Evidence for dissociable linkage of dimensions of psychopathology to brain structure in youths
Open accessAbstract
OBJECTIVE: High comorbidity among psychiatric disorders suggests that they may share underlying neurobiological deficits. Abnormalities in cortical thickness and volume have been demonstrated in clinical samples of adults, but less is known when these structural differences emerge in youths. The purpose of this study was to examine the association between dimensions of psychopathology and brain structure. METHODS: The authors studied 1,394 youths who underwent brain imaging as part of the Philadelphia Neurodevelopmental Cohort. Dimensions of psychopathology were constructed using a bifactor model of symptoms. Cortical thickness and volume were quantified using high-resolution 3-T MRI. Structural covariance networks were derived using nonnegative matrix factorization and analyzed using generalized additive models with penalized splines to capture both linear and nonlinear age-related effects. RESULTS: Fear symptoms were associated with reduced cortical thickness in most networks, and overall psychopathology was associated with globally reduced gray matter volume across all networks. Structural covariance networks predicted psychopathology symptoms above and beyond demographic characteristics and cognitive performance. CONCLUSIONS: The results suggest a dissociable relationship whereby fear is most strongly linked to reduced cortical thickness and overall psychopathology is most strongly linked to global reductions in gray matter volume. Such results have implications for understanding how abnormalities of brain development may be associated with divergent dimensions of psychopathology.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The p factor is associated with altered perfusion of the dorsal anterior cingulate cortex, reduced gray matter volume across the brain, and reduced brain activation in task control systems during a working memory task.
“Using cross-sectional samples of over 1000 children ages 11 to 23 years, in- vestigators found that increased p showed altered perfusion of the dorsal anterior cingulate cortex (34), reduced gray matter volume across the brain (35), and reduced brain activation in task control systems when engaged in a working memory task (36).”
From Methods and challenges for assessing heterogeneity (2020) · cites this paper as [35]
A common framework is comparisons between bifactor and correlated factor models using confirmatory factor analysis.
“A common framework is comparisons between bifactor (Figure 2A) and correlated factor models (Figure 2B) using confirmatory factor analysis (27,28,32–35,37–39).”
From Methods and challenges for assessing heterogeneity (2020) · cites this paper as [35]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Dissociable intrinsic connectivity networks for salience processing and executive control
Seeley, W. W., Menon, V., Schatzberg, A. F., Keller, J., Glover, G. H., Kenna, H., Reiss, A. L., & Greicius, M. D. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5587-06.2007 · Cited by 7,426 · see citing works
Cognitive and emotional influences in anterior cingulate cortex
Bush, G., Luu, P., & Posner, M. I. (2000) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(00)01483-2 · Cited by 6,259 · see citing works
Age of onset of mental disorders: a review of recent literature
Kessler, R. C., Amminger, G. P., Aguilar-Gaxiola, S., Alonso, J., Lee, S., & ??st??n, T. B. (2007) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e32816ebc8c · Cited by 3,457 · see citing works
The attention system of the human brain: 20 years after
Petersen, S. E., & Posner, M. I. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062111-150525 · Cited by 3,439 · see citing works
Kessler, R. C., Petukhova, M., Sampson, N. A., Zaslavsky, A. M., & Wittchen, H. (2012) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.1359 · Cited by 2,947 · cited 1× · see citing works
“This is an important caveat, as most psychiatric disorders first manifest during childhood, adolescence, or young adulthood (10, 11), suggesting that large studies of brain structure in youths are needed.”
