Background: Alterations in the brain serotonin (5-HT) system have been found in patients with depression. We used the selective 5-HT transporter site ligand [11C](+)McN5652 and positron emission tomography (PET) to examine the hypothesis that alterations in 5-HT transporter levels may be present in selected regions of the brain in depressed patients.
Methods: Four drug free depressed patients and four healthy control subjects were studied using [11C](+)McN5652 and PET. The distribution volume (DV) ratio of the PET ligand in selected regions of interest (ROIs) compared to cerebellum were calculated for the ROIs.
Results: Patients showed significantly larger DV ratios in the left frontal cortex (P=0.013) and right cingulate cortex (P=0.043) compared to control subjects.
Limitation: The sample size was modest with gender differences between the subject groups. The PET agent, [11C](+)McN5652, may have a lower binding affinity for the 5-HT transporter in the cortical regions compared to other brain regions.
Conclusion: These findings suggest that 5-HT transporter sites may be increased in the frontal and cingulate cortices of depressed patients. These alterations in 5-HT transporter sites may be of pathophysiologic significance in the etiology of depression and its treatment.
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http://dx.doi.org/10.1016/j.jad.2003.12.014 | DOI Listing |
BMC Chem
January 2025
LAQV@REQUIMTE/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, 4169-007, Portugal.
Mood disorders affect the daily lives of millions of people worldwide. The search for more efficient therapies for mood disorders remains an active field of research. In silico approaches can accelerate the search for inhibitors against protein targets related to mood disorders.
View Article and Find Full Text PDFNat Commun
January 2025
Shanghai Fifth People's Hospital, Fudan University, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Vesicular monoamine transporter 2 (VMAT2) is crucial for packaging monoamine neurotransmitters into synaptic vesicles, with their dysregulation linked to schizophrenia, mood disorders, and Parkinson's disease. Tetrabenazine (TBZ) and valbenazine (VBZ), both FDA-approved VMAT2 inhibitors, are employed to treat chorea and tardive dyskinesia (TD). Our study presents the structures of VMAT2 bound to substrates serotonin (5-HT) and dopamine (DA), as well as the inhibitors TBZ and VBZ.
View Article and Find Full Text PDFJ Nucl Med
January 2025
Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Parkinson disease (PD) is a multisystem disorder marked by progressive dopaminergic neuronal degeneration in the substantia nigra, as well as nondopaminergic systems. Our aim was to investigate longitudinal changes in -(3-[F]fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (F-FP-CIT) binding at the putamen, substantia nigra, and raphe nuclei in PD. This retrospective cohort study enrolled 127 patients with PD, who underwent F-FP-CIT PET scans twice or more, and 71 age- and sex-matched healthy controls.
View Article and Find Full Text PDFJ 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 PDFAnal Chem
January 2025
School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116, China.
Conventional solid/liquid electrochemical interfaces typically encounter challenges with impeded mass transport for poor electrochemical quantification due to the intricate pathways of reactants from the bulk solution. To address this issue, this work reports an innovative approach integrating a target-activated DNA framework nanomachine with electrochemically driven metal-organic framework (MOF) conversion for self-sacrificial biosensing. The presence of the target biomarker serotonin initiates the DNA framework nanomachine by an entropy-driven circuit to form a cross-linked nanostructure and subsequently release the Fe-MOF probe.
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