Monozygotic Twins Discordant for Chronic Fatigue Syndrome: Regional Cerebral Blood Flow SPECT

PURPOSE: To evaluate the relationship between regional cerebral blood flow (rCBF) and chronic fatigue syndrome (CFS) in monozygotic twins discordant for CFS.

MATERIALS AND METHODS: The authors conducted a co-twin control study of 22 monozygotic twins in which one twin met criteria for CFS and the other was healthy. Twins underwent a structured psychiatric interview and resting technetium 99m–hexamethyl-propyleneamine oxime single photon emission computed tomography of the brain. They also rated their mental status before the procedure. Scans were interpreted independently by two physicians blinded to illness status and then at a blinded consensus reading. Imaging fusion software with automated three-dimensional matching of rCBF images was used to coregister and quantify results. Outcomes were the number and distribution of abnormalities at both reader consensus and automated quantification. Mean rCBF levels were compared by using random effects regression models to account for the effects of twin matching and potential confounding factors.

RESULTS: The twins with and those without CFS were similar in mean number of visually detected abnormalities and in mean differences quantified by using image registration software. These results were unaltered with adjustments for fitness level, depression, and mood before imaging.

CONCLUSION: The study results did not provide evidence of a distinctive pattern of resting rCBF abnormalities associated with CFS. The described method highlights the importance of selecting well-matched control subjects.

