Differential serotonin transporter (5‐HTT) and 5‐HT 2 receptor density in limbic and neocortical areas of adults and children with autism spectrum disorders: implications for selective serotonin reuptake inhibitor efficacy
| العنوان: | Differential serotonin transporter (5‐HTT) and 5‐HT 2 receptor density in limbic and neocortical areas of adults and children with autism spectrum disorders: implications for selective serotonin reuptake inhibitor efficacy |
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| المؤلفون: | Gene J. Blatt, Cheryl Brandenburg |
| المصدر: | Journal of Neurochemistry |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Autism Spectrum Disorder, Biochemistry, 0302 clinical medicine, Cortex (anatomy), Medicine, Child, Serotonin transporter, Serotonin Plasma Membrane Transport Proteins, biology, Clinical Studies, Biomakers & Imaging, Brain, 3. Good health, anterior cingulate cortex, medicine.anatomical_structure, Original Article, Female, Selective Serotonin Reuptake Inhibitors, Neurotypical, Adult, medicine.medical_specialty, Adolescent, Serotonin reuptake inhibitor, autism, selective serotonin reuptake inhibitors (SSRIs), behavioral disciplines and activities, serotonin receptors (5‐HT2, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, 5‐HT1A), Internal medicine, mental disorders, Humans, Anterior cingulate cortex, 5-HT receptor, business.industry, serotonin transporter (5‐HTT), medicine.disease, 030104 developmental biology, Endocrinology, nervous system, Posterior cingulate, biology.protein, Autism, ORIGINAL ARTICLES, Receptors, Serotonin, 5-HT2, business, 030217 neurology & neurosurgery |
| الوصف: | As selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed medications in autism, we aimed to determine whether targets for SSRIs are differentially affected in three cortical areas in children and adults with autism compared to neurotypical individuals. Utilizing a large cohort of postmortem brain tissue (n = 14–19 per group), saturation ligand binding assays were conducted on sections from the anterior cingulate cortex (ACC), posterior cingulate cortex, and fusiform gyrus (FG). Specific binding to the 5‐HT transporter (5‐HTT) as well as to 5‐HT2 and 1A receptors (5‐HT₂, 5‐HT1A) was quantified in superficial and deep layers of each region using the ligands [3H]‐citalopram (5‐HTT), [3H]‐ketanserin (5‐HT2), and [3H]‐8‐OH‐DPAT (5‐HT1A). A Welch’s t‐test was utilized to compare receptor densities (B max), revealing a statistically significant decrease in 5‐HTT within the ACC of the entire autism cohort. There was also a decrease in 5‐HT2 receptor density in the ACC in the adult cohort, but not in child postmortem autism cases as compared to controls. Comparing linear regression lines of B max values plotted against age, shows a significantly lower intercept for 5‐HTT in autism (p = 0.025). 5‐HT₂ density increases with age in control cases, whereas in autism there is a decrease with age and significantly different slopes between regression lines (p = 0.032). This suggests a deficit in 5‐HTT within the ACC in individuals with autism, while decreases in 5‐HT₂ density are age‐dependent. There were no differences in receptor densities in the posterior cingulate cortex or FG in autism and no differences in ligand affinity (K D) across all regions and ligands examined. Although selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed medications in autism, several studies show variable efficacy with SSRI use. Some of this variability may be a result of differential expression of serotonin receptors across individuals. The objective of this study was to determine differences in density and/or affinity of the serotonin transporter (5‐HTT), serotonin 2 receptor (5‐HT2) and serotonin 1A receptor (5‐HT1A) between autism and neurotypical individuals through saturation binding assays within three cortical areas. Our findings support the growing evidence for caution when administering SSRIs to children, while adults may benefit from these treatments. |
| تدمد: | 1471-4159 0022-3042 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1a9b8d8b791a521f5c812b27d26c682Test https://doi.org/10.1111/jnc.14832Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a1a9b8d8b791a521f5c812b27d26c682 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14714159 00223042 |
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