Advanced search
Publication Cover
Harvard Review of Psychiatry Volume 11, 2003 - Issue 5
Journal homepage
20
Views
4
CrossRef citations to date
0
Altmetric
Research Article

Clinical Significance of Brain White Matter Hyperintensities in Young Adults with Psychiatric Illness

Janis L. Breeze From the Pediatric Psychotic Disorders Research Program, McLean Hospital, Belmont, MA
,
Dale C. Hesdorffer Child Psychiatry Outpatient Department, McLean Hospital, Belmont, MA
,
Xiaoni Hong Brain Imaging Center, McLean Hospital, Belmont, MA
,
Jean A. Frazier Department of Epidemiology, Mailman School of Public Health, Columbia University
&
Perry F. Renshaw GH Sergievsky Center, Columbia University; Department of Neurology, College of Physicians and Surgeons, Columbia University; Department of Psychiatry, Harvard Medical School
Pages 269-283 | Published online: 03 Jul 2009

  • Altshuler LL, Curran JG, Hauser P, Mintz J, Denicoff K, Post R. T2 hyperintensities in bipolar disorder: magnetic resonance imaging comparison and literature meta-analysis. Am J Psychiatry 1995;151:1139-44.
  • Aylward EH, Roberts-Twillie JV, Barta PE, Kumar AJ, Harris GJ, Geer M, et al. Basal ganglia volumes and white matter hyperintensities in patients with bipolar disorder. Am J Psychiatry 1994;151:687-93.
  • Brown FW, Lewine RJ, Hudgins PA, Risch SC. White matter hyperintensity signals in psychiatric and nonpsychiatric subjects. Am J Psychiatry 1992;149:620-5.
  • Deicken RF, Reus VI, Manfredi L, Wolkowitz OM. MRI deep white matter hyperintensity in a psychiatric population. Biol Psychiatry 1991;29:918-22.
  • Dupont RM, Jernigan TL, Gillin JC, Butters N, Delis DC, Hesselink JR. Subcortical signal hyperintensities in bipolar patients detected by MRI [Letter]. Psychiatry Res 1987;21:357-8.
  • Dupont RM, Jernigan TL, Butters N, Delis D, Hesselink JR, Heindel W, et al. Subcortical abnormalities detected in bipolar affective disorder using magnetic resonance imaging: clinical and neuropsychological significance. Arch Gen Psychiatry 1990;47:55-9.
  • Dupont RM, Jernigan TL, Heindel W, Butters N, Shafer K, Wilson T, et al. Magnetic resonance imaging and mood disorders: localization of white matter and other subcortical abnormalities. Arch Gen Psychiatry 1995;52:747-55.
  • Dupont RM, Butters N, Schafer K, Wilson T, Hesselink J, Gillin JC. Diagnostic specificity of focal white matter abnormalities in bipolar and unipolar mood disorder. Biol Psychiatry 1995;38:482-6.
  • Figiel GS, Krishnan KR, Rao VP, Doraiswamy M, Ellinwood EH Jr, Nemeroff CB, et al. Subcortical hyperintensities on brain magnetic resonance imaging: a comparison of normal and bipolar subjects. J Neuropsychiatry Clin Neurosci 1991;3:18-22.
  • McDonald WM, Tupler LA, Marsteller FA, Figiel GS, DiSouza S, Nemeroff CB, et al. Hyperintense lesions on magnetic resonance images in bipolar disorder. Biol Psychiatry 1999;45:965-71.
  • Moore PB, Shepherd DJ, Eccleston D, Macmillan IC, Goswami U, McAllister VL, et al. Cerebral white matter lesions in bipolar affective disorder: relationship to outcome. Br J Psychiatry 2001;178:172-6.
  • Swayze VW, Andreasen NC, Alliger RJ, Ehrhardt JC, Yuh WT. Structural brain abnormalities in bipolar affective disorder. Arch Gen Psychiatry 1990;47:1054-9.
  • Coffey CE, Figiel GS, Djang WT, Weiner RD. Subcortical hyperintensity on magnetic resonance imaging: a comparison of normal and depressed elderly subjects. Am J Psychiatry 1990;147:187-9.
  • Greenwald BS, Kramer-Ginsberg E, Krishnan KR, Hu J, Ashtari M, Wu H, et al. A controlled study of MRI signal hyperintensities in older depressed patients with and without hypertension. J Am Geriatr Soc 2001;49:1218-25.
  • Hickie I, Scott E, Mitchell P, Wilhelm K, Austin MP, Bennett B. Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression. Biol Psychiatry 1995;37:151-60.
