Research Article| Volume 54, ISSUE 7, P674-681, October 01, 2003

Apolipoprotein E genotype and subcortical vascular lesions in older depressed patients and control subjects



      Several studies have linked geriatric depression with cerebrovascular disease. The apolipoprotein E gene (APOE) ε4 allele has been associated with a variety of late-life neuropsychiatric disorders, including Alzheimer’s disease, vascular dementia, and depression.


      The sample consisted of 145 elderly depressive individuals and 100 nondepressed elderly control subjects. After a standardized clinical assessment, all subjects underwent a magnetic resonance imaging brain scan. Volumes of subcortical white and gray matter lesions were determined using a semi-automated method. Apolipoprotein E genotype was determined on blood sample using a standard protocol. A series of linear regression models were developed to assess the relationships between APOE genotype and white and gray matter lesion volumes.


      Older age, lower Mini-Mental State Examination score, and having any APOE ε4 allele were each correlated with gray-matter lesion volume in depressed patients. Apolipoprotein E genotype was not associated with any lesion volume among control subjects. In a subsequent linear regression model, gray matter lesion volume was associated with older age, having at least one APOE ε4 allele, and white matter lesion volume among depressed patients.


      These results are consistent with previous reports linking cerebrovascular disease and APOE genotype. Further studies are needed to replicate this finding in elderly depressive individuals and to explain the relationship between the APOE locus and development of central nervous system vascular pathology.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Bartres-Faz D.
        • Junque C.
        • Clemente I.C.
        • Serra-Grabulosa J.M.
        • Guardia J.
        • Lopez-Alomar A.
        • et al.
        MRI and genetic correlates of cognitive function in elders with memory impairment.
        Neurobiol Aging. 2001; 22: 449-459
        • Bronge L.
        • Fernaeus S.E.
        • Blomberg M.
        • Ingelson M.
        • Lannfelt L.
        • Isberg B.
        • et al.
        White matter lesions in Alzheimer patients are influenced by apolipoprotein E genotype.
        Dement Geriatr Cogn Disord. 1999; 10: 89-96
        • Byrum C.E.
        • MacFall J.R.
        • Charles H.C.
        • Chitilla V.R.
        • Boyko O.B.
        • Upchurch L.
        • et al.
        Accuracy and reproductibility of brain and tissue volumes using a magnetic resonance imaging segmentation method.
        Psychiatry Res. 1996; 67: 215-234
        • Class C.A.
        • Unverzagt F.W.
        • Gao S.
        • Sahota A.
        • Hall K.S.
        • Hendrie H.C.
        The association between Apo E genotype and depressive symptoms in elderly African-American subjects.
        Am J Geriatr Psychiatry. 1997; 5: 339-343
        • Corder E.H.
        • Saunders A.M.
        • Strittmatter W.J.
        • Schmechel D.E.
        • Gaskell P.C.
        • Small G.W.
        • et al.
        Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families.
        Science. 1993; 261: 921-923
        • DeCarli C.
        • Reed T.
        • Miller B.L.
        • Wolf P.A.
        • Swan G.E.
        • Carmelli D.
        Impact of apolipoprotein E epsilon4 and vascular disease on brain morphology in men from the NHLBI twin study.
        Stroke. 1999; 30: 1548-1553
        • Doody R.S.
        • Azher S.N.
        • Haykal H.A.
        • Dunn J.K.
        • Liao T.
        • Schneider L.
        Does APO epsilon4 correlate with MRI changes in Alzheimer’s disease?.
        J Neurol Neurosurg Psychiatry. 2000; 69: 668-771
        • Folstein M.F.
        • Folstein S.E.
        • McHugh P.R.
        Mini-Mental state. A practical method for grading the cognitive state of patients for the clinician.
        J Psychiatr Res. 1975; 12: 189-198
        • Forsell Y.
        • Corder E.H.
        • Basun H.
        • Lannfelt L.
        • Viitanen M.
        • Winblad B.
        Depression and dementia in relation to apolipoprotein E polymorphism in a population sample age 75+.
        Biol Psychiatry. 1997; 42: 898-903
        • Grossman H.T.
        • Jacobson S.
        • Folstein M.F.
        Neuroimaging and the normal elderly.
        in: Ames D. Chui E. Neuroimaging in the Psychiatry of Late Life. Cambridge University Press, New York1997
        • Hamilton M.
