Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-10T05:15:19.462Z Has data issue: false hasContentIssue false
  • English
  • Français

Altered amygdala and hippocampus function in adolescents with hypercortisolemia: A functional magnetic resonance imaging study of Cushing syndrome

Published online by Cambridge University Press:  07 October 2008

Françoise S. Maheu ,
Luigi Mazzone ,
Deborah P. Merke ,
Margaret F. Keil ,
Constantine A. Stratakis ,
Daniel S. Pine  and
Monique Ernst
Françoise S. Maheu
Affiliation:
National Institute of Mental Health
Luigi Mazzone
Affiliation:
National Institute of Mental Health
Deborah P. Merke
Affiliation:
The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Warren Grant Magnuson Clinical Center
Margaret F. Keil
Affiliation:
The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Warren Grant Magnuson Clinical Center
Constantine A. Stratakis
Affiliation:
The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Warren Grant Magnuson Clinical Center
Daniel S. Pine
Affiliation:
National Institute of Mental Health
Monique Ernst*
Affiliation:
National Institute of Mental Health
*
Address correspondence and reprint requests to: Monique Ernst, Emotional Development and Affective Neuroscience Branch, Mood and Anxiety Disorders Program, National Institute of Mental Health (NIMH), 15K North Drive, Room 118, Bethesda, MD, 20892-2670; E-mail: ernstm@mail.nih.gov.
Get access Rights & Permissions [Opens in a new window]

Abstract

Chronic elevations of endogenous cortisol levels have been shown to alter medial temporal cortical structures and to be accompanied by declarative memory impairments and depressive symptoms in human adults. These effects of elevated endogenous levels of cortisol have not been directly studied in adolescents. Because adolescents with Cushing syndrome show endogenous elevations in cortisol, they represent a unique natural model to study the effects of prolonged hypercortisolemia on brain function, and memory and affective processes during this developmental stage. Using functional magnetic resonance imaging (fMRI), we compared 12 adolescents with Cushing syndrome with 22 healthy control adolescents on amygdala and anterior hippocampus activation during an emotional faces encoding task. None of these adolescents manifested depressive symptoms. Encoding success was assessed using a memory recognition test performed after the scan. The fMRI analyses followed an event-related design and were conducted using the SPM99 platform. Compared to healthy adolescents, patients with Cushing syndrome showed greater left amygdala and right anterior hippocampus activation during successful face encoding. Memory performance for faces recognition did not differ between groups. This first study of cerebral function in adolescents with chronic endogeneous hypercortisolemia due to Cushing syndrome demonstrates the presence of functional alterations in amygdala and hippocampus, which are not associated with affective or memory impairments. Such findings need to be followed by work examining the role of age and related brain maturational stage on these effects, as well as the identification of possible protective factors conferring resilience to affective and cognitive consequences in this disease and/or during this stage of cerebral development.

Type
Research Article
Information
Development and Psychopathology , Volume 20 , Special Issue 4: Imaging Brain Systems in Normality and Psychopathology , Fall 2008 , pp. 1177 - 1189
Copyright
Copyright © Cambridge University Press 2008

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.)

Footnotes

The first author was supported by a postdoctoral fellowship from the Fonds de la Recherche en Santé du Québec (FRSQ).