  • Lenze E, Cross D, McKeel D, Neuman RJ, Sheline YI. White matter hyperintensities and gray matter lesions in physically healthy depressed subjects. Am J Psychiatry 1999;156:1602-7.
  • Lesser IM, Boone KB, Mehringer CM, Wohl MA, Miller BL, Berman NG. Cognition and white matter hyperintensities in older depressed patients. Am J Psychiatry 1996;153:1280-7.
  • Bartzokis G, Garber HJ, Griswold VJ, Oldendorf WH, Mintz J, Marder SR. T2 hyperintense foci on magnetic resonance images of schizophrenic patients and controls. Psychiatry Res 1991;40:239-45.
  • Persaud R, Russow H, Harvey I, Lewis SW, Ron M, Murray RM, et al. Focal signal hyperintensities in schizophrenia. Schizophr Res 1997;27:55-64.
  • Rivkin P, Kraut M, Barta PE, Anthony J, Arria AM, Pearlson G. White matter hyperintensity volume in late-onset and earlyonset schizophrenia. Int J Geriatr Psychiatry 2000;15:1085-9.
  • Sachdev P, Brodaty H. Quantitative study of signal hyperintensities on T2-weighted magnetic resonance imaging in late-onset schizophrenia. Am J Psychiatry 1999;156:1958-67.
  • Pillai JJ, Friedman L, Stuve TA, Trinidad S, Jesberger JA, Lewin JS, et al. Increased presence of white matter hyperintensities in adolescent patients with bipolar disorder. Psychiatry Res 2002;114:51-6.
  • Pitman RK, Shin LM, Rauch SL. Investigating the pathogenesis of posttraumatic stress disorder with neuroimaging. J Clin Psychiatry 2001;62(suppl 17):47-54.
  • Awad IA, Spetzler RF, Hodak JA, Awad CA, Williams F Jr, Carey R. Incidental lesions noted on magnetic resonance imaging of the brain: prevalence and clinical significance in various age groups. Neurosurgery 1987;20:222-7.
  • Austrom MG, Thompson RF Jr, Hendrie HC, Norton J, Farlow MR, Edwards MK, et al. Foci of increased T2 signal intensity in MR images of healthy elderly subjects: a follow-up study. J Am Geriatr Soc 1990;38:1133-8.
  • Baum KA, Schulte C, Girke W, Reischies FM, Felix R. Incidental white-matter foci on MRI in "healthy" subjects: evidence of subtle cognitive dysfunction. Neuroradiol 1996;38: 755-60.
  • Boone KB, Miller BL, Lesser IM, Mehringer CM, Hill-Gutierrez E, Goldberg MA, et al. Neuropsychological correlates of white-matter lesions in healthy elderly subjects. Arch Neurol 1992;49:549-54.
  • DeCarli C, Murphy DG, Tranh M, Grady CL, Haxby JV, Gillette JA, et al. The effect of white matter hyperintensity on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology 1995;45:2077-84.
  • Gunning-Dixon FM, Raz N. The cognitive correlates of white matter abnormalities in normal aging: a quantitative review. Neuropsychology 2000;14:224-32.
  • Junque C, Pujol J, Vendrell P, Bruna O, Jodar M, Ribas JC, et al. Leuko-araiosis on magnetic resonance imaging and speed of mental processing. Arch Neurol 1990;47:151-6.
  • Schmidt R, Fazekas F, Offenbacher H, Dusek T, Zach E, Reinhart B, et al. Neuropsychological correlates of MRI white matter hyperintensities: a study of 150 normal volunteers. Neurology 1993;43:2490-4.
  • Ylikoski R, Ylikoski A, Erkinjuntti T, Sulkava R, Raininko R, Tilvis R. White matter changes in healthy elderly persons correlate with attention and speed of mental processing. Arch Neurol 1993;50:818-24.
  • Katzman GL, Dagher AP, Patronas NJ. Incidental findings on brain magnetic resonance imaging from 1000 asymptomatic volunteers. JAMA 1999;282:36-9.
  • Autti T, Raininko R, Vanhanen SL, Kallio M, Santavuori P. MRI of the normal brain from early childhood to middle age. I. Appearances on T2- and proton density-weighted images and occurrence of incidental high-signal foci. Neuroradiology 1994;36:644-8.
  • de Leeuw FE, de Groot JC, Achten E, Oudkerk M, Ramos LM, Heijboer R, et al. Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 2001;70:9-14.
