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Orbitofrontal cortex volume in late life depression: influence of hyperintense lesions and genetic polymorphisms

Published online by Cambridge University Press:  05 March 2007

WARREN D. TAYLOR*
Affiliation:
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA
JAMES R. MacFALL
Affiliation:
Department of Radiology, Duke University Medical Center, Durham, NC, USA
MARTHA E. PAYNE
Affiliation:
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA
DOUGLAS R. McQUOID
Affiliation:
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA
DAVID C. STEFFENS
Affiliation:
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA
JAMES M. PROVENZALE
Affiliation:
Department of Radiology, Duke University Medical Center, Durham, NC, USA
K. RANGA R. KRISHNAN
Affiliation:
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA
*
*Address for correspondence: Warren D. Taylor, M.D., Duke University Medical Center, DUMC 3903, Duke South Clinic, Room 3547, Blue Zone, Durham, NC 27710, USA. (Email: Taylo066@mc.duke.edu)

Abstract

Background

Orbitofrontal cortex (OFC) volumetric differences have been reported in depression, but in relatively small samples. Factors associated with these differences are not well described. We examined OFC volumes in a large sample of elderly depressed and non-depressed subjects, exploring the relationship between OFC volume, 5HTTLPR genotype, apolipoprotein E (APOE) genotype and hyperintense lesion volume. We hypothesized that smaller OFC volume would be associated with depression, greater hyperintense lesion volume and severity, and APOE ε4 or 5HTTLPR short allele carriers.

Method

A total of 226 depressed and 144 non-depressed older subjects completed 1·5 T magnetic resonance imaging (MRI) and genotyping. OFC volumes and lesion volumes were measured using standardized methods. Lesion severity was additionally rated using the Coffey rating scale. Differences between groups were compared while controlling for age, sex and total cerebral volume; separate models added lesion measures and genetic polymorphisms.

Results

Depressed subjects exhibited smaller OFC volumes. There was a trend for a negative association between white-matter lesion volume and OFC volume; however, rated white-matter lesion severity was significantly negatively associated with OFC volume. There was no association between gray-matter lesion measures or 5HTTLPR genotype and OFC volume. Contrary to our hypothesis, subjects who were APOE ε4 allele positive exhibited larger OFC volumes; in secondary analyses, this finding was limited to the non-depressed group.

Conclusions

Reduced OFC volumes are seen in depression and associated with greater severity of white-matter lesions. Healthy subjects who are APOE ε4 allele positive exhibited larger OFC volumes. This finding should be examined in other populations.

