phosphocreatine and Attention-Deficit-Disorder-with-Hyperactivity

Increasing numbers of youth are presenting for psychiatric evaluation with markedly irritable mood plus "hyperarousal" symptoms. Diagnostically homeless in current nosology, the syndrome (as well as its underlying neurobiology) is little understood. To address this problem, we conducted an exploratory proton magnetic resonance spectroscopy (MRS) study in a large sample of youth with chronic, functionally disabling irritability accompanied by hyperarousal, a clinical syndrome known as "severe mood dysregulation" (SMD), which may represent a broad phenotype of pediatric bipolar disorder. Medication-free SMD youth (N=36) and controls (N=48) underwent 1.5 Tesla MRS in four regions of interest. The following three neurometabolites, relative to creatine (Cr), were quantified with LCModel Software: (a) myo-inositol (mI), a marker of intra-cellular second messengers linked to the neurobiology of bipolar disorder; (b) glutamate/glutamine (GLX), a marker of the major excitatory neurotransmitter glutamate; and (c) N-acetyl aspartate (NAA), a marker of neuronal energetics. SMD subjects had significantly lower temporal mI/Cr versus controls. However, this difference did not survive correction for multiple comparisons. Given studies implicating mI in lithium's action in BD adults and youth, further work is necessary to determine potential therapeutic implications of our present finding and how SMD youth differ pathophysiologically from those with strictly defined BD.

Topics: Antimanic Agents; Arousal; Aspartic Acid; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Brain Mapping; Cerebral Cortex; Chronic Disease; Creatine; Diagnosis, Differential; Dominance, Cerebral; Double-Blind Method; Glutamine; Humans; Image Processing, Computer-Assisted; Inositol; Irritable Mood; Lithium Compounds; Magnetic Resonance Spectroscopy; Mood Disorders; Phosphocreatine

In this study, short echo time (1)H-magnetic resonance spectroscopy (MRS) was applied for quantification of neurometabolites using the LC Model algorithm in Taiwanese adolescents with attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectra were acquired bilaterally on the prefrontal area (part of the anterior cingulate gyrus and part of the medial frontal gyrus) in 15 adolescents with ADHD (average age of 13.88years) and 22 controls (average age of 14.85years). Absolute metabolite levels and ratios relative to creatine plus phosphocreatine (Cr+PCr) were obtained to be compared between groups. Results showed that adolescents with ADHD had significantly lower mean right prefrontal levels of Cr+PCr as compared with the controls. No significant differences between groups were noted in the remainder of the prefrontal metabolites. As for the group comparison of relative ratios, the N-acetylaspartate/Cr+PCr ratio was significantly higher in the right prefrontal regions of ADHD adolescents. This finding provides evidence of a right prefrontal neurochemical alteration in ADHD adolescents, which is consistent with current ADHD theory of prefrontal neuropathology with developmental mechanism. In addition, it highlights the importance of the method in interpretation of MRS findings in the context of ADHD.

Topics: Adolescent; Analysis of Variance; Aspartic Acid; Attention Deficit Disorder with Hyperactivity; Child; Creatine; Female; Humans; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Prefrontal Cortex; Protons; Radionuclide Imaging

The glutamatergic prefrontal-striatal pathway has been implicated previously in the neurobiology of attention-deficit/hyperactivity disorder (ADHD). We used short echo proton magnetic resonance spectroscopy (1H-MRS) to examine glutamate in the prefrontal cortex, left striatum, and, as a control area, the occipital lobe.. Thirteen treatment-naïve ADHD children and 10 healthy comparison subjects participated. All were males between the ages of 6 to 11 years of age. Twelve ADHD subjects were scanned after 8 weeks of treatment.. Striatal glutamate, glutamate/glutamine (Glx) and creatine concentrations were greater in the ADHD subjects at baseline as compared to controls. Only striatal creatine, not glutamate or Glx, was reduced after stimulant treatment in the ADHD patients. No significant differences between groups were noted in the remainder of the striatal metabolites or any of the occipital lobe or prefrontal cortex metabolites.. These findings provide initial evidence of a striatal creatine/glutamatergic dysregulation in ADHD.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Choline; Corpus Striatum; Creatine; Dose-Response Relationship, Drug; Glutamic Acid; Glutamine; Humans; Inositol; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Methylphenidate; Neural Pathways; Occipital Lobe; Phosphocreatine; Prefrontal Cortex; Reference Values

The authors' goal was to investigate phosphatidylinositol and glutamatergic metabolism in the anterior cingulate cortex of children and adolescents with attention deficit hyperactivity disorder (ADHD) alone, children with ADHD plus bipolar disorder, and children with no axis I diagnosis.. Proton spectra were acquired from a 4.8-ml voxel placed in the anterior cingulate cortex of 30 subjects who were 6 to 13 years old. Fifteen subjects had ADHD and no comorbid disorder, eight had ADHD plus bipolar disorder, and seven were healthy comparison subjects.. Children with ADHD had a significantly higher ratio of glutamate plus glutamine to myo-inositol-containing compounds than children with ADHD plus bipolar disorder and healthy children.. myo-Inositol-containing compounds may provide information on the action of antimanic treatments such as lithium, valproate, and carbamazepine. Glutamate and glutamine are measures of glutamatergic neurotransmission and thus may also reflect changes in serotonin and dopamine pathways.

Topics: Adolescent; Age Factors; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Brain Chemistry; Child; Comorbidity; Creatine; Dopamine; Glutamic Acid; Glutamine; Gyrus Cinguli; Humans; Inositol; Magnetic Resonance Spectroscopy; Phosphocreatine; Protons; Serotonin; Tissue Distribution

This study of children (ages 7 through 12) wishes to determine (a) whether variation in frontal lobe brain chemistry, determined from proton magnetic resonance spectroscopy (1H-MRS), is related to performance on a working memory task in children, and (b) whether developmental instability (DI; the imprecise expression of the genetic plan for development due to several known genetic and environmental effects) underlies phenotypic variation in brain chemistry. 1H-MRS assessed neurometabolites in a right frontal white matter voxel. The Visual Two-Back test assessed working memory. A composite measure of DI was created from measures of minor physical anomalies, fluctuating asymmetry of body characteristics, and fluctuating asymmetry of dermatoglyphic features. Greater DI strongly predicted lower concentrations of creatine-phosphocreatine (Cre) and choline-containing compounds, whereas Cre and N-acetyl-aspartate positively correlated with working memory skills. Working memory skills thus seem related to frontal lobe energy metabolism, which in turn is related to DI.

Topics: Aspartic Acid; Attention Deficit Disorder with Hyperactivity; Child; Choline; Creatine; Energy Metabolism; Female; Frontal Lobe; Humans; Magnetic Resonance Spectroscopy; Male; Mental Recall; Phenotype; Phosphocreatine; Reference Values