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Normal Neurochemistry in the Prefrontal and Cerebellar Brain of Adults with Attention-Deficit Hyperactivity Disorder.

Endres D, Perlov E, Maier S, Feige B, Nickel K, Goll P, Bubl E, Lange T, Glauche V, Graf E, Ebert D, Sobanski E, Philipsen A, Tebartz van Elst L - Front Behav Neurosci (2015)

Bottom Line: In the patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar spectra in the control group.We did not find any significant neurometabolic differences between the ADHD and control group in the ACC (Wilks' lambda test: p = 0.97) or in the cerebellum (p = 0.62).Thus, we were unable to replicate earlier findings in this methodologically sophisticated study.

View Article: PubMed Central - PubMed

Affiliation: Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, University Medical Center Freiburg , Freiburg , Germany.

ABSTRACT
Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. In an attempt to extend earlier neurochemical findings, we organized a magnetic resonance spectroscopy (MRS) study as part of a large, government-funded, prospective, randomized, multicenter clinical trial comparing the effectiveness of specific psychotherapy with counseling and stimulant treatment with placebo treatment (Comparison of Methylphenidate and Psychotherapy Study). We report the baseline neurochemical data for the anterior cingulate cortex (ACC) and the cerebellum in a case-control setting. For the trial, 1,480 adult patients were contacted for participation, 518 were assessed for eligibility, 433 were randomized, and 187 were potentially eligible for neuroimaging. The control group included 119 healthy volunteers. Single-voxel proton MRS was performed. In the patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar spectra in the control group. We did not find any significant neurometabolic differences between the ADHD and control group in the ACC (Wilks' lambda test: p = 0.97) or in the cerebellum (p = 0.62). Thus, we were unable to replicate earlier findings in this methodologically sophisticated study. We discuss our findings in the context of a comprehensive review of other MRS studies on ADHD and a somewhat skeptical neuropsychiatric research perspective. As in other neuropsychiatric disorders, the unclear nosological status of ADHD might be an explanation for false-negative findings.

No MeSH data available.


Related in: MedlinePlus

MRI data acquisition and spectroscopic analyses. MPRAGE, magnetization-prepared rapid-acquisition gradient echo; FOV, field of view; TR, repetition time; TE, echo time; ACC, anterior cingulate cortex; PRESS, point-resolved spectroscopy; LCModel, linear combination of model spectra; Cre, creatine; t-Cho, phosphorylcholine + glycerylphosphorylcholine; Glx, glutamate + glutamine; NAA, N-acetylaspartate; mI, myo-Inositol; ppm, parts per million; CRLBs, Cramér-Rao lower bounds; SPM8, Statistical Parametric Mapping – Version 8; GM, gray matter; WM, white matter; CSF, cerebrospinal fluid.
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Figure 1: MRI data acquisition and spectroscopic analyses. MPRAGE, magnetization-prepared rapid-acquisition gradient echo; FOV, field of view; TR, repetition time; TE, echo time; ACC, anterior cingulate cortex; PRESS, point-resolved spectroscopy; LCModel, linear combination of model spectra; Cre, creatine; t-Cho, phosphorylcholine + glycerylphosphorylcholine; Glx, glutamate + glutamine; NAA, N-acetylaspartate; mI, myo-Inositol; ppm, parts per million; CRLBs, Cramér-Rao lower bounds; SPM8, Statistical Parametric Mapping – Version 8; GM, gray matter; WM, white matter; CSF, cerebrospinal fluid.

Mentions: Magnetic resonance spectroscopy measurement and analysis were performed following a method established in previous studies (Tebartz van Elst et al., 2014a,b). All measurements were obtained at the University of Freiburg on a 3-Tesla whole-body scanner (Siemens Magnetom Trio a TIM system; Erlangen, Germany) using a 12-channel head-coil for signal reception. First, a T1-weighted 3D data set was recorded using a magnetization-prepared rapid-acquisition gradient echo (MPRAGE) sequence with the following parameters: field of view (FOV) = 256 mm × 256 mm, repetition time (TR) = 2200 ms, echo time (TE) = 4.11 ms, flip angle = 12°, and voxel size = 1 mm × 1 mm × 1 mm. For spectroscopic measurements, voxels were placed in the pregenual ACC (16 mm × 25 mm × 20 mm) and in the center of the left cerebellar hemisphere (20 mm × 20 mm × 20 mm). A point-resolved spectroscopy (PRESS) sequence with a TR of 3000 ms and a TE of 30 ms was used. For the absolute quantification of metabolites, we also acquired a non-water-suppressed reference spectrum. For spectroscopic analysis, the well-established LCModel (linear combination of model spectra) algorithm was used. The absolute quantification of metabolites (Cre, t-Cho, Glx, NAA, and mI) was estimated using an internal water signal reference (Provencher, 1993, 2001; Helms, 2008; Tebartz van Elst et al., 2014a,b). For further analyses, only spectra with Cramér-Rao lower bounds (CRLBs) for the main metabolites <20% were included (Provencher, 1993, 2001).3 To estimate the water content in the VOI, the MPRAGE was segmented into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF), using the unified-segmentation approach according to Ashburner and Friston (2005) and as implemented in Statistical Parametric Mapping, Version 8 (SPM8). For each spectroscopy voxel, the partial volumes of GM, WM, and CSF were computed from this segmentation. The metabolic concentrations of each VOI were correct for the contents of GM, WM, and CSF. Figure 1 summarizes all the details.


