scholarly journals Effects of 12-Week Methylphenidate Treatment on Neurometabolism in Adult Patients with ADHD: The First Double-Blind Placebo-Controlled MR Spectroscopy Study

2020 ◽  
Vol 9 (8) ◽  
pp. 2601
Author(s):  
Simon Maier ◽  
Ludger Tebartz van Elst ◽  
Alexandra Philipsen ◽  
Thomas Lange ◽  
Bernd Feige ◽  
...  
Keyword(s):  
Adult Adhd ◽  
Neurodevelopmental Disorder ◽  
Synaptic Cleft ◽  
Anterior Cingulate ◽  
Cerebellar Hemisphere ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Double Blind ◽  
Neuronal Tissue ◽  
Metabolite Concentrations

Attention deficit hyperactivity disorder (ADHD) is a frequent neurodevelopmental disorder that often persists into adulthood. Methylphenidate (MPH) is the first-line treatment for ADHD; however, despite its wide usage, little is known about its neurometabolic effects. Until now, no randomized and blinded clinical trials have been conducted addressing the neurometabolic signals of MPH administration in adults with ADHD. In the current study, the authors investigated how MPH intake and group psychotherapy (GPT) influence brain neurometabolism over the course of three months. The authors hypothesized a decrease in the anterior cingulate cortex (ACC) glutamate concentration following MPH administration. This study was part of a double-blind multicenter trial (Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS)) investigating the effects of MPH and GPT in patients with adult ADHD. Using single-voxel magnetic resonance spectroscopy (MRS) of the pregenual ACC and the left cerebellar hemisphere (CHL), we investigated the concentration of glutamate plus glutamine (Glx), N-acetyl-aspartate, creatine, total choline containing compounds, and myo-inositol in patients before and after 12 weeks of treatment. Neither MPH nor GPT significantly influenced the Glx concentration or any of the other metabolite concentrations in the ACC and CHL after 12 weeks. Therefore, contrary to the hypothesis, no change in the prefrontal Glx signal was detected after MPH treatment. Given that MRS does not differentiate between glutamate in the synaptic cleft and in neuronal tissue, MPH-induced down-regulation of glutamatergic neurotransmission in the ACC might only affect the concentration of glutamate in the synaptic cleft, while the general availability of glutamate in the respective neuronal tissue might be unaffected by MPH intake. The observed lack of any MPH-induced normalization in metabolite concentrations is less surprising, considering that the baseline sample did not significantly differ from a healthy control group. Future studies of other regions, such as the basal ganglia, and the use of novel methods, such as whole brain MRS and multimodal imaging approaches, are necessary.

scholarly journals Neurochemical sex differences in adult ADHD patients: an MRS study

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Dominique Endres ◽  
Ludger Tebartz van Elst ◽  
Simon J. Maier ◽  
Bernd Feige ◽  
Peter Goll ◽  
...  
Keyword(s):  
Sex Differences ◽  
Adult Adhd ◽  
Neurodevelopmental Disorder ◽  
Anterior Cingulate ◽  
Cerebellar Hemisphere ◽  
Resonance Spectroscopy ◽  
Hyperactivity Disorder ◽  
Single Voxel ◽  
Left Cerebellar Hemisphere ◽  
Level Of Significance

Abstract Objective Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Relevant sex differences in symptomatology are discussed. This study compared brain neurometabolism in the anterior cingulate cortex (ACC) and left cerebellar hemisphere in age- and IQ-matched adult male (mADHD) and female (fADHD) ADHD patients. Methods We studied 48 (ACC) and 42 (cerebellum) male/female pairs of stimulant-free patients with adult ADHD. Single voxel magnetic resonance spectroscopy (MRS) was used to investigate creatine (Cre), total choline (t-Cho), glutamate + glutamine (Glx), N-acetylaspartate, and myo-inositol. The mADHD and fADHD groups were compared using robust linear regression. The level of significance was corrected for multiple tests using the Benjamini-Hochberg approach. Results For the ACC, the signals of Cre (p = 0.008) and t-Cho (p = 0.004) showed significant effects of the age covariate as well as an interaction of sex and age (Cre: p = 0.033; t-Cho: p = 0.040). For the Glx signal, an interaction of sex and age could also be observed (p = 0.033). For cerebellar neurometabolites, the signals of t-Cho (p = 0.049) and Glx (p = 0.049) showed significant effects of the factor sex. Conclusion This is the largest study yet to analyze sex differences in brain neurochemistry in adult patients with ADHD. Different age-dependent t-Cho signals in the ACC might be associated with delayed myelinization in mADHD. Further MRS studies in adult ADHD, accounting for possible sex effects, are warranted to validate the present findings.

