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      Serotonin and serotonin transporter levels in autistic children

      research-article
      , MSc, PhD, , MSc, PhD, , MBChB, FIBMS
      Saudi Medical Journal
      Saudi Medical Journal

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          Abstract

          Objectives

          To assess the possible correlation between serotonin and serotonin transporter (SERT) with the autism severity and investigate the association between these parameters in autistic children to assess their possible role for diagnosis of autism severity.

          Methods

          A comparative cross-sectional study was carried out in the Chemistry and Biochemistry Department, College of Medicine, Al-Nahrain University, Baghdad, Iraq while the samples were taken from 60 male autistic children recruited to the Department of Pediatrics at Al-Sader Hospital, Baghdad, Iraq between November 2014 amd April 2015. Levels of serotonin and serotonin transporters (SERT) were determined in 60 male autistic Iraqi patients classified into mild, moderate and severe (20 for each). These levels were compared with those of 26 healthy control children.

          Results

          Levels of serotonin and SERT were significantly increased in autistic children than that of gender and age-matched controls. Serotonin levels were 80.63± 21.83 ng/ml in mild, 100.39±23.07 ng/ml moderate, and 188.7±31.72 ng/ml severe autistic patients. Serotonin transporter levels were 10.13±4.51 ng/ml in mild, 13.15±4.71 ng/ml moderate, and 16.32±6.7 ng/ml in severe autistic patients. The increase of both serotonin and SERT levels were associated with severity of autism. Receiver operating characteristic (ROC) analysis can be used for diagnostic and prognostic purposes.

          Conclusions

          High serotonin and SERT levels may indicate that these biomarkers have a role in the autism pathogenesis and support the possibility of using serotonin and SERT to diagnose autism severity.

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          Most cited references32

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          The role of emotion regulation in autism spectrum disorder.

          Autism spectrum disorder (ASD) is associated with amplified emotional responses and poor emotional control, but little is known about the underlying mechanisms. This article provides a conceptual and methodologic framework for understanding compromised emotion regulation (ER) in ASD. After defining ER and related constructs, methods to study ER were reviewed with special consideration on how to apply these approaches to ASD. Against the backdrop of cognitive characteristics in ASD and existing ER theories, available research was examined to identify likely contributors to emotional dysregulation in ASD. Little is currently known about ER in youth with ASD. Some mechanisms that contribute to poor ER in ASD may be shared with other clinical populations (e.g., physiologic arousal, degree of negative and positive affect, alterations in the amygdala and prefrontal cortex), whereas other mechanisms may be more unique to ASD (e.g., differences in information processing/perception, cognitive factors [e.g., rigidity], less goal-directed behavior and more disorganized emotion in ASD). Although assignment of concomitant psychiatric diagnoses is warranted in some cases, poor ER may be inherent in ASD and may provide a more parsimonious conceptualization for the many associated socioemotional and behavioral problems in this population. Further study of ER in youth with ASD may identify meaningful subgroups of patients and lead to more effective individualized treatments. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
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            Neuroimaging in autism spectrum disorder: brain structure and function across the lifespan.

            Over the past decade, in-vivo MRI studies have provided many invaluable insights into the neural substrates underlying autism spectrum disorder (ASD), which is now known to be associated with neurodevelopmental variations in brain anatomy, functioning, and connectivity. These systems-level features of ASD pathology seem to develop differentially across the human lifespan so that the cortical abnormalities that occur in children with ASD differ from those noted at other stages of life. Thus, investigation of the brain in ASD poses particular methodological challenges, which must be addressed to enable the comparison of results across studies. Novel analytical approaches are also being developed to facilitate the translation of findings from the research to the clinical setting. In the future, the insights provided by human neuroimaging studies could contribute to biomarker development for ASD and other neurodevelopmental disorders, and to new approaches to diagnosis and treatment.
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              The serotonin system in autism spectrum disorder: From biomarker to animal models.

              Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker.
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                Author and article information

                Journal
                Saudi Med J
                Saudi Med J
                Saudi Medical Journal
                Saudi Medical Journal (Saudi Arabia )
                0379-5284
                May 2018
                : 39
                : 5
                : 487-494
                Affiliations
                [1] From the Department of Pharmacy (Abdulamir), Al Yarmouk University College, from the Department of Chemistry and Biochemistry (Abdul-Rasheed), College of Medicine, Al-Nahrain University; and from the Mental Health (Abdulghani), Ministry of Health, Baghdad, Iraq
                Author notes
                Address correspondence and reprint request to: Prof. Dr. Omar F. Abdul-Rasheed, Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq. E-mail: omar_rasheed39@ 123456yahoo.com ORCID ID: orcid.org/0000-0003-3016-9176
                Article
                SaudiMedJ-39-487
                10.15537/smj.2018.5.21751
                6118182
                29738009
                63656d5f-68b7-41b2-905a-cf336fd0bb39
                Copyright: © Saudi Medical Journal

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 November 2017
                : 11 April 2018
                Categories
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