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Juan Carlos Soliva Cognitive Neuroscience Research Unit (URNC)

Decreased cerebebelar myo-inositol and N-acetylaspartate concentrations in pediatric attention/deficit hyperactivity disorder. Juan Carlos Soliva Cognitive Neuroscience Research Unit (URNC) Dept . of Psychiatry . Autonomous University of Barcelona (UAB). Introduction.

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Juan Carlos Soliva Cognitive Neuroscience Research Unit (URNC)

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  1. Decreased cerebebelarmyo-inositol andN-acetylaspartate concentrations in pediatric attention/deficit hyperactivity disorder Juan Carlos Soliva CognitiveNeuroscienceResearchUnit (URNC) Dept. of Psychiatry. AutonomousUniversity of Barcelona (UAB)

  2. Introduction • Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in childhood • Between 8-12 % of the pediatric population • Half of children with ADHD will display the disorder in adulthood • The diagnosis is made according to the DSM-IV-TR

  3. IntroductionDSM-IV Criteriafor ADHD • Six or more symptoms of inattention have been present for at least 6 months to a point that is disruptive and inappropriate for developmental level • Six or more symptoms of hyperactivity-impulsivity have been present for at least 6 months to an extent that is disruptive and inappropriate for developmental level • Some symptoms that cause impairment were present before age 7 years • Some impairment from the symptoms is present in two or more settings (e.g. at school/work and at home) • There must be clear evidence of significant impairment in social, school, or work functioning

  4. Introduction • Cerebello–thalamo-striatal-prefrontal circuitdysfunction could partially explain ADHD motor control/inhibition and executivefunctiondeficits • In a voxel-based morphometry (VBM) study (Carmona et al, 2005), we found decreased gray matter volume in several regions, especially in the right prefrontal cortex and left cerebellar posterior lobe • Employinga diffusion tensorimaging (DTI) technique, Ashtari et al (2005) has reportedwhite matter abnormalities in these regions

  5. Objective • To examine theabsoluteconcentration of NAA (N-acetylaspartate), Cre (creatine), Cho (choline), MI (myo-inositol) and Glx (glutamate-glutamine) in the right prefrontal region and left cerebellar posterior lobe

  6. Hypotesis • We hypothesize that the prefrontal region and the left cerebellar hemisphere in ADHD subjects should show neurometabolite abnormalities

  7. Material and Methods: studydesign and sample • Case–control proton magnetic resonance spectroscopic study comparing the cerebellar and prefrontal regions • Sample: a group of 17 ADHD medicated children and a group of 17 control children matched for laterality, gender and age.

  8. Material and Methods: MR adquisition • FSPGR-T1 3D axial sequence (TR = 13.2 ms; TE = 4.2 ms; FA= 15; NEX= 1; 256×256 matrix) with 2mm partitions • FSE-PD-T2 axial sequence (TR = 3980 ms; TE = 20/100 ms; NEX= 2; 512×512 matrix), with 5mm sections and 2mm gap • Spectral acquisition: single-voxel PRESS sequence (TR = 2000 ms; TE = 30ms; NEX= 256; bandwidth = 2500 Hz)

  9. Material and Methods: MR adquisition • Two volumes of interest of 2cm×2cm×2 cm were selected using the FSPGR-T1 3D axial sequence in the right dorsolateral prefrontal region and the left cerebellar hemisphere (posterior lobe) by a experienced neuroradiologist encompassing gray and white matter

  10. Material and Methods: MR adquisition

  11. Material and Methods: post-processing • Water signal was first modeled by a non-linear time-domain analysis procedure (AMARES) • Water resonance intensity and metabolite resonance intensity were quantified as damping-sinusoids amplitude • Water resonance intensity was suppressed using the HSVD method • Normalized values were obtained by dividing the intensity of each peak by the water signal

  12. Material and Methods: statisticalanalyses • Due to the violation of the normality assumption (Shapiro-Wilk tested), non-parametric statistical analyses were used (Mann–Whitney U for two independent samples) • Multiple comparisons Bonferroni correction was applied (p-value = 0.005)

  13. Results

  14. Results

  15. Results *F: frontal; ** cerebelar

  16. Discussion • This is the first proton MR spectroscopic study examining the cerebellum in pediatric ADHD • NAA and MI roles in the CNS are not fully understood • NAA isfound almost exclusively in neurons; hystopathologically, changes in NAA peaks are associated with neuronal density • MI is primarily found in glia and MI increases indicate gliosis

  17. Discussion • The decrease in NAA absolute concentration in our ADHD sample could be related to a gray matter decrease in the same cerebellar region found in our previous voxel-based morphometry MRI study with a differentsample (Carmona et al, 2005)

  18. Discussion • The decrease in MI absolute concentration could express a decreased glial density • Ashtari et al (2005) found a decreased fractional anisotropy (FA) in the left cerebellar hemisphere in a pediatric ADHD sample • FA and glial density decreases have beencorrelated

  19. Conclusion • The main results of our study, consistent with previously reported findings from morphometric andfunctional MRI studies, reinforce the emerging role of the cerebellum in ADHD neurobiology.

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