Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-25T09:10:27.344Z Has data issue: false hasContentIssue false

The influence of negative life events on hippocampal and amygdala volumes in old age: a life-course perspective

Published online by Cambridge University Press:  02 October 2014

L. Gerritsen*
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Ageing Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden
G. Kalpouzos
Affiliation:
Ageing Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden
E. Westman
Affiliation:
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK
A. Simmons
Affiliation:
Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK NIHR Biomedical Research Centre and Biomedical Research Unit for Dementia at South London and Maudsley NHS foundation Trust and Institute of Psychiatry, King's College London, London, UK
L.-O. Wahlund
Affiliation:
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
L. Bäckman
Affiliation:
Ageing Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden
L. Fratiglioni
Affiliation:
Ageing Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden Stockholm Gerontology Research Center, Stockholm, Sweden
H.-X. Wang
Affiliation:
Ageing Research Center (ARC), Karolinska Institutet and Stockholm University, Stockholm, Sweden
*
* Address for correspondence: Dr L. Gerritsen, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, 171 77 Stockholm, Sweden. (Email: [email protected])

Abstract

Background.

Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults.

Method.

In 466 non-demented old adults (age range 60–96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning.

Results.

Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women.

Conclusions.

These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Andersen, SL, Teicher, MH (2008). Stress, sensitive periods and maturational events in adolescent depression. Trends in Neurosciences 31, 183191.Google Scholar
Andersen, SL, Tomada, A, Vincow, ES, Valente, E, Polcari, A, Teicher, MH (2008). Preliminary evidence for sensitive periods in the effect of childhood sexual abuse on regional brain development. Journal of Neuropsychiatry and Clinical Neurosciences 20, 292301.CrossRefGoogle ScholarPubMed
Ashburner, J (2007). A fast diffeomorphic image registration algorithm. Neuroimage 38, 95113.Google Scholar
Bennur, S, Shankaranarayana Rao, BS, Pawlak, R, Strickland, S, McEwen, BS, Chattarji, S (2007). Stress-induced spine loss in the medial amygdala is mediated by tissue-plasminogen activator. Neuroscience 144, 816.Google Scholar
Bremner, JD (2006). Stress and brain atrophy. CNS & Neurological Disorders – Drug Targets 5, 503512.CrossRefGoogle ScholarPubMed
Bremner, JD, Elzinga, B, Schmahl, C, Vermetten, E (2008). Structural and functional plasticity of the human brain in posttraumatic stress disorder. Progress in Brain Research 167, 171186.Google Scholar
Davidson, RJ, McEwen, BS (2012). Social influences on neuroplasticity: stress and interventions to promote well-being. Nature Neuroscience 15, 689695.CrossRefGoogle ScholarPubMed
De Bellis, MD (2001). Developmental traumatology: the psychobiological development of maltreated children and its implications for research, treatment, and policy. Developmental Psychopathology 13, 539564.Google Scholar
De Bellis, MD, Keshavan, MS (2003). Sex differences in brain maturation in maltreatment-related pediatric posttraumatic stress disorder. Neuroscience & Biobehavioral Reviews 27, 103117.Google Scholar
Fischl, B, Salat, DH, Busa, E, Albert, M, Dieterich, M, Haselgrove, C, van der Kouwe, A, Killiany, R, Kennedy, D, Klaveness, S, Montillo, A, Makris, N, Rosen, B, Dale, AM (2002). Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33, 341355.CrossRefGoogle ScholarPubMed
