Skip to main content
SpringerLink
Log in

Regional Cerebral Blood Flow Changes in Dogs with Anxiety Disorders, Measured with SPECT

  • Published:
Brain Imaging and Behavior Aims and scope Submit manuscript

Abstract

Alterations of regional brain activity in the prefrontal cortex and in limbic areas have been reported in humans with anxiety disorders. This animal study reports the results of brain perfusion imaging with single photon emission computed tomography (SPECT) in dogs with anxiety disorders. Based on the human literature, we hypothesized altered prefrontal and higher temporal brain perfusion. SPECT acquisitions were performed using the 99mTc-labelled tracer ethyl cysteinate dimer (ECD). Eighteen dogs with pathological anxiety were compared with 18 normally behaving reference dogs. We found, in the group of dogs with anxiety disorders, lower perfusion in the left frontal cortex (p = 0.003), in the subcortical region (p = 0.007) and increased perfusion in the right (p = 0.05) temporal cortex. Taken together, our rCBF findings are suggestive for a dysfunction of the prefrontal cortex and the limbic system in canine anxiety disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Agarwal, N., Rambaldelli, G., Perlini, C., Dusi, N., Kitis, O., Bellani, M., et al. (2008). Microstructural thalamic changes in schizophrenia: a combined anatomic and diffusion weighted magnetic resonance imaging study. Journal of Psychiatry & Neuroscience, 33, 440–448.

    Google Scholar 

  • Bannerman, D. M., Grubb, M., Deacon, R. M., Yee, B. K., Feldon, J., & Rawlins, J. N. (2003). Ventral hippocampal lesions affect anxiety but not spatial learning. Behavioural Brain Research, 139, 197–213.

    Article  CAS  PubMed  Google Scholar 

  • Bisaga, A., Katz, J. L., Antonini, A., Wright, C. E., Margouleff, C., Gorman, J. M., et al. (1998). Cerebral glucose metabolism in women with panic disorder. American Journal of Psychiatry, 155, 1178–1183.

    CAS  PubMed  Google Scholar 

  • Bluhm, R. L., Williamson, P. C., Osuch, E. A., Frewen, P. A., Stevens, T. K., Boksman, K., et al. (2009). Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma. Journal of Psychiatry & Neuroscience, 34, 187–194.

    Google Scholar 

  • Bremner, J. D. (2004). Brain imaging in anxiety disorders. Expert Reviews in Neurotherapeutics, 4, 275–284.

    Article  Google Scholar 

  • Bufkin, J. L., & Luttrell, V. R. (2005). Neuroimaging studies of aggressive and violent behavior: current findings and implications for criminology and criminal justice. Trauma Violence Abuse, 6, 176–191.

    Article  PubMed  Google Scholar 

  • Case, L. P. (2005). The Dog: its behavior, nutrition, and health (2nd ed.). Iowa, USA: Blackwell Publishing.

    Google Scholar 

  • Dasari, M., Friedman, L., Jesberger, J., Stuve, T. A., Findling, R. L., Swales, T. P., et al. (1999). A magnetic resonance imaging study of thalamic area in adolescent patients with either schizophrenia or bipolar disorder as compared to healthy controls. Psychiatry Research, 91, 155–162.

    Article  CAS  PubMed  Google Scholar 

  • De Cristofaro, M. T., Sessarego, A., Pupi, A., Biondi, F., & Faravelli, C. (1993). Brain perfusion abnormalities in drug-naive, lactate-sensitive panic patients: a SPECT study. Biological Psychiatry, 33, 505–512.

    Article  PubMed  Google Scholar 

  • Engel, K., Bandelow, B., Gruber, O., & Wedekind, D. (2009). Neuroimaging in anxiety disorders. Journal of Neural Transmission, 116, 703–716.

    Article  PubMed  Google Scholar 

  • Eren, I., Tukel, R., Polat, A., Karaman, R., & Unal, S. (2003). Evaluation of regional cerebral blood flow changes in panic disorder with Tc99m-HMPAO SPECT. Psychiatry Research, 123, 135–143.

