Quantifying Midbrain Serotonin Transporter in Depression: A Preliminary Study of Diagnosis and Naturalistic Treatment Outcome

H. C. Tsai; S.-H. Lin; P. S. Chen; H. H. Chang; I. H. Lee; T. L. Yeh; K. C. Chen; N. T. Chiu; W. J. Yao; M.-H. Liao; Y. K. Yang

doi:10.1055/s-0034-1396800

Pharmacopsychiatry, Inhaltsverzeichnis

Pharmacopsychiatry 2015; 48(02): 58-64
DOI: 10.1055/s-0034-1396800

Original Paper

Quantifying Midbrain Serotonin Transporter in Depression: A Preliminary Study of Diagnosis and Naturalistic Treatment Outcome

H. C. Tsai

¹Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

²Department of Psychiatry, National Cheng Kung University Hospital, Douliou Branch, Yunlin, Taiwan

,

S.-H. Lin

¹Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

³Addiction Research Center, National Cheng Kung University, Tainan, Taiwan

,

P. S. Chen

¹Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

²Department of Psychiatry, National Cheng Kung University Hospital, Douliou Branch, Yunlin, Taiwan

³Addiction Research Center, National Cheng Kung University, Tainan, Taiwan

,

H. H. Chang

⁴Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

I. H. Lee

¹Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

³Addiction Research Center, National Cheng Kung University, Tainan, Taiwan

,

T. L. Yeh

¹Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

³Addiction Research Center, National Cheng Kung University, Tainan, Taiwan

,

K. C. Chen

¹Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

²Department of Psychiatry, National Cheng Kung University Hospital, Douliou Branch, Yunlin, Taiwan

³Addiction Research Center, National Cheng Kung University, Tainan, Taiwan

,

N. T. Chiu

⁵Department of Nuclear Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

W. J. Yao

⁵Department of Nuclear Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

,

M.-H. Liao

⁶Institute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan, Taoyuan, Taiwan

,

Y. K. Yang

¹Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

³Addiction Research Center, National Cheng Kung University, Tainan, Taiwan

› Institutsangaben

Abstract

Introduction: Serotonin may play an important role in the pathology of major depressive disorder (MDD). However, the relationship between serotonin transporter (SERT) availability and the medical outcome of antidepressant treatment is uncertain.

Methods: In this naturalistic study, SERT availability (expressed as the specific uptake ratio, SUR) in the midbrain of 17 drug-free patients with MDD and 17 controls matched for age and gender was measured using SPECT with [¹²³I]ADAM. The severity of MDD was measured by the Hamilton Depression Rating Scale before, and after 6 weeks of non-standardized antidepressant treatment.

Results: A total of 12 patients completed the study. The SUR of the patients with MDD was significantly lower than that of the healthy controls. The SUR of SERT was not found to have a linear relationship with the treatment outcome; however, supplemental analysis found a curvilinear relationship between treatment outcome and the SUR of SERT.

Discussion: The findings indicate that the SUR of SERT is lower in patients with MDD; however it did not predict treatment outcome in a linear fashion. Studies with larger sample sizes are required.

Key words

ADAM - major depressive disorder - serotonin transporter - SPECT - treatment response

Volltext

Referenzen

References
1 Byrum CE, Ahearn EP, Krishnan KRR. A neuroanatomic model for depression. Prog Neuropsychopharmacol Biol Psychiatry 1999; 23: 175-193
2 Olivier B, Soudijn W, van Wijngaarden I. Serotonin, dopamine and norepinephrine transporters in the central nervous system and their inhibitors. Prog Drug Res 2000; 54: 59-119
3 Rudnick G, Clark J. From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters. Biochim Biophys Acta 1993; 1144: 249-263
4 Ketter TA, George MS, Kimbrell TA et al. Functional brain imaging, limbic function, and affective disorders. Neuroscientist 1996; 2: 55-65
5 Malison RT, Price LH, Berman R et al. Reduced brain serotonin transporter availability in major depression as measured by [¹²³I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane and single photon emission computed tomography. Biol Psychiatry 1998; 44: 1090-1098
6 Newberg AB, Amsterdam JD, Wintering N et al. ¹²³I-ADAM binding to serotonin transporters in patients with major depression and healthy controls: a preliminary study. J Nucl Med 2005; 46: 973-977
7 Meyer JH, Wilson AA, Ginovart N et al. Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: A [C-11]DASB PET imaging study. Am J Psychiatry 2001; 158: 1843-1849
8 Klein N, Sacher J, Geiss-Granadia T et al. In vivo imaging of serotonin transporter occupancy by means of SPECT and I-123 ADAM in healthy subjects administered different doses of escitalopram or citalopram. Psychopharmacology (Berl) 2006; 188: 263-272
9 Leake A, Fairbairn AF, McKeith IG et al. Studies on the serotonin uptake binding site in major depressive disorder and control post-mortem brain: neurochemical and clinical correlates. Psychiatry Res 1991; 39: 155-165
10 Joensuu M, Tolmunen T, Saarinen PI et al. Reduced midbrain serotonin transporter availability in drug-naive patients with depression measured by SERT-specific [⁽¹²³⁾I] nor-beta-CIT SPECT imaging. Psychiatry Res 2007; 154: 125-131
11 Lehto SM, Tolmunen T, Kuikka J et al. Midbrain serotonin and striatum dopamine transporter binding in double depression: a one-year follow-up study. Neurosci Lett 2008; 441: 291-295
12 Lehto S, Tolmunen T, Joensuu M et al. Midbrain binding of [¹²³I]nor-beta-CIT in atypical depression. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 1251-1255
13 Willeit M, Praschak-Rieder N, Neumeister A et al. [¹²³I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. Biol Psychiatry 2000; 47: 482-489
14 Hsieh PC, Lee IH, Yeh TL et al. Distribution volume ratio of serotonin and dopamine transporters in euthymic patients with a history of major depression – a dual-isotope SPECT study. Psychiatry Res Neuroimaging 2010; 184: 157-161
15 Ahonen A, Heikman P, Kauppinen T et al. Serotonin transporter availability in drug free depression patients using a novel SERT ligand. Eur J Nucl Med Mol Imaging 2004; 31: S227-S228
16 Catafau AM, Perez V, Plaza P et al. Serotonin transporter occupancy induced by paroxetine in patients with major depression disorder: a I-123-ADAM SPECT study. Psychopharmacology (Berl) 2006; 189: 145-153
17 Herold N, Uebelhack K, Franke L et al. Imaging of serotonin transporters and its blockade by citalopram in patients with major depression using a novel SPECT ligand I-123-ADAM. J Neural Transm 2006; 113: 659-670
18 Oya S, Choi SR, Hou C et al. 2-((2-((Dimethylamino)methyl)phenyl)thio-5-iodophenylamine (ADAM): An improved serotonin transporter ligand. Nucl Med Biol 2000; 27: 249-254
19 Sacher J, Asenbaum S, Klein N et al. Binding kinetics of ¹²³I[ADAM] in healthy controls: a selective SERT radioligand. Int J Neuropsychopharmacol 2007; 10: 211-218
20 Chou YH, Yang BH, Chung MY et al. Imaging the serotonin transporter using I-123-ADAM in the human brain. Psychiatry Res Neuroimaging 2009; 172: 38-43
21 Lundgren JD, Newberg AB, Allison KC et al. ¹²³I-ADAM SPECT imaging of serotonin transporter binding in patients with night eating syndrome: A preliminary report. Psychiatry Res Neuroimaging 2008; 162: 214-220
22 Yang YK, Yao WJ, Yeh TL et al. Association between serotonin transporter availability and hostility scores in healthy volunteers – A single photon emission computed tomography study with I-123 ADAM. Psychiatry Res Neuroimaging 2007; 154: 281-284
23 Wu IT, Lee IH, Yeh TL et al. The association between the harm avoidance subscale of the Tridimensional Personality Questionnaire and serotonin transporter availability in the brainstem of male volunteers. Psychiatry Res 2010; 181: 241-244
24 Tsai HC, Yeh TL, Hsieh MH et al. Association between serotonin transporter availability and overall rating scores of quality of life in healthy volunteers. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 711-714
25 Pogarell O, Koch W, Schaaff N et al. [¹²³I] ADAM brainstem binding correlates with the loudness dependence of auditory evoked potentials. Eur Arch Psychiatry Clin Neurosci 2008; 258: 40-47
26 Lee IH, Yang YK, Chen PS et al. Loudness dependence of auditory evoked potentials (LDAEP) correlates with the availability of dopamine transporters and serotonin transporters in healthy volunteers – a two isotopes SPECT study. Psychopharmacology (Berl) 2011; 214: 617-624
27 Kugaya A, Seneca NM, Snyder PJ et al. Changes in human in vivo serotonin and dopamine transporter availabilities during chronic antidepressant administration. Neuropsychopharmacology 2003; 28: 413-420
28 de Win MML, Habraken JBA, Reneman L et al. Validation of I-121 beta-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
29 Eggers B, Hermann W, Barthel H et al. 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: 576-580
30 Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56-62
31 Moberg PJ, Lazarus LW, Mesholam RI et al. Comparison of the standard and structured interview guide for the Hamilton Depression Rating Scale in depressed geriatric inpatients. Am J Geriatr Psychiatry 2001; 9: 35-40
32 Kugaya A, Sanacora G, Staley JK et al. Brain serotonin transporter availability predicts treatment response to selective serotonin reuptake inhibitors. Biol Psychiatry 2004; 56: 497-502
33 Miller JM, Oquendo MA, Ogden RT et al. Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder. J Psychiatr Res 2008; 42: 1137-1144
34 Lanzenberger R, Kranz GS, Haeusler D et al. Prediction of SSRI treatment response in major depression based on serotonin transporter interplay between median raphe nucleus and projection areas. Neuroimage 2012; 63: 874-881
35 Cavanagh J, Patterson J, Pimlott S et al. Serotonin transporter residual availability during long-term antidepressant therapy does not differentiate responder and nonresponder unipolar patients. Biol Psychiatry 2006; 59: 301-308
36 Levinson AJ, Fitzgerald PB, Favalli G et al. Evidence of cortical inhibitory deficits in major depressive disorder. Biol Psychiatry 2010; 67: 458-464
37 Yeh TL, Lee IH, Chen KC et al. The relationships between daily life events and the availabilities of serotonin transporters and dopamine transporters in healthy volunteers – a dual-isotope SPECT study. Neuroimage 2009; 45: 275-279
38 Laasonen-Balk T, Viinamaki H, Kuikka JT et al. ¹²³I-beta-CIT binding and recovery from depression. A six-month follow-up study. Eur Arch Psychiatry Clin Neurosci 2004; 254: 152-155
39 Sheehan DV, Lecrubier Y, Sheehan KH et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998; 59 (Suppl. 20) 22-33 quiz 34–57
40 Yeh TL, Chen KC, Lin SH et al. Availability of dopamine and serotonin transporters in opioid-dependent users – a two-isotope SPECT study. Psychopharmacology (Berl) 2012; 220: 55-64
41 Huang HY, Lee IH, Chen KC et al. Serotonin transporter availability in the midbrain and perceived social support in healthy volunteers. J Psychosom Res 2013; 75: 577-581
42 Chang LT. Method for attenuation correction in radionuclide computed tomography. IEEE Trans Nucl Sci 1978; 25: 638-643
43 Huang CI, Yao WJ, Sun YN. New methods for registering long-time I-123 ADAM SPECT image sequences to magnetic resonance images. Nucl Med Commun 2010; 31: 734-740
44 Nye JA, Purselle D, Plisson C et al. Decreased brainstem and putamen SERT binding potential in depressed suicide attempters using [¹¹C]-zient PET imaging. Depress Anxiety 2013; 30: 902-907
45 Kirsch I, Deacon BJ, Huedo-Medina TB et al. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008; 5: e45
46 Kim DK, Lim SW, Lee S et al. Serotonin transporter gene polymorphism and antidepressant response. Neuroreport 2000; 11: 215-219
47 Pollock BG, Ferrell RE, Mulsant BH et al. Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology 2000; 23: 587-590
48 Ruhe HG, Ooteman W, Booij J et al. Serotonin transporter gene promoter polymorphisms modify the association between paroxetine serotonin transporter occupancy and clinical response in major depressive disorder. Pharmacogenet Genomics 2009; 19: 67-76
49 Uher R, Perlis RH, Henigsberg N et al. Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms. Psychol Med 2012; 42: 967-980
50 Vallejo J, Gasto C, Catalan R et al. Predictors of antidepressant treatment outcome in melancholia: psychosocial, clinical and biological indicators. J Affect Disord 1991; 21: 151-162
51 Ezquiaga E, Garcia A, Pallares T et al. Psychosocial predictors of outcome in major depression: a prospective 12-month study. J Affect Disord 1999; 52: 209-216
52 Tsai HY, Lee IH, Yeh TL et al. Association between the dexamethasone suppression test and serotonin transporter availability in healthy volunteer: a SPECT with [⁽¹²³⁾I] ADAM study. Eur Neuropsychopharmacol 2012; 22: 641-646
53 Frokjaer VG, Pinborg LH, Madsen J et al. Evaluation of the serotonin transporter ligand ¹²³I-ADAM for SPECT studies on humans. J Nucl Med 2008; 49: 247-254
54 Catafau AM, Perez V, Penengo MM et al. SPECT of serotonin transporters using ¹²³I-ADAM: optimal imaging time after bolus injection and long-term test-retest in healthy volunteers. J Nucl Med 2005; 46: 1301-1309