3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile and Schizophrenia

The serotonin transporter (SERT) is an integral protein that provides an index of serotonergic innervation. Until recently, few studies have investigated SERT binding in thalamic subregions in schizophrenia. The purpose of this study was to examine SERT availability in thalamic subdivisions (anterior nucleus, mediodorsal nucleus, and pulvinar) using 7.0-T magnetic resonance imaging (MRI) and high-resolution positron emission tomography (PET) with (11)C-3-amino-4-(2-dimethylaminomethylphenylthio)benzonitrile ([(11)C]DASB) in schizophrenia. Antipsychotic-free patients with schizophrenia (n=12) and healthy controls (n=15) underwent PET and MRI scans. For SERT availability, the binding potential with respect to non-displaceable compartment (BPND) was derived using the simplified reference tissue model (SRTM2). The analysis revealed that there were no significant differences in SERT availability between the two groups. In patients with schizophrenia, the severity of negative symptoms had a negative correlation with SERT availability in the anterior nucleus of the left thalamus. The present study did not reveal significant differences in SERT availability in thalamic subdivisions between patients with schizophrenia and control subjects. The association of SERT availability in the anterior nucleus with negative symptoms may suggest a role for the anterior thalamic nucleus in the pathophysiology of symptoms of schizophrenia. The ultra-high resolution imaging system could be an important asset for in vivo psychiatric research by combining structural and molecular information.

Topics: Adult; Aniline Compounds; Brain; Case-Control Studies; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Membrane Transport Proteins; Middle Aged; Positron-Emission Tomography; Schizophrenia; Serotonin Plasma Membrane Transport Proteins; Sulfides; Thalamus

Postmortem studies have reported several alterations in serotonin transporter (SERT) binding parameters in patients with schizophrenia. The aim of this study was to compare SERT availability in vivo in patients with schizophrenia and matched control subjects.. Ten medication-free patients with schizophrenia and 10 healthy subjects underwent positron emission tomography (PET) scans for 90 min after 11C-3-amino-4-(2-dimethylaminomethylphenylthio)benzonitrile ([11C]DASB) injection. Metabolite-corrected arterial input function was measured. Regional distribution volumes (mL/g) were derived with a two tissue compartment kinetic model. Outcome measures for SERT availability included binding potential (BP) and the specific-to-nonspecific equilibrium partition coefficient (V3''). Ten brain regions with high density of SERT and where SERT availability can be reliably quantified with [11C]DASB were included in the analysis.. No significant differences were observed in regional BP or V3'' between patients and control subjects. No significant relationships were observed between regional SERT availability and severity of positive, negative, and depressive symptoms.. This study failed to detect alterations of SERT availability in patients with schizophrenia; however, this study does not rule out the possibility that schizophrenia might be associated with alterations of SERT density in the cortical regions, where the [11C]DASB-specific binding signal is too low for reliable quantification of SERT.

Topics: Adult; Analysis of Variance; Aniline Compounds; Brain; Carbon Radioisotopes; Case-Control Studies; Demography; Female; Humans; Image Processing, Computer-Assisted; Male; Membrane Glycoproteins; Membrane Transport Modulators; Membrane Transport Proteins; Nerve Tissue Proteins; Positron-Emission Tomography; Postmortem Changes; Protein Binding; Schizophrenia; Serotonin Plasma Membrane Transport Proteins; Sulfides; Tissue Distribution