Chakraborti Barnali, Verma Deepak, Guhathakurta Subhrangshu, Jaiswal Preeti, Singh Asem Surindro, Sinha Swagata, Ghosh Saurabh, Mukhopadhyay Kanchan, Mohanakumar Kochupurackal P, Rajamma Usha
Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, Kolkata, India.
Division of Neuroscience, Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL, United States.
Front Neurosci. 2020 Jan 8;13:1375. doi: 10.3389/fnins.2019.01375. eCollection 2019.
Platelet hyperserotonemia in a subset of Autism Spectrum Disorder (ASD) probands, efficacy of selective serotonin reuptake inhibitors (SSRIs) in reducing behavioral deficits and gender-bias in normal serotonin (5-hydroxy tryptamine or 5-HT) synthesis suggest disruption in stringent regulation of serotonin metabolism in ASD. Therefore, we investigated the changes in 5-HT and 5-hydroxy indole acetic acid (5-HIAA) in ASD probands to assess its effect on the behavior of male and female probands. ASD cases ( = 215) were examined using childhood autism rating scale (CARS). Platelet 5-HT (104 cases and 26 controls) and platelet/plasma 5-HIAA (73 cases and 17 controls) were estimated using high performance liquid chromatography coupled with electrochemical detector (HPLC-ECD). In male probands, we observed increase in platelet 5-HT content in association with increase in the score for adaptive responses and increase in platelet 5-HIAA levels with concomitant decline in the score for intellectual response. Age did not influence the neurochemical parameters, but imitation, listening responses and nonverbal communication scores decreased with age. Conversely in female probands, plasma 5-HIAA level significantly attenuated with age, when platelet 5-HT content remained unchanged. Interestingly, platelet/plasma 5-HT and plasma 5-HIAA were higher in female controls. Female probands displayed severe autism-associated behaviors. Overall results indicate gender-bias in 5-HT and 5-HIAA regulation, which probably increases the threshold level of ASD phenotypes in the females, thereby affecting ASD prevalence in a sex-specific manner.
在一部分自闭症谱系障碍（ASD）先证者中存在血小板高血清素血症，选择性5-羟色胺再摄取抑制剂（SSRIs）在减少行为缺陷方面的疗效以及正常血清素（5-羟色胺或5-HT）合成中的性别偏差表明ASD中血清素代谢的严格调节受到破坏。因此，我们研究了ASD先证者中5-HT和5-羟吲哚乙酸（5-HIAA）的变化，以评估其对男性和女性先证者行为的影响。使用儿童自闭症评定量表（CARS）对215例ASD病例进行检查。采用高效液相色谱-电化学检测法（HPLC-ECD）测定血小板5-HT（104例病例和26例对照）以及血小板/血浆5-HIAA（73例病例和17例对照）。在男性先证者中，我们观察到血小板5-HT含量增加，同时适应性反应得分升高，血小板5-HIAA水平升高，同时智力反应得分下降。年龄并未影响神经化学参数，但模仿、听力反应和非语言交流得分随年龄下降。相反，在女性先证者中，随着年龄增长，血浆5-HIAA水平显著降低，而血小板5-HT含量保持不变。有趣的是，女性对照的血小板/血浆5-HT和血浆5-HIAA较高。女性先证者表现出严重的自闭症相关行为。总体结果表明5-HT和5-HIAA调节存在性别偏差，这可能会提高女性ASD表型的阈值水平，从而以性别特异性方式影响ASD患病率。