BackgroundIntellectual ability and cortical development in children and adolescents
Shaw, P., Greenstein, D., Lerch, J., Clasen, L., Lenroot, R., Gogtay, N., Evans, A., Rapoport, J., & Giedd, J. (2006) · Nature · doi:10.1038/nature04513 · Cited by 1,543 · see citing works
Identification of a Common Neurobiological Substrate for Mental Illness
Goodkind, M., Eickhoff, S. B., Oathes, D. J., Jiang, Y., Chang, A., Jones-Hagata, L. B., Ortega, B. N., Zaiko, Y. V., Roach, E. L., Korgaonkar, M. S., et al. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.2206 · Cited by 1,404 · see citing works
for the ENIGMA-Major Depressive Disorder Working Group, Schmaal, L., Hibar, D. P., Sämann, P. G., Hall, G. B., Baune, B. T., Jahanshad, N., Cheung, J. W., van Erp, T. G. M., Bos, D., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.60 · Cited by 1,330 · see citing works
Winkler, A. M., Kochunov, P., Blangero, J., Almasy, L., Zilles, K., Fox, P. T., Duggirala, R., & Glahn, D. C. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2009.12.028 · Cited by 1,172 · see citing works
Regier, D. A., Narrow, W. E., Clarke, D. E., Kraemer, H. C., Kuramoto, S. J., Kuhl, E. A., & Kupfer, D. J. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.12070999 · Cited by 1,163 · see citing works
All for One and One for All: Mental Disorders in One Dimension
Caspi, A., & Moffitt, T. E. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.17121383 · Cited by 918 · see citing works
Tamnes, C. K., Herting, M. M., Goddings, A.-L., Meuwese, R., Blakemore, S.-J., Dahl, R. E., Güroğlu, B., Raznahan, A., Sowell, E. R., Crone, E. A., et al. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3302-16.2017 · Cited by 685 · see citing works
Is there a general factor of prevalent psychopathology during adulthood?
Lahey, B. B., Applegate, B., Hakes, J. K., Zald, D. H., Hariri, A. R., & Rathouz, P. J. (2012) · Journal of Abnormal Psychology · doi:10.1037/a0028355 · Cited by 641 · see citing works
Cannon, T. D., Chung, Y., He, G., Sun, D., Jacobson, A., van Erp, T. G. M., McEwen, S., Addington, J., Bearden, C. E., Cadenhead, K., et al. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.05.023 · Cited by 599 · see citing works
Functional network dysfunction in anxiety and anxiety disorders
Sylvester, C. M., Corbetta, M., Raichle, M. E., Rodebaugh, T. L., Schlaggar, B. L., Sheline, Y. I., Zorumski, C. F., & Lenze, E. J. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.04.012 · Cited by 579 · see citing works
Neuroimaging of the Philadelphia Neurodevelopmental Cohort
Satterthwaite, T. D., Elliott, M. A., Ruparel, K., Loughead, J., Prabhakaran, K., Calkins, M. E., Hopson, R., Jackson, C., Keefe, J., Riley, M., et al. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.07.064 · Cited by 504 · see citing works
Self-citationMakris, N., Biederman, J., Valera, E. M., Bush, G., Kaiser, J., Kennedy, D. N., Caviness, V. S., Faraone, S. V., & Seidman, L. J. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhl047 · Cited by 450 · see citing works
Quantitative Assessment of Structural Image Quality
Rosen, A. F. G., Roalf, D., Ruparel, K., Blake, J., Seelaus, K., Villa, L., Ciric, R., Cook, P. A., Davatzikos, C., Elliott, M., et al. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.12.059 · Cited by 443 · see citing works
Self-citationA Hierarchical Taxonomy of Psychopathology Can Transform Mental Health Research
Conway, C. C., Forbes, M. K., Forbush, K. T., Fried, E. I., Hallquist, M. N., Kotov, R., Mullins-Sweatt, S. N., Shackman, A. J., Skodol, A. E., South, S. C., et al. (2019) · Perspectives on Psychological Science · doi:10.1177/1745691618810696 · Cited by 426 · see citing works
Sex differences in the developing brain: insights from multimodal neuroimaging
Kaczkurkin, A. N., Raznahan, A., & Satterthwaite, T. D. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-018-0111-z · Cited by 403 · see citing works
Self-citationAnnual Research Review: Parenting and children’s brain development: the end of the beginning
Belsky, J., & de Haan, M. D. H. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02281.x · Cited by 397 · see citing works
Satterthwaite, T. D., Connolly, J. J., Ruparel, K., Calkins, M. E., Jackson, C., Elliott, M. A., Roalf, D. R., Hopson, R., Prabhakaran, K., Behr, M., et al. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2015.03.056 · Cited by 335 · cited 6× · see citing works
“Data from the PNC can be accessed at https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study. cgi?study_id=phs000607.v3.p2.”
BackgroundMethodInfluentialSelf-citationThe structure of psychopathology in adolescence and its common personality and cognitive correlates.
