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Depression, depressive symptoms, and rate of hippocampal atrophy in a longitudinal cohort of older men and women

  • M. Elbejjani (a1), R. Fuhrer (a1), M. Abrahamowicz (a1), B. Mazoyer (a2) (a3) (a4), F. Crivello (a2) (a3) (a4), C. Tzourio (a4) (a5) and C. Dufouil (a4) (a5)...
Abstract
Background

Several studies have reported smaller hippocampal volume (HcV) in depression patients; however, the temporality of the association remains unknown. One proposed hypothesis is that depression may cause HcV loss. This study evaluates whether previous depression and recent depressive symptoms are associated with HcV and HcV loss.

Method

We used a prospective cohort of older adults (n = 1328; age = 65–80 years) with two cerebral magnetic resonance imaging examinations at baseline and 4-year follow-up. Using multivariable linear regression models, we estimated, in stratified analyses by gender, the association between indicators of history of depression and its severity (age at onset, recurrence, hospitalization for depression), proximal depressive symptoms [Center for Epidemiologic Studies-Depression (CES-D) scale], baseline antidepressant use, and the outcomes: baseline HcV and annual percentage change in HcV.

Results

At baseline, women with more depressive symptoms had smaller HcV [−0.05 cm3, 95% confidence interval (CI) −0.1 to −0.01 cm3 per 10-unit increase in CES-D scores]. History of depression was associated with a 0.2% faster annual HcV loss in women (95% CI 0.01–0.36%). More baseline depressive symptoms and worsening of these symptoms were also associated with accelerated HcV loss in women. No associations were observed in men. Treatment for depression was associated with slower HcV loss in women and men.

Conclusions

While only concomitant depressive symptoms were associated with HcV, both previous depression and more proximal depressive symptoms were associated with faster HcV loss in women.