Type
Original Article
Copyright
Copyright © Cambridge University Press 2007

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References

REFERENCES

An, X., Bandler, R., Ongur, D. & Price, J. L. (1998). Prefrontal cortical projections to longitudinal columns in the midbrain periaqueductal gray in macaque monkeys. Journal of Comparative Neurology 401, 429436.Google ScholarPubMed
Ballmaier, M., Sowell, E. R., Thompson, P. M., Kumar, A., Narr, K. L., Lavretsky, H., Welcome, S. E., DeLuca, H. & Toga, A. W. (2004 a). Mapping brain size and cortical gray matter changes in elderly depression. Biological Psychiatry 55, 382389.CrossRefGoogle ScholarPubMed
Ballmaier, M., Toga, A. W., Blanton, R. E., Sowell, E. R., Lavretsky, H., Peterson, J., Pham, D. & Kumar, A. (2004 b). Anterior cingulate, gyrus rectus, and orbitofrontal abnormalities in elderly depressed patients: an MRI-based parcellation of the prefrontal cortex. American Journal of Psychiatry 161, 99108.Google Scholar
Biver, F., Goldman, S., Delvenne, V., Luxen, A., De Maertelaer, V., Hubain, P., Mendlewicz, J. & Lotstra, F. (1994). Frontal and parietal metabolic disturbances in unpolar depression. Biological Psychiatry 36, 381388.Google Scholar
Bremner, J. D., Vythilingam, M., Ng, C. K., Vermetten, E., Nazeer, A., Oren, D. A., Berman, R. M. & Charney, D. S. (2003). Regional brain metabolic correlates of alpha-methylparatyrosine-induced depressive symptoms: implications for the neural circuitry of depression. Journal of the American Medical Association 289, 31253134.CrossRefGoogle ScholarPubMed
Bremner, J. D., Vythilingam, M., Vermetten, E., Nazeer, A., Adil, J., Khan, S., Staib, L. H. & Charney, D. S. (2002). Reduced volume of orbitofrontal cortex in major depression. Biological Psychiatry 51, 273279.CrossRefGoogle ScholarPubMed
Byrum, C. E., MacFall, J. R., Charles, H. C., Chitilla, V. R., Boyko, O. B., Upchurch, L., Smith, J. S., Rajagopalan, P., Passe, T., Kim, D., Xanthakos, S. & Krishnan, K. R. R. (1996). Accuracy and reproducibility of brain and tissue volumes using a magnetic resonance segmentation method. Psychiatry Research 67, 215234.CrossRefGoogle ScholarPubMed
Carmichael, S. T. & Price, J. L. (1995). Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys. Journal of Comparative Neurology 363, 615641.CrossRefGoogle ScholarPubMed
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A. & Poulton, R. (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386389.CrossRefGoogle ScholarPubMed
Coffey, C. E., Figiel, G. S., Djang, W. T., Cress, M., Saunders, W. B. & Weiner, R. D. (1988). Leukoencephalopathy in elderly depressed patients referred for ECT. Biological Psychiatry 24, 143161.CrossRefGoogle ScholarPubMed
Collier, D. A., Stober, G., Li, T., Heils, A., Catalano, M., Di Bella, D., Arranz, M. J., Murray, R. M., Vallada, H. P., Bengel, D., Muller, C. R., Roberts, G. W., Smeraldi, E., Kirov, G., Sham, P. & Lesch, K. P. (1996). A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role of susceptibility to affective disorders. Molecular Psychiatry 1, 453460.Google Scholar
Eley, T. C., Sugden, K., Corsico, A., Gregory, A. M., Sham, P., McGuffin, P., Plomin, R. & Craig, I. W. (2004). Gene–environment interaction analysis of serotonin system markers with adolescent depression. Molecular Psychiatry 9, 908915.Google Scholar
Folstein, M. F., Folstein, S. E. & McHugh, P. R. (1975). ‘Mini-mental state’: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189198.CrossRefGoogle Scholar
Forsell, Y., Corder, E. H., Basun, H., Lannfelt, L., Viitanen, M. & Winblad, B. (1997). Depression and dementia in relation to apolipoprotein E polymorphism in a population sample age 75+. Biological Psychiatry 42, 898903.CrossRefGoogle Scholar
Frodl, T., Meisenzahl, E. M., Zill, P., Baghai, T., Rujescu, D., Leinsinger, G., Bottlender, R., Schule, C., Zwanzger, P., Engel, R. R., Rupprecht, R., Bondy, B., Reiser, M. & Moller, H. J. (2004). Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression. Archives of General Psychiatry 61, 177183.CrossRefGoogle Scholar
Fujikawa, T., Yamawaki, S. & Touhouda, Y. (1993). Incidence of silent cerebral infarction in patients with major depression. Stroke 24, 16311634.CrossRefGoogle ScholarPubMed