    Article  PubMed  Google Scholar 

  • Etkin, A., & Wager, T. D. (2007). Functional Neuroimaging of Anxiety: A Meta-Analysis of Emotional Processing in PTSD, Social Anxiety Disorder, and Specific Phobia. American Journal of Psychiatry, 164, 1476–1488.

    Article  PubMed  Google Scholar 

  • Ettinger, U., Picchioni, M., Landau, S., Matsumoto, K., van Haren, N. E., Marshall, N., et al. (2007). Magnetic resonance imaging of the thalamus and adhesio interthalamica in twins with schizophrenia. Archives of General Psychiatry, 64, 401–409.

    Article  PubMed  Google Scholar 

  • Gilbert, A. R., Rosenberg, D. R., Harenski, K., Spencer, S., Sweeney, J. A., & Keshavan, M. S. (2001). Thalamic volumes in patients with first-episode schizophrenia. American Journal of Psychiatry, 158, 618–624.

    Article  CAS  PubMed  Google Scholar 

  • Goodman, W. K., Price, L. H., Rasmussen, S. A., Mazure, C., Fleischmann, R. L., Hill, C. L., et al. (1989). The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Archives of General Psychiatry, 46, 1006–1011.

    CAS  PubMed  Google Scholar 

  • Gorman, J. M., Kent, J. M., Sullivan, G. M., & Coplan, J. D. (2000). Neuroanatomical hypothesis of panic disorder, revised. American Journal of Psychiatry, 157, 493–505.

    Article  CAS  PubMed  Google Scholar 

  • Gur, R. E., Maany, V., Mozley, P. D., Swanson, C., Bilker, W., & Gur, R. C. (1998). Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. American Journal of Psychiatry, 155, 1711–1717.

    CAS  PubMed  Google Scholar 

  • Hsu, Y. Y., & Serpell, J. A. (2003). Development and validation of a questionnaire for measuring behavior and temperament traits in pet dogs. Journal of the American Veterinary Medical Association, 223, 1293–1300.

    Article  PubMed  Google Scholar 

  • Ichise, M., Golan, H., Ballinger, J. R., Vines, D., Blackman, A., & Moldofsky, H. (1997). Regional differences in technetium-99 m-ECD clearance on brain SPECT in healthy subjects. Journal of Nuclear Medicine, 38, 1253–1260.

    CAS  PubMed  Google Scholar 

  • Kent, J. M., Coplan, J. D., Mawlawi, O., Martinez, J. M., Browne, S. T., Slifstein, M., et al. (2005). Prediction of panic response to a respiratory stimulant by reduced orbitofrontal cerebral blood flow in panic disorder. American Journal of Psychiatry, 162, 1379–1381.

    Article  PubMed  Google Scholar 

  • Kent, J. M., & Rauch, S. L. (2003). Neurocircuitry of anxiety disorders. Current Psychiatry Reports, 5, 266–273.

    Article  PubMed  Google Scholar 

  • Kessler, R. C., McGonagle, K. A., Zhao, S., Nelson, C. B., Hughes, M., Eshleman, S., et al. (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Archives of General Psychiatry, 51, 8–19.

    CAS  PubMed  Google Scholar 

  • Kim, J. J., & Fanselow, M. S. (1992). Modality-specific retrograde amnesia of fear. Science, 256, 675–677.

    Article  CAS  PubMed  Google Scholar 

  • Kim, S. J., Lyoo, I. K., Lee, Y. S., Kim, J., Sim, M. E., Bae, S. J., et al. (2007). Decreased cerebral blood flow of thalamus in PTSD patients as a strategy to reduce re-experience symptoms. Acta Psychiatrica Scandinavica, 116, 145–153.

    Article  CAS  PubMed  Google Scholar 

  • Lanius, R. A., Williamson, P. C., Densmore, M., Boksman, K., Gupta, M. A., Neufeld, R. W., et al. (2001). Neural correlates of traumatic memories in posttraumatic stress disorder: a functional MRI investigation. American Journal of Psychiatry, 158, 1920–1922.

