Search

Introduction The serotonergic system modulates brain functions that are considered to underlie affective states, emotion and cognition. Several lines of evidence point towards a strong lateralization of these mental processes, indicating similar asymmetries in associated neurotransmitter systems. Objectives To investigate a potential brain asymmetry of the serotonin transporter (SERT) distribution using Positron Emission Tomography (PET). Aims As brain asymmetries differ between sexes, we aimed to compare serotonin transporter asymmetry between females, males and male-to-female transsexuals whose brains are considered to be partly feminized. Methods 36 subjects aged 19-54 years (9 female controls, 13 male controls and 14 male-to-female transsexuals) were measured with PET and [ 11 C]DASB. Whole-brain voxel-wise SERT binding potential (BP ND ) maps were computed using a tracer-specific symmetric template. Statistics comprised repeated measures ANOVA with group as the between subjects factor, voxel-wise SERT asymmetry as repeated factor and group*asymmetry as interaction term. Results SERT binding in all groups showed both strong left and rightward asymmetries in several cortical and subcortical structures including temporal and frontal cortices, anterior cingulate, hippocampus, caudate and thalamus (p 0.05 FDR-corrected) which was absent in females and male-to-female transsexuals. Conclusions Our data support the notion of a lateralized serotonergic system, which is in line with previous findings of asymmetric serotonin-1A receptor distributions, extracellular serotonin concentrations, serotonin turnover and uptake. The absence of serotonin transporter asymmetry in the midcingulate in male-to-female transsexuals may be attributed to an absence of brain masculinization in this region.

IntroductionThere is evidence that psychiatric diseases are accompanied by structural alterations in the human brain, partly reversible by pharmacological treatments. Several studies including Tost et al. (Nat.Neurosci.2010;13(8):920-2) investigated the effect of psychotropic drugs on neuronal plasticity pointing towards rapid pharmacologically induced brain grey matter variations, apart from already presumed slow structural changes within weeks. Here, we investigated the short-term (days) structural effects of SSRIs.ObjectiveTo identify structural changes of grey and white matter following 10d of oral administration (citalopram/escitalopram vs. placebo) in 18 healthy subjects investigated by magnetic resonance imaging (MRI) using voxel-based morphometry (VBM).MethodsStudy design: Randomized, cross-over, placebo-controlled, double-blind study.Subjects: 18 healthy caucasian subjects (6 female 24.8 ± 2.5 years, 12 males 28.9 ± 6.7 years) MRI: 3 MRI scans/subject (3 Tesla scanner)Treatment: 10d of oral medication intake of either 20 mg citalopram/d, 10 mg escitalopram/d or placebo in alternating order of administrationData analysis: VBM, as implemented in SPM8.Statistical analysis: analysis of variance (ANOVA, FWE corrected), post-hoc pair-wise comparisons.ResultsANOVA (grey matter: F(2,48) = 18.85, p < 0.05; white matter: F(2,48) = 17.79, p < 0.05) did not reveal suprathreshold clusters in grey or white matter.ConclusionThis VBM-study does not support previous short-time (days) MR findings of pharmacologically-induced structural alterations in the brain, considering the lack of significant changes in grey and white matter volumes following 10d of SSRI administration. This divergence may be caused by dissent pharmacological effects of SSRIs compared to other psychotropic drugs.

IntroductionClinical studies point toward a potential role of the serotonin transporter (SERT) binding as a predictor of clinical outcome in the treatment of depression. After long-term treatment with clinical doses of SSRIs the expected SERT occupancy is about 80%. Here, we were interested to investigate the relationship of SERT occupancy values between short- and longterm treatment.ObjectivesTo test if the SERT occupancy at steady-state can be predicted based on the single dose occupancy by escitalopram (S-citalopram) or citalopram (racemate of S-citalopram and R-citalopram).Methods18 patients with major depressive disorder received either escitalpram (10 mg/d) or citalopram (20 mg/d) in a double-blind, randomized, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 6 hours after first drug intake and PET3 after three weeks of daily oral treatment. Occupancy of SERT was quantified in six subcortical regions: thalamus, N. caudatus, putamen, mibrain, dorsal raphe and median raphe nuclei. Data was analyzed by means of multiple linear regression models corrected for baseline SERT availability values using SPSS 15.0.ResultsSingle dose occupancy of the SERT significantly predicted steady-state occupancy after three weeks in three regions: thalamus (r2 = 0.45, p = 0.009), N. caudatus (r2 = 0.4, p = 0.006) and putamen (r2 = 0.43, p = 0.005). Other regions did not show significant relationships.ConclusionsIn this study we demonstrated that single-dose occupancy in SERT rich regions such as thalamus, N. caudatus and the putamen could serve as reliable predictors for steady-state occupancy. However, a linear model failed to explain the relationship in regions known for serotonergic cell origin.

IntroductionAlterations of the serotonin-1A receptor (5-HT1A) and the hypothalamic-pituitary-adrenal (HPA) axis have been reported in depression and anxiety disorders. We previously showed a strong negative correlation between cortisol plasma levels and 5-HT1A receptor binding potential (BP) in patients with social anxiety disorder but not in healthy controls using PET [1].ObjectivesTo investigate the relationship of cortisol and the 5-HT1A BP in postmenopausal women, a population that is at increased risk of suffering from depressive symptoms.MethodsSubjects: 19 postmenopausal women, aged 55.26 ± 4.98, medication free, no current substance abuse or hormone replacement therapy.PETDynamic measurements (50 frames, 90 min) were performed using the radioligand [carbonyl-11C]WAY100635 and a GE-Advance scanner. PET data were normalized to a ligand-specific template [2]. Regions-of-interest (ROI) were defined as given in [3]. TACs within ROIs were averaged and the 5-HT1A receptor BP was quantified using Logan-plot and PMOD 3.1. Measurement of total cortisol plasma levels was done using electrochemoluminescence.ResultsWe found negative correlations between cortisol and 5-HT1A BP in the midbrain (Spearman's rs = −0.54, p = 0.02), the median raphe nucleus (rs = −0.47, p = 0.04) and the nucleus accumbens (rs = −0.505, p = 0.03).ConclusionsIn line with our previous findings [1], the observed negative association between cortisol plasma levels and 5-HT1A BP might reflect an increased vulnerability for mood disorders in postmenopausal women.