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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-05-2009 | Original Article

Serotonin transporter binding with [¹²³I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Authors: Henricus G. Ruhé, Jan Booij, Johannes B. Reitsma, Aart H. Schene

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 5/2009

Abstract

Purpose

The serotonin system is undoubtedly involved in the pathogenesis of major depressive disorder (MDD). More specifically the serotonin transporter (SERT) serves as a major target for antidepressant drugs. There are conflicting results about SERT availability in depressed patients versus healthy controls. We aimed to measure SERT availability and study the effects of age, gender and season of scanning in MDD patients in comparison to healthy controls.

Methods

We included 49 depressed outpatients (mean±SD 42.3 ± 8.3 years) with a Hamilton depression rating scale score above 18, who were drug-naive or drug-free for ≥4 weeks, and 49 healthy controls matched for age (±2 years) and sex. Subjects were scanned with single photon emission computed tomography (SPECT) using [¹²³I]β-CIT. SERT availability was expressed as specific to nonspecific binding ratios (BP_ND) in the midbrain and diencephalon with cerebellar binding as a reference.

Results

In crude comparisons between patients and controls, we found no significant differences in midbrain or diencephalon SERT availability. In subgroup analyses, depressed males had numerically lower midbrain SERT availability than controls, whereas among women SERT availability was not different (significant diagnosis×gender interaction; p = 0.048). In the diencephalon we found a comparable diagnosis×gender interaction (p = 0.002) and an additional smoking×gender (p = 0.036) interaction. In the midbrain the season of scanning showed a significant main effect (p = 0.018) with higher SERT availability in winter.

Conclusion

Differences in SERT availability in the midbrain and diencephalon in MDD patients compared with healthy subjects are affected by gender. The season of scanning is a covariate in the midbrain. The diagnosis×gender and gender×smoking interactions in SERT availability should be considered in future studies of the pathogenesis of MDD.

Kennedy SH, Lam RW, Cohen NL, Ravindran AV; CANMAT Depression Work Group. Clinical guidelines for the treatment of depressive disorders. IV. Medications and other biological treatments. Can J Psychiatry 2001;46 (Suppl 1):38S–58S.PubMed

Ruhe HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry 2007;12:331–59.PubMedCrossRef

Owens MJ. Selectivity of antidepressants: from the monoamine hypothesis of depression to the SSRI revolution and beyond. J Clin Psychiatry 2004;65(Suppl 4):5–10.PubMed

Stockmeier CA. Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psychiatr Res 2003;37:357–73.PubMedCrossRef

Innis R, Baldwin R, Sybirska E, Zea Y, Laruelle M, al Tikriti M, et al. Single photon emission computed tomography imaging of monoamine reuptake sites in primate brain with [123I]CIT. Eur J Pharmacol 1991;200:369–70.PubMedCrossRef

Laruelle M, Baldwin RM, Malison RT, Zea-Ponce Y, Zoghbi SS, al Tikriti MS, et al. SPECT imaging of dopamine and serotonin transporters with [123I] β-CIT: pharmacological characterization of brain uptake in nonhuman primates. Synapse 1993;13:295–309.PubMedCrossRef

Lehto S, Tolmunen T, Joensuu M, Saarinen PI, Vanninen R, Ahola P, et al. Midbrain binding of [123I]nor-β-CIT in atypical depression. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1251–5.PubMedCrossRef

Malison RT, Price LH, Berman R, van Dyck CH, Pelton GH, Carpenter L, et al. Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 β-carbomethoxy-3 β-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry 1998;44:1090–8.PubMedCrossRef

Newberg AB, Amsterdam JD, Wintering N, Ploessl K, Swanson RL, Shults J, et al. 123I-ADAM binding to serotonin transporters in patients with major depression and healthy controls: a preliminary study. J Nucl Med 2005;46:973–7.PubMed

10.

Parsey RV, Hastings RS, Oquendo MA, Huang YY, Simpson N, Arcement J, et al. Lower serotonin transporter binding potential in the human brain during major depressive episodes. Am J Psychiatry 2006;163:52–8.PubMedCrossRef

11.

Staley JK, Sanacora G, Tamagnan G, Maciejewski PK, Malison RT, Berman RM, et al. Sex differences in diencephalon serotonin transporter availability in major depression. Biol Psychiatry 2006;59:40–7.PubMedCrossRef

12.

Willeit M, Praschak-Rieder N, Neumeister A, Pirker W, Asenbaum S, Vitouch O, et al. [123I] β-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. Biol Psychiatry 2000;47:482–9.PubMedCrossRef

13.

Joensuu M, Tolmunen T, Saarinen PI, Tiihonen J, Kuikka J, Ahola P, et al. Reduced midbrain serotonin transporter availability in drug-naive patients with depression measured by SERT-specific [123I] nor-β-CIT SPECT imaging. Psychiatry Res 2007;154:125–31.PubMedCrossRef

14.

