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Radioligand Studies in Depression

  • Hugo D’haenen
Chapter
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Abstract

The availability of suitable radioligands is one of the important limiting factors in the further development of positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of human cerebral receptors and transporters. Currently, the available ligands allow the investigation of 5-HT2A, 5-HT1A and dopamine D2 receptors, and the serotonin and dopamine transporter. 5-HT2A receptors have been investigated most extensively. Overall findings are rather discordant. Among others, heterogeneity and size of clinical samples, previous treatments and, more particularly as far as 5-HT2A receptors are concerned, suicidality could be major confounding variables. Most, albeit not all, studies find an increased 5-HT2A ligand binding after SSRI treatment. Findings on the dopamine D2 receptors in depression are controversial, but successful SSRI treatment seems to be associated with increased D2 ligand binding. A few studies have looked at the 5-HT1A receptor and demonstrated decreases in binding. The one study which looked at the effect of an SSRI treatment found no effect. Serotonin transporter availability seems to be reduced in depression; its blockade was confirmed in those studies that investigated this transporter on SSRI treatment. Only one study has looked at the dopamine transporter and showed an increased ligand uptake.

Keywords

Positron Emission Tomography Depressed Patient Positron Emission Tomography Imaging Dopamine Transporter Serotonin Transporter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Attar-Lévy D, Martinot J-L, Blin J et al (1999) The cortical serotonin2 receptors studies with positron-emission tomography and [18F]setoperone during depressive illness and antidepressant treatment with clomipramine. Biol Psychiatry 45:180–186PubMedCrossRefGoogle Scholar
  2. Audenaert K, Van Laere K, Dumont F et al (2001) Decreased frontal serotonin 5-HT2A receptor binding index in deliberate self-harm patients. Eur J Nuc Med 28:175–182CrossRefGoogle Scholar
  3. Baeken C, D’haenen H, Flamen P et al (1998) 123I-5-I-R91150, a new single-photon emission tomography ligand for 5-HT2A receptors: influence of age and gender in healthy subjects. Eur J Nucl Med 25:1617–1622PubMedCrossRefGoogle Scholar
  4. Biver F, Wikler D, Lotstra F et al (1997) Serotonin 5-HT2 receptor imaging in major depression: focal changes in orbito-insular cortex. Br J Psychiatry 171:444–448PubMedCrossRefGoogle Scholar
  5. D’haenen H, Bossuyt A (1994) Dopamine D2 receptors in depression measured with single photon emission computed tomography. Biol Psychiatry 35:128–132CrossRefGoogle Scholar
  6. D’haenen H, Schins A et al (2003) Eur Neuropsychopharmacol (in press)Google Scholar
  7. D’haenen H, Bossuyt A, Mertens J et al (1992) SPECT imaging of serotonin2 receptors in depression. Psychiatry Res Neuroimaging 45:227–237CrossRefGoogle Scholar
  8. D’haenen H, Steenssens D, Bossuyt A (1999) Successful antidepressant treatment with SSRIs is associated with an increase in D2 binding. Int J Neuropsychopharmacol 2:S14Google Scholar
  9. Drevets WC, Frank E, Price JC et al (1999) PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 46:1375–1387PubMedCrossRefGoogle Scholar
  10. Ebert D, Feistel H, Kaschka W et al (1994) Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation-preliminary results. Biol Psychiatry 35:880–885PubMedCrossRefGoogle Scholar
  11. Ebert D, Feistel H, Loew T, Pirner A (1996) Dopamine and depression — striatal dopamine D2 receptor SPECT before and after antidepressant therapy. Psychopharmacol 126:91–94CrossRefGoogle Scholar
  12. Ebmeier K, Kronhaus D (2002) Brain imaging in mood disorders. In: D’haenen H, den Boer J, Willner P (eds) Biological psychiatry. Wiley, Chichester, pp 815–828CrossRefGoogle Scholar
  13. Hargreaves R (2002) Imaging substance P receptors (NK1) in the living human brain using positron emission tomography. J Clin Psychiatry 63[Suppl 11]: 18–24PubMedGoogle Scholar
  14. Klimke A, Larisch R, Janz A et al (1999) Dopamine D2 receptor binding before and after treatment of major depression measured by [123I]IBZM SPECT. Psychiatry Res Neuroimaging 90: 91–101CrossRefGoogle Scholar
  15. Laasonen-Balk T, Kuikka J, Viinamäki J et al (1999) Striatal dopamine transporter density in major depression. Psychopharmacology 144:282–285PubMedCrossRefGoogle Scholar
  16. Larisch R, Klimke A, Vosberg H et al (1997) In vivo evidence for the involvement of dopamine D2 receptors in striatum and anterior cingulate gyrus in major depression. Neuroimage 5: 251–260PubMedCrossRefGoogle Scholar
  17. Malison RT, Price LH, Berman R et al (1998) Reduced brain serotonin transporter availability in major depression as measured by [123I]-2-β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry 44:1090–1098PubMedCrossRefGoogle Scholar
