The pathogenetic role of central serotonin transporters (SERT) in obsessive-compulsive disorder (OCD) has been investigated in vivo by positron emission tomography (PET) or single-photon emission computed tomography (SPECT) studies with inconsistent results. This might reflect methodological differences but possibly also the pathophysiological heterogeneity of the disorder, i.e. the age at onset of OCD. The aim of our study was to compare SERT availability in patients with OCD to healthy controls (HC) taking into account the onset type, other factors and covariates (e.g. SERT genotype, age, depression level, gender). We studied 19 drug-naive OCD patients (36±13 yr, eight females) with early onset (EO-OCD, n=6) or with late onset (LO-OCD, n=13), and 21 HC (38±8 yr, nine females) with PET and the SERT-selective radiotracer [11C]DASB. Statistical models indicated that a variety of covariates and their interaction influenced SERT availability measured by distribution volume ratios (DVR). These models revealed significant effects of onset type on DVR with lower values in LO-OCD (starting at age 18 yr) compared to EO-OCD and HC in limbic (e.g. the amygdala), paralimbic brain areas (the anterior cingulate cortex), the nucleus accumbens and striatal regions, as well as borderline significance in the thalamus and the hypothalamus. The putamen, nucleus accumbens and hypothalamus were found with significant interaction between two SERT gene polymorphisms (SERT-LPR and VNTR). These findings suggest that late but not early onset of OCD is associated with abnormally low SERT availability. In part, functional polymorphisms of the SERT gene might determine the differences.
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http://dx.doi.org/10.1017/S1461145710001604 | DOI Listing |
J Nucl Med
January 2025
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden.
Serotonin transporter (SERT) availability was assessed using 2 tracers, [C],-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ([C]DASB) and [C],-dimethyl-2-(2-amino-4-fluoromethylphenylthio)benzylamine) ([C]MADAM), in independent cohorts of patients and controls. This study aimed to independently confirm whether SERT remains intact in nondepressed individuals with early-stage Parkinson disease (PD), because the use of diverse methodologies could potentially yield disparate results. Seventeen PD patients (5 women and 12 men; age, 64 ± 7 y; Unified Parkinson's Disease Rating Scale motor score, 23 ± 5; Beck Depression Inventory score, 5 ± 4) and 20 age- and sex-matched healthy controls underwent [C]MADAM PET at Karolinska Institutet.
View Article and Find Full Text PDFNeurobiol Dis
November 2024
Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713, GZ, Groningen, the Netherlands. Electronic address:
Most pharmacological treatments for depression target monoamine transporters and about 50 % of treated patients attain symptomatic remission. Once remission is attained, it is hard to distinguish the changes on brain monoaminergic transmission induced by the antidepressants, from those associated to remission per se. In this study, we aimed at studying the brain of spontaneously remitted rats from repeated social defeat (RSD)-induced depression in terms of dopamine D/D receptor and serotonin transporter (SERT) availability, showing absence of depressive symptoms 2 weeks after RSD.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College in Kraków, Medyczna 9, 30-688 Krakow, Poland.
Perry disease (PeD) is a rare, neurodegenerative, genetic disorder inherited in an autosomal dominant manner. The disease manifests as parkinsonism, with psychiatric symptoms on top, such as depression or sleep disorders, accompanied by unexpected weight loss, central hypoventilation, and aggregation of DNA-binding protein (TDP-43) in the brain. Due to the genetic cause, no causal treatment for PeD is currently available.
View Article and Find Full Text PDFFront Med Technol
September 2024
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
Lipids Health Dis
August 2024
Department of Biology and Anatomy, National Defense Medical Center, Taipei, 114, Taiwan.
Introduction: Hypercholesterolemia is associated with increased inflammation and impaired serotonin neurotransmission, potentially contributing to depressive symptoms. However, the role of statins, particularly pitavastatin, in modulating serotonin transporter (SERT) function within this context remains underexplored. This study aimed to investigate whether pitavastatin counteracts the neurobiological effects of hypercholesterolemia.
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