Ahonen A, Heikman P, Kauppinen T, Koskela A, Bergström K. Serotonin transporter availability in drug free depression patients using a novel SERT ligand (abstract 106). Eur J Nucl Med 2004;31(Suppl 1):S227.

15.

Catafau AM, Perez V, Plaza P, Pascual JC, Bullich S, Suarez M, et al. Serotonin transporter occupancy induced by paroxetine in patients with major depression disorder: a [123I]-ADAM SPECT study. Psychopharmacology (Berl) 2006;189:145–53.CrossRef

16.

Herold N, Uebelhack K, Franke L, Amthauer H, Luedemann L, Bruhn H, et al. Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand [123I]-ADAM. J Neural Transm 2006;113:659–70.PubMedCrossRef

17.

Meyer JH, Houle S, Sagrati S, Carella A, Hussey DF, Ginovart N, et al. Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: effects of major depressive episodes and severity of dysfunctional attitudes. Arch Gen Psychiatry 2004;61:1271–9.PubMedCrossRef

18.

Reivich M, Amsterdam JD, Brunswick DJ, Shiue CY. PET brain imaging with [11C](+)McN5652 shows increased serotonin transporter availability in major depression. J Affect Disord 2004;82:321–7.PubMedCrossRef

19.

Ichimiya T, Suhara T, Sudo Y, Okubo Y, Nakayama K, Nankai M, et al. Serotonin transporter binding in patients with mood disorders: a PET study with [11C]McN5652. Biol Psychiatry 2002;51:715–22.PubMedCrossRef

20.

Eggers B, Hermann W, Barthel H, Sabri O, Wagner A, Hesse S. The degree of depression in Hamilton rating scale is correlated with the density of presynaptic serotonin transporters in 23 patients with Wilson’s disease. J Neurol 2003;250:576–80.PubMedCrossRef

21.

Staley JK, Krishnan-Sarin S, Zoghbi S, Tamagnan G, Fujita M, Seibyl JP, et al. Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers. Synapse 2001;41:275–84.PubMedCrossRef

22.

Pirker W, Asenbaum S, Hauk M, Kandlhofer S, Tauscher J, Willeit M, et al. Imaging serotonin and dopamine transporters with [123I] β-CIT SPECT: binding kinetics and effects of normal aging. J Nucl Med 2000;41:36–44.PubMed

23.

van Dyck CH, Malison RT, Seibyl JP, Laruelle M, Klumpp H, Zoghbi SS, et al. Age-related decline in central serotonin transporter availability with [123I] β-CIT SPECT. Neurobiol Aging 2000;21:497–501.PubMedCrossRef

24.

Buchert R, Schulze O, Wilke F, Berding G, Thomasius R, Petersen K, et al. Is correction for age necessary in SPECT or PET of the central serotonin transporter in young, healthy adults? J Nucl Med 2006;47:38–42.PubMed

25.

Praschak-Rieder N, Willeit M, Wilson AA, Houle S, Meyer JH. Seasonal variation in human brain serotonin transporter binding. Arch Gen Psychiatry 2008;65:1072–8.PubMedCrossRef

26.

de Win MM, Habraken JB, Reneman L, van den Brink W, den Heeten GJ, Booij J. Validation of [123I]b-CIT SPECT to assess serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram. Neuropsychopharmacology 2005;30:996–1005.PubMedCrossRef

27.

Verhoeff NP, Kapucu O, Sokole-Busemann E, Van Royen EA, Janssen AG. Estimation of dopamine D2 receptor binding potential in the striatum with iodine-123-IBZM SPECT: technical and interobserver variability. J Nucl Med 1993;34:2076–84.PubMed

28.

Laruelle M, Vanisberg MA, Maloteaux JM. Regional and subcellular localization in human brain of [3H]paroxetine binding, a marker of serotonin uptake sites. Biol Psychiatry 1988;24:299–309.PubMedCrossRef

29.

Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 2007;27:1533–9.PubMedCrossRef

30.

Dahlstrom M, Ahonen A, Ebeling H, Torniainen P, Heikkila J, Moilanen I. Elevated hypothalamic/midbrain serotonin (monoamine) transporter availability in depressive drug-naive children and adolescents. Mol Psychiatry 2000;5:514–22.PubMedCrossRef

31.

Meyer JH, Wilson AA, Ginovart N, Goulding V, Hussey D, Hood K, et al. Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [11C]DASB PET imaging study. Am J Psychiatry 2001;158:1843–9.PubMedCrossRef

32.

Meyer JH. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci 2007;32:86–102.PubMed

33.

Fink G, Sumner BE, McQueen JK, Wilson H, Rosie R. Sex steroid control of mood, mental state and memory. Clin Exp Pharmacol Physiol 1998;25:764–75.PubMedCrossRef

34.

Lu NZ, Eshleman AJ, Janowsky A, Bethea CL. Ovarian steroid regulation of serotonin reuptake transporter (SERT) binding, distribution, and function in female macaques. Mol Psychiatry 2003;8:353–60.PubMedCrossRef

35.