Castellanos-Ryan, N., The IMAGEN Consortium, Brière, F. N., O'Leary-Barrett, M., Banaschewski, T., Bokde, A., Bromberg, U., Büchel, C., Flor, H., Frouin, V., et al. (2016) · Journal of Abnormal Psychology · doi:10.1037/abn0000193 · Cited by 299 · see citing works
Shanmugan, S., Wolf, D. H., Calkins, M. E., Moore, T. M., Ruparel, K., Hopson, R. D., Vandekar, S. N., Roalf, D. R., Elliott, M. A., Jackson, C., et al. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15060725 · Cited by 219 · see citing works
Self-citationOlbert, C. M., Gala, G. J., & Tupler, L. A. (2014) · Journal of Abnormal Psychology · doi:10.1037/a0036068 · Cited by 209 · see citing works
A polygenic p factor for major psychiatric disorders
Selzam, S., Coleman, J. R. I., Caspi, A., Moffitt, T. E., & Plomin, R. J. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0217-4 · Cited by 171 · see citing works
Fox, A. S., & Kalin, N. H. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.14040449 · Cited by 160 · see citing works
Finding imaging patterns of structural covariance via Non-Negative Matrix Factorization
Sotiras, A., Resnick, S. M., & Davatzikos, C. A. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2014.11.045 · Cited by 147 · see citing works
Self-citationSotiras, A., Toledo, J. B., Gur, R. E., Gur, R. C., Satterthwaite, T. D., & Davatzikos, C. A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620928114 · Cited by 144 · see citing works
Self-citationRomer, A. L., Knodt, A. R., Houts, R., Brigidi, B. D., Moffitt, T. E., Caspi, A., & Hariri, A. R. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.57 · Cited by 142 · see citing works
Comorbidity of Physical and Mental Disorders in the Neurodevelopmental Genomics Cohort Study
Merikangas, K. R., Calkins, M. E., Burstein, M., He, J., Chiavacci, R. M., Lateef, T. M., Ruparel, K., Gur, R. C., Lehner, T., Hakonarson, H. H., et al. (2015) · PEDIATRICS · doi:10.1542/peds.2014-1444 · Cited by 129 · see citing works
Self-citationLindemer, E., Salat, D. H., Leritz, E. C., McGlinchey, R. E., & Milberg, W. (2013) · NeuroImage Clinical · doi:10.1016/j.nicl.2013.04.009 · Cited by 112 · see citing works
Grey matter abnormalities in social anxiety disorder: a pilot study
Syal, S., Hattingh, C. J., Fouché, J., Spottiswoode, B. S., Carey, P. D., Löchner, C., & Stein, D. J. (2012) · Metabolic Brain Disease · doi:10.1007/s11011-012-9299-5 · Cited by 102 · see citing works
Kaczkurkin, A. N., Moore, T. M., Calkins, M. E., Ciric, R., Detre, J. A., Elliott, M. A., Foa, E. B., Garcia de la Garza, A., Roalf, D. R., Rosen, A., et al. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.174 · Cited by 86 · see citing works
Self-citationSnyder, H. R., Hankin, B. L., Sandman, C. A., Head, K., & Davis, E. P. (2017) · Clinical Psychological Science · doi:10.1177/2167702617714563 · Cited by 77 · see citing works
Implications of the Hierarchical Structure of Psychopathology for Psychiatric Neuroimaging
Zald, D. H., & Lahey, B. B. (2017) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2017.02.003 · Cited by 76 · see citing works
The hippocampus in families with schizophrenia in relation to obstetric complications
Ebner, F. H., Tepest, R., Dani, I., Pfeiffer, U., Schulze, T. G., Rietschel, M., Maier, W., Träber, F., Block, W., Schild, H. H., et al. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.06.007 · Cited by 35 · see citing works
Shackman, A. J., & Fox, A. S. (2018) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2018.02.009 · Cited by 33 · see citing works
Linares, I. M. P., Jackowski, A. P., Trzesniak, C. M. F., Arrais, K. C., Chagas, M. H. N., Sato, J. R., dos Santos, A. C., Hallak, J. E. C., Zuardi, A. W., Nardi, A. E., et al. (2014) · Brain Research · doi:10.1016/j.brainres.2014.05.040 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [20]Wood SN: mgcv: GAMs and generalized ridge regression for R. R News 2001; 1: 20– 25
Cited by
Sorted by citations