Hastings, R. S., Parsey, R. V., Oquendo, M. A., Arango, V. & Mann, J. J. (2004). Volumetric analysis of the prefrontal cortex, amygdala, and hippocampus in major depression. Neuropsychopharmacology 29, 952959.Google Scholar
Janke, A. L., de Zubicaray, G., Rose, S. E., Griffin, M., Chalk, J. B. & Galloway, G. J. (2001). 4D deformation modeling of cortical disease progression in Alzheimer's dementia. Magnetic Resonance in Medicine 46, 661666.Google Scholar
Janssen, J., Pol, H. E. H., Lampe, I. K., Schnack, H. G., de Leeuw, F.-E., Kahn, R. S. & Heeren, T. J. (2004). Hippocampal changes and white matter lesions in early-onset depression. Biological Psychiatry 56, 825831.Google Scholar
Kikinis, R., Shenton, M. E., Gerig, G., Martin, J., Anderson, M., Metcalf, D., Guttman, C. R., McCarley, R. W., Lorensen, W., Cline, H. & Jolesz, F. A. (1992). Routine quantitative analysis of brain and cerebrospinal fluid spaces with MR imaging. Journal of Magnetic Resonance Imaging 2, 619629.Google Scholar
Koschack, J. & Irle, E. (2005). Small hippocampal size in cognitively normal subjects with coronary artery disease. Neurobiology of Aging 26, 865871.CrossRefGoogle ScholarPubMed
Krishnan, K. R. R., Hays, J. C. & Blazer, D. G. (1997). MRI-defined vascular depression. American Journal of Psychiatry 154, 497501.Google ScholarPubMed
Kumar, A., Bilker, W., Jin, Z. & Udupa, J. (2000). Atrophy and high intensity lesions: complementary neurobiological mechanisms in late-life depression. Neuropsychopharmacology 22, 264274.CrossRefGoogle Scholar
Lacerda, A. L., Keshavan, M. S., Hardan, A. Y., Yorbik, O., Brambilla, P., Sassi, R. B., Nicoletti, M., Mallinger, A. G., Frank, E., Kupfer, D. J. & Soares, J. C. (2004). Anatomic evaluation of the orbitofrontal cortex in major depressive disorder. Biological Psychiatry 55, 353358.CrossRefGoogle ScholarPubMed
Lai, T. J., Payne, M. E., Byrum, C. E., Steffens, D. E. & Krishnan, K. R. R. (2000). Reduction of orbital frontal cortex volume in geriatric depression. Biological Psychiatry 48, 971975.CrossRefGoogle ScholarPubMed
Landerman, R., George, L. K., Campbell, R. T. & Blazer, D. G. (1989). Alternative models of the stress buffering hypothesis. American Journal of Community Psychology 17, 626642.CrossRefGoogle ScholarPubMed
Lee, S. H., Payne, M. E., Steffens, D. C., McQuoid, D. R., Lai, T. J., Provenzale, J. M. & Krishnan, K. R. (2003). Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression. Biological Psychiatry 54, 529533.CrossRefGoogle ScholarPubMed
Lenze, E. J., Munin, M. C., Ferrell, R. E., Pollock, B. G., Skidmore, E., Lotrich, F., Rogers, J. C., Quear, T., Houck, P. & Reynolds, C. F. 3rd (2005). Association of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) genotype with depression in elderly persons after hip fracture. American Journal of Geriatric Psychiatry 13, 428432.CrossRefGoogle ScholarPubMed
Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., Benjamin, J., Muller, C. R., Hamer, D. H. & Murphy, D. L. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 15271531.Google Scholar
Lesser, I. M., Mena, I., Boone, K. B., Miller, B. L., Mehringer, M. C. & Wohl, M. (1994). Reduction of cerebral blood flow in older depressed patients. Archives of General Psychiatry 51, 677686.Google Scholar
Matsuda, H., Kitayama, N., Ohnishi, T., Asada, T., Nakano, S., Sakamoto, S., Imabayashi, E. & Katoh, A. (2002). Longitudinal evaluation of both morphologic and functional changes in the same individuals with Alzheimer's disease. Journal of Nuclear Medicine 43, 304311.Google ScholarPubMed
Montgomery, S. A. & Asberg, M. (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry 134, 382389.CrossRefGoogle ScholarPubMed
Mori, S., Kaufmann, W. E., Davatzikos, C., Stieltjes, B., Amodei, L., Fredericksen, K., Pearlson, G. D., Melhelm, E. R., Solaiyappan, M., Raymond, G. V., Moser, H. W. & van Zijl, P. C. M. (2002). Imaging cortical association tracts in the human brain using diffusion-tensor-based axonal tracking. Magnetic Resonance in Medicine 47, 215223.Google Scholar
O'Brien, J., Desmond, P., Ames, D., Schweitzer, I., Harrigan, S. & Tress, B. (1996). A magnetic resonance imaging study of white matter lesions in depression and Alzheimer's disease. British Journal of Psychiatry 168, 477485.CrossRefGoogle ScholarPubMed