Copyright
Corresponding author
* Address for correspondence: R. Fuhrer, Ph.D., Department of Epidemiology, Biostatistics, and Occupational Health, McGill University Faculty of Medicine, 1020 Pine Avenue West, Montreal, Quebec H3A 1A2, Canada. (Email: rebecca.fuhrer@mcgill.ca)
References
Hide All
3C Study Group (2003). Vascular factors and risk of dementia: design of the Three-City Study and baseline characteristics of the study population. Neuroepidemiology 22, 316325.
Abrahamowicz, M, Beauchamp, M-E, Fournier, P, Dumont, A (2013). Evidence of subgroup-specific treatment effect in the absence of an overall effect: is there really a contradiction? Pharmacoepidemiology and Drug Safety 22, 11781188.
Bell-McGinty, S, Butters, MA, Meltzer, CC, Greer, PJ, Reynolds, CF, Becker, JT (2002). Brain morphometric abnormalities in geriatric depression: long-term neurobiological effects of illness duration. American Journal of Psychiatry 159, 14241427.
Bis, JC, DeCarli, C, Smith, AV, van der Lijn, F, Crivello, F, Fornage, M, Debette, S, Shulman, JM, Schmidt, H, Srikanth, V, Schuur, M, Yu, L, Choi, SH, Sigurdsson, S, Verhaaren, BF, DeStefano, AL, Lambert, JC, Jack, CR Jr., Struchalin, M, Stankovich, J, Ibrahim-Verbaas, CA, Fleischman, D, Zijdenbos, A, den Heijer, T, Mazoyer, B, Coker, LH, Enzinger, C, Danoy, P, Amin, N, Arfanakis, K, van Buchem, MA, de Bruijn, RF, Beiser, A, Dufouil, C, Huang, J, Cavalieri, M, Thomson, R, Niessen, WJ, Chibnik, LB, Gislason, GK, Hofman, A, Pikula, A, Amouyel, P, Freeman, KB, Phan, TG, Oostra, BA, Stein, JL, Medland, SE, Vasquez, AA, Hibar, DP, Wright, MJ, Franke, B, Martin, NG, Thompson, PM, Nalls, MA, Uitterlinden, AG, Au, R, Elbaz, A, Beare, RJ, van Swieten, JC, Lopez, OL, Harris, TB, Chouraki, V, Breteler, MM, De Jager, PL, Becker, JT, Vernooij, MW, Knopman, D, Fazekas, F, Wolf, PA, van der Lugt, A, Gudnason, V, Longstreth, WT Jr, Brown, MA, Bennett, DA, van Duijn, CM, Mosley, TH, Schmidt, R, Tzourio, C, Launer, LJ, Ikram, MA, Seshadri, S (2012). Common variants at 12q14 and 12q24 are associated with hippocampal volume. Nature Genetics 44, 545551.
Boldrini, M, Hen, R, Underwood, MD, Rosoklija, GB, Dwork, AJ, Mann, JJ, Arango, V (2012). Hippocampal angiogenesis and progenitor cell proliferation are increased with antidepressant use in major depression. Biological Psychiatry 72, 562571.
Boldrini, M, Underwood, MD, Hen, R, Rosoklija, GB, Dwork, AJ, Mann, JJ, Arango, V (2009). Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology 34, 23762389.
Boldrini, M, Underwood, MD, Lau, J, Mann, JJ, Arango, V (2008). Antidepressants increase progenitors cells in the human dentate gyrus. Biological Psychiatry 63, 96S.
Bremner, JD (1999). Does stress damage the brain? Biological Psychiatry 45, 797805.
Bremner, JD, Narayan, M, Anderson, ER, Staib, LH, Miller, HL, Charney, DS (2000). Hippocampal volume reduction in major depression. American Journal of Psychiatry 157, 115117.
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, Marriott, M, Nahmias, C, MacQueen, GM (2004). Lower hippocampal volume in patients suffering from depression: a meta-analysis. American Journal of Psychiatry 161, 598607.
Chen, PJ, Ganguli, M, Mulsant, BH, DeKosky, ST (1999). The temporal relationship between depressive symptoms and dementia – a community-based prospective study. Archives of General Psychiatry 56, 261266.
Crivello, F, Lemaitre, H, Dufouil, C, Grassiot, B, Delcroix, N, Tzourio-Mazoyer, N, Tzourio, C, Mazoyer, B (2010). Effects of ApoE-ε4 allele load and age on the rates of grey matter and hippocampal volumes loss in a longitudinal cohort of 1186 healthy elderly persons. NeuroImage 53, 10641069.
Dedovic, K, Engert, V, Duchesne, A, Lue, SD, Andrews, J, Efanov, SI, Beaudry, T, Pruessner, JC (2010). Cortisol awakening response and hippocampal volume: vulnerability for major depressive disorder? Biological Psychiatry 68, 847853.
den Heijer, T, Oudkerk, M, Launer, LJ, van Duijn, CM, Hofman, A, Breteler, MM (2002). Hippocampal, amygdalar, and global brain atrophy in different apolipoprotein E genotypes. Neurology 59, 746748.
den Heijer, T, Tiemeier, H, Luijendijk, HJ, van der Lijn, F, Koudstaal, PJ, Hofman, A, Breteler, MMB (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, 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.