  • Liao D, Cooper L, Cai J, Toole J, Bryan N, Burke G, et al. The prevalence and severity of white matter lesions, their relationship with age, ethnicity, gender, and cardiovascular risk factors: the ARIC study. Neuroepidemiology 1997;16:149-63.
  • Salonen O, Autti T, Raininko R, Ylikoski A, Erkinjuntti T. MRI of the brain in neurologically healthy middle-aged and elderly individuals. Neuroradiology 1997;39:537-45.
  • Claus JJ, Breteler MM, Kasan D, Krenning EP, Bots ML, Grobbee DE, et al. Vascular risk factors, atherosclerosis, cerebral white matter lesions and cerebral perfusion in a population-based study. Eur J Nucl Med 1996;23:675-82.
  • Dufouil C, de Kersaint-Gilly A, Besancon V, Levy C, Auffray E, Brunnereau L, et al. Longitudinal study of blood pressure and white matterhyperintensities: the EVAMRI Cohort. Neurology 2001;56:921-6.
  • Fazekas F. Magnetic resonance signal abnormalities in asymptomatic individuals: their incidence and functional correlates. EurNeurol 1989;29:164-8.
  • Fazekas F, Niederkorn K, Schmidt R, Offenbacher H, Homer S, Bertha G, et al. White matter signal abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors. Stroke 1988;19:1285-8.
  • Figiel GS, Krishnan KR, Doraiswamy PM, Rao VP, Nemeroff CB, Boyko OB. Subcortical hyperintensities on brain magnetic resonance imaging: a comparison between late age onset and early onset elderly depressed subjects. Neurobiol Aging 1991;12:245-7.
  • Fukuda H, Kitani M. Differences between treated and untreated hypertensive subjects in the extent of periventricular hyperintensities observed on brain MRI. Stroke 1995;26:15937.
  • Goldstein IB, Bartzokis G, Hance DB, Shapiro D. Relationship between blood pressure and subcortical lesions in healthy elderly people. Stroke 1998;29:765-72.
  • Hendrie HC, Farlow MR, Austrom MG, Edwards MK, Williams MA. Foci of increased T2 signal intensity on brain MR scans of healthy elderly subjects. Am J Neuroradiol 1989;10:703-7.
  • Kertesz A, Black SE, Tokar G, Benke T, Carr T, Nicholson L. Periventricular and subcortical hyperintensities on magnetic resonance imaging. 'Rims, caps, and unidentified bright objects.' Arch Neurol 1988;45:404-8.
  • Lechner H, Schmidt R, Bertha G, Justich E, Offenbacher H, Schneider G. Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals. Stroke 1988;19:263-5.
  • Longstreth WT Jr, Manolio TA, Arnold A, Burke GL, Bryan N, Jungreis CA, et al. Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people. Stroke 1996;27:1274-82.
  • Manolio TA, Kronmal RA, Burke GL, Poirier V, O'Leary DH, Gardin JM, et al. Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study. Stroke 1994;25:318-27.
  • Mirsen TR, Lee DH, Wong CJ, Diaz JF, Fox AJ, Hachinski VC, et al. Clinical correlates of white-matter changes on magnetic resonance imaging scans of the brain. Arch Neurol 1991;48:1015-21.
  • O'Brien J, Perry R, Barber R, Gholkar A, Thomas A. The association between white matter lesions on magnetic resonance imaging and noncognitive symptoms. Ann NY Acad Sci 2000;903:482-9.
  • Oyama H, Kida Y, Tanaka T, Iwakoshi T, Niwa M, Kobayashi T. Incidental white matter lesions identified on magnetic resonance images of normal Japanese individuals--correlation with age and hypertension. Neurol Med Chir (Tokyo) 1994; 34:286-90.
  • Schmidt R. Comparison of magnetic resonance imaging in Alzheimer's disease, vascular dementia and normal aging. Eur Neurol 1992;32:164-9.
  • Schmidt R, Fazekas F, Kapeller P, Schmidt H, Hartung HP. MRI white matter hyperintensities: three-year follow-up of the Austrian Stroke Prevention Study. Neurology 1999;63: 132-9.
  • Schmidt R, Fazekas F, Kleinert G, Offenbacher H, Gindl K, Payer F, et al. Magnetic resonance imaging signal hyperintensities in the deep and subcortical white matter: a comparative study between stroke patients and normal volunteers. Arch Neurol 1992;49:826-7.