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.Google Scholar
Frodl, T, Reinhold, E, Koutsouleris, N, Reiser, M, Meisenzahl, EM (2010). Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression. Journal of Psychiatric Research 44, 799807.Google Scholar
Gerritsen, L, Rijpkema, M, van Oostrom, I, Buitelaar, J, Franke, B, Fernández, G, Tendolkar, I (2012). Amygdala to hippocampal volume ratio is associated with negative memory bias in healthy subjects. Psychological Medicine 42, 335343.Google Scholar
Gillespie, CF, Phifer, J, Bradley, B, Ressler, KJ (2009). Risk and resilience: genetic and environmental influences on development of the stress response. Depression & Anxiety 26, 984992.Google Scholar
Kessler, RC, Davis, CG, Kendler, KS (1997). Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey. Psychological Medicine 27, 11011119.Google Scholar
Kirschbaum, C, Kudielka, BM, Gaab, J, Schommer, NC, Hellhammer, DH (1999). Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosomatic Medicine 61, 154162.Google Scholar
Knoops, AJ, Gerritsen, L, van der, GY, Mali, WP, Geerlings, MI (2010). Basal hypothalamic pituitary adrenal axis activity and hippocampal volumes: the SMART-Medea study. Biological Psychiatry 67, 11911198.Google Scholar
Kuo, JR, Kaloupek, DG, Woodward, SH (2012). Amygdala volume in combat-exposed veterans with and without posttraumatic stress disorder: a cross-sectional study. Archives of General Psychiatry 69, 10801086.Google Scholar
Lagergren, M, Fratiglioni, L, Hallberg, IR, Berglund, J, Elmståhl, S, Hagberg, B, Holst, G, Rennemark, M, Sjölund, BM, Thorslund, M, Wiberg, I, Winblad, B, Wimo, A (2004). A longitudinal study integrating population, care and social services data. The Swedish National study on Aging and Care (SNAC). Aging Clinical & Experimental Research 16, 158168.Google Scholar
Lupien, SJ, McEwen, BS, Gunnar, MR, Heim, C (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience 10, 434445.Google Scholar
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.Google Scholar
McEwen, BS (2001). Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Annals of New York Academy of Science 933, 265277.CrossRefGoogle ScholarPubMed
McEwen, BS (2007). Physiology and neurobiology of stress and adaptation: central role of the brain. Physiological Reviews 87, 873904.Google Scholar
McEwen, BS, Akama, KT, Spencer-Segal, JL, Milner, TA, Waters, EM (2012). Estrogen effects on the brain: actions beyond the hypothalamus via novel mechanisms. Behavioral Neuroscience 126, 416.Google Scholar
McEwen, BS, Gianaros, PJ (2011). Stress- and allostasis-induced brain plasticity. Annual Review in Medicine 62, 431445.CrossRefGoogle ScholarPubMed
McLaughlin, KJ, Baran, SE, Conrad, CD (2009). Chronic stress- and sex-specific neuromorphological and functional changes in limbic structures. Molecular Neurobiology 40, 166182.CrossRefGoogle ScholarPubMed
Miller, MA, Rahe, RH (1997). Life changes scaling for the 1990s. Journal of Psychosomatic Research 43, 279292.Google Scholar
Montgomery, SA, Asberg, M (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382389.Google Scholar
Morey, RA, Gold, AL, Labar, KS, Beall, SK, Brown, VM, Haswell, CC, Nasser, JD, Wagner, HR, McCarthy, G, Mid-Atlantic MIRECC Workgroup (2012). Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Archives of General Psychiatry 69, 11691178.Google Scholar
Nestler, EJ, Barrot, M, DiLeone, RJ, Eisch, AJ, Gold, SJ, Monteggia, LM (2002). Neurobiology of depression. Neuron 34, 1325.Google Scholar
Roozendaal, B, McEwen, BS, Chattarji, S (2009). Stress, memory and the amygdala. Nature Reviews Neuroscience 10, 423433.Google Scholar