References

Abercrombie, H. C., Kalin, N. H., Thurow, M. E., Rosenkranz, M. A., & Davidson, R. J. (2003). Cortisol variation in humans affects memory for emotionally-laden and neutral information. Behavioral Neuroscience, 117, 505–516.CrossRefGoogle ScholarPubMed
Adolphs, R. (2003). Cognitive neuroscience of human social behaviour. Nature Reviews in Neuroscience, 4, 165–167.CrossRefGoogle ScholarPubMed
Bannerman, D., Rawlins, J., McHugh, S., Deacon, R., Yee, B., Bast, T., et al. (2004). Regional dissociations within the hippocampus—Memory and anxiety. Neuroscience and Biobehavioral Reviews, 28, 273–283.CrossRefGoogle ScholarPubMed
Birmaher, B., Dahl, R. E., Perel, J., Williamson, D. E., Nelson, B., Stull, S., et al. (1996). Corticotropin-releasing hormone challenge in prepubertal major depression. Biological Psychiatry, 39, 267–277.CrossRefGoogle ScholarPubMed
Bourdeau, I., Bard, C., Forget, H., Boulanger, Y., Cohen, H., & Lacroix, A. (2005). Cognitive function and cerebral assessment in patients who have Cushing's syndrome. Endocrinology and Metabolism Clinics of North America, 34, 357–369.CrossRefGoogle ScholarPubMed
Buchanan, T. W., & Lovallo, W. R. (2001). Enhanced memory for emotional material following stress-level cortisol treatment in humans. Psychoneuroendocrinology, 26, 307–317.CrossRefGoogle ScholarPubMed
Cahill, L., Gorski, L., & Le, K. (2003). Enhanced human memory consolidation with post-learning stress: Interaction with the degree of arousal at encoding. Learning and Memory, 10, 270–274.CrossRefGoogle ScholarPubMed
Charney, D. S. (2004). Psychobiological mechanisms of resilience and vulnerability: Implications for successful adaptation to extreme stress. American Journal of Psychiatry, 161, 195–216.CrossRefGoogle ScholarPubMed
Cicchetti, D. (2003). Experiments of nature: Contributions to developmental theory [Editorial]. Development and Psychopathology, 15, 833–835.CrossRefGoogle ScholarPubMed
Curtis, W. J., & Cicchetti, D. (2003). Moving research on resilience into the 21st century theoretical and methodological considerations in examining the biological contributors to resilience. Development and Psychopathology, 15, 773–810.CrossRefGoogle ScholarPubMed
Dahl, R., Puig-Antich, J., Ryan, N., Nelson, B., Novacenko, H., Twomey, J., et al. (1989). Cortisol secretion in adolescents with major depressive disorder. Acta Psychiatrica Scandinavica, 80, 18–26.CrossRefGoogle ScholarPubMed
Dahl, R. E., Ryan, N. D., Puig-Antich, J., Nguyen, N. A., al-Shabbout, M., Meyer, V. A., et al. (1991). 24-hour cortisol measures in adolescents with major depression: A controlled study. Biological Psychiatry, 30, 25–36.CrossRefGoogle ScholarPubMed
de Kloet, E., Joels, M., & Holsboer, F. (2005). Stress and the brain: From adaptation to disease. Nature Reviews in Neuroscience, 6, 463–475.CrossRefGoogle ScholarPubMed
Dolcos, F., LaBar, K., & Cabeza, R. (2004). Interaction between the amygdala and the medial temporal lobe memory system predicts better memory for emotional events. Neuron, 42, 855–863.CrossRefGoogle ScholarPubMed
Duke, P. M., Litt, I. F., & Gross, R. T. (1980). Adolescents' self-assessment of sexual maturation. Pediatrics, 66, 918–920.CrossRefGoogle ScholarPubMed
Ekman, P., & Friesen, W. V. (1976). Pictures of facial affect. Palo Alto, CA: Consulting Psychologists Press.Google Scholar
Ernst, M., Pine, D. S., & Hardin, M. (2006). Triadic model of the neurobiology of motivated behavior in adolescence. Psychological Medicine, 36, 299–312.CrossRefGoogle ScholarPubMed
Forbes, E. E., Williamson, D. E., Ryan, N. D., Birmaher, B., Axelson, D. A., & Dahl, R. E. (2006). Peri-sleep-onset cortisol levels in children and adolescents with affective disorders. Biological Psychiatry, 59, 24–30.CrossRefGoogle ScholarPubMed
Forget, H., Lacroix, A., Somma, A., & Cohen, H. (2000). Cognitive decline in patients with Cushing's syndrome. Journal of the International Neurospychological Society, 6, 20–29.Google ScholarPubMed
Friston, K., Mechelli, A., Turner, R., & Price, C. (2000). Nonlinear responses in fMRI: The balloon model, Volterra kernels, and other hemodynamics. NeuroImage, 12, 466–477.CrossRefGoogle ScholarPubMed
