2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Serotonergic modulation of normal and abnormal brain dynamics: The genetic influence of the TPH2 G-703T genotype and DNA methylation on wavelet variance in children and adolescents with and without ADHD

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. Core symptoms of ADHD, such as impulsivity, are caused by an interaction of genetic and environmental factors. Epigenetic modifications of DNA, such as DNA methylation, are thought to mediate the interplay of these factors. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin synthesis. The TPH2 gene has frequently been investigated in relation to ADHD, e.g., showing that TPH2 G-703T (rs4570625) polymorphism influences response control and prefrontal signaling in ADHD patients. In this (epi)genetic imaging study we examined 144 children and adolescents (74 patients, 14 females) using fMRI at rest and during performing a waiting impulsivity (WI) paradigm. Both, TPH2 G-703T (rs4570625) genotype and DNA methylation in the 5’ untranslated region (5’UTR) of TPH2 were associated with wavelet variance in fronto-parietal regions and behavioral performance, taking TPH2 genotype into account. In detail, comparisons between genotypes of patients and controls revealed highest wavelet variance and longest reaction times in patients carrying the T allele [indicative for a gene-dosage effect, i.e., the WI phenotype is a direct result of the cumulative effect of ADHD and TPH2 variation]. Regressions revealed a significant effect on one specific DNA methylation site in ADHD patients but not controls, in terms of a significant prediction of wavelet variance in fronto-parietal regions as well as premature responses. By the example of the TPH2 G-703T (rs4570625) polymorphism, we provide insight into how interactive genetic and DNA methylation affect the ADHD and/or impulsive endophenotype.

          Related collections

          Most cited references60

          • Record: found
          • Abstract: found
          • Article: not found

          Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.

          An MRI time course of 512 echo-planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodology (FMRI). Time courses of low frequency (< 0.1 Hz) fluctuations in resting brain were observed to have a high degree of temporal correlation (P < 10(-3)) within these regions and also with time courses in several other regions that can be associated with motor function. It is concluded that correlation of low frequency fluctuations, which may arise from fluctuations in blood oxygenation or flow, is a manifestation of functional connectivity of the brain.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Neurophysiological investigation of the basis of the fMRI signal.

            Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trial-by-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Attention-deficit hyperactivity disorder.

              Attention-deficit hyperactivity disorder (ADHD) is a disorder of inattention, impulsivity, and hyperactivity that affects 8-12% of children worldwide. Although the rate of ADHD falls with age, at least half of children with the disorder will have impairing symptoms in adulthood. Twin, adoption, and molecular genetic studies show ADHD to be highly heritable, and other findings have recorded obstetric complications and psychosocial adversity as predisposing risk factors. Converging evidence from animal and human studies implicates the dysregulation of frontal-subcortical-cerebellar catecholaminergic circuits in the pathophysiology of ADHD, and molecular imaging studies suggest that abnormalities of the dopamine transporter lead to impaired neurotransmission. Studies during the past decade have shown the safety and effectiveness of new non-stimulant drugs and long-acting formulations of methylphenidate and amfetamine. Other investigations have also clarified the appropriate role of targeted psychosocial treatments in the context of ongoing pharmacotherapy.
                Bookmark

                Author and article information

                Contributors
                Role: MethodologyRole: Writing – original draft
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Role: Investigation
                Role: Investigation
                Role: Resources
                Role: Data curationRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 April 2023
                2023
                : 18
                : 4
                : e0282813
                Affiliations
                [1 ] Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
                [2 ] Department of Child and Adolescent Psychiatry, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
                [3 ] Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
                [4 ] Division of Molecular Psychiatry, Center of Mental Health, University of Wuerzburg, Wuerzburg, Germany
                [5 ] Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands
                UCSI: UCSI University, MALAYSIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-4927-2969
                Article
                PONE-D-22-28504
                10.1371/journal.pone.0282813
                10138254
                37104367
                296447c5-4b87-41c7-bf4f-19305bcae99e
                © 2023 Akhrif et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 October 2022
                : 22 February 2023
                Page count
                Figures: 3, Tables: 4, Pages: 20
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: 404502177
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: 404502177
                Award Recipient :
                Funded by: Horizon 2020 Research and Innovation Programme
                Award ID: 728018
                Award Recipient :
                Funded by: ERA-Net NEURON
                Award ID: FKZ01EW1902
                Award Recipient :
                (I) SN & MR: Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) 404502177, https://gepris.dfg.de/gepris/OCTOPUS?keywords_criterion=404502177&findButton=Finden&task=doSearchSimple&context=projekt (II) KLP: Horizon 2020 Research and Innovation Programme No. 728018 (Eat2beNICE), https://cordis.europa.eu/project/id/728018/reporting (III) KPL: ERA-Net NEURON under grant No. FKZ01EW1902 (DECODE!), https://www.neuron-eranet.eu/projects/DECODE/ The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Neurodevelopmental Disorders
                Adhd
                Biology and Life Sciences
                Neuroscience
                Developmental Neuroscience
                Neurodevelopmental Disorders
                Adhd
                Medicine and Health Sciences
                Neurology
                Neurodevelopmental Disorders
                Adhd
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Neuropsychiatric Disorders
                Adhd
                Biology and life sciences
                Cell biology
                Chromosome biology
                Chromatin
                Chromatin modification
                DNA methylation
                Biology and life sciences
                Genetics
                Epigenetics
                Chromatin
                Chromatin modification
                DNA methylation
                Biology and life sciences
                Genetics
                Gene expression
                Chromatin
                Chromatin modification
                DNA methylation
                Biology and life sciences
                Genetics
                DNA
                DNA modification
                DNA methylation
                Biology and life sciences
                Biochemistry
                Nucleic acids
                DNA
                DNA modification
                DNA methylation
                Biology and life sciences
                Genetics
                Epigenetics
                DNA modification
                DNA methylation
                Biology and life sciences
                Genetics
                Gene expression
                DNA modification
                DNA methylation
                Engineering and Technology
                Signal Processing
                Signal Filtering
                Biology and Life Sciences
                Neuroscience
                Brain Mapping
                Functional Magnetic Resonance Imaging
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Functional Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Functional Magnetic Resonance Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Functional Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Functional Magnetic Resonance Imaging
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Functional Magnetic Resonance Imaging
                Biology and Life Sciences
                Anatomy
                Brain
                Prefrontal Cortex
                Medicine and Health Sciences
                Anatomy
                Brain
                Prefrontal Cortex
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognition
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Reaction Time
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Reaction Time
                Biology and Life Sciences
                Psychology
                Personality
                Personality Traits
                Impulsivity
                Social Sciences
                Psychology
                Personality
                Personality Traits
                Impulsivity
                Custom metadata
                Data cannot be made publicly available because the participants are minors and therefore belong to a vulnerable group. The restriction was imposed by the ethics committee of the medical faculty Heinrich Heine University and the university Hospital Würzburg. Data access queries may be directed to the Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University Hospital Würzburg (email: kj_office@ 123456ukw.de , tel:+49 931 201-78600). All data that can be shared are available on Dryad (DOI: 10.5061/dryad.d51c5b06x).

                Uncategorized
                Uncategorized

                Comments

                Comment on this article