    Article  CAS  PubMed  Google Scholar 

  • Lanius, R. A., Williamson, P. C., Hopper, J., Densmore, M., Boksman, K., Gupta, M. A., et al. (2003). Recall of emotional states in posttraumatic stress disorder: an fMRI investigation. Biological Psychiatry, 53, 204–210.

    Article  PubMed  Google Scholar 

  • LeDoux, J. E. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23, 155–184.

    Article  CAS  PubMed  Google Scholar 

  • Liebowitz, M. R. (1987). Social phobia. Modern Problems of Pharmacopsychiatry, 22, 141–173.

    CAS  PubMed  Google Scholar 

  • Lindauer, R. J., Booij, J., Habraken, J. B., Uylings, H. B., Olff, M., Carlier, I. V., et al. (2004). Cerebral blood flow changes during script-driven imagery in police officers with posttraumatic stress disorder. Biological Psychiatry, 56, 853–861.

    Article  PubMed  Google Scholar 

  • Lorberbaum, J. P., Kose, S., Johnson, M. R., Arana, G. W., Sullivan, L. K., Hamner, M. B., et al. (2004). Neural correlates of speech anticipatory anxiety in generalized social phobia. Neuroreport, 15, 2701–2705.

    PubMed  Google Scholar 

  • Lucey, J. V., Costa, D. C., Busatto, G., Pilowsky, L. S., Marks, I. M., Ell, P. J., et al. (1997). Caudate regional cerebral blood flow in obsessive-compulsive disorder, panic disorder and healthy controls on single photon emission computerised tomography. Psychiatry Research-Neuroimaging, 74, 25–33.

    Article  CAS  Google Scholar 

  • McNaughton, N. (1997). Cognitive dysfunction resulting from hippocampal hyperactivity–a possible cause of anxiety disorder? Pharmacology, Biochemistry and Behavior, 56, 603–611.

    Article  CAS  Google Scholar 

  • Morgan, M. A., Romanski, L. M., & LeDoux, J. E. (1993). Extinction of emotional learning: contribution of medial prefrontal cortex. Neuroscience Letters, 163, 109–113.

    Article  CAS  PubMed  Google Scholar 

  • O’Carroll, R. E., Moffoot, A. P., Van, B. M., Dougall, N., Murray, C., Ebmeier, K. P., et al. (1993). The effect of anxiety induction on the regional uptake of 99mTc-exametazime in simple phobia as shown by single photon emission tomography (SPET). Journal of Affective Disorders, 28, 203–210.

    Article  PubMed  Google Scholar 

  • Peremans, K., Audenaert, K., Blanckaert, P., Jacobs, F., Coopman, F., Verschooten, F., et al. (2002). Effects of aging on brain perfusion and serotonin-2A receptor binding in the normal canine brain measured with single photon emission tomography. Progress in Neuro-psychopharmacology and Biological Psychiatry, 26, 1393–1404.

    Article  CAS  PubMed  Google Scholar 

  • Peremans, K., Audenaert, K., Coopman, F., Blanckaert, P., Jacobs, F., Otte, A., et al. (2003). Estimates of regional cerebral blood flow and 5-HT2A receptor density in impulsive, aggressive dogs with 99mTc-ECD and 123I–5-I-R91150. European Journal of Nuclear Medicine and Molecular Imaging, 30, 1538–1546.

    Article  CAS  PubMed  Google Scholar 

  • Peremans, K., De Bondt, P., Audenaert, K., Van Laere, K., Gielen, I., Koole, M., et al. (2001). Regional brain perfusion in 10 normal dogs measured using Technetium-99 m ethyl cysteinate dimer spect. Veterinary Radiology & Ultrasound, 42, 562–568.

    Article  CAS  Google Scholar 

  • Reiman, E. M., Raichle, M. E., Butler, F. K., Herscovitch, P., & Robins, E. (1984). A focal brain abnormality in panic disorder, a severe form of anxiety. Nature, 310, 683–685.

    Article  CAS  PubMed  Google Scholar 

  • Schmahmann, J. D. (2004). Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome. Journal of Neuropsychiatry and Clinical Neuroscience, 16, 367–378.