  • Schmidt R, Fazekas F, Offenbacher H, Lytwyn H, Blematl B, Niederkorn K, et al. Magnetic resonance imaging white matter lesions and cognitive impairment in hypertensive individuals. Arch Neurol 1991;48:417-20.
  • Strassburger TL, Lee HC, DaIy EM, Szczepanik J, Krasuski JS, Mentis MJ, et al. Interactive effects of age and hypertension on volumes of brain structures. Stroke 1997;28:1410-7.
  • van Swieten JC, Geyskes GG, Derix MM, Peeck BM, Ramos LM, van Latum JC, et al. Hypertension in the elderly is associated with white matter lesions and cognitive decline. Ann Neurol 1991;30:826-30.
  • Veldink JH, Schedltens P, Jonker C, Launer LJ. Progression of cerebral white matter hyperintensities on MRI is related to diastolic blood pressure. Neurology 1998;61:319-20.
  • Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5T in Alzheimer's dementia and normal aging. Am J Neuroradiol 1987;8:421-6.
  • Fazekas F, Kapeller P, Schmidt R, Offenbacher H, Payer F, Fazekas G. The relation of cerebral magnetic resonance signal hyperintensities to Alzheimer's disease. J Neurol Sci 1996;142:121-5.
  • Rothman KJ, Greenland S. Case-control studies. In: Rothman KJ, Greenland S, eds. Modern epidemiology. 2nd ed. Philadelphia: Lippincott-Raven, 1998:93-114.
  • Greenwald BS, Kramer-Ginsberg E, Krishnan RR, Ashtari M, Aupperle PM, Patel M. MRI signal hyperintensities in geriatric depression. Am J Psychiatry 1996;163:1212-6.
  • Kramer-Ginsberg E, Greenwald BS, Krishnan KR, Christiansen B, Hu J, Ashtari M, et al. Neuropsychological functioning and MRI signal hyperintensities in geriatric depression. Am J Psychiatry 1999;166:438-44.
  • Simpson SW, Jackson A, Baldwin RC, Burns A. Subcortical hyperintensities in late-life depression: acute response to treatment and neuropsychological impairment. Int Psychogeriatr 1997;9:257-75.
  • Tupler LA, Krishnan KR, McDonald WM, Dombeck CB, D'Souza S, Steffens DC. Anatomic location and laterality of MRI signal hyperintensities in late-life depression. J Psychosom Res 2002;63:666-76.
  • Murata T, Kimura H, Omori M, Kado H, Kosaka H, Iidaka T, et al. MRI white matter hyperintensities, (1)H-MR spectroscopy and cognitive function in geriatric depression: a comparison of early- and late-onset cases, bit J Geriatr Psychiatry 2001;16:1129-35.
  • Salloway S, Malloy P, Kohn R, Gillard E, Duffy J, Rogg J, et al. MRI and neuropsychological differences in early- and late-lifeonset geriatric depression. Neurology 1996;46:1567-74.
  • Novaretti TM, Marcelin MA, Meira S Jr, Gelas PL, Baudelin CG, Bottino CM. Subcortical hyperintensities on magnetic resonance imaging: a comparison of normal and depressed elderly subjects. Arq Neuropsiquiatr 2001;59(3-B):754-60.
  • Lyoo IK, Mino I, Renshaw PF, Lee HK. White matter hyperintensities [Letter]. J Am Acad Child Adolesc Psychiatry 1995;34:833-4.
  • Strakowski SM, Wilson DR, Tohen M, Woods BT, Douglass AW, Stoll AL. MRI subcortical signal hyperintensities in mania at first hospitalization. Biol Psychiatry 1993;33:204-6.
  • Woods BT, Yurgelun-Todd D, Mikulis D, Pillay SS. Age-related MRI abnormalities in bipolar illness: a clinical study. Biol Psychiatry 1995;38:846-7.
  • Lyoo IK, Lee HK, Jung JH, Noam GG, Renshaw PF. White matter hyperintensities on magnetic resonance imaging of the brain in children with psychiatric disorders. Compr Psychiatry 2002;43:361-8.
  • Gonzalez-Pinto A, Gutierrez M, Ezcurra J, Aizpuru F, Mosquera F, Lopez P, et al. Tobacco smoking and bipolar disorder. J Clin Psychiatry 1998;59:225-8.
  • Cassidy F, Ahearn E, Carroll J. Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients. Am J Psychiatry 1999;156:1417-20.
  • Yates WR, Wallace R. Cardiovascular risk factors in affective disorder. J Affect Disord 1987;12:129-34.