Kotov, R., Krueger, R. F., Watson, D., Cicero, D. C., Conway, C. C., DeYoung, C. G., Eaton, N. R., Forbes, M. K., Hallquist, M. N., Latzman, R. D., et al. (2021) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-081219-093304 · Cited by 596 · see citing works
Hierarchical models of psychopathology: empirical support, implications, and remaining issues
Lahey, B. B., Moore, T. M., Kaczkurkin, A. N., & Zald, D. H. (2021) · World Psychiatry · doi:10.1002/wps.20824 · Cited by 188 · see citing works
Self-citationMethods and challenges for assessing heterogeneity
Feczko, E., & Fair, D. A. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.02.015 · Cited by 96 · see citing works
Pervasively Thinner Neocortex as a Transdiagnostic Feature of General Psychopathology
Romer, A. L., Elliott, M. L., Knodt, A. R., Sison, M. L., Ireland, D., Houts, R., Ramrakha, S., Poulton, R., Keenan, R., Melzer, T. R., et al. (2021) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.19090934 · Cited by 87 · see citing works
Liloia, D., Rocca, P., Brasso, C., Tanaka, M., Manuello, J., Crocetta, A., Duca, S., Costa, T., & Cauda, F. (2026) · Psychological Medicine · doi:10.1017/s0033291726103511 · Cited by 4 · see citing works
- Authors
- Kaczkurkin, A. N., Park, S. S., Sotiras, A., Moore, T. M., Calkins, M. E., Cieslak, M., Rosen, A. F. G., Ciric, R., Xia, C. H., Cui, Z., Sharma, A., Wolf, D. H., Ruparel, K., Pine, D. S., Shinohara, R. T., Roalf, D. R., Gur, R. C., Davatzikos, C., Gur, R. E., & Satterthwaite, T. D.
- Affiliations
- Washington University in St. Louis (US)
- The Department of Psychiatry (Kaczkurkin, Moore, Calkins, Cieslak, Rosen, Ciric, Xia, Cui, Sharma, Wolf, Ruparel, Roalf, R.C. Gur, R.E. Gur, Satterthwaite) and the Department of Radiology (Sotiras, R.C. Gur, Davatzikos, R.E. Gur), Perelman School of Medicine, University of Pennsylvania, Philadelphia; the Department of Psychiatry, Lewis Katz School of Medicine, Temple University, Philadelphia (Park); the Department of Radiology, Washington University, St. Louis (Sotiras); the Emotion and Development...
- ORCID
- Kaczkurkin, Antonia N.
- Sotiras, Aristeidis
- Moore, Tyler M.
- Calkins, Monica E.
- Cieslak, Matthew
- Rosen, Adon F.G.
- Xia, Cedric Huchuan
- Cui, Zaixu
- Sharma, Anup
- Wolf, Daniel H.
- Ruparel, Kosha
- Pine, Daniel S.
- Shinohara, Russell T.
- Roalf, David R.
- Gur, Ruben C.
- Davatzikos, Christos
- Gur, Raquel E.
- Satterthwaite, Theodore D.
- Venue
- American Journal of Psychiatry
- Published
- 2019-12-01
- Volume
- 176
- Issue
- 12
- Pages
- 1000-1009
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC6888993
- OpenAlex
- W2953773456
- Cited by
- 110
- References
- 39
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 19 · 2023: 20 · 2022: 20 · 2021: 14 · 2020: 10 · 2019: 5
- FWCI
- 7.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Multiple Sclerosis Society
- Race to Erase MS
- Multiple Sclerosis Society
- National Institutes of Health (5r01mh107235-03, 5r01ns099348-04, 1s10od023495-01)
- Genentech
- National Institute of Mental Health (RC2MH089983, R01-MH-107235, R01MH112070, RC2MH089924, R00MH117274, K99MH117274, R01MH107703, R01MH112847, R01MH113550)
- National Institute of Neurological Disorders and Stroke (R01NS085211, (R01 NS099348)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD085848)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Mental Health Research Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- psychopathology dimensions, cortical thickness, gray matter volume, structural covariance networks, psychiatric comorbidity, brain development, adolescents, bifactor model, Philadelphia Neurodevelopmental Cohort, neuroimaging
- MeSH terms
- Adolescent, Atrophy, Mental Disorders, Cerebral Cortex, Child, Cognition, Fear, Female, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Neuropsychological Tests, Psychopathology, Gray Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
