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Structural alterations within cerebellar circuitry are associated with general liability for common mental disorders

Molecular Psychiatry volume 23, pages 1084–1090 (2018)Cite this article

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Abstract

Accumulating mental-health research encourages a shift in focus toward transdiagnostic dimensional features that are shared across categorical disorders. In support of this shift, recent studies have identified a general liability factor for psychopathology—sometimes called the ‘p factor’— that underlies shared risk for a wide range of mental disorders. Identifying neural correlates of this general liability would substantiate its importance in characterizing the shared origins of mental disorders and help us begin to understand the mechanisms through which the ‘p factor’ contributes to risk. Here we believe we first replicate the ‘p factor’ using cross-sectional data from a volunteer sample of 1246 university students, and then using high-resolution multimodal structural neuroimaging, we demonstrate that individuals with higher ‘p factor’ scores show reduced structural integrity of white matter pathways, as indexed by lower fractional anisotropy values, uniquely within the pons. Whole-brain analyses further revealed that higher ‘p factor’ scores are associated with reduced gray matter volume in the occipital lobe and left cerebellar lobule VIIb, which is functionally connected with prefrontal regions supporting cognitive control. Consistent with the preponderance of cerebellar afferents within the pons, we observed a significant positive correlation between the white matter integrity of the pons and cerebellar gray matter volume associated with higher ‘p factor’ scores. The results of our analyses provide initial evidence that structural alterations in corticocerebellar circuitry supporting core functions related to the basic integration, coordination and monitoring of information may contribute to a general liability for common mental disorders.

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Acknowledgements

We thank the Duke Neurogenetics Study participants and the staff of the Laboratory of NeuroGenetics. The Duke Neurogenetics Study received support from Duke University as well as US-National Institutes of Health Grants R01DA033369 and R01DA031579. ALR was supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE 1106401. ARK, RH, AC, TEM and ARH received further support from US-National Institutes of Health Grant R01AG049789.

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Authors and Affiliations

  1. Department of Psychology and Neuroscience, Laboratory of NeuroGenetics, Duke University, Durham, NC, USA

    A L Romer, A R Knodt, B D Brigidi & A R Hariri

  2. Department of Psychology and Neuroscience, Duke University, Durham, NC, USA

    A L Romer, A R Knodt, R Houts, T E Moffitt, A Caspi & A R Hariri

  3. Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA

    T E Moffitt & A Caspi

  4. Center for Genomic and Computational Biology, Duke University, Durham, NC, USA

    T E Moffitt & A Caspi

  5. Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    T E Moffitt & A Caspi

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  1. A L Romer
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Correspondence to A L Romer.

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Romer, A., Knodt, A., Houts, R. et al. Structural alterations within cerebellar circuitry are associated with general liability for common mental disorders. Mol Psychiatry 23, 1084–1090 (2018). https://doi.org/10.1038/mp.2017.57

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