Eisch, AJ, Petrik, D (2012). Depression and hippocampal neurogenesis: a road to remission? Science 338, 7275.
Everaerd, D, Gerritsen, L, Rijpkema, M, Frodl, T, van Oostrom, I, Franke, B, Fernandez, G, Tendolkar, I (2012). Sex modulates the interactive effect of the serotonin transporter gene polymorphism and childhood adversity on hippocampal volume. Neuropsychopharmacology 37, 18481855.
Folstein, MF, Folstein, SE, McHugh, PR (1975). “Mini-mental state”. A practical method for grading cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189198.
Frodl, T, Meisenzahl, EM, Zetzsche, T, Born, C, Groll, C, Jager, M, Leinsinger, G, Bottlender, R, Hahn, K, Moller, HJ (2002). Hippocampal changes in patients with a first episode of major depression. American Journal of Psychiatry 159, 11121118.
Fuhrer, R, Dufouil, C, Dartigues, JF, Paquid, S (2003). Exploring sex differences in the relationship between depressive symptoms and dementia incidence: prospective results from the PAQUID study. Journal of the American Geriatrics Society 51, 10551063.
Fuhrer, R, Rouillon, F (1989). La version française de l'echelle CES-D. Psychiatrie et Psychobiologie 4, 163166.
Galea, LAM (2008). Gonadal hormone modulation of neurogenesis in the dentate gyrus of adult male and female rodents. Brain Research Reviews 57, 332341.
Garcia-Segura, LM, Azcoitia, I, DonCarlos, LL (2001). Neuroprotection by estradiol. Progress in Neurobiology 63, 2960.
Geerlings, MI, den Heijer, T, Koudstaal, PJ, Hofman, A, Breteler, MMB (2008). History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease. Neurology 70, 12581264.
Geerlings, MI, Sigurdsson, S, Eiriksdottir, G, Garcia, ME, Harris, TB, Sigurdsson, T, Gudnason, V, Launer, LJ (2013). Associations of current and remitted major depressive disorder with brain atrophy: the AGES–Reykjavik Study. Psychological Medicine 43, 317328.
Good, CD, Johnsrude, IS, Ashburner, J, Henson, RNA, Friston, KJ, Frackowiak, RSJ (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage 14, 2136.
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.
Hajszan, T, Milner, TA, Leranth, C (2007). Sex steroids and the dentate gyrus. Progress in Brain Research 163, 399415.
Hastings, RS, Parsey, RV, Oquendo, MA, Arango, V, Mann, JJ (2004). Volumetric analysis of the prefrontal cortex, amygdala, and hippocampus in major depression. Neuropsychopharmacology 29, 952959.
Holden, C (2005). Sex and the suffering brain. Science 308, 15741577.
Holland, D, Desikan, RS, Dale, AM, McEvoy, LK (2013). Higher rates of decline for women and apolipoprotein E ε4 carriers. AJNR. American Journal of Neuroradiology 34, 22872293.
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.
Jack, CR, Petersen, RC, Xu, Y, O'Brien, PC, Smith, GE, Ivnik, RJ, Boeve, BF, Tangalos, EG, Kokmen, E (2000). Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology 55, 484489.
Kaup, AR, Mirzakhanian, H, Jeste, DV, Eyler, LT (2011). A review of the brain structure correlates of successful cognitive aging. Journal of Neuropsychiatry and Clinical Neurosciences 23, 615.
Keers, R, Aitchison, KJ (2010). Gender differences in antidepressant drug response. International Review of Psychiatry 22, 485500.
Kempton, MJ, Salvador, Z, Munafo, MR, Geddes, JR, Simmons, A, Frangou, S, Williams, SCR (2011). Structural neuroimaging studies in major depressive disorder meta-analysis and comparison with bipolar disorder. Archives of General Psychiatry 68, 675690.
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.
Koolschijn, P, van Haren, NEM, Lensvelt-Mulders, G, Pol, HEH, Kahn, RS (2009). Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Human Brain Mapping 30, 37193735.
Kronmüller, KT, Schroder, J, Kohler, S, Gotz, B, Victor, D, Unger, J, Giesel, F, Magnotta, V, Mundt, C, Essig, M, Pantel, J (2009). Hippocampal volume in first episode and recurrent depression. Psychiatry Research 174, 6266.
Lemaitre, H, Crivello, F, Grassiot, B, Alperovitch, A, Tzourio, C, Mazoyer, B (2005). Age- and sex-related effects on the neuroanatomy of healthy elderly. NeuroImage 26, 900911.
Lister, JP, Barnes, CA (2009). Neurobiological changes in the hippocampus during normative aging. Archives of Neurology 66, 829833.