References

  • 1 Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study—International Chronic Fatigue Syndrome Study group. Ann Intern Med 1994; 121:953-959. Crossref, MedlineGoogle Scholar
  • 2 Komaroff AL, Buchwald D. Symptoms and signs of chronic fatigue syndrome. Rev Infect Dis 1991; 13:S8-11. Crossref, MedlineGoogle Scholar
  • 3 Christodoulou C, DeLuca J, Lange G, et al. Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry 1998; 64:431-434. Crossref, MedlineGoogle Scholar
  • 4 DeLuca J, Johnson SK, Ellis SP, Natelson BH. Cognitive functioning is impaired in patients with chronic fatigue syndrome devoid of psychiatric disease. J Neurol Neurosurg Psychiatry 1997; 62:151-155. Crossref, MedlineGoogle Scholar
  • 5 Fiedler N, Kipen HM, DeLuca J, Kelly-McNeil K, Natelson B. A controlled comparison of multiple chemical sensitivities and chronic fatigue syndrome. Psychosom Med 1996; 58:38-49. Crossref, MedlineGoogle Scholar
  • 6 DeLuca J, Johnson SK, Beldowicz D, Natelson BH. Neuropsychological impairments in chronic fatigue syndrome, multiple sclerosis, and depression. J Neurol Neurosurg Psychiatry 1995; 58:38-43. Crossref, MedlineGoogle Scholar
  • 7 DeLuca J, Johnson SK, Natelson BH. Information processing efficiency in chronic fatigue syndrome and multiple sclerosis. Arch Neurol 1993; 50:301-304. Crossref, MedlineGoogle Scholar
  • 8 Abu-Judeh HH, Levine S, Kumar M, et al. Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Nucl Med Commun 1998; 19:1065-1071. Crossref, MedlineGoogle Scholar
  • 9 Ichise M, Salit IE, Abbey SE, et al. Assessment of regional cerebral perfusion by 99mTc-HMPAO SPECT in chronic fatigue syndrome. Nucl Med Commun 1992; 13:767-772. Crossref, MedlineGoogle Scholar
  • 10 Schwartz RB, Garada BM, Komaroff AL, et al. Detection of intracranial abnormalities in patients with chronic fatigue syndrome: comparison of MR imaging and SPECT. AJR Am J Roentgenol 1994; 162:935-941. Crossref, MedlineGoogle Scholar
  • 11 Schwartz RB, Komaroff AL, Garada BM, et al. SPECT imaging of the brain: comparison of findings in patients with chronic fatigue syndrome, AIDS dementia complex, and major unipolar depression. AJR Am J Roentgenol 1994; 162:943-951. Crossref, MedlineGoogle Scholar
  • 12 Costa DC, Tannock C, Brostoff J. Brainstem perfusion is impaired in chronic fatigue syndrome. QJM 1995; 88:767-773. MedlineGoogle Scholar
  • 13 Fischler B, D’Haenen H, Cluydts R, et al. Comparison of 99mTc HMPAO SPECT scan between chronic fatigue syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow. Neuropsychobiology 1996; 34:175-183. Crossref, MedlineGoogle Scholar
  • 14 Machale SM, Lawrie SM, Cavanagh JT, et al. Cerebral perfusion in chronic fatigue syndrome and depression. Br J Psychiatry 2000; 176:550-556. Crossref, MedlineGoogle Scholar
  • 15 Assessment of brain SPECT: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.Neurology1996; 46:278-285. Crossref, MedlineGoogle Scholar
  • 16 Mayberg HS. Functional neuroimaging in CFS: applications and limitations. J Chron Fat Syn 1996; 1:9-20. Google Scholar
  • 17 Lange G, Wang S, DeLuca J, Natelson BH. Neuroimaging in chronic fatigue syndrome. Am J Med 1998; 105:50S-53S. Crossref, MedlineGoogle Scholar
  • 18 Hrubec Z, Robinette CD. The study of human twins in medical research. N Engl J Med 1984; 310:435-441. Crossref, MedlineGoogle Scholar
  • 19 Buchwald DS, Herrell R, Ashton S, Belcourt M, Schmaling K, Goldberg J. The chronic fatigue twin registry: method of construction, composition and zygosity assignment. Twin Res 1999; 2:203-211. Crossref, MedlineGoogle Scholar
  • 20 Robins LN, Helzer JE. Diagnostic interview schedule (DIS): version III-A St Louis, Mo: Washington University School of Medicine, 1985. Google Scholar
  • 21 American Psychiatric Association. Diagnostic and statistical manual of mental disorders 3rd ed. Washington, DC: American Psychiatric Association, 1987. Google Scholar
  • 22 Torgersen S. The determination of twin zygosity by means of a mailed questionnaire. Acta Genet Med Gemellol (Roma) 1979; 28:225-236. Crossref, MedlineGoogle Scholar
  • 23 Eisen S, Neuman R, Goldberg J, Rice J, True W. Determining zygosity in the Vietnam Era Twin Registry: an approach using questionnaires. Clin Genet 1989; 35:423-432. MedlineGoogle Scholar
  • 24 Keith L, Machin G. Zygosity testing: current status and evolving issues. J Reprod Med 1997; 42:699-707. MedlineGoogle Scholar
  • 25 Fletcher JW, Woolf SH, Royal HD. Consensus development for producing diagnostic procedure guidelines: SPECT brain perfusion imaging with exametazime. J Nucl Med 1994; 35:2003-2010. MedlineGoogle Scholar
