n-n-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine and Obsessive-Compulsive-Disorder

Although preclinical studies clearly indicate an effect of 5-HTTLPR genotype on 5-HT transporter (5-HTT) expression, studies in humans provided inconclusive results, hypothetically due to environmental factors and differences in individual behavior. For example, nicotine and other constituents of tobacco smoke elevate serotonin (5-HT) levels in the brain and may thereby cause homeostatic adaptations in 5-HTT availability that moderate effects of 5-HTTLPR genotype. To test whether 5-HTT availability in the midbrain is affected by smoking status and 5-HTTLPR genotype, we pooled data from prior studies on in vivo 5-HTT availability (BP

Topics: Adult; Benzylamines; Brain; Carbon Radioisotopes; Depressive Disorder, Major; Female; Genotype; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Polymorphism, Genetic; Positron-Emission Tomography; Serotonin Plasma Membrane Transport Proteins; Smoking

Early-onset obsessive-compulsive disorder (EOCD) and late-onset obsessive-compulsive disorder (LOCD) are distinct subtypes of obsessive-compulsive disorder (OCD). OCD patients are treated with serotonin reuptake inhibitors, but the difference in serotonin transporter (SERT) availability between medicated EOCD and LOCD is unexplored yet.. Six EOCD and 6 LOCD patients were enrolled. They underwent serial [. In comparison with LOCD patients, SERT availability was significantly higher in the putamen of EOCD patients (U = 4, p = .026), but not in the caudate nucleus (U = 14, p = .589), thalamus (U = 16, p = .818), and dorsal raphe nucleus (U = 7, p = .093). Binding potential of putamen showed a negative correlation (r = -.580, p = .048) with age of onset of the disease, but not with the Yale-Brown Obsessive Compulsive Scale scores.. These findings indicate that the earlier the age of onset of OCD, the less serotonergic pathology there is and that this difference remains even after long-term serotonin reuptake inhibitor treatment. Clinically, it might suggest that nonserotonergic treatments would be a better option for EOCD patients.

Topics: Adult; Age of Onset; Benzylamines; Brain; Brain Mapping; Carbon Radioisotopes; Case-Control Studies; Citalopram; Humans; Male; Models, Biological; Obsessive-Compulsive Disorder; Positron-Emission Tomography; Psychiatric Status Rating Scales; Radiopharmaceuticals; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins

Obsessive-compulsive disorder (OCD) is a chronic, relapsing mental illness. Selective serotonin reuptake inhibitors block serotonin transporters (SERTs) and are the mainstay of treatment for OCD. SERT abnormalities are reported in drug-free patients with OCD, but it is not known what happens to SERT levels during treatment. This is important as alterations in SERT levels in patients under treatment could underlie poor response, or relapse during or after treatment. The aim of the present study was first to validate a novel approach to measuring SERT levels in people taking treatment and then to investigate SERT binding potential (BP) using [11C]DASB PET in patients with OCD currently treated with escitalopram in comparison with healthy controls.. Twelve patients and age- and sex-matched healthy controls were enrolled. The patients and healthy controls underwent serial PET scans after administration of escitalopram and blood samples for drug concentrations were collected simultaneously with the scans. Drug-free BPs were obtained by using an inhibitory E max model we developed previously.. The inhibitory E max model was able to accurately predict drug-free SERT BP in people taking drug treatment. The drug-free BP in patients with OCD currently treated with escitalopram was significantly different from those in healthy volunteers [Cohen's d = 0.03 (caudate), 1.16 (putamen), 1.46 (thalamus), -5.67 (dorsal raphe nucleus)].. This result extends previous findings showing SERT abnormalities in drug-free patients with OCD by indicating that altered SERT availability is seen in OCD despite treatment. This could account for poor response and the high risk of relapse in OCD.

Topics: Adult; Benzylamines; Brain; Carbon Radioisotopes; Case-Control Studies; Caudate Nucleus; Citalopram; Female; Humans; Male; Obsessive-Compulsive Disorder; Positron-Emission Tomography; Putamen; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Thalamus; Young Adult