, Dost Öngür & Mei-Hua Hall

  3. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    Shi Yu Chan, Roscoe O. Brady, Kathryn E. Lewandowski, Dost Öngür & Mei-Hua Hall

  4. Department of Psychiatry, Beth Israel Deaconess Medical Center and Massachusetts Mental Health Center, Boston, MA, USA

    Roscoe O. Brady

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SYC contributed to the study design, processing and analysis of the data, and preparation of the manuscript. AH contributed to data collection and processing. ROB, KEL, DO and MHH contributed to the study design, interpretation of data and preparation of the paper. All authors gave final approval of the version to be published.

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Correspondence to Shi Yu Chan.

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Dr. Lewandowski has received research funding from diaMentis. All other authors report no financial relationships with commercial interests.

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Chan, S.Y., Brady, R.O., Lewandowski, K.E. et al. Dynamic and progressive changes in thalamic functional connectivity over the first five years of psychosis. Mol Psychiatry 27, 1177–1183 (2022). https://doi.org/10.1038/s41380-021-01319-3

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