Gispen-de Wied, C. C., Jansen, L. M., Duyx, J. H., Thijssen, J. H., & van Engeland, H. (2000). Pituitary–adrenal function in adolescent psychiatric patients: Impact of depressive symptoms. Journal of Affective Disorders, 59, 71–76.CrossRefGoogle ScholarPubMed
Greenhouse, S., & Geisser, S. (1959). On methods in the analysis of profile data. Psychometrika, 24, 95–112.CrossRefGoogle Scholar
Gogtay, N., Giedd, J. N., Lusk, L., Hayashi, K. M., Greenstein, D., Vaituzis, A. C., et al. (2004). Dynamic mapping of the human cortical development during childhood through early adulthood. Proceedings of the National Academy of Science of the United States of America, 101, 8174–8179.CrossRefGoogle ScholarPubMed
Goodyer, I. M., Park, R. J., & Herbert, J. (2001). Psychosocial and endocrine features of chronic first-episode major depression in 8–16 year olds. Biological Psychiatry, 50, 351–357.CrossRefGoogle ScholarPubMed
Goodyer, I. M., Park, R. J., Netherton, C. M., & Herbert, J. (2001). Possible role of cortisol and dehydroepiandrosterone in human development and psychopathology. British Journal of Psychiatry, 179, 243–249.CrossRefGoogle ScholarPubMed
Hariri, A., Tessitore, A., Mattay, V., Fera, F., & Weinberger, D. (2002). The amygdala response to emotional stimuli: A comparison of faces and scenes. NeuroImage, 17, 317–323.CrossRefGoogle ScholarPubMed
Isgor, C., Kabbaj, M., Akil, H., & Watson, S. J. (2004). Delayed effects of chronic variable stress during peripubertal–juvenile period of hippocampal morphology and on cognitive and stress axis function in rats. Hippocampus, 14, 636–648.CrossRefGoogle ScholarPubMed
Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., et al. (1997). Schedule for affective disorders and schizophrenia for school-age children—Present and life-time version (K-SADS-PL): Initial reliability and validity data. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 980–988.CrossRefGoogle Scholar
Kim, J. J., & Diamond, D. D. (2002). The stressed hippocampus, synaptic plasticity and lost memories. Nature Reviews in Neuroscience, 3, 453–462.CrossRefGoogle ScholarPubMed
Kutcher, S., & Sokolov, S. (2001). Adolescent depression: Neuroendocrine aspects. In Goodyer, I. (Ed.), The depressed child and adolescent: Developmental and clinical perspectives (pp. 195–215). Cambridge: Cambridge University Press.Google Scholar
Lupien, S. J., Fiocco, A., Wan, N., Maheu, F. S., Lord, C., Schramek, T. E., et al. (2005). Stress hormones and human memory function across the lifespan. Psychoneuroendocrinology, 30, 225–242.CrossRefGoogle ScholarPubMed
Lupien, S. J., & Lepage, M. (2001). Stress, memory, and the hippocampus: Can't live with it, can't live without it. Behavioral Brain Research, 127, 137–158.CrossRefGoogle Scholar
Magiakou, M. A., & Chrousos, G. P. (2002). Cushing's syndrome in children and adolescents: Current diagnostic and therapeutic strategies. Journal of Endocrinological Investigation, 25, 181–194.CrossRefGoogle ScholarPubMed
McEwen, B. S. (1998). Protective and damaging effects of stress mediators. New England Journal of Medicine, 338, 171–179.CrossRefGoogle ScholarPubMed
Merke, D. P., Giedd, J. N., Keil, M. F., Mehlinger, S. L., Wiggs, E. A., Holzer, S., et al. (2005). Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome. Journal of Clinical Endocrinology and Metabolism, 90, 2531–2536.CrossRefGoogle ScholarPubMed
Mitra, R., Jadhav, S., McEwen, B. S., Vyas, A., & Chattarji, S. (2005). Stress duration modualtes the spatiotemporal patterns of spine formation in the basolateral amygdala. Proceedings of the National Academy of Sciences of the United States of America, 102, 9371–9376.CrossRefGoogle ScholarPubMed
Nelson, E. E., McClure, E. B., Monk, C. S., Zarahn, E., Leibenluft, E., Pine, D. S., et al. (2003). Developmental differences in neuronal engagement during implicit encoding of emotional faces: An event-related fMRI study. Journal of Child Psychology and Psychiatry, 44, 1015–1024.CrossRefGoogle ScholarPubMed
Nemeroff, C. B. (2004). Neurobiological consequences of childhood trauma. Journal of Clinical Psychiatry, 65(Suppl. 1), 18–28.Google ScholarPubMed