Swaab DF, Bao AM, Lucassen PJ. The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 2005;4:141–94.PubMedCrossRef

36.

McIntyre RS, Mancini D, Eisfeld BS, Soczynska JK, Grupp L, Konarski JZ, et al. Calculated bioavailable testosterone levels and depression in middle-aged men. Psychoneuroendocrinology 2006;31:1029–35.PubMedCrossRef

37.

Fink G, Sumner B, Rosie R, Wilson H, McQueen J. Androgen actions on central serotonin neurotransmission: relevance for mood, mental state and memory. Behav Brain Res 1999;105:53–68.PubMedCrossRef

38.

Best SE, Sarrel PM, Malison RT, Laruelle M, Zoghbi SS, Baldwin RM, et al. Striatal dopamine transporter availability with [123I] β-CIT SPECT is unrelated to gender or menstrual cycle. Psychopharmacology (Berl) 2005;183:181–9.CrossRef

39.

Neumeister A, Pirker W, Willeit M, Praschak-Rieder N, Asenbaum S, Brucke T, et al. Seasonal variation of availability of serotonin transporter binding sites in healthy female subjects as measured by [123I]-2 β-carbomethoxy-3 β-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry 2000;47:158–60.PubMedCrossRef

40.

Buijs RM, Scheer FA, Kreier F, Yi C, Bos N, Goncharuk VD, et al. Organization of circadian functions: interaction with the body. Prog Brain Res 2006;153:341–60.PubMedCrossRef

41.

Pickard GE, Weber ET, Scott PA, Riberdy AF, Rea MA. 5HT1B receptor agonists inhibit light-induced phase shifts of behavioral circadian rhythms and expression of the immediate-early gene c-fos in the suprachiasmatic nucleus. J Neurosci 1996;16:8208–20.PubMed

42.

Moore RY, Speh JC. Serotonin innervation of the primate suprachiasmatic nucleus. Brain Res 2004;1010:169–73.PubMedCrossRef

43.

Kent JM, Coplan JD, Lombardo I, Hwang DR, Huang Y, Mawlawi O, et al. Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with [11C]McN 5652. Psychopharmacology (Berl) 2002;164:341–8.CrossRef

44.

Parsey RV, Kent JM, Oquendo MA, Richards MC, Pratap M, Cooper TB, et al. Acute occupancy of brain serotonin transporter by sertraline as measured by [11C]DASB and positron emission tomography. Biol Psychiatry 2006;59:821–8.PubMedCrossRef

45.

Kish SJ, Furukawa Y, Chang LJ, Tong J, Ginovart N, Wilson A, et al. Regional distribution of serotonin transporter protein in postmortem human brain: is the cerebellum a SERT-free brain region? Nucl Med Biol 2005;32:123–8.PubMedCrossRef

46.

Yang YK, Yeh TL, Yao WJ, Lee IH, Chen PS, Chiu NT, et al. Greater availability of dopamine transporters in patients with major depression – a dual-isotope SPECT study. Psychiatry Res 2008;162:230–5.PubMedCrossRef

47.

Heinz A, Jones DW, Zajicek K, Gorey JG, Juckel G, Higley JD, et al. Depletion and restoration of endogenous monoamines affects beta-CIT binding to serotonin but not dopamine transporters in non-human primates. J Neural Transm Suppl 2004;(68):29–38.

48.

Praschak-Rieder N, Wilson AA, Hussey D, Carella A, Wei C, Ginovart N, et al. Effects of tryptophan depletion on the serotonin transporter in healthy humans. Biol Psychiatry 2005;58:825–30.PubMedCrossRef

49.

Talbot PS, Frankle WG, Hwang DR, Huang Y, Suckow RF, Slifstein M, et al. Effects of reduced endogenous 5-HT on the in vivo binding of the serotonin transporter radioligand 11C-DASB in healthy humans. Synapse 2005;55:164–75.PubMedCrossRef

50.

Hummerich R, Reischl G, Ehrlichmann W, Machulla HJ, Heinz A, Schloss P. DASB – in vitro binding characteristics on human recombinant monoamine transporters with regard to its potential as positron emission tomography (PET) tracer. J Neurochem 2004;90:1218–26.PubMedCrossRef

51.

Strauss WL, Layton ME, Dager SR. Brain elimination half-life of fluvoxamine measured by 19F magnetic resonance spectroscopy. Am J Psychiatry 1998;155:380–4.PubMed

52.

Reneman L, Booij J, de Bruin K, Reitsma JB, de Wolff FA, Gunning WB, et al. Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons. Lancet 2001;358:1864–9.PubMedCrossRef

Title: Serotonin transporter binding with [123I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender
Authors: Henricus G. Ruhé
Jan Booij
Johannes B. Reitsma
Aart H. Schene
Publication date: 01-05-2009
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 5/2009
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-008-1057-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Serotonin transporter binding with [¹²³I]β-CIT SPECT in major depressive disorder versus controls: effect of season and gender

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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