Sapolsky, RM (2003). Stress and plasticity in the limbic system. Neurochemical Research 28, 17351742.Google Scholar
Simmons, A, Westman, E, Muehlboeck, S, Mecocci, P, Vellas, B, Tsolaki, M, Kłoszewska, I, Wahlund, LO, Soininen, H, Lovestone, S, Evans, A, Spenger, C (2011). The AddNeuroMed framework for multi-centre MRI assessment of Alzheimer's disease: experience from the first 24 months. International Journal of Geriatric Psychiatry 26, 7582.Google Scholar
Takuma, K, Matsuo, A, Himeno, Y, Hoshina, Y, Ohno, Y, Funatsu, Y, Arai, S, Kamei, H, Mizoguchi, H, Nagai, T, Koike, K, Inoue, M, Yamada, K (2007). 17beta-estradiol attenuates hippocampal neuronal loss and cognitive dysfunction induced by chronic restraint stress in ovariectomized rats. Neuroscience 146, 6068.Google Scholar
Tanapat, P, Hastings, NB, Reeves, AJ, Gould, E (1999). Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. Journal of Neuroscience 19, 57925801.Google Scholar
Teicher, MH, Anderson, CM, Polcari, A (2012). Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. Proceedings of the National Academy of Sciences USA 109, E563E572.Google Scholar
Teicher, MH, Tomoda, A, Andersen, SL (2006). Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable? Annals of New York Academy of Science 1071, 313323.Google Scholar
Tottenham, N, Hare, TA, Quinn, BT, McCarry, TW, Nurse, M, Gilhooly, T, Millner, A, Galvan, A, Davidson, MC, Eigsti, IM, Thomas, KM, Freed, PJ, Booma, ES, Gunnar, MR, Altemus, M, Aronson, J, Casey, BJ (2010). Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation. Developmental Sciences 13, 4661.Google Scholar
Troisi, A (2001). Gender differences in vulnerability to social stress: a Darwinian perspective. Physiology & Behavior 73, 443449.Google Scholar
van Harmelen, AL, van Tol, MJ, van der Wee, NJ, Veltman, DJ, Aleman, A, Spinhoven, P, van Buchem, MA, Zitman, FG, Penninx, BW, Elzinga, BM (2010). Reduced medial prefrontal cortex volume in adults reporting childhood emotional maltreatment. Biological Psychiatry 68, 832838.Google Scholar
Vyas, A, Mitra, R, Shankaranarayana Rao, BS, Chattarji, S (2002). Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. Journal of Neuroscience 22, 68106818.Google Scholar
Wang, HX, Wahlberg, M, Karp, A, Winblad, B, Fratiglioni, L (2012). Psychosocial stress at work is associated with increased dementia risk in late life. Alzheimer's Dementia 8, 114120.Google Scholar
Wolf, OT, Schommer, NC, Hellhammer, DH, McEwen, BS, Kirschbaum, C (2001). The relationship between stress induced cortisol levels and memory differs between men and women. Psychoneuroendocrinology 26, 711720.Google Scholar
Wolkowitz, OM, Epel, ES, Reus, VI, Mellon, SH (2010). Depression gets old fast: do stress and depression accelerate cell aging? Depression and Anxiety 27, 327338.Google Scholar
Woon, F, Hedges, DW (2011). Gender does not moderate hippocampal volume deficits in adults with posttraumatic stress disorder: A meta-analysis. Hippocampus 21, 243252.CrossRefGoogle Scholar
Woon, FL, Hedges, DW (2009). Amygdala volume in adults with posttraumatic stress disorder: a meta-analysis. Journal of Neuropsychiatry & Clinical Neurosciences 21, 512.CrossRefGoogle ScholarPubMed
Yehuda, R, Golier, JA, Tischler, L, Harvey, PD, Newmark, R, Yang, RK, Buchsbaum, MS (2007). Hippocampal volume in aging combat veterans with and without post-traumatic stress disorder: relation to risk and resilience factors. Journal of Psychiatric Research 41, 435445.Google Scholar
Zhang, W, Rosenkranz, JA (2012). Repeated restraint stress increases basolateral amygdala neuronal activity in an age-dependent manner. Neuroscience 226, 459474.Google Scholar