Psychological Medicine

Original Articles

Associations of current and remitted major depressive disorder with brain atrophy: the AGES–Reykjavik Study

M. I. Geerlingsa1a2 c2, S. Sigurdssona3, G. Eiriksdottira3, M. E. Garciaa2, T. B. Harrisa2, T. Sigurdssona4, V. Gudnasona3a5 and L. J. Launera2 c1

a1 University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, The Netherlands

a2 Laboratory for Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes on Health, Bethesda, MD, USA

a3 Icelandic Heart Association, Kopavogur, Iceland

a4 Landspitali University Hospital, Reykjavik, Iceland

a5 University of Iceland, Reykjavik, Iceland


Background To examine whether lifetime DSM-IV diagnosis of major depressive disorder (MDD), including age at onset and number of episodes, is associated with brain atrophy in older persons without dementia.

Method Within the population-based Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study, 4354 persons (mean age 76 ± 5 years, 58% women) without dementia had a 1.5-T brain magnetic resonance imaging (MRI) scan. Automated brain segmentation total and regional brain volumes were calculated. History of MDD, including age at onset and number of episodes, and MDD in the past 2 weeks was diagnosed according to DSM-IV criteria using the Mini-International Neuropsychiatric Interview (MINI).

Results Of the total sample, 4.5% reported a lifetime history of MDD; 1.5% had a current diagnosis of MDD (including 75% with a prior history of depression) and 3.0% had a past but no current diagnosis (remission). After adjusting for multiple covariates, compared to participants never depressed, those with current MDD (irrespective of past) had more global brain atrophy [B = –1.25%, 95% confidence interval (CI) −2.05 to −0.44], including more gray- and white-matter atrophy in most lobes, and also more atrophy of the hippocampus and thalamus. Participants with current, first-onset MDD also had more brain atrophy (B = –1.62%, 95% CI −3.30 to 0.05) whereas those remitted did not (B = 0.06%, 95% CI −0.54 to 0.66).

Conclusions In older persons without dementia, current MDD, irrespective of prior history, but not remitted MDD was associated with widespread gray- and white-matter brain atrophy. Prospective studies should examine whether MDD is a consequence of, or contributes to, brain volume loss and development of dementia.

(Received November 30 2011)

(Revised April 24 2012)

(Accepted April 24 2012)

(Online publication May 30 2012)

Key words

  • Brain;
  • cohort;
  • depression;
  • elders;
  • MRI


c1 Address for correspondence: Dr L. J. Launer, Laboratory for Epidemiology, Demography, and Biometry, National Institute on Aging, Gateway Building, Room 3C309, 7201 Wisconsin Avenue, Bethesda, MD 208920, USA. (Email: [L. J. Launer]

c2 (Email: [M. I. Geerlings]