O'Connor, T. G. (2003). Natural experiments to study the effects of early experience: Progress and limitations. Development and Psychopathology, 15, 837–852.CrossRefGoogle Scholar
Pariante, C. M. (2006). The glucocorticoid receptor: Part of the solution or part of the problem ? Journal of Psychopharmacology, 20(Suppl.), 79–84.CrossRefGoogle ScholarPubMed
Pariante, C. M., & Miller, A. H. (2001). Glucocorticoid receptors in major depression: Relevance to pathophysiology and treatment. Biological Psychiatry, 49, 391–404.CrossRefGoogle Scholar
Phelps, E. A., & LeDoux, J. E. (2005). Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron, 48, 175–187.CrossRefGoogle ScholarPubMed
Phillips, M., Drevets, W., Rauch, S., & Lane, R. (2003). Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biological Psychiatry, 54, 504–514.CrossRefGoogle ScholarPubMed
Pine, D. S., Lissek, S., Klein, R., Mannuzza, S., Moulton, J. III, Guardino, M., et al. (2004). Face-memory and emotion: Associations with major depression in children and adolescents. Journal of Child Psychology and Psychiatry, 45, 1199–1208.CrossRefGoogle ScholarPubMed
Poeggel, G., Helmeke, C., Abraham, A., Schwabe, T., Friedrich, P., & Braun, K. (2003). Juvenile emotional experience alters synaptic composition in the rodent cortex, hippocampus, and lateral amygdala. Proceedings of the National Academy of Science of the United Sates of America, 100, 16137–16142.CrossRefGoogle ScholarPubMed
Puig-Antich, J., Dahl, R. E., Ryan, N., Novacenko, H., Goetz, D., Goetz, R., et al. (1989). Cortisol secretion in prepubertal children with major depressive disorder. Episode and recovery. Archives of General Psychiatry, 46, 801–809.Google ScholarPubMed
Roberson-Nay, R., McClure, E. B., Monk, C. S., Nelson, E. E., Guyer, A. E., Froom, S., et al. (2006). Increased amygdala activity during successful memory encoding in adolescent major depressive disorder: An fMRI study. Biological Psychiatry, 60, 966–973.CrossRefGoogle ScholarPubMed
Romeo, R. D., & McEwen, B. S. (2006). Stress and the adolescent brain. Annals of the New York Academy of Sciences, 14, 1094–2002.Google Scholar
Roozendaal, B. (2003). Systems mediating acute glucocorticoid effects on memory consolidation and retrieval. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 27, 1213–1223.CrossRefGoogle ScholarPubMed
Snodgrass, J. G., & Corwin, J. (1988). Pragmatics of measuring recognition memory: Applications to dementia and amnesia. Journal of Experimental Psychology, General, 117, 34–50.CrossRefGoogle ScholarPubMed
Spear, L. P. (2000). The adolescent brain development and animal models. Annals of the New York Academy of Sciences, 1021, 23–26.CrossRefGoogle Scholar
Szeszko, P., Robinson, D., Alvir, J., Bilder, R., Lencz, T., Ashtari, M., et al. (1999). Orbital frontal and amygdala volume reductions in obsessive–compulsive disorder. Archives of General Psychiatry, 56, 913–919.CrossRefGoogle ScholarPubMed
Szeszko, P., Strous, R., Goldman, R., Ashtari, M, Knuth, K., Lieberman, J., et al. (2002). Neuropsychological correlates of hippocampal volumes in patients experiencing a first episode of schizophrenia. American Journal of Psychiatry, 159, 217–226.CrossRefGoogle ScholarPubMed
Vyas, A., Mitra, R., Shankaranarayana Rao, B., & Chattarji, S. (2002). Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. Journal of Neuroscience, 22, 6810–6818.CrossRefGoogle ScholarPubMed
Wechsler, D. (1999). Wechsler Abbreviated Scale of Intelligence. San Antonio, TX: Psychological Corporation.Google Scholar
Winston, J., Strange, B., O'Doherty, J., & Dolan, R. (2002). Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nature Neuroscience, 5, 277–283.CrossRefGoogle ScholarPubMed
Worsley, K., Marrett, S., Neelin, P., Vandal, A., Friston, K., & Evans, A. (1996). A unified statistical approach for determining significant signals in images of cerebral activation. Human Brain Mapping, 4, 8–73.3.0.CO;2-O>CrossRefGoogle ScholarPubMed
Zarahn, E., Aguirre, G., & D'Esposito, M. (1997). Empirical analyses of BOLD fMRI statistics. I. Spatially unsmoothed data collected under null-hypothesis conditions. NeuroImage, 5, 179–197.CrossRefGoogle ScholarPubMed