Depressive Disorders: Focally Altered Cerebral Perfusion Measured with Arterial Spin-labeling MR Imaging

Purpose: To assess focal cerebral perfusion in patients with refractory depressive disorder (RDD), patients with nonrefractory depressive disorder (NDD), and healthy control subjects by using arterial spin-labeling (ASL) magnetic resonance (MR) imaging.

Materials and Methods: This study was approved by the local ethical committee, and written informed consent was obtained from all participants. Twenty-four patients with RDD, 37 patients with NDD, and 42 healthy control subjects were included. From February 2006 to July 2007, all participants were imaged with a 3-T MR system. ASL and echo-planar images were subtracted and averaged to give perfusion-weighted images. Voxel-based analysis was performed. Region-of-interest analysis was applied to the bilateral hippocampi, thalami, and lentiform nuclei.

Results: Patients with NDD showed reduced perfusion in the left prefrontal cortex versus control subjects and increased perfusion mainly in the limbic-striatal areas (P < .05). In contrast, patients with RDD had decreased perfusion predominantly in the bilateral frontal and bilateral thalamic regions (P < .05). Compared with patients with RDD, patients with NDD showed higher perfusion mainly in the limbic-striatal areas (P < .05). In region-of-interest analysis, the NDD group showed higher regional cerebral blood flow than both RDD and control groups in the left hippocampus (P = .045), right hippocampus (P = .001), and right lentiform nucleus (P = .049).

Conclusion: This study revealed alterations of regional perfusion in the brains of patients with RDD that differed from those in patients with NDD. These results are consistent with the concept that RDD is associated with decreased activity of the bilateral prefrontal areas; and NDD, with decreased activity of left frontal areas in conjunction with overactivity of the bilateral limbic system.

