Brain cortical and subcortical morphology in adolescents with depression and a history of suicide attempt

Brain cortical and subcortical morphology in adolescents with depression and a history of suicide attempt

J Psychiatry Neurosci 2021;46(3):E347-E357 | PDF | Appendix

Anthony J. Gifuni, MD, MSc; M. Mallar Chakravarty, PhD; Martin Lepage, PhD; Tiffany C. Ho, PhD; Marie-Claude Geoffroy, PhD; Eric Lacourse, PhD; Ian H. Gotlib, PhD; Gustavo Turecki, MD, PhD; Johanne Renaud, MD, MSc*; Fabrice Jollant, MD, PhD*

Background: Suicidal behaviours are a major source of mortality and morbidity among adolescents. Given the maturational changes that occur in cortical and subcortical structures during adolescence, we tested whether atypical brain structural measurements were associated with a history of suicide attempt.

Methods: We assessed 3 groups of adolescents (n = 92; 79% female, mean age 15.9 years, range 11.6–18.1 years): patients with a depressive disorder and a history of suicide attempt (n = 28); patient controls, who had a depressive disorder but no history of suicide attempt (n = 34); and healthy controls (n = 30). We derived regional cortical thickness and surface area, and subcortical volumes, from T1-weighted anatomic MRI scans acquired at 3 T.

Results: We found significant group differences in surface area in the prefrontal, temporal and parietal regions, as well as in the volume of several subcortical nuclei (pFDR ≤ 0.05), but not in cortical thickness. Post hoc analyses indicated that morphological alterations primarily differentiated patients with a history of suicide attempt from healthy controls, but not from patient controls. However, patients with a history of suicide attempt exhibited positive correlations between age and cortical thickness in the temporal cortices and right insula, and between age and right putamen volume (i.e., thicker regional cortex and larger subcortical volumes with age). These correlations were negative in both patient controls and healthy controls (i.e., thinner regional cortex and smaller subcortical volumes).

Limitations: Sample sizes, cross-sectional findings and psychiatric heterogeneity were limitations of this study.

Conclusion: Macroscopic structural differences in several brain regions differentiated adolescents with a history of suicide attempt from healthy controls, but not from patient controls. However, adolescents with a history of suicide attempt may present with atypical maturation of specific cortical and subcortical regions that might contribute to the risk of suicidal behaviour.


Submitted Oct. 21, 2020; Revised Dec. 23, 2020; Accepted Jan. 14, 2021

*Co-senior authors.

Acknowledgements: This research was financed by Manulife Research Fund in Teen Depression, which supports the Manulife Centre for Breakthroughs in Teen Depression and Suicide Prevention. AJG was supported the Fonds de Recherche du Québec–Santé (FRQS/MSSS Resident Physician Health Research Career Training Program). MMC was supported by a Junior 2 Research Scholar Salary from the FRQS. ML was supported by a Research Chair from FRQS and from a James McGill Professorship. MCG holds a Canada Research Chair Tier-2 and a Young Investigator Award of the American Foundation for Suicide Prevention. IHG was supported by the National Institutes of Health (NIH; R37MH101495) and the Stanford University Precision Health and Integrated Diagnostics Center. TCH was supported by the National Institutes of Health (NIH; K01MH117442), the Stanford University Precision Health and Integrated Diagnostics Center and The Ray and Dagmar Dolby Family Fund. The content is solely the responsibility of the authors. The funding agencies played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. We thank Daysi Zentner, Geneviève Laurent, and Léa Perret for their assistance with data collection and organization. Finally, we thank the participants and their families participating in this study as well as the clinicians involved with adolescents and their families (Theodora Mikedis, Jean-Chrysostome Zanga, Didier Blondin-Lavoie).

Affiliations: From the McGill Group for Suicide Studies, Douglas Mental Health University Institute, Montréal, Canada (Gifuni, Geoffroy, Turecki, Renaud, Jollant); the Department of Psychiatry, McGill University, Montréal, Canada (Gifuni, Chakravarty, Lepage, Turecki, Renaud, Jollant); the Manulife Centre for Breakthroughs in Teen Depression and Suicide Prevention, Montréal, Canada (Gifuni, Renaud); the Department of Psychology, Stanford University, Stanford, USA (Gifuni, Gotlib); the Department of Psychiatry & Behavioral Sciences and Weill Institute for Neurosciences, University of California at San Francisco, San Francisco, USA (Ho); the Department of Educational and Counselling Psychology, McGill University, Montréal, Canada (Geoffroy); the Department of Sociology, Université de Montréal, Montréal, Canada (Lacourse); the Université de Paris, Paris, France (Jollant); the GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte-Anne, Paris, France (Jollant); and the Academic Hospital (CHU) Nîmes, Nîmes, France (Jollant).

Competing interests: M. Chakravarty is an associate editor of JPN; he was not involved in the review or decision to accept this manuscript for publication. M. Lepage reports grants from Otsuka Lundbeck Alliance, diaMentis and Roche, research support from Cogsate and personal fees from Otsuka, all outside the submitted work. No other competing interests declared.

Contributors: M.-C. Geoffroy, E. Lacourse, J. Renaud and F. Jollant designed the study. A. Gifuni, J. Renaud and F. Jollant acquired the data, which A. Gifuni, M. Chakravarty, M. Lepage, T. Ho, E. Lacourse, I. Gotlib, G. Turecki, J. Renaud and F. Jollant analyzed. A. Gifuni wrote the article, which M. Chakravarty, M. Lepage, T. Ho, M.-C. Geoffroy, E. Lacourse, I. Gotlib, G. Turecki, J. Renaud and F. Jollant reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

Content licence: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BYNC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is non-commercial (i.e. research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/

DOI: 10.1503/jpn.200198

Correspondence to: F. Jollant, Clinique des Maladies Mentales et de l’Encéphale (CMME), Hôpital Sainte-Anne, 100 rue de la santé, 75674 Paris, Cedex 14, France; fabrice.jollant@parisdescartes.fr