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Abstract

Objective:

Neuroimaging research has revealed that structural brain alterations are common across broad diagnostic families of disorders rather than specific to a single psychiatric disorder. Such overlap in the structural brain correlates of mental disorders mirrors already well-documented phenotypic comorbidity of psychiatric symptoms and diagnoses, which can be indexed by a general psychopathology or p factor. The authors hypothesized that if general psychopathology drives the convergence of structural alterations common across disorders, then 1) there should be few associations unique to any one diagnostic family of disorders, and 2) associations with the p factor should overlap with those for the broader diagnostic families.

Methods:

Analyses were conducted on structural MRI and psychopathology data collected from 861 members of the population-representative Dunedin Multidisciplinary Health and Development Study at age 45.

Results:

Study members with high scores across three broad diagnostic families of disorders (externalizing, internalizing, thought disorder) exhibited highly overlapping patterns of reduced global and widely distributed parcel-wise neocortical thickness. Study members with high p factor scores exhibited patterns of reduced global and parcel-wise neocortical thickness nearly identical to those associated with the three broad diagnostic families.

Conclusions:

A pattern of pervasively reduced neocortical thickness appears to be common across all forms of mental disorders and may represent a transdiagnostic feature of general psychopathology. As has been documented with regard to symptoms and diagnoses, the underlying brain structural correlates of mental disorders may not exhibit specificity, and the continued pursuit of such specific correlates may limit progress toward more effective strategies for etiological understanding, prevention, and intervention.

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Supplementary Material

File (appi.ajp.2020.19090934.ds001.pdf)

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 174 - 182
PubMed: 32600153

History

Received: 10 September 2019
Revision received: 25 February 2020
Accepted: 30 March 2020
Published online: 30 June 2020
Published in print: February 01, 2021

Keywords

  1. Neuroimaging
  2. Cortical Thickness
  3. General Psychopathology
  4. Transdiagnostic
  5. p Factor

Authors

Affiliations

Adrienne L. Romer, Ph.D.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Maxwell L. Elliott, M.A.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Annchen R. Knodt, M.S.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Maria L. Sison, B.S.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
David Ireland, Ph.D.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Renate Houts, Ph.D.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Sandhya Ramrakha, Ph.D.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Richie Poulton, Ph.D.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Ross Keenan, M.B.Ch.B
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Tracy R. Melzer, Ph.D.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Terrie E. Moffitt, Ph.D.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Avshalom Caspi, Ph.D.
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).
Ahmad R. Hariri, Ph.D. [email protected]
Laboratory of NeuroGenetics (Romer, Elliott, Knodt, Sison, Hariri), Department of Psychology and Neuroscience (Romer, Knodt, Houts, Moffitt, Caspi, Hariri), Department of Psychiatry and Behavioral Sciences (Moffitt, Caspi), and Center for Genomic and Computational Biology (Moffitt, Caspi), Duke University, Durham, N.C.; Dunedin Multidisciplinary Health and Development Research Unit, Department of Psychology, University of Otago, Dunedin, New Zealand (Ireland, Ramrakha, Poulton); Christchurch Radiology Group, Christchurch, New Zealand (Keenan); Department of Medicine, University of Otago, Christchurch (Melzer); New Zealand Brain Research Institute, Christchurch (Melzer); Social, Genetic, and Developmental Psychiatry Research Center, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London (Moffitt, Caspi); and McLean Hospital/Harvard Medical School, Belmont, Mass. (Romer).

Notes

Send correspondence to Dr. Hariri ([email protected]).

Competing Interests

The authors report no financial relationships with commercial interests.

Funding Information

Supported by National Institute on Aging grants R01AG032282 and R01AG049789 and UK Medical Research Council grant MR/P005918/1. Additional support was provided by the Jacobs Foundation. Dr. Romer and Mr. Elliott received support from the National Science Foundation Graduate Research Fellowship under grants DGE-1106401 and DGE-1644868, respectively. Dr. Melzer received support from a Sir Charles Hercus Career Development Fellowship from the New Zealand Health Research Council (17/039). The Dunedin Multidisciplinary Health and Development Research Unit was supported by the New Zealand Health Research Council and the New Zealand Ministry of Business, Innovation, and Employment.

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