Normal Neurochemistry in the Prefrontal and Cerebellar Brain of Adults with Attention-Deficit Hyperactivity Disorder.

Endres D, Perlov E, Maier S, Feige B, Nickel K, Goll P, Bubl E, Lange T, Glauche V, Graf E, Ebert D, Sobanski E, Philipsen A, Tebartz van Elst L - Front Behav Neurosci (2015)

MRI data acquisition and spectroscopic analyses. MPRAGE, magnetization-prepared rapid-acquisition gradient echo; FOV, field of view; TR, repetition time; TE, echo time; ACC, anterior cingulate cortex; PRESS, point-resolved spectroscopy; LCModel, linear combination of model spectra; Cre, creatine; t-Cho, phosphorylcholine + glycerylphosphorylcholine; Glx, glutamate + glutamine; NAA, N-acetylaspartate; mI, myo-Inositol; ppm, parts per million; CRLBs, Cramér-Rao lower bounds; SPM8, Statistical Parametric Mapping – Version 8; GM, gray matter; WM, white matter; CSF, cerebrospinal fluid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585345&req=5

Figure 1: MRI data acquisition and spectroscopic analyses. MPRAGE, magnetization-prepared rapid-acquisition gradient echo; FOV, field of view; TR, repetition time; TE, echo time; ACC, anterior cingulate cortex; PRESS, point-resolved spectroscopy; LCModel, linear combination of model spectra; Cre, creatine; t-Cho, phosphorylcholine + glycerylphosphorylcholine; Glx, glutamate + glutamine; NAA, N-acetylaspartate; mI, myo-Inositol; ppm, parts per million; CRLBs, Cramér-Rao lower bounds; SPM8, Statistical Parametric Mapping – Version 8; GM, gray matter; WM, white matter; CSF, cerebrospinal fluid.
Mentions: Magnetic resonance spectroscopy measurement and analysis were performed following a method established in previous studies (Tebartz van Elst et al., 2014a,b). All measurements were obtained at the University of Freiburg on a 3-Tesla whole-body scanner (Siemens Magnetom Trio a TIM system; Erlangen, Germany) using a 12-channel head-coil for signal reception. First, a T1-weighted 3D data set was recorded using a magnetization-prepared rapid-acquisition gradient echo (MPRAGE) sequence with the following parameters: field of view (FOV) = 256 mm × 256 mm, repetition time (TR) = 2200 ms, echo time (TE) = 4.11 ms, flip angle = 12°, and voxel size = 1 mm × 1 mm × 1 mm. For spectroscopic measurements, voxels were placed in the pregenual ACC (16 mm × 25 mm × 20 mm) and in the center of the left cerebellar hemisphere (20 mm × 20 mm × 20 mm). A point-resolved spectroscopy (PRESS) sequence with a TR of 3000 ms and a TE of 30 ms was used. For the absolute quantification of metabolites, we also acquired a non-water-suppressed reference spectrum. For spectroscopic analysis, the well-established LCModel (linear combination of model spectra) algorithm was used. The absolute quantification of metabolites (Cre, t-Cho, Glx, NAA, and mI) was estimated using an internal water signal reference (Provencher, 1993, 2001; Helms, 2008; Tebartz van Elst et al., 2014a,b). For further analyses, only spectra with Cramér-Rao lower bounds (CRLBs) for the main metabolites <20% were included (Provencher, 1993, 2001).3 To estimate the water content in the VOI, the MPRAGE was segmented into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF), using the unified-segmentation approach according to Ashburner and Friston (2005) and as implemented in Statistical Parametric Mapping, Version 8 (SPM8). For each spectroscopy voxel, the partial volumes of GM, WM, and CSF were computed from this segmentation. The metabolic concentrations of each VOI were correct for the contents of GM, WM, and CSF. Figure 1 summarizes all the details.

Bottom Line: In the patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar spectra in the control group.We did not find any significant neurometabolic differences between the ADHD and control group in the ACC (Wilks' lambda test: p = 0.97) or in the cerebellum (p = 0.62).Thus, we were unable to replicate earlier findings in this methodologically sophisticated study.

View Article: PubMed Central - PubMed

Affiliation: Section for Experimental Neuropsychiatry, Department for Psychiatry and Psychotherapy, University Medical Center Freiburg , Freiburg , Germany.

ABSTRACT
Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. In an attempt to extend earlier neurochemical findings, we organized a magnetic resonance spectroscopy (MRS) study as part of a large, government-funded, prospective, randomized, multicenter clinical trial comparing the effectiveness of specific psychotherapy with counseling and stimulant treatment with placebo treatment (Comparison of Methylphenidate and Psychotherapy Study). We report the baseline neurochemical data for the anterior cingulate cortex (ACC) and the cerebellum in a case-control setting. For the trial, 1,480 adult patients were contacted for participation, 518 were assessed for eligibility, 433 were randomized, and 187 were potentially eligible for neuroimaging. The control group included 119 healthy volunteers. Single-voxel proton MRS was performed. In the patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar spectra in the control group. We did not find any significant neurometabolic differences between the ADHD and control group in the ACC (Wilks' lambda test: p = 0.97) or in the cerebellum (p = 0.62). Thus, we were unable to replicate earlier findings in this methodologically sophisticated study. We discuss our findings in the context of a comprehensive review of other MRS studies on ADHD and a somewhat skeptical neuropsychiatric research perspective. As in other neuropsychiatric disorders, the unclear nosological status of ADHD might be an explanation for false-negative findings.

No MeSH data available.


Related in: MedlinePlus