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Effects of dopaminergic genes, prenatal adversities, and their interaction on attention-deficit/hyperactivity disorder and neural correlates of response inhibition.
J Psychiatry Neurosci
March 2017
From the University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands (van der Meer, Hartman, Hoekstra); the Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands (van Rooij); the Departments of Human Genetics and Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands (Franke); the Clinical Neuropsychology Section, VU University Amsterdam, Amsterdam, the Netherlands (Heslenfeld, Oosterlaan); the Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York, USA (Faraone); the K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway (Faraone); the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands (Buitelaar); and the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, Netherlands (Buitelaar).
Background: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by impaired response inhibition; both have been associated with aberrant dopamine signalling. Given that prenatal exposure to alcohol or smoking is known to affect dopamine-rich brain regions, we hypothesized that individuals carrying the ADHD risk alleles of the dopamine receptor D4 () and dopamine transporter () genes may be especially sensitive to their effects.
Methods: Functional MRI data, information on prenatal adversities and genetic data were available for 239 adolescents and young adults participating in the multicentre ADHD cohort study NeuroIMAGE (average age 17.
Dyskinesias in Parkinson's disease: views from positron emission tomography studies.
Eur J Neurol
May 2014
Department of Medicine, Hammersmith Hospital, Imperial College London, London, UK; Neurodegeneration Imaging Group, Department of Clinical Neuroscience, King's College London, London, UK.
Levodopa-induced dyskinesias (LIDs) and graft-induced dyskinesias (GIDs) are serious and common complications of Parkinson's disease (PD) management following chronic treatment with levodopa or intrastriatal transplantation with dopamine-rich foetal ventral mesencephalic tissue, respectively. Positron emission tomography (PET) molecular imaging provides a powerful in vivo tool that has been employed over the past 20 years for the elucidation of mechanisms underlying the development of LIDs and GIDs in PD patients. PET used together with radioligands tagging molecular targets has allowed the functional investigation of several systems in the brain including the dopaminergic, serotonergic, glutamatergic, opioid, endocannabinoid, noradrenergic and cholinergic systems.
View Article and Find Full Text PDFEffects of prenatal methamphetamine exposure: a review of cognitive and neuroimaging studies.
Metab Brain Dis
June 2014
University of Cape Town, Rondebosch, Western Cape, South Africa,
Prenatal methamphetamine exposure (PME) is a significant problem in several parts of the world and poses important health risks for the developing fetus. Research on the short- and long-term outcomes of PME is scarce, however. Here, we summarize present knowledge on the cognitive and behavioral outcomes of PME, based on a review of the neuroimaging, neuropsychology, and neuroscience literature published in the past 15 years.
View Article and Find Full Text PDFDeveloping dopaminergic cell therapy for Parkinson's disease--give up or move forward?
Mov Disord
March 2013
Lund Stem Cell Center, University Hospital, Lund, Sweden.
Despite 3 decades of basic and clinical studies, there is still no dopaminergic cell therapy for Parkinson's disease. Several arguments have been put forward why this approach, so far tested with transplantation of human fetal mesencephalic dopamine-rich tissue, will never be of clinical use and should be abandoned: (1) Lack of efficacy in 2 sham surgery-controlled trials; (2) occurrence of troublesome off-medication dyskinesias in a subgroup of grafted patients; (3) disease process destroys grafted neurons; and (4) non-motor symptoms will not be influenced by intrastriatal dopaminergic grafts. Here, the author argues that, based on recent scientific advancements, the development of a dopaminergic cell therapy for Parkinson's disease should continue.
View Article and Find Full Text PDFDopamine-rich grafts alleviate deficits in contralateral response space induced by extensive dopamine depletion in rats.
Exp Neurol
September 2013
The Brain Repair Group, School of Bioscience, Cardiff University, Cardiff, UK.
Unilateral infusion of 6-hydroxydopamine into the nigro-striatal pathway in the rat is the most common dopamine lesion model of Parkinson's disease. In the present study, we explore the impact of near complete unilateral loss of dopamine along the nigro-striatal pathway and subsequent cell replacement therapy in a choice reaction time task in rats, with assessment of spatial responding towards either side of the body (ipsilateral or contralateral to the lesion) on alternate days. Results indicated a stable contralateral deficit in response accuracy, reaction times and motor function for 50 consecutive days of testing, with no signs of recovery or compensation.
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