  • 26 Chang LT. A method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 1978; NS-25:638-643. Google Scholar
  • 27 Slomka PJ, Reid BR, Hurwitz GA, Stephenson JA. Automated template-based quantification of brain SPECT. In: DeDeyn PP, Dierckx RA, Alavi A, Pickut BA, eds. A textbook of SPECT in neurology and psychiatry. London, England: Libbey, 1997; 507-512. Google Scholar
  • 28 Zifko UA, Slomka PJ, Reid RH, Young GB, Remtulla H, Bolton CF. The cortical representation of somatosensory evoked potentials of the phrenic nerve. J Neurol Sci 1996; 139:197-202. Crossref, MedlineGoogle Scholar
  • 29 Radau P, Linke R, Slomka P, Tatsch K. Optimization of automated quantification of iodine-123-IBZM uptake in the striatum applied to Parkinsonism. J Nucl Med 2000; 41:220-227. MedlineGoogle Scholar
  • 30 Deutsch G, Mountz JM, Katholi CR, Liu HG, Harrell LE. Regional stability of cerebral blood flow measured by repeated technetium-99m-HMPAO SPECT: implications for the study of state-dependent change. J Nucl Med 1997; 38:6-13. MedlineGoogle Scholar
  • 31 Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 1988; 54:1063-70. Crossref, MedlineGoogle Scholar
  • 32 Hedeker D, Gibbons RD. mixreg: a computer program for mixed-effects regression analysis with autocorrelated errors. Comput Methods Programs Biomed 1996; 49:229-252. Crossref, MedlineGoogle Scholar
  • 33 Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics 1982; 38:963-974. Crossref, MedlineGoogle Scholar
  • 34 Waldemar G, Haselbach SG, Andersen AR, et al. 99mTc-d,1HMPAO and SPECT of the brain in normal aging. J Cereb Blood Flow Metab 1991; 11:508-521. Crossref, MedlineGoogle Scholar
  • 35 Buchwald D, Cheney PR, Peterson DL, et al. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection. Ann Intern Med 1992; 116:103-113. Crossref, MedlineGoogle Scholar
  • 36 Lange G, DeLuca J, Maldjian JA, Lee H, Tiersky LA, Natelson BH. Brain MRI abnormalities exist in a subset of patients with chronic fatigue syndrome. J Neurol Sci 1999; 171:3-7. Crossref, MedlineGoogle Scholar
  • 37 Mayberg HS, Liotti M, Brannan SK, et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 1999; 156:675-682. MedlineGoogle Scholar
  • 38 Schlaepfer TE, Strain EC, Greenberg BD, et al. Site of opioid action in the human brain: mu and kappa agonists’ subjective and cerebral blood flow effects. Am J Psychiatry 1998; 155:470-473. Crossref, MedlineGoogle Scholar
  • 39 Roy-Byrne P, Fleishaker J, Arnett C, et al. Effects of acute and chronic alprazolam treatment on cerebral blood flow, memory, sedation and plasma catecholamines. Neuropsychopharmacology 1993; 8:161-169. Crossref, MedlineGoogle Scholar
  • 40 Bok BD, Scheffel U, Goldfarb HW, et al. Comparison of 99Tc-m complexes (NEP-DADT, ME-NEP-DADT and HMPAO) with 123IAMP for brain SPECT imaging in dogs. Nucl Med Comm 1987; 8:631-641. Crossref, MedlineGoogle Scholar
  • 41 Kinnunen E, Jarvinen P, Ketonen L, Sepponen R. Co-twin control study on cerebral manifestations of systemic lupus erythematosus. Acta Neurol Scand 1993; 88:422-426. Crossref, MedlineGoogle Scholar
  • 42 Uitdehaag BM, Polman CH, Valk J, Koetsier JC, Lucas CJ. Magnetic resonance imaging studies in multiple sclerosis twins. J Neurol Neurosurg Psychiatry 1989; 52:1417-1419. Crossref, MedlineGoogle Scholar
  • 43 Berman KF, Torrey EF, Daniel DG, Weinberger DR. Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia. Arch Gen Psychiatry 1992; 49:927-934. Crossref, MedlineGoogle Scholar
  • 44 Weinberger DR, Berman KF, Suddath R, Torrey EF. Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am J Psychiatry 1992; 149:890-897. Crossref, MedlineGoogle Scholar
  • 45 Clark CM, Klonoff H, Tyhurst JS, et al. Regional cerebral glucose metabolism in identical twins. Neuropsychologia 1988; 26:615-621. Crossref, MedlineGoogle Scholar
  • 46 Bartley AJ, Jones DW, Weinberger DR. Genetic variability of human brain size and cortical gyral patterns. Brain 1997; 120:257-269. Crossref, MedlineGoogle Scholar
  • 47 Tramo MJ, Loftus WC, Stukel TA, Green RL, Weaver JB, Gazzaniga MS. Brain size, head size, and intelligence quotient in monozygotic twins. Neurology 1998; 50:1246-1252. Crossref, MedlineGoogle Scholar
  • 48 Deary IJ, Ebmeier KP, MacLeod KM, et al. PASAT performance and the pattern of uptake of 99mTc-exametazime in brain estimated with single photon emission tomography. Biol Psychol 1994; 38:1-18. Crossref, MedlineGoogle Scholar
  • 49 Peterson PK, Sirr SA, Grammith FC, et al. Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients. Clin Diagn Lab Immun 1994; 1:222-226. Crossref, MedlineGoogle Scholar

Article History

Published in print: June 2001