Background: Previous Positron Emission Tomography (PET) studies of 5-HT1A receptors have shown an influence of several genetic factors, including the triallelic serotonin transporter gene-linked polymorphic region on the binding potential (BPND) of these receptors. The aim of our study was to investigate the relationship between a 5-HT1A promoter polymorphism and the binding potential of another selective 5-HT1A receptor antagonist, [18F]MPPF, in healthy subjects.
Methods: Thirty-five volunteers, including 23 women, underwent an [18F]MPPF scan and were genotyped for both the C(-1019)G 5-HT1A promoter polymorphism and the triallelic serotonin transporter gene-linked polymorphic region. We used a simplified reference tissue model to generate parametric images of BPND. Whole brain Statistical Parametric Mapping and raphe nuclei region of interest analyses were performed to look for an association of [18F]MPPF BPND with the C(-1019)G 5-HT1A promoter polymorphism.
Results: Among the 35 subjects, 5-HT1A promoter genotypes occurred with the following frequencies: three G/G, twenty-one G/C, and eleven C/C. No difference of [18F]MPPF BPND between groups was observed, except for two women who were homozygote carriers for the G allele and showed greater binding potential compared to other age-matched women over the frontal and temporal neocortex. However, the biological relevance of this result remains uncertain due to the very small number of subjects with a G/G genotype. These findings were not modified by excluding individuals carrying the S/S genotype of the serotonin transporter gene-linked polymorphic region.
Conclusions: We failed to observe an association between the C(-1019)G 5-HT1A promoter polymorphism and [18F]MPPF binding in healthy subjects. However our data suggest that the small number of women homozygote for the G allele might have greater [18F]MPPF BPND relative to other individuals. This finding should be confirmed in a larger sample.
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http://dx.doi.org/10.1186/1744-9081-6-37 | DOI Listing |
Aging (Albany NY)
August 2024
Department of Psychiatry, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
HTR1A C-1019G polymorphism (rs6295) and serotonin transporter promoter polymorphism (5-HTTLPR) have been linked with panic disorder (PD) in different ethnic backgrounds. Both these polymorphisms are in the promoter regions. However, results are inconsistent and contrasting evidence makes reliable conclusions even more challenging.
View Article and Find Full Text PDFJ Affect Disord
December 2024
Department of Psychiatry, Columbia University, New York, NY, United States of America; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, NY, United States of America. Electronic address:
Background: Early life adversity is a risk factor for psychopathology and is associated with epigenetic alterations in the 5-HT receptor gene promoter. The 5-HT receptor mediates neurotrophic effects, which could affect brain structure and function. We examined relationships between self-reported early childhood abuse, 5-HT receptor promoter DNA methylation, and gray matter volume (GMV) in Major Depressive Disorder (MDD).
View Article and Find Full Text PDFNeuropharmacology
March 2024
Mercer University, College of Pharmacy, Department of Pharmaceutical Sciences, 3001 Mercer University Drive, Atlanta, GA, 30341, USA. Electronic address:
There are no approved pharmacotherapies for fragile X syndrome (FXS), a rare neurodevelopmental disorder caused by a mutation in the FMR1 promoter region that leads to various symptoms, including intellectual disability and auditory hypersensitivity. The gene that encodes inhibitory serotonin 1A receptors (5-HTRs) is differentially expressed in embryonic brain tissue from individuals with FXS, and 5-HTRs are highly expressed in neural systems that are disordered in FXS, providing a rationale to focus on 5-HTRs as targets to treat symptoms of FXS. We examined agonist-labeled 5-HTR densities in male and female Fmr1 knockout mice and found no differences in whole-brain 5-HTR expression in adult control compared to Fmr1 knockout mice.
View Article and Find Full Text PDFBr J Psychiatry
September 2023
Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA; Molecular Imaging and Neuropathology Area, New York State Psychiatric Institute, New York, New York, USA; and Department of Radiology, Columbia University, New York, New York, USA.
Background: Childhood and lifetime adversity may reduce brain serotonergic (5-HT) neurotransmission by epigenetic mechanisms.
Aims: We tested the relationships of childhood adversity and recent stress to serotonin 1A (5-HT) receptor genotype, DNA methylation of this gene in peripheral blood monocytes and 5-HT receptor binding potential (BP) determined by positron emission tomography (PET) in 13 brain regions, in participants with major depressive disorder (MDD) and healthy volunteers (controls).
Method: Medication-free participants with MDD ( = 192: 110 female, 81 male, 1 other) and controls ( = 88: 48 female, 40 male) were interviewed about childhood adversity and recent stressors and genotyped for rs6295.
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