Dopamine transporter binding in social anxiety disorder: the effect of treatment with escitalopram.

Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using (123)I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects' Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration.

The Role of CT-Based Attenuation Correction and Collimator Blurring Correction in Striatal Spect Quantification.

Purpose. Striatal single photon emission computed tomography (SPECT) imaging of the dopaminergic system is becoming increasingly used for clinical and research studies. The question about the value of nonuniform attenuation correction has become more relevant with the increasing availability of hybrid SPECT-CT scanners. In this study, the value of nonuniform attenuation correction and correction for collimator blurring were determined using both phantom data and patient data. Methods. SPECT imaging was performed using 7 anthropomorphic phantom measurements, and 14 patient studies using [I-123]-FP-CIT (DATSCAN). SPECT reconstruction was performed using uniform and nonuniform attenuation correction and collimator blurring corrections. Recovery values (phantom data) or average-specific uptake ratios (patient data) for the different reconstructions were compared at similar noise levels. Results. For the phantom data, improved recovery was found with nonuniform attenuation correction and collimator blurring corrections, with further improvement when performed together. However, for patient data the highest average specific uptake ratio was obtained using collimator blurring correction without nonuniform attenuation correction, probably due to subtle SPECT-CT misregistration. Conclusions. This study suggests that an optimal brain SPECT reconstruction (in terms of the lowest bias) in patients would include a correction for collimator blurring and uniform attenuation correction.

The influence of the physicochemical characteristics and pharmacokinetic properties of selected NSAID's on their transdermal absorption.

The purpose of this study was to determine the plasma concentrations of selected NSAIDs after topical gel administration and to determine the influence of the physicochemical characteristics of these drugs on transdermal absorption. Plasma concentrations of the drugs were determined using high performance liquid chromatography. The logP values obtained from literature for piroxicam, ketoprofen, naproxen, ibuprofen and indomethacin, (1.8, 0.97, 3.22, 3.6 and 3.8, respectively) correlated with the area under the plasma-time curve (AUC) values. The AUC values determined were 527.00 (piroxicam) 269. 45 (ketoprofen) 258.65 (naproxen) 243.22 (indomethacin) and 88.09 (ibuprofen) microg/ml per h. It was concluded that the most reliable parameter for transdermal absorption was the lipophilic character of a drug (logP value). The molecular mass, solubility constraint and percentage unionized moiety can only be used in combination with other properties in the prediction of possible transdermal drug delivery.