© RSNA, 2009

References

  • 1 Stimpson N, Agrawal N, Lewis G. Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression: systematic review. Br J Psychiatry 2002; 181: 284–294. Crossref, MedlineGoogle Scholar
  • 2 Bench CJ, Friston KJ, Brown RG, Scott LC, Frackowiak RS, Dolan RJ. The anatomy of melancholia: focal abnormalities of cerebral blood flow in major depression. Psychol Med 1992; 22: 607–615. Crossref, MedlineGoogle Scholar
  • 3 Biver F, Goldman S, Delvenne V, et al. Frontal and parietal metabolic disturbances in unipolar depression. Biol Psychiatry 1994; 36: 381–388. Crossref, MedlineGoogle Scholar
  • 4 de Asis JM, Stern E, Alexopoulos GS, et al. Hippocampal and anterior cingulate activation deficits in patients with geriatric depression. Am J Psychiatry 2001; 158: 1321–1323. Crossref, MedlineGoogle Scholar
  • 5 Saxena S, Brody AL, Ho ML, et al. Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently. Biol Psychiatry 2001; 50: 159–170. Crossref, MedlineGoogle Scholar
  • 6 Ebmeier KP, Cavanagh JT, Moffoot AP, Glabus MF, O'Carroll RE, Goodwin GM. Cerebral perfusion correlates of depressed mood. Br J Psychiatry 1997; 170: 77–81. Crossref, MedlineGoogle Scholar
  • 7 Ebert D, Ebmeier KP. The role of the cingulate gyrus in depression: from functional anatomy to neurochemistry. Biol Psychiatry 1996; 39: 1044–1050. Crossref, MedlineGoogle Scholar
  • 8 Abercrombie HC, Schaefer SM, Larson CL, et al. Metabolic rate in the right amygdala predicts negative affect in depressed patients. Neuroreport 1998; 9: 3301–3307. Crossref, MedlineGoogle Scholar
  • 9 Parkes LM, Rashid W, Chard DT, Tofts PS. Normal cerebral perfusion measurements using arterial spin labeling: reproducibility, stability, and age and gender effects. Magn Reson Med 2004; 51: 736–743. Crossref, MedlineGoogle Scholar
  • 10 Zhao JM, Clingman CS, Narvainen MJ, Kauppinen RA, van Zijl PC. Oxygenation and hematocrit dependence of transverse relaxation rates of blood at 3T. Magn Reson Med 2007; 58: 592–597. Crossref, MedlineGoogle Scholar
  • 11 Wolf RL, Detre JA. Clinical neuroimaging using arterial spin-labeled perfusion magnetic resonance imaging. Neurotherapeutics 2007; 4: 346–359. Crossref, MedlineGoogle Scholar
  • 12 van Laar PJ, van der Grond J, Hendrikse J. Brain perfusion territory imaging: methods and clinical applications of selective arterial spin-labeling MR imaging. Radiology 2008; 246: 354–364. LinkGoogle Scholar
  • 13 Clark CP, Brown GG, Frank L, Thomas L, Sutherland AN, Gillin JC. Improved anatomic delineation of the antidepressant response to partial sleep deprivation in medial frontal cortex using perfusion-weighted functional MRI. Psychiatry Res 2006; 146: 213–222. Crossref, MedlineGoogle Scholar
  • 14 Clark CP, Brown GG, Archibald SL, et al. Does amygdalar perfusion correlate with antidepressant response to partial sleep deprivation in major depression? Psychiatry Res 2006; 146: 43–51. Crossref, MedlineGoogle Scholar
  • 15 First M, Spitzer R, Gibbon M, Williams J. Structured clinical interview for DSM-IV axis I disorders. Washington, DC: American Psychiatric Press, 1997. Google Scholar
  • 16 Williams JB. A structured interview guide for the Hamilton Depression Rating Scale. Arch Gen Psychiatry 1988; 45: 742–747. Crossref, MedlineGoogle Scholar
  • 17 Guy W. ECDEU assessment manual for psychopharmacology. Rev ed. Rockville, Md: National Institutes of Mental Health, 1976. Google Scholar
  • 18 World Psychiatric Association. Symposium on therapy resistant depression. Pharmacopsychiatry 1974; 7: 69–224. Google Scholar
  • 19 Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry 2007; 52: 46–54. Crossref, MedlineGoogle Scholar
  • 20 Parkes LM, Tofts PS. Improved accuracy of human cerebral blood perfusion measurements using arterial spin labeling: accounting for capillary water permeability. Magn Reson Med 2002; 48: 27–41. Crossref, MedlineGoogle Scholar
  • 21 Roberts DA, Rizi R, Lenkinski RE, Leigh JS Jr. Magnetic resonance imaging of the brain: blood partition coefficient for water—application to spin-tagging measurement of perfusion. J Magn Reson Imaging 1996; 6: 363–366. Crossref, MedlineGoogle Scholar
  • 22 Buxton RB, Frank LR, Wong EC, Siewert B, Warach S, Edelman RR. A general kinetic model for quantitative perfusion imaging with arterial spin labeling. Magn Reson Med 1998; 40: 383–396. Crossref, MedlineGoogle Scholar
  • 23 Lu H, Clingman C, Golay X, van Zijl PC. Determining the longitudinal relaxation time (T1) of blood at 3.0 Tesla. Magn Reson Med 2004; 52: 679–682. Crossref, MedlineGoogle Scholar
  • 24 Wansapura JP, Holland SK, Dunn RS, Ball WS Jr. NMR relaxation times in the human brain at 3.0 tesla. J Magn Reson Imaging 1999; 9: 531–538. Crossref, MedlineGoogle Scholar
  • 25 Honea R, Crow TJ, Passingham D, Mackay CE. Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am J Psychiatry 2005; 162: 2233–2245. Crossref, MedlineGoogle Scholar
  • 26 Worsley KJ. An improved theoretical P value for SPMs based on discrete local maxima. Neuroimage 2005; 28: 1056–1062. Crossref, MedlineGoogle Scholar
  • 27 Worsley KJ, Marrett S, Neelin P, Vandal AC, Friston KJ, Evans AC. A unified statistical approach for determining significant signals in images of cerebral activation. Hum Brain Mapp 1996; 4: 58–73. Crossref, MedlineGoogle Scholar
  • 28 Maldjian JA, Laurienti PJ, Kraft RA, Burdette JH. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 2003; 19: 1233–1239. Crossref, MedlineGoogle Scholar
  • 29 Drevets WC, Raichle ME. Neuroanatomical circuits in depression: implications for treatment mechanisms. Psychopharmacol Bull 1992; 28: 261–274. MedlineGoogle Scholar
