Striatal Creatine and Glutamate/Glutamine in Attention-Deficit/Hyperactivity Disorder

Carrey, Normand; MacMaster, Frank P.; Gaudet, Laura; Schmidt, Matthias

doi:10.1089/cap.2006.0008

Cited by 92 publications

(79 citation statements)

References 27 publications

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“…Furthermore, there is a growing interest in the role of Glu, whether it is through DA/Glu interactions or dysregulation of Glu neurotransmission, as a potential contributor to ADHD symptomatology (Carrey et al, , 2007MacMaster et al, 2003;Russell et al, 2005). Additionally, Carrey et al (2007) found evidence of increased levels of Glu in the Str of ADHD patients by c13 magnetic resonance imaging (MRI), which complemented the proton magnetic resonance spectroscopy studies done in . There is also evidence of striatal dysfunction in ADHD patients shown by emission topography and functional MRI studies (Lou et al, 1989;Teicher et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Decreased Dopamine D4 Receptor Expression Increases Extracellular Glutamate and Alters Its Regulation in Mouse Striatum

Thomas

Grandy

Gerhardt

et al. 2008

Neuropsychopharmacol

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To better understand the effect of the dopamine D4 receptor (DRD4) on glutamate (Glu) neurotransmission in the brain, we utilized transgenic mice with partial or complete removal of functional DRD4 plasma membrane expression (DRD4 + /À and DRD4À/À, respectively). We measured resting extracellular Glu levels, Glu clearance kinetics, and KCl-evoked release of Glu in the striatum and nucleus accumbens core of these mice using in vivo amperometry coupled to a novel microelectrode array configured for sub-second detection of Glu. Recordings from DRD4À/À and DRD4 + /À mice were compared with their wild-type littermates (DRD4 + / + ). Resting extracellular levels of Glu were increased in the striatum of DRD4À/À mice (po0.01). Glu clearance kinetics were significantly decreased in the dorsal striatum of DRD4À/À mice (po0.05). KCl-evoked overflow of Glu was reliably measured but unchanged in the striatum of the three groups. By contrast, no changes in resting Glu, Glu uptake kinetics, or KCl-evoked release of Glu were observed in the nucleus accumbens core among the three genotypes. These data indicate that the DRD4 receptor is involved in modulation of Glu neurotransmission, primarily in the striatum. A better understanding of Glu control by the DRD4 may improve our understanding of the physiological role of the DRD4 in disorders such as attention-deficit/hyperactivity disorder and schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Decreased Dopamine D4 Receptor Expression Increases Extracellular Glutamate and Alters Its Regulation in Mouse Striatum

Thomas

Grandy

Gerhardt

et al. 2008

Neuropsychopharmacol

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“…31,32,38,45,46,48 Glutamate is the principal excitatory neurotransmitter in the brain, and it plays a central role in neurotransmission, especially within the ACC where high glutamate levels have been associated with impulsivity. 57 to which ADHD could be considered an energy-deficit syndrome, altered energy metabolism of monoamines can cause the excess in glutamate, which is then not correctly absorbed into astrocytes.…”

Section: Discussionmentioning

confidence: 99%

MR Imaging-Detectable Metabolic Alterations in Attention Deficit/Hyperactivity Disorder: From Preclinical to Clinical Studies

Altabella

Zoratto

Adriani

et al. 2014

American Journal of Neuroradiology

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MR spectroscopy represents one of the most suitable in vivo tool to assess neurochemical dysfunction in several brain disorders, including attention deficit/hyperactivity disorder. This is the most common neuropsychiatric disorder in childhood and adolescence, which persists into adulthood (in approximately 30%-50% of cases). In past years, many studies have applied different MR spectroscopy techniques to investigate the pathogenesis and effect of conventional treatments. In this article, we review the most recent clinical and preclinical MR spectroscopy results on subjects with attention deficit/hyperactivity disorder and animal models, from childhood to adulthood. We found that the most investigated brain regions were the (pre)frontal lobes and striatum, both involved in the frontostriatal circuits and networks that are known to be impaired in this pathology. Neurometabolite alterations were detected in several regions: the NAA, choline, and glutamatergic compounds. The creatine pool was also altered when an absolute quantitative protocol was adopted. In particular, glutamate was increased in children with attention deficit/hyperactivity disorder, and this can apparently be reversed by methylphenidate treatment. The main difficulties in reviewing MR spectroscopy studies were in the nonhomogeneity of the analyzed subjects, the variety of the investigated brain regions, and also the use of different MR spectroscopy techniques. As for possible improvements in future studies, we recommend the use of standardized protocols and the analysis of other brain regions of particular interest for attention deficit hyperactivity disorder, like the hippocampus, limbic structures, thalamus, and cerebellum.ABBREVIATIONS: ACC ϭ anterior cingulate cortex; ADHD ϭ attention deficit/hyperactivity disorder; Cho ϭ total choline (phosphorylcholine ϩ glycerolphosphorylcholine); GABA ϭ ␥-aminobutyric acid; PFC ϭ prefrontal cortex; PRESS ϭ point-resolved spectroscopy sequence; tCr ϭ total creatine (creatine ϩ phosphorylcreatine) A ttention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disease in children and adolescents. Marked differences in the ADHD prevalence are thought to exist among countries. In fact, the estimated prevalence is 4%-7% in the United States and 1%-3% in Europe.1 ADHD, which is 2-4 times more frequent in males than in females, is characterized by traits of inattention, impulsivity, and motor hyperactivity. These can significantly impact many aspects of behavior in children and adolescents and can affect their performance, both at school and at home. The symptoms of ADHD have a negative impact on the individual throughout childhood, adolescence, and well into adult life, especially if not managed optimally. In approximately 80% of children with ADHD, symptoms persist into adolescence and may persist into adulthood in approximately 30%-50% of cases. ADHD adolescents and adults retain from infancy the traits of inattention and impulsivity. Moreover, they start to show a propensity for ...

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“…Participants were recruited by word of mouth and through advertisements posted at local physicians' offices, hospitals, and university campuses to participate in a proton magnetic resonance spectroscopy ( 1 H-MRS) study on pediatric ADHD at the IWK Health Sciences Centre in Halifax, Canada (Carrey et al, 2007). Children of both sexes aged 5e12 years were recruited, with no known serious physical, intellectual or mental health problems (except ADHD, as applicable), and with normal range estimated IQ as assessed with the Vocabulary normed score of the Wechsler Intelligence Scale for Children (Wechsler, 1991).…”

Section: Participantsmentioning

confidence: 99%

Smaller volumes of caudate nuclei in prepubertal children with ADHD: Impact of age

Carrey¹,

Bernier²,

Emms³

et al. 2012

Journal of Psychiatric Research

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Striatal Creatine and Glutamate/Glutamine in Attention-Deficit/Hyperactivity Disorder

Abstract: These findings provide initial evidence of a striatal creatine/glutamatergic dysregulation in ADHD.

Cited by 92 publications

References 27 publications

Decreased Dopamine D4 Receptor Expression Increases Extracellular Glutamate and Alters Its Regulation in Mouse Striatum

Decreased Dopamine D4 Receptor Expression Increases Extracellular Glutamate and Alters Its Regulation in Mouse Striatum

MR Imaging-Detectable Metabolic Alterations in Attention Deficit/Hyperactivity Disorder: From Preclinical to Clinical Studies

Smaller volumes of caudate nuclei in prepubertal children with ADHD: Impact of age

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