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

  • M. I. Geerlings (a1) (a2), S. Sigurdsson (a3), G. Eiriksdottir (a3), M. E. Garcia (a2), T. B. Harris (a2), T. Sigurdsson (a4), V. Gudnason (a3) (a5) and L. J. Launer (a2)...
Abstract
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.

Copyright
Corresponding author
*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: launerl@nia.nih.gov) [L. J. Launer]
(Email: m.geerlings@umcutrecht.nl) [M. I. Geerlings]
References
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Ahdidan J, Hviid LB, Chakravarty MM, Ravnkilde B, Rosenberg R, Rodell A, Stodkilde-Jorgensen H, Videbech P (2011). Longitudinal MR study of brain structure and hippocampus volume in major depressive disorder. Acta Psychiatrica Scandinavia 123, 211219.
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn.American Psychiatric Association: Washington, DC.
Ashtari M, Greenwald BS, Kramer-Ginsberg E, Hu J, Wu H, Patel M, Aupperle P, Pollack S (1999). Hippocampal/amygdala volumes in geriatric depression. Psychological Medicine 29, 629638.
Ballmaier M, Sowell ER, Thompson PM, Kumar A, Narr KL, Lavretsky H, Welcome SE, DeLuca H, Toga AW (2004). Mapping brain size and cortical gray matter changes in elderly depression. Biological Psychiatry 55, 382389.
Byers AL, Yaffe K (2011). Depression and risk of developing dementia. Nature Reviews Neurology 7, 323331.
Caetano SC, Hatch JP, Brambilla P, Sassi RB, Nicoletti M, Mallinger AG, Frank E, Kupfer DJ, Keshavan MS, Soares JC (2004). Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression. Psychiatry Research 132, 141147.
Campbell S, MacQueen G (2004). The role of the hippocampus in the pathophysiology of major depression. Journal of Psychiatry and Neuroscience 29, 417426.
Campbell S, MacQueen G (2006). An update on regional brain volume differences associated with mood disorders. Current Opinion in Psychiatry 19, 2533.
den Heijer T, Tiemeier H, Luijendijk HJ, van der Lijn F, Koudstaal PJ, Hofman A, Breteler MM (2011). A study of the bidirectional association between hippocampal volume on magnetic resonance imaging and depression in the elderly. Biological Psychiatry 70, 191197.
Dotson VM, Beydoun MA, Zonderman AB (2010). Recurrent depressive symptoms and the incidence of dementia and mild cognitive impairment. Neurology 75, 2734.
Dotson VM, Davatzikos C, Kraut MA, Resnick SM (2009). Depressive symptoms and brain volumes in older adults: a longitudinal magnetic resonance imaging study. Journal of Psychiatry and Neuroscience 34, 367375.
Folstein MF, Folstein SE, McHugh PR (1975). ‘Mini-mental state’. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189198.
Geerlings MI, Brickman AM, Schupf N, Devanand DP, Luchsinger JA, Mayeux R, Small SA (2012). Depressive symptoms, antidepressant use, and brain volumes on MRI in a population-based cohort of old persons without dementia. Journal of Alzheimers Disease. Published online 29 February 2012. doi:10.3233/JAD-2012-112009.
Geerlings MI, den Heijer T, Koudstaal PJ, Hofman A, Breteler MM (2008). History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease. Neurology 70, 12581264.
Gerritsen L, Comijs HC, van der Graaf Y, Knoops AJ, Penninx BW, Geerlings MI (2011). Depression, hypothalamic pituitary adrenal axis, and hippocampal and entorhinal cortex volumes – the SMART Medea study. Biological Psychiatry 70, 373380.
Geuze E, Vermetten E, Bremner JD (2005). MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Molecular Psychiatry 10, 160184.
Goveas JS, Espeland MA, Hogan P, Dotson V, Tarima S, Coker LH, Ockene J, Brunner R, Woods NF, Wassertheil-Smoller S, Kotchen JM, Resnick S (2011). Depressive symptoms, brain volumes and subclinical cerebrovascular disease in postmenopausal women: the Women's Health Initiative MRI Study. Journal of Affective Disorders 132, 275284.
Harris TB, Launer LJ, Eiriksdottir G, Kjartansson O, Jonsson PV, Sigurdsson G, Thorgeirsson G, Aspelund T, Garcia ME, Cotch MF, Hoffman HJ, Gudnason V (2007). Age, Gene/Environment Susceptibility-Reykjavik Study: multidisciplinary applied phenomics. American Journal of Epidemiology 165, 10761087.
Hsieh MH, McQuoid DR, Levy RM, Payne ME, MacFall JR, Steffens DC (2002). Hippocampal volume and antidepressant response in geriatric depression. International Journal of Geriatric Psychiatry 17, 519525.
Ikram MA, Vrooman HA, Vernooij MW, den Heijer T, Hofman A, Niessen WJ, van der Lugt A, Koudstaal PJ, Breteler MM (2010). Brain tissue volumes in relation to cognitive function and risk of dementia. Neurobiology of Aging 31, 378386.