  • 30 Hasler G, van der Veen JW, Tumonis T, Meyers N, Shen J, Drevets WC. Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Arch Gen Psychiatry 2007; 64: 193–200. Crossref, MedlineGoogle Scholar
  • 31 Cotter D, Mackay D, Chana G, Beasley C, Landau S, Everall IP. Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cereb Cortex 2002; 12: 386–394. Crossref, MedlineGoogle Scholar
  • 32 Matsuo K, Onodera Y, Hamamoto T, Muraki K, Kato N, Kato T. Hypofrontality and microvascular dysregulation in remitted late-onset depression assessed by functional near-infrared spectroscopy. Neuroimage 2005; 26: 234–242. Crossref, MedlineGoogle Scholar
  • 33 Thomas AJ, O'Brien JT, Davis S, et al. Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study. Arch Gen Psychiatry 2002; 59: 785–792. Crossref, MedlineGoogle Scholar
  • 34 Reiman EM, Lane RD, Ahern GL, et al. Neuroanatomical correlates of externally and internally generated human emotion. Am J Psychiatry 1997; 154: 918–925. Crossref, MedlineGoogle Scholar
  • 35 Herting B, Beuthien-Baumann B, Pottrich K, et al. Prefrontal cortex dysfunction and depression in atypical parkinsonian syndromes. Mov Disord 2007; 22: 490–497. Crossref, MedlineGoogle Scholar
  • 36 Fregni F, Ono CR, Santos CM, et al. Effects of antidepressant treatment with rTMS and fluoxetine on brain perfusion in PD. Neurology 2006; 66: 1629–1637. Crossref, MedlineGoogle Scholar
  • 37 Teneback CC, Nahas Z, Speer AM, et al. Changes in prefrontal cortex and paralimbic activity in depression following 2 weeks of daily left prefrontal TMS. J Neuropsychiatry Clin Neurosci 1999; 11: 426–435. MedlineGoogle Scholar
  • 38 Fujikawa T, Yokota N, Muraoka M, Yamawaki S. Response of patients with major depression and silent cerebral infarction to antidepressant drug therapy, with emphasis on central nervous system adverse reactions. Stroke 1996; 27: 2040–2042. Crossref, MedlineGoogle Scholar
  • 39 Isenberg K, Downs D, Pierce K, et al. Low frequency rTMS stimulation of the right frontal cortex is as effective as high frequency rTMS stimulation of the left frontal cortex for antidepressant-free, treatment-resistant depressed patients. Ann Clin Psychiatry 2005; 17: 153–159. Crossref, MedlineGoogle Scholar
  • 40 Dougherty DD, Weiss AP, Cosgrove GR, et al. Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression. J Neurosurg 2003; 99: 1010–1017. Crossref, MedlineGoogle Scholar
  • 41 Mayberg HS, Lewis PJ, Regenold W, Wagner HN Jr. Paralimbic hypoperfusion in unipolar depression. J Nucl Med 1994; 35: 929–934. MedlineGoogle Scholar
  • 42 Surguladze S, Brammer MJ, Keedwell P, et al. A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biol Psychiatry 2005; 57: 201–209. Crossref, MedlineGoogle Scholar
  • 43 Zobel A, Joe A, Freymann N, et al. Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach. Psychiatry Res 2005; 139: 165–179. Crossref, MedlineGoogle Scholar
  • 44 Mayberg HS, Brannan SK, Tekell JL, et al. Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 2000; 48: 830–843. Crossref, MedlineGoogle Scholar
  • 45 Kohn Y, Freedman N, Lester H, et al. 99mTc-HMPAO SPECT study of cerebral perfusion after treatment with medication and electroconvulsive therapy in major depression. J Nucl Med 2007; 48: 1273–1278. Crossref, MedlineGoogle Scholar
  • 46 Frodl T, Meisenzahl EM, Zetzsche T, et al. Hippocampal changes in patients with a first episode of major depression. Am J Psychiatry 2002; 159: 1112–1118. Crossref, MedlineGoogle Scholar
  • 47 Fountoulakis KN, Iacovides A, Gerasimou G, et al. The relationship of regional cerebral blood flow with subtypes of major depression. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 537–546. Crossref, MedlineGoogle Scholar
  • 48 Sanchez MM, Young LJ, Plotsky PM, Insel TR. Autoradiographic and in situ hybridization localization of corticotropin-releasing factor 1 and 2 receptors in nonhuman primate brain. J Comp Neurol 1999; 408: 365–377. Crossref, MedlineGoogle Scholar
  • 49 Strome EM, Wheler GH, Higley JD, Loriaux DL, Suomi SJ, Doudet DJ. Intracerebroventricular corticotropin-releasing factor increases limbic glucose metabolism and has social context-dependent behavioral effects in nonhuman primates. Proc Natl Acad Sci U S A 2002; 99: 15749–15754. Crossref, MedlineGoogle Scholar
  • 50 Gold SM, Dziobek I, Rogers K, Bayoumy A, McHugh PF, Convit A. Hypertension and hypothalamo-pituitary-adrenal axis hyperactivity affect frontal lobe integrity. J Clin Endocrinol Metab 2005; 90: 3262–3267. Crossref, MedlineGoogle Scholar
  • 51 Lopez JF, Chalmers DT, Little KY, Watson SJ. A.E. Bennett Research Award: regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus—implications for the neurobiology of depression. Biol Psychiatry 1998; 43: 547–573. Crossref, MedlineGoogle Scholar
  • 52 Sargent PA, Kjaer KH, Bench CJ, et al. Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 2000; 57: 174–180. Crossref, MedlineGoogle Scholar
  • 53 Calamante F, Thomas DL, Pell GS, Wiersma J, Turner R. Measuring cerebral blood flow using magnetic resonance imaging techniques. J Cereb Blood Flow Metab 1999; 19: 701–735. Crossref, MedlineGoogle Scholar
  • 54 Alsop DC, Detre JA. Reduced transit-time sensitivity in noninvasive magnetic resonance imaging of human cerebral blood flow. J Cereb Blood Flow Metab 1996; 16: 1236–1249. Crossref, MedlineGoogle Scholar
  • 55 Kennedy SH, Evans KR, Kruger S, et al. Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry 2001; 158: 899–905. Crossref, MedlineGoogle Scholar

Article History

Published in print: 2009