O'Doherty, J., Kringelbach, M. L., Rolls, E. T., Hornak, J. & Andrews, C. (2001). Abstract reward and punishment representations in the human orbitofrontal cortex. Nature Neuroscience 4, 95102.CrossRefGoogle ScholarPubMed
Payne, M. E., Fetzer, D. L., MacFall, J. R., Provenzale, J. M., Byrum, C. E. & Krishnan, K. R. R. (2002). Development of a semi-automated method for quantification of MRI gray and white matter lesions in geriatric subjects. Psychiatry Research: Neuroimaging 115, 6377.CrossRefGoogle ScholarPubMed
Pezawas, L., Meyer-Lindenberg, A., Drabant, E. M., Verchinski, B. A., Munoz, K. E., Kolachana, B. S., Egan, M. F., Mattay, V. S., Hariri, A. R. & Weinberger, D. R. (2005). 5-HTTLPR polymorphism impacts human cingulate–amygdala interactions: a genetic susceptibility mechanism for depression. Nature Neuroscience 8, 828834.CrossRefGoogle ScholarPubMed
Price, J. L. (1999). Prefrontal cortical networks related to visceral function and mood. Annals of the New York Academy of Sciences 877, 383396.Google Scholar
Rajkowska, G., Miguel-Hidalgo, J. J., Wei, J., Dilley, G., Pittman, S. D., Meltzer, H. Y., Overholser, J. C., Roth, B. L. & Stockmeier, C. A. (1999). Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biological Psychiatry 45, 10851098.CrossRefGoogle ScholarPubMed
Robins, L. N., Helzer, J. E., Croughan, J. & Ratcliff, K. S. (1981). National Institute of Mental Health Diagnostic Interview Schedule. Its history, characteristics, and validity. Archives of General Psychiatry 38, 381389.CrossRefGoogle ScholarPubMed
Rolls, E. T., Hornak, J., Wade, D. & McGrath, J. (1994). Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. Journal of Neurology, Neurosurgery and Psychiatry 57, 15181524.CrossRefGoogle ScholarPubMed
Saunders, A. M., Strittmatter, W. J., Schmechel, D., George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., Gusella, J. F., Crapper-MacLachlan, D. R. & Alberts, M. J. (1993). Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 48, 14671472.CrossRefGoogle Scholar
Steffens, D. C., McQuoid, D. R., Welsh-Bohmer, K. A. & Krishnan, K. R. R. (2003 a). Left orbital frontal cortex volume and performance on the Benton Visual Retention Test in older depressives and controls. Neuropsychopharmacology 28, 21792183.CrossRefGoogle ScholarPubMed
Steffens, D. C., Norton, M. C., Hart, A. D., Skoog, I., Corcoran, C. & Breitner, J. C. (2003 b). Apolipoprotein E genotype and major depression in a community of older adults. The Cache County Study. Psychological Medicine 33, 541547.Google Scholar
Steffens, D. C., Svenson, I., Marchuk, D. A., Levy, R. M., Hays, J. C., Flint, E. P., Krishnan, K. R. & Siegler, I. C. (2002). Allelic differences in the serotonin transporter-linked polymorphic region in geriatric depression. American Journal of Geriatric Psychiatry 10, 185191.Google Scholar
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S. & Roses, A. D. (1993). Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America 90, 19771981.CrossRefGoogle ScholarPubMed
Taylor, W. D., MacFall, J. R., Payne, M. E., McQuoid, D. R., Steffens, D. C., Provenzale, J. M. & Krishnan, K. R. (2005 a). Greater MRI lesion volumes in elderly depressed subjects than in control subjects. Psychiatry Research Neuroimaging 139, 17.Google Scholar
Taylor, W. D., McQuoid, D. R. & Krishnan, K. R. (2004). Medical comorbidity in late-life depression. International Journal of Geriatric Psychiatry 19, 935943.CrossRefGoogle ScholarPubMed
Taylor, W. D., Steffens, D. C., McQuoid, D. R., Payne, M. E., Lee, S.-H., Lai, T.-J. & Krishnan, K. R. R. (2003). Smaller orbital frontal cortex volumes associated with functional disability in depressed elders. Biological Psychiatry 53, 144149.Google Scholar
Taylor, W. D., Steffens, D. C., Payne, M. E., MacFall, J. R., Marchuk, D. A., Svenson, I. K. & Krishnan, K. R. (2005 b). Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. Archives of General Psychiatry 62, 537544.Google Scholar
Tekin, S. & Cummings, J. L. (2002). Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. Journal of Psychosomatic Research 53, 647654.Google Scholar
Van Hoesen, G. W., Parvizi, J. & Chu, C. C. (2000). Orbitofrontal cortex pathology in Alzheimer's disease. Cerebral Cortex 10, 243251.Google Scholar