        A rating scale for depression.
        J Neurol Neurosurg Psychiatry. 1960; 23: 55-61
        • Harris G.J.
        • Schlaepfer T.E.
        • Peng L.W.
        • Lee S.
        • Federman E.B.
        • Pearlson G.D.
        Magnetic resonance imaging evaluation of the effects of ageing on grey-white ratio in the human brain.
        Neuropathol Appl Neurobiol. 1994; 20: 290-293
        • Hirono N.
        • Yasuda M.
        • Tanimukai S.
        • Kitagaki H.
        • Mori E.
        Effect of the apolipoprotein E epsilon4 allele on white matter hyperintensities in dementia.
        Stroke. 2000; 31: 1263-1268
        • Iidaka T.
        • Nakajima T.
        • Kawamoto K.
        • Fukuda H.
        • Suzuki Y.
        • Maehara T.
        • et al.
        Signal hyperintensities on brain magnetic resonance imaging in elderly depressed patients.
        Eur Neurol. 1996; 36: 293-299
        • Kikinis R.
        • Shenton M.E.
        • Gerig G.
        • Martin J.
        • Anderson M.
        • Metcalf D.
        • et al.
        Routine quantitative analysis of brain and cerebrospinal fluid spaces with MR imaging.
        J Magn Reson Imaging. 1992; 2: 619-629
        • Krishnan K.R.
        • Tupler L.A.
        • Ritchie J.C.
        • McDonald W.M.
        • Knight D.L.
        • Nemeroff C.B.
        • et al.
        Apolipoprotein E-epsilon 4 frequency in geriatric depression.
        Biol Psychiatry. 1996; 40: 69-71
        • Krishnan K.R.R.
        • Hays J.C.
        • Blazer D.G.
        MRI defined vascular depression.
        Am J Psychiatry. 1997; 154: 497-501
        • Landerman R.
        • George L.K.
        • Campbell R.T.
        • Blazer D.G.
        Alternative models of the stress buffering hypothesis.
        Am J Community Psychol. 1989; 17: 626-642
        • McCarron M.O.
        • Delong D.
        • Alberts M.J.
        APOE genotype as a risk factor for ischemic cerebrovascular disease.
        Neurology. 1999; 53: 1308-1311
        • Miller A.K.
        • Alston R.L.
        • Corsellis J.A.
        Variation with age in the volumes of grey and white matter in the cerebral hemispheres of man.
        Neuropathol Appl Neurobiol. 1980; 6: 119-132
        • Montgomery S.A.
        • Asberg M.
        A new depression scale designed to be sensitive to change.
        Br J Psychiatry. 1979; 134: 382-389
        • Nebes R.D.
        • Vora I.J.
        • Meltzer C.C.
        • Fukui M.B.
        • Williams R.L.
        • Kamboh M.I.
        • et al.
        Relationship of deep white matter hyperintensities and apolipoprotein E genotype to depressive symptoms in older adults without clinical depression.
        Am J Psychiatry. 2001; 158: 878-884
        • Robins N.
        • Helzer J.E.
        • Croughan J.
        • Ratcliff K.S.
        National Institute of Mental Health diagnostic interview schedule.
        Arch Gen Psychiatry. 1981; 38: 381-389
        • Saunders A.M.
        • Strittmatter W.J.
        • Schmechel D.
        • St. George-Hyslop P.H.
        • Pericak-Vance M.A.
        • Joo S.H.
        • et al.
        Association of apolipoprotein E allele e4 with late-onset familial and sporadic Alzheimer’s disease.
        Neurology. 1993; 43: 1467-1472
        • Schmand B.
        • Hooijer C.
        • Jonker C.
        • Lindeboom J.
        • Havekes L.M.
        Apolipoprotein E phenotype is not related to late-life depression in a population-based sample.
        Soc Psychiatry Psychiatr Epidemiol. 1998; 33: 21-26
        • Schmidt H.
        • Schmidt R.
        • Fazekas F.
        • Semmler J.
        • Kapeller P.
        • Reinhart B.
        • et al.
        Apolipoprotein E e4 allele in the normal elderly.
        Clin Genet. 1996; 50: 293-299
        • Schmidt R.
        • Schmidt H.
        • Fazekas F.
        • Schumacher M.
        • Niederkorn K.
        • Kapeller P.
        • et al.
        Apolipoprotein E polymorphism and silent microangiopathy-related cerebral damage. Results of the Austrian Stroke Prevention Study.
        Stroke. 1997; 28: 951-956
        • Steffens D.C.
        • Helms M.J.
        • Krishnan K.R.
        • Burke G.L.
        Cerebrovascular disease and depression symptoms in the cardiovascular health study.
        Stroke. 1999; 30: 2159-2166
        • Strittmatter W.J.
        • Saunders A.M.
        • Schmechel D.
        • Pericak-Vance M.
        • Enghild I.
        • Salvesen G.S.
        • et al.
        Apolipoprotein E.
        Proc Natl Acad Sci U S A. 1993; 90: 1977-1981