  • Glueck C, Tieger M, Kunkel R, Hamer T, Tracy T, Speirs J. Hypocholesterolemia and affective disorders. Am J Med Sei 1994;309:218-25.
  • Swartz CM. Albumin decrement in depression and cholesterol decrement in mania. J Affect Disord 1990;19:173-6.
  • Lyoo IK, Seol HY, Byun HS, Renshaw PF. Unsuspected multiple sclerosis in patients with psychiatric disorders: a magnetic resonance imaging study. J Neuropsychiatry Clin Neurosci 1996;8:54-9.
  • Abeam EP, Steffens DC, Cassidy F, Van Meter SA, Provenzale JM, Seldin MF, et al. Familial leukoencephalopathy in bipolar disorder. Am J Psychiatry 1998;155:1605-7.
  • Silverstone T, McPherson H, Li Q, Doyle T. Deep white matter hyperintensities in patients with bipolar depression, unipolar depression and age-matched control subjects. Bipolar Disord 2003;5:53-7.
  • Awad IA, Spetzler RF, Kodak JA, Awad CA, Carey R. Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. I. Correlation with age and cerebrovascular risk factors. Stroke 1986;17:1084-9.
  • Tzourio C, Levy C, Dufouil C, Touboul PJ, Ducimetiere P, Alperovitch A. Low cerebral blood flow velocity and risk of white matter hyperintensities. Ann Neurol 2001;49:411-4.
  • Lim KO, Hedehus M, Moseley M, de Crespigny A, Sullivan EV, Pfefferbaum A. Compromized white matter tract integrity Ui schizophrenia inferred from diffusion tensor imaging. Arch Gen Psychiatry 1999;56:367-74.
  • Foong J, Maier M, Clark CA, Barker GJ, Miller DH, Ron MA. Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study. J Neurol Neurosurg Psychiatry 2000;68:242-4.
  • Steel RM, Bastin ME, McConnell S, Marshall I, CunninghamOwens DG, Lawrie SM, et al. Diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (IH MRS) in schizophrenic subjects and normal controls. Psychiatry Res 2001;106:161-70.
  • Foong J, Symms MR, Barker GJ, Maier M, Miller DH, Ron MA. Investigating regional white matter in schizophrenia using diffusion tensor imaging. Neuroreport 2002;13:333-6.
  • Lim KO, Choi SJ, Pomara N, Wolkin A, Rotrosen JP. Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study. Biol Psychiatry 2002;15:890-5.
  • Taylor WD, Payne ME, Krishnan KR, Wagner HR, Provenzale JM, Steffens DC, et al. Evidence of white matter tract disruption in MRI hyperintensities. Biol Psychiatry 2001;50:179-83.
  • Pike GB, De Stefano N, Narayanan S, Worsley KJ, Pelletier D, Francis GS, et al. Multiple sclerosis: magnetization transfer MR imaging of white matter before lesion appearance on T2weighted images. Radiology 2000;215:824-30.
  • Santos AC, Narayanan S, de Stefano N, Tartaglia MC, Francis SJ, Amaoutelis R, et al. Magnetization transfer can predict clinical evolution in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2002;249:662-8.
  • Fazekas F, Ropele S, Enzinger C, Seifert T, Strasser-Fuchs S. Quantitative magnetization transfer imaging of prelesional white-matter changes in multiple sclerosis. Mult Scler 2002;8:479-84.
  • Foong J, Symms MR, Barker GJ, Maier M, Woermann FG, Miller DH, et al. Neuropathological abnormalities in schizophrenia: evidence from magnetization transfer imaging. Brain 2001;124:882-92.
  • Bagary MS, Foong J, Maier M, duBoulay G, Barker GJ, Miller DH, et al. A magnetization transfer analysis of the thalamus in schizophrenia. J Neuropsychiatry Clin Neurosci 2002;14:4438.
  • Mantyla R, Erkinjuntti T, Salonen O, Aronen HJ, Peltonen T, Pohjasvaara T, et al. Variable agreement between visual rating scales for white matter hyperintensities on MRI: comparison of 13 rating scales in a poststroke cohort. Stroke 1997;28:1614-23.
  • Erkinjuntti T, Gao F, Lee DH, Eliasziw M, Merskey H, Hachinski VC. Lack of difference in brain hyperintensities between patients with early Alzheimer's disease and control subjects. Arch Neurol 1994;51:260-8.
  • Greenland S. Analysis of polytomous exposures and outcomes. In: Rothman KJ, Greenland S, eds. Modern epidemiology. 2nd ed. Philadelphia: Lippincott-Raven, 1998:301-28.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.