    Google Scholar 

  • Shin, L. M., Orr, S. P., Carson, M. A., Rauch, S. L., Macklin, M. L., Lasko, N. B., et al. (2004). Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD. Archives of General Psychiatry, 61, 168–176.

    Article  PubMed  Google Scholar 

  • Shin, L. M., Shin, P. S., Heckers, S., Krangel, T. S., Macklin, M. L., Orr, S. P., et al. (2004). Hippocampal function in posttraumatic stress disorder. Hippocampus, 14, 292–300.

    Article  PubMed  Google Scholar 

  • Starkey, M. P., Scase, T. J., Mellersh, C. S., & Murphy, S. (2005). Dogs really are man’s best friend–canine genomics has applications in veterinary and human medicine!. Briefings in Functional Genomics & Proteomics, 4, 112–128.

    Article  CAS  Google Scholar 

  • Stewart, R. S., Devous, M. D., Sr., Rush, A. J., Lane, L., & Bonte, F. J. (1988). Cerebral blood flow changes during sodium-lactate-induced panic attacks. American Journal of Psychiatry, 145, 442–449.

    CAS  PubMed  Google Scholar 

  • Tillfors, M., Furmark, T., Marteinsdottir, I., & Fredrikson, M. (2002). Cerebral blood flow during anticipation of public speaking in social phobia: a PET study. Biological Psychiatry, 52, 1113–1119.

    Article  PubMed  Google Scholar 

  • Vermeire, S. T., Audenaert, K. R., Dobbeleir, A. A., De Meester, R. H., De Vos, F. J., & Peremans, K. Y. (2009). Evaluation of the brain 5-HT2A receptor binding index in dogs with anxiety disorders, measured with 123I–5I-R91150 and SPECT. Journal of Nuclear Medicine, 50, 284–289.

    Article  PubMed  Google Scholar 

  • Walovitch, R. C., Cheesman, E. H., Maheu, L. J., & Hall, K. M. (1994). Studies of the retention mechanism of the brain perfusion imaging agent 99mTc-bicisate (99mTc-ECD). Journal of Cerebral Blood Flow and Metabolism, 14(Suppl 1), S4–11.

    CAS  PubMed  Google Scholar 

  • Warwick, J. M., Carey, P., Jordaan, G. P., Dupont, P., & Stein, D. J. (2008). Resting brain perfusion in social anxiety disorder: A voxel-wise whole brain comparison with healthy control subjects. Progress in Neuro-psychopharmacology and Biological Psychiatry, 32, 1251–1256.

    Article  CAS  PubMed  Google Scholar 

  • Whalen, P. J. (2007). The uncertainty of it all. Trends in Cognitive Sciences, 11, 499–500.

    Article  PubMed  Google Scholar 

  • Woods, S. W. (1992). Regional cerebral blood flow imaging with SPECT in psychiatric disease: focus on schizophrenia, anxiety disorders, and substance abuse. Journal of Clinical Psychiatry, 53(Suppl), 20–25.

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a scientific research grant of the Ghent University Special Research Fund (BOF 07/24 J/152). We would like to express our gratitude the owners of these dogs and to Tiny De Keuster, DVM, Diplomate ECVBM for referral of several cases.

Author information

Authors and Affiliations

  1. Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, 9000, Ghent, Belgium

    Simon Vermeire, André Dobbeleir, Rudy De Meester, Eva Vandermeulen & Kathelijne Peremans

  2. Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, Ghent, Belgium

    Kurt Audenaert

  3. Department of Nuclear Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

    André Dobbeleir

  4. Department of Clinical Biology and Medicine of Small Animals, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium

    Tim Waelbers

Authors
  1. Simon Vermeire
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kurt Audenaert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. André Dobbeleir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rudy De Meester
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eva Vandermeulen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tim Waelbers
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kathelijne Peremans
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Simon Vermeire.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vermeire, S., Audenaert, K., Dobbeleir, A. et al. Regional Cerebral Blood Flow Changes in Dogs with Anxiety Disorders, Measured with SPECT. Brain Imaging and Behavior 3, 342–349 (2009). https://doi.org/10.1007/s11682-009-9076-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11682-009-9076-1

Keywords

Search

Navigation