Jack Jr. CR, Shiung MM, Weigand SD, O'Brien PC, Gunter JL, Boeve BF, Knopman DS, Smith GE, Ivnik RJ, Tangalos EG, Petersen RC (2005). Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology 65, 12271231.
Jorm AF (2001). History of depression as a risk factor for dementia: an updated review. Australian and New Zealand Journal of Psychiatry 35, 776781.
Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 593602.
Kessler RC, Birnbaum H, Bromet E, Hwang I, Sampson N, Shahly V (2010). Age differences in major depression: results from the National Comorbidity Survey Replication (NCS-R). Psychological Medicine 40, 225237.
Knoops AJ, Gerritsen L, van der Graaf Y, Mali WP, Geerlings MI (2010). Basal hypothalamic pituitary adrenal axis activity and hippocampal volumes: the SMART-Medea study. Biological Psychiatry 67, 11911198.
Konarski JZ, McIntyre RS, Kennedy SH, Rafi-Tari S, Soczynska JK, Ketter TA (2008). Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder. Bipolar Disorders 10, 137.
Koolschijn PC, van Haren NE, Lensvelt-Mulders GJ, Hulshoff Pol HE, Kahn RS (2009). Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Human Brain Mapping 30, 37193735.
Kumar A, Jin Z, Bilker W, Udupa J, Gottlieb G (1998). Late-onset minor and major depression: early evidence for common neuroanatomical substrates detected by using MRI. Proceedings of the National Academy of Sciences USA 95, 76547658.
Kupfer DJ, Frank E, Phillips ML (2012). Major depressive disorder: new clinical, neurobiological, and treatment perspectives. Lancet 379, 10451055.
Lorenzetti V, Allen NB, Fornito A, Yucel M (2009). Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. Journal of Affective Disorders 117, 117.
MacQueen G, Frodl T (2011). The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? Molecular Psychiatry 16, 252264.
MacQueen GM, Yucel K, Taylor VH, Macdonald K, Joffe R (2008). Posterior hippocampal volumes are associated with remission rates in patients with major depressive disorder. Biological Psychiatry 64, 880883.
Mathers CD, Loncar D (2006). Projections of global mortality and burden of disease from 2002 to 2030. PLoS Medicine 3, e442.
McKinnon MC, Yucel K, Nazarov A, MacQueen GM (2009). A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. Journal of Psychiatry and Neuroscience 34, 4154.
Neumeister A, Wood S, Bonne O, Nugent AC, Luckenbaugh DA, Young T, Bain EE, Charney DS, Drevets WC (2005). Reduced hippocampal volume in unmedicated, remitted patients with major depression versus control subjects. Biological Psychiatry 57, 935937.
Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D (2006). Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Archives of General Psychiatry 63, 530538.
Penninx BW, Geerlings SW, Deeg DJ, van Eijk JT, Van Tilburg W, Beekman AT (1999). Minor and major depression and the risk of death in older persons. Archives of General Psychiatry 56, 889895.
Rubin DB, Schenker N (1991). Multiple imputation in health-care databases: an overview and some applications. Statistics in Medicine 10, 585598.
Saczynski JS, Beiser A, Seshadri S, Auerbach S, Wolf PA, Au R (2010). Depressive symptoms and risk of dementia: the Framingham Heart Study. Neurology 75, 3541.
Schoevers RA, Geerlings MI, Beekman AT, Penninx BW, Deeg DJ, Jonker C, van Tilburg W (2000). Association of depression and gender with mortality in old age. Results from the Amsterdam Study of the Elderly (AMSTEL). British Journal of Psychiatry 177, 336342.
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry 59 (Suppl. 20), 2233.
Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW (1996). Hippocampal atrophy in recurrent major depression. Proceedings of the National Academy of Sciences USA 93, 39083913.
Sigurdsson S, Aspelund T, Forsberg L, Fredriksson J, Kjartansson O, Oskarsdottir B, Jonsson PV, Eiriksdottir G, Harris TB, Zijdenbos A, van Buchem MA, Launer LJ, Gudnason V (2012). Brain tissue volumes in the general population of the elderly: the AGES-Reykjavik study. NeuroImage 59, 38623870.
Thomas AJ, O'Brien JT (2008). Depression and cognition in older adults. Current Opinion in Psychiatry 21, 813.
van Tol MJ, van der Wee NJ, van den Heuvel OA, Nielen MM, Demenescu LR, Aleman A, Renken R, van Buchem MA, Zitman FG, Veltman DJ (2010). Regional brain volume in depression and anxiety disorders. Archives of General Psychiatry 67, 10021011.
Videbech P, Ravnkilde B (2004). Hippocampal volume and depression: a meta-analysis of MRI studies. American Journal of Psychiatry 161, 19571966.
Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO (1982). Development and validation of a geriatric depression screening scale: a preliminary report. Journal of Psychiatric Research 17, 3749.
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