  18. Massou JM, Trichard C, Attar-Levy D et al (1997) Frontal 5-HT2A receptors studies in depressive patients during chronic treatment by selective serotonin reuptake inhibitors. Psychopharmacology 133:99–101PubMedCrossRefGoogle Scholar
  19. Mayberg HD, Robinson RG, Wong DF et al (1988) PET imaging of cortical S2 serotonin receptors after stroke: lateralized changes and relationship to depression. Am J Psychiatry 145: 937–943PubMedGoogle Scholar
  20. Meltzer CC, Price JC, Mathis CA et al (1999) PET imaging of serotonin type 2A receptors in late-life neuropsychiatric disorders. Am J Psychiatry 156:1871–1878PubMedGoogle Scholar
  21. Mertens J, Terriere D (1994) Radiosynthesis of a new radioiodinated ligand for serotonin 5-HT2 receptors, a promising tracer for λ emission tomography. J Labelled Comp Radiopharm 34: 795–806CrossRefGoogle Scholar
  22. Meyer JH, Kapur S, Houle S et al (1999) Prefrontal cortex 5-HT2 receptors in depression: an [18F]setoperone PET imaging study. Am J Psychiatry 156:1029–1034PubMedGoogle Scholar
  23. Meyer JH, Kapur S, Eisfeld B et al (2001) The effect of paroxetine on 5-HT2A receptors in depression: an [18F]setoperone PET imaging study. Am J Psychiatry 158:78–85PubMedCrossRefGoogle Scholar
  24. Meyer JH, Wilson AA, Ginovart N et al (2001) Occupancy of serotonin transporters by paroxetine and Citalopram during treatment of depression: a 11C-DASB PET imaging study. Am J Psychiatry 158:1843–1849PubMedCrossRefGoogle Scholar
  25. Neumeister A, Pirker W, Willeit M et al (2000) Seasonal variation of availability of serotonin transporter binding sites in healthy female subjects as measured by [123I]-2-β-carbonmeth-oxy-3β-(4-diodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry 47:158–160PubMedCrossRefGoogle Scholar
  26. Paillère-Martinot ML, Bragulat V, Dollé F et al (2001) Decreased presynaptic dopamine function in the left caudate of depressed patients with affective flattening and psychomotor retardation. Am J Psychiatry 158:314–316CrossRefGoogle Scholar
  27. Peroutka SJ, Snyder SH (1980) Long-term antidepressant treatment decreases spiroperidol labeled serotonin receptor binding. Science 210:88–90PubMedCrossRefGoogle Scholar
  28. Pirker W, Asenbaum S, Kasper S et al (1995) β-CIT SPECT demonstrates blockade of 5-HT uptake sites by Citalopram in the human brain in vivo. J Neural Transm Gen Sect 100:247–256PubMedCrossRefGoogle Scholar
  29. Rabiner EA, Gunn RB, Wilkins MR et al (2000) Drug action at the 5-HT1A receptor in vivo: autoreceptor and postsynaptic receptor occupancy examined with PET and [carbonyl-11C]WAY-100635. Nucl Med Biol 27:509–513PubMedCrossRefGoogle Scholar
  30. Sargent PA, Husted K, Bench CJ et al (2000) Brain serotonin1A receptor binding measured by positron emission tomography with [11C] WAY-100635. Effects of depression and antidepressant treatment. Arch Gen Psychiatry 57:174–180Google Scholar
  31. Shah PJ, Ogilvie AD, Goodwin GM, Ebmeier KP (1997) Clinical and psychometric correlates of dopamine D2 binding in depression. Psychol Med 27:1247–1256CrossRefGoogle Scholar
  32. Staley JK, Malison RT, Jnnis RB (1998) Imaging of the serotonergic system: interactions of neuro-anatomical and functional abnormalities of depression. Biol Psychiatry 44:534–549PubMedCrossRefGoogle Scholar
  33. Tauscher J, Pirker W, de Zwaan M et al (1999) In vivo visualization of serotonin transporters in the human brain during fluoxetine treatment. Eur Neuropsychopharmacol 9:177–179PubMedCrossRefGoogle Scholar
  34. Tauscher J, Verhoeff PLG, Christensen BK et al (2001) Serotonin 5-HT1A receptor binding potential declines with age as measured by [11C] WAY-100635 and PET. Neuropsychopharmacology 24:522–530PubMedCrossRefGoogle Scholar
  35. Willeit M, Praschak-Rieder N, Neumeister A et al (2000) [123I]β-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. Biol Psychiatry 47:482–489PubMedCrossRefGoogle Scholar
  36. Wust F, Carlson KE, Katzenellenbogen JA (2003) Synthesis of novel arylpyrazolocorticosteroids as potential ligands for imaging brain glucocorticoid receptors. Steroids 68:177–191PubMedCrossRefGoogle Scholar
  37. Yatham LN, Liddle PF, Dennie J et al (1999) Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment. Arch Gen Psychiatry 56:705–711PubMedCrossRefGoogle Scholar
  38. Yatham LN, Liddle PF, Shiah I-S et al (2000) Brain serotonin2 receptors in major depression. A positron emission tomography study. Arch Gen Psychiatry 57:850–858CrossRefGoogle Scholar
  39. Yatham LN, Liddle PF, Shiah IS et al (2001) Effects of rapid tryptophan depletion on brain 5-HT2 receptors: a PET study. Br J Psychiatry 178:448–453PubMedCrossRefGoogle Scholar
  40. Zanardi R, Artigas F, Moresco R et al (2001) Increased 5-hydroxytryptamine-2 receptor binding in the frontal cortex of depressed patients responding to paroxetine treatment: a positron emission tomography scan study. J Clin Psychopharmacol 21:53–58PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • Hugo D’haenen
    • 1
  1. 1.Psychiatric Department, Academic HospitalFree University of Brussels (V.U.B.)BrusselsBelgium

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