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, GM, Campbell, S, McEwen, B, Macdonald, K, Young, T (2003). Course of illness, hippocampal function and volume in major depression. Biological Psychiatry 53, 31S.
Maillard, P, Delcroix, N, Crivello, F, Dufouil, C, Gicquel, S, Joliot, M, Tzourio-Mazoyer, N, Alperovitch, A, Tzourio, C, Mazoyer, B (2008). An automated procedure for the assessment of white matter hyperintensities by multispectral (T1, T2, PD) MRI and an evaluation of its between-centre reproducibility based on two large community databases. Neuroradiology 50, 3142.
Marcus, SM, Young, EA, Kerber, KB, Kornstein, S, Farabaugh, AH, Mitchell, J, Wisniewski, SR, Balasubramani, GK, Trivedi, MH, Rush, AJ (2005). Gender differences in depression: findings from the STAR*D study. Journal of Affective Disorders 87, 141150.
McEwen, BS, Gianaros, PJ (2010). Central role of the brain in stress and adaptation: links to socioeconomic status, health, and disease. Annals of the New York Academy of Sciences 1186, 190222.
Nordanskog, P, Dahlstrand, U, Larsson, MR, Larsson, EM, Knutsson, L, Johanson, A (2010). Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study. Journal of ECT 26, 6267.
Pitychoutis, PM, Dalla, C, Sideris, AC, Tsonis, PA, Papadopoulou-Daifoti, Z (2012). 5-HT1A, 5-HT2A, and 5-HT2C receptor mRNA modulation by antidepressant treatment in the chronic mild stress model of depression: sex differences exposed. Neuroscience 210, 152167.
Radloff, LS (1977). The CES-D scale: a self-report depression scale for research in the general population. Applied Psychological Measurement 1, 385401.
Royston, P, Altman, DG (1994). Regression using fractional polynomials of continuous covariates – parsimonious parametric modeling. Journal of Royal Statistical Society Series C Applied Statistics 43, 429467.
Sapolsky, RM (2000). Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Archives of General Psychiatry 57, 925935.
Sapolsky, RM, Krey, LC, McEwen, BS (1986). The neuroendocrinology of stress and aging – the glucocorticoid cascade hypothesis. Endocrine Reviews 7, 284301.
Schweitzer, I, Tuckwell, V, O'Brien, J, Ames, D (2002). Is late onset depression a prodrome to dementia? International Journal of Geriatric Psychiatry 17, 9971005.
Sheline, YI, Gado, MH, Kraemer, HC (2003). Untreated depression and hippocampal volume loss. American Journal of Psychiatry 160, 15161518.
Sheline, YI, Sanghavi, M, Mintun, MA, Gado, MH (1999). Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. Journal of Neuroscience 19, 50345043.
Sheline, YI, Wang, PW, Gado, MH, Csernansky, JG, Vannier, MW (1996). Hippocampal atrophy in recurrent major depression. Proceedings of the National Academy of Sciences of the United States of America 93, 39083913.
Shimizu, E, Hashimoto, K, Okamura, N, Koike, K, Komatsu, N, Kumakiri, C, Nakazato, M, Watanabe, H, Shinoda, N, Okada, S, Iyo, M (2003). Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biological Psychiatry 54, 7075.
Steffens, DC, McQuoid, DR, Payne, ME, Potter, GG (2011). Change in hippocampal volume on magnetic resonance imaging and cognitive decline among older depressed and nondepressed subjects in the Neurocognitive Outcomes of Depression in the Elderly Study. American Journal of Geriatric Psychiatry 19, 412.
Thomas, AJ, Gallagher, P, Robinson, LJ, Porter, RJ, Young, AH, Ferrier, IN, O'Brien, JT (2009). A comparison of neurocognitive impairment in younger and older adults with major depression. Psychological Medicine 39, 725733.
Tisserand, DJ, van Boxtel, MPJ, Pruessner, JC, Hofman, P, Evans, AC, Jolles, J (2004). A voxel-based morphometric study to determine individual differences in gray matter density associated with age and cognitive change over time. Cerebral Cortex 14, 966973.
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273289.
Videbech, P, Ravnkilde, B (2004). Hippocampal volume and depression: a meta-analysis of MRI studies. American Journal of Psychiatry 161, 19571966.
Zhang, Y, Qiu, C, Lindberg, O, Bronge, L, Aspelin, P, Backman, L, Fratiglioni, L, Wahlund, LO (2010). Acceleration of hippocampal atrophy in a non-demented elderly population: the SNAC-K study. International Psychogeriatrics 22, 1425.
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