Marie-Laure Ancelin, PhD; Isabelle Carrière, PhD; Sylvaine Artero, PhD; Jerome Maller, PhD; Chantal Meslin, PhD; Karen Ritchie, PhD; Joanne Ryan, PhD; Isabelle Chaudieu, PhD
Background: There is evidence of structural brain alterations in major depressive disorder (MDD), but little is known about how these alterations might be affected by age at onset or genetic vulnerability. This study examines whether lifetime episodes of MDD are associated with specific alterations in grey-matter volume, and whether those alterations vary according to sex or serotonin transporter-linked promoter region (5-HTTLPR) genotype (LL, SL or SS).
Methods: We used structural MRI to acquire anatomic scans from 610 community-dwelling participants. We derived quantitative regional estimates of grey-matter volume in 16 subregions using FreeSurfer software. We diagnosed MDD according to DSM-IV criteria. We adjusted analyses for age, sex, total brain volume, education level, head injury and comorbidities.
Results: Lifetime MDD was associated with a smaller insula, thalamus, ventral diencephalon, pallidum and nucleus accumbens and with a larger pericalcarine region in both men and women. These associations remained after adjustment for false discovery rate. Lifetime MDD was also associated with a smaller caudate nucleus and amygdala in men and with a larger rostral anterior cingulate cortex in women. Late-onset first episodes of MDD (after age 50 years) were associated with a larger rostral anterior cingulate cortex and lingual and pericalcarine regions; early-onset MDD was associated with a smaller ventral diencephalon and nucleus accumbens. Some associations differed according to 5-HTTLPR genotype: the thalamus was smaller in participants with MDD and the LL genotype; pericalcarine and lingual volumes were higher in those with the SL genotype.
Limitations: This study was limited by its cross-sectional design.
Conclusion: Major depressive disorder was associated with persistent volume reductions in the deep nuclei and insula and with enlargements in visual cortex subregions; alterations varied according to age of onset and genotype.
Submitted Feb. 14, 2018; Revised Apr. 11, 2018; Accepted May 7, 2018; Published online Sept. 18, 2018
Acknowledgements: The ESPRIT project is financed by the regional government of Languedoc-Roussillon, the Agence Nationale de la Recherche Project 07 LVIE 004 and an unconditional grant from Novartis. This work was also supported by France Alzheimer. The funders had no role in the design and conduct of the study, or in data collection, management, analysis or interpretation, and they were not involved with the writing, preparation, review or approval of the manuscript.
Affiliations: From INSERM, Univ Montpellier, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France (Ancelin, Carrière, Artero, Ritchie, Ryan, Chaudieu); Monash Alfred Psychiatry Research Centre, Central Clinical School, Monash University and Alfred Hospital, Australia (Maller); Centre for Mental Health Research, Australian National University, Canberra, Australia (Maller, Meslin); General Electric Healthcare, Australia (Maller); Center for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom (Ritchie); and Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia (Ryan).
Competing interests: None declared.
Contributors: M-L. Ancelin designed the study. M-L. Ancelin and K. Ritchie led the ESPRIT study and the collection of data. J. Maller and C. Meslin processed all neuroimaging data. I. Carrière performed all statistical analyses. M-L. Ancelin, S. Artero, J. Ryan and I. Chaudieu were involved in the interpretation of the data. M-L. Ancelin drafted the manuscript, which all authors 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.
Correspondence to: M.-L. Ancelin, INSERM U1061, Hôpital La Colombière, 39 Avenue Flahault, BP 34493, 34093 Montpellier Cedex 5, France; email@example.com