scholarly journals Glutamatergic and GABAergic reactivity and cognition in 22q11.2 deletion syndrome and healthy volunteers: A randomized double-blind 7-Tesla pharmacological MRS study

2020 ◽  
Vol 34 (8) ◽  
pp. 856-863
Author(s):  
Claudia Vingerhoets ◽  
Desmond HY Tse ◽  
Mathilde van Oudenaren ◽  
Dennis Hernaus ◽  
Esther van Duin ◽  
...  
Keyword(s):  
Single Dose ◽  
22Q11.2 Deletion Syndrome ◽  
Anterior Cingulate ◽  
7 Tesla ◽  
Deletion Syndrome ◽  
Resonance Spectroscopy ◽  
Long Term Effects ◽  
22Q11.2 Deletion ◽  
Double Blind ◽  
Metabolite Concentrations

Aims: 22q11.2 deletion syndrome (22q11.2DS) is associated with impaired cognitive functioning. Glutamatergic pathways have been linked with cognition and are hypothesized to be disrupted in 22q11.2DS patients, possibly ‘shifting’ the excitatory (glutamate)/inhibitory (GABA) balance. Hence, the glutamate/GABA balance may constitute a target for pharmacological treatment. We aimed to examine alterations of glutamate/GABA metabolites in 22q11.2DS in vivo using riluzole, a compound with glutamate/GABA-modulating action, as pharmacological challenge. Methods: Seventeen 22q11.2DS patients and 20 matched healthy controls were enrolled in this randomized double-blind placebo-controlled crossover study. Glutamate and glutamine concentrations in the anterior cingulate cortex (ACC) and striatum, as well as ACC GABA concentrations were obtained after placebo and after a single dose of 50 mg riluzole using 7-Tesla magnetic resonance spectroscopy (MRS). Within the 22q11.2DS group, the relationship between metabolite concentrations and cognition was examined. Results: No group differences were found in ACC and striatal metabolite concentrations following placebo. Riluzole numerically decreased ACC ( η2 = 0.094) but not striatal glutamate concentrations as well as ACC GABA concentrations ( η2 = 0.176) in all subjects. In both regions, riluzole did not alter glutamine concentration. No interaction effects were found. Although not significant after Bonferroni correction, ACC glutamate concentrations were inversely correlated with cognitive functions in 22q11.2DS patients. Discussion: We did not demonstrate altered ACC and striatal metabolite concentrations in 22q11.2DS. Nevertheless, these results suggest that glutamate and GABA can be modulated with a single dose of riluzole. Possibly, riluzole may have memory-enhancing effects in 22q11.2DS. Future studies should examine the long-term effects of riluzole on cognition.

scholarly journals Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia

2019 ◽  
Vol 237 (2) ◽  
pp. 443-451 ◽  
Author(s):  
Grant McQueen ◽  
Aderlee Lay ◽  
John Lally ◽  
Anthony S. Gabay ◽  
Tracy Collier ◽  
...  
Keyword(s):  
Single Dose ◽  
Functional Connectivity ◽  
Resting State ◽  
Pharmacological Action ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Frontal Pole ◽  
Resting State Functional Connectivity ◽  
Placebo Condition ◽  
Double Blind

Abstract Rationale There is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce. Objectives The aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC). Methods In a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions. Results Compared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6). Conclusions These findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.

A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior Cingulate Cortex and the Left Cerebellum

2017 ◽  
Vol 32 (8) ◽  
pp. 731-739 ◽  
Author(s):  
Hiromichi Ito ◽  
Kenji Mori ◽  
Masafumi Harada ◽  
Sonoka Hisaoka ◽  
Yoshihiro Toda ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Magnetic Resonance ◽  
Anterior Cingulate Cortex ◽  
Proton Magnetic Resonance ◽  
Cingulate Cortex ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Anterior Cingulate ◽  
Control Group ◽  
Resonance Spectroscopy

The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, γ-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.

scholarly journals Relationship of Brain Glutamate Response to D-Cycloserine and Lurasidone to Antidepressant Response in Bipolar Depression: A Pilot Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengchao Dong ◽  
Michael F. Grunebaum ◽  
Martin J. Lan ◽  
Vashti Wagner ◽  
Tse-Hwei Choo ◽  
...  
Keyword(s):  
Rating Scale ◽  
Bipolar Depression ◽  
Anterior Cingulate ◽  
Antidepressant Effect ◽  
Resonance Spectroscopy ◽  
Open Label ◽  
Double Blind ◽  
Open Label Phase ◽  
Relationship Of ◽  
The Impact

N-methyl-D-aspartate glutamate-receptor (NMDAR) antagonists such as ketamine have demonstrated efficacy in both major depressive disorder (MDD) and bipolar disorder depression (BP-D). We have previously reported that reduction in Glx (glutamate + glutamine) in the ventromedial prefrontal cortex/anterior cingulate cortex (vmPFC/ACC), measured by proton magnetic resonance spectroscopy (1H MRS) at 3T during a ketamine infusion, mediates the relationship of ketamine dose and blood level to improvement in depression. In the present study, we assessed the impact of D-cycloserine (DCS), an oral NMDAR antagonist combined with lurasidone in BP-D on both glutamate and Glx. Subjects with DSM-V BP-D-I/II and a Montgomery-Asberg Depression Rating Scale (MADRS) score&gt;17, underwent up to three 1H MRS scans. During Scan 1, subjects were randomized to receive double-blind lurasidone 66 mg or placebo. During Scan 2, all subjects received single-blind DCS 950 mg + lurasidone 66 mg, followed by 4 weeks of open label phase of DCS+lurasidone and an optional Scan 3. Five subjects received lurasidone alone and three subjects received placebo for Scan 1. Six subjects received DCS+lurasidone during Scan 2. There was no significant baseline or between treatment-group differences in acute depression improvement or glutamate response. In Scan 2, after a dose of DCS+lurasidone, peak change in glutamate correlated negatively with improvement from baseline MADRS (r = −0.83, p = 0.04). There were no unexpected adverse events. These preliminary pilot results require replication but provide further support for a link between antidepressant effect and a decrease in glutamate by the NMDAR antagonist class of antidepressants.

scholarly journals Positive Effect of Vitamin D and Magnesium Supplementation on Mental health Status of Attention-Deficit Hyperactive Children; A Randomized Double blind Controlled Clinical Trial

2020 ◽  
Author(s):  
Mostafa Hemamy ◽  
Naseh Pahlavani ◽  
Gholamreza Askari ◽  
Mahsa Malekahmadi
Keyword(s):  
Mental Health ◽  
Vitamin D ◽  
Attention Deficit ◽  
Controlled Trial ◽  
Neurodevelopmental Disorder ◽  
Intervention Group ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Magnesium Supplementation ◽  
Double Blind

Abstract Background: Attention-Deficit / Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, characterized by varying severity in attention deficit and hyperactivity. Studies have shown deficiencies in the serum level of magnesium and vitamin D in ADHD. The aim of this study is to determine the effect of Vitamin D and magnesium supplementation on mental health in children with ADHD.Method: This double‑blind, randomized controlled trial was performed on 66 ADHD children. participants were randomly allocated to receive both Vitamin D (50,000 IU/week) and magnesium (6 mg/kg/day) supplements (n = 33) or placebos (n = 33) for 8 weeks. Strengths and difficulties questionnaire were used to evaluate children’s mental health at baseline and at the end of the study.Results: After 8 weeks of intervention, the serum levels of 25‑hydroxy‑Vitamin D3 and magnesium increased significantly in the intervention group compared with the control group. Also a significant decrease in changes of emotional problems (p=0.001), conduct problems (p=0.002), peer problems (p=0.001), prosocial score (p=0.007), total difficulties (p=0.001), externalizing score (p=0.001), and internalizing score (p=0.001) was seen in intervention group at the end of study.Conclusion: Vitamin D (50,000 IU/week) and magnesium (6 mg/kg/day) co-supplementation during 8-week could improve the behavioral function and mental health in ADHD. Although further well-designed studies with a larger sample size are needed.the IRCT registration: IRCT2016030326886N1.

scholarly journals Neurophysiological Effects of Whole Coffee Cherry Extract in Older Adults with Subjective Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Pilot Study

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 144
Author(s):  
Jennifer L. Robinson ◽  
Julio A. Yanes ◽  
Meredith A. Reid ◽  
Jerry E. Murphy ◽  
Jessica N. Busler ◽  
...  
Keyword(s):  
Decision Making ◽  
Reaction Time ◽  
Magnetic Resonance ◽  
Primary Objective ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Phytochemical Analysis ◽  
Acute Administration ◽  
Gamma Aminobutyric Acid ◽  
Double Blind

Bioactive plant-based compounds have shown promise as protective agents across multiple domains including improvements in neurological and psychological measures. Methodological challenges have limited our understanding of the neurophysiological changes associated with polyphenol-rich supplements such as whole coffee cherry extract (WCCE). In the current study, we (1) compared 100 mg of WCCE to a placebo using an acute, randomized, double-blind, within-subject, cross-over design, and we (2) conducted a phytochemical analysis of WCCE. The primary objective of the study was to determine the neurophysiological and behavioral changes that resulted from the acute administration of WCCE. We hypothesized that WCCE would increase brain-derived neurotrophic factor (BDNF) and glutamate levels while also increasing neurofunctional measures in cognitive brain regions. Furthermore, we expected there to be increased behavioral performance associated with WCCE, as measured by reaction time and accuracy. Participants underwent four neuroimaging scans (pre- and post-WCCE and placebo) to assess neurofunctional/metabolic outcomes using functional magnetic resonance imaging and magnetic resonance spectroscopy. The results suggest that polyphenol-rich WCCE is associated with decreased reaction time and may protect against cognitive errors on tasks of working memory and response inhibition. Behavioral findings were concomitant with neurofunctional changes in structures involved in decision-making and attention. Specifically, we found increased functional connectivity between the anterior cingulate and regions involved in sensory and decision-making networks. Additionally, we observed increased BDNF and an increased glutamate/gamma-aminobutyric acid (GABA) ratio following WCCE administration. These results suggest that WCCE is associated with acute neurophysiological changes supportive of faster reaction times and increased, sustained attention.

scholarly journals Proinflammatory Cytokines Predict Brain Metabolite Concentrations in the Anterior Cingulate Cortex of Patients With Bipolar Disorder

2020 ◽  
Vol 11 ◽  
Author(s):  
Sara Poletti ◽  
Mario Gennaro Mazza ◽  
Benedetta Vai ◽  
Cristina Lorenzi ◽  
Cristina Colombo ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Brain Metabolism ◽  
Anterior Cingulate ◽  
Resonance Spectroscopy ◽  
Healthy Controls ◽  
Oxygen Species ◽  
Brain Metabolite ◽  
Metabolite Concentrations ◽  
Bipolar Patients ◽  
Glia Activation

Bipolar disorder (BD) is a severe psychiatric illness characterized by abnormalities in the immune/inflammatory function and in brain metabolism. Evidences suggest that inflammation may affect the levels of brain metabolites as measured by single-proton magnetic resonance spectroscopy (1H-MRS). The aim of the study was to investigate whether a wide panel of inflammatory markers (i.e., cytokines, chemokines, and growth factors) can predict brain metabolite concentrations of glutamate, myo-inositol, N-acetylaspartate, and glutathione in a sample of 63 bipolar patients and 49 healthy controls. Three cytokines influenced brain metabolite concentrations: IL-9 positively predicts glutamate, IL-1β positively predicts Myo-inositol, and CCL5 positively predicts N-acetylaspartate concentrations. Furthermore, patients showed higher concentrations of glutamate, Myo-inositol, and glutathione and lower concentrations of N-acetylaspartate in respect to healthy controls. Our results confirm that inflammation in BD alters brain metabolism, through mechanisms possibly including the production of reactive oxygen species and glia activation.

scholarly journals Effects of fructose restriction on liver steatosis (FRUITLESS); a double-blind randomized controlled trial

2020 ◽  
Author(s):  
Nynke Simons ◽  
Pandichelvam Veeraiah ◽  
Pomme I H G Simons ◽  
Nicolaas C Schaper ◽  
M Eline Kooi ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Serum Lipids ◽  
Controlled Trial ◽  
Intervention Group ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Double Blind ◽  
Randomized Controlled

ABSTRACT Background There is an ongoing debate on whether fructose plays a role in the development of nonalcoholic fatty liver disease. Objectives The aim of this study was to investigate the effects of fructose restriction on intrahepatic lipid (IHL) content in a double-blind randomized controlled trial using an isocaloric comparator. Methods Between March 2017 and October 2019, 44 adult overweight individuals with a fatty liver index ≥ 60 consumed a 6-wk fructose-restricted diet (&lt;7.5 g/meal and &lt;10 g/d) and were randomly assigned to supplementation with sachets of glucose (= intervention group) or fructose (= control group) 3 times daily. Participants and assessors were blinded to the allocation. IHL content, assessed by proton magnetic resonance spectroscopy, was the primary outcome and glucose tolerance and serum lipids were the secondary outcomes. All measurements were conducted in Maastricht University Medical Center. Results Thirty-seven participants completed the study protocol. After 6 wk of fructose restriction, dietary fructose intake and urinary fructose excretion were significantly lower in the intervention group (difference: −57.0 g/d; 95% CI: −77.9, −39.5 g/d; and −38.8 μmol/d; 95% CI: −91.2, −10.7 μmol/d, respectively). Although IHL content decreased in both the intervention and control groups (P &lt; 0.001 and P = 0.003, respectively), the change in IHL content was more pronounced in the intervention group (difference: