title: Altered serotonin and dopamine transporter availabilities in brain of depressed patients upon treatment with escitalopram: A [123 I]β-CIT SPECT study.
abstract: Altered SERT and DAT availabilities during treatment with escitalopram were investigated with [(123)I]2β-carbomethoxy-3β-(4-iodophenyl)tropane (β-CIT) SPECT in a series of patients fulfilling the criteria for unipolar major depressive disorder (MDD). 27 patients (10m, 42±16y) with diagnosis of MDD were recruited for the study. All patients underwent neuropsychiatric testing for assessment of Hamilton Depression (HAM-D) and Beck Depression Inventory (BDI) scores. At baseline, [(123)I]β-CIT SPECT recordings were acquired 4h (SERT-weighted) and 20-24h p.i (DAT-weighted). Follow-up scans and neuropsychiatric testing were performed after six weeks of stable escitalopram medication. Voxel-wise parametric maps of specific/ non-specific ratios-1 (~BPND) were calculated. At baseline, DAT-weighted BPND was 5.06±0.81 in striatum and SERT-weighted BPND was 0.94±0.18 in thalamus. There were significant negative correlations with age for DAT in striatum (R=-0.60; p<0.01) and SERT in thalamus (R=-0.45; p<0.05). Under SSRI treatment there was an apparent 42% occupancy of SERT in thalamus (p<0.0001), whereas DAT availability increased significantly by 20% in striatum (p<0.001); higher apparent SERT occupancy in thalamus was associated with lesser DAT increase in striatum (R=-0.62; p<0.005). The low apparent SERT occupancy may be confounded by alterations in SERT expression during treatment. Thus, [(123)I]β-CIT SPECT revealed age-dependent declines in DAT and SERT availabilities in un-medicated MDD patients, comparable to that seen previously in healthy controls. At follow-up, the SSRI-evoked increase in DAT was less pronounced in the older patients, even though apparent SERT occupancy and clinical improvement were not age-dependent. Present findings may have implications for escitalopram dosage and side effect profile in younger MDD patients.
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany. Electronic address: axel.rominger@med.uni-muenchen.de.
authors.forename: A
authors.initials: A
authors.lastname: Rominger
authors.affiliation: Department of Psychiatry, University of Oslo, Oslo, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Cumming
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Brendel
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Xiong
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Zach
authors.affiliation: Department of Psychiatry, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Karch
authors.affiliation: Department of Nuclear Medicine, Municipal Hospital Karlsruhe Inc., Karlsruhe, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Tatsch
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: Department of Nuclear Medicine, University of Tubingen, Tubingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: la Fougère
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Koch
authors.affiliation: Department of Psychiatry, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Pogarell
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D015283:Citalopram / Q000627:therapeutic use*; D003863:Depression / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000378:metabolism*; D013223:Statistics as Topic; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D014326:Tropanes; D015283:Citalopram; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; D012701:Serotonin
keywords: DAT; Escitalopram; Major depressive disorder; SERT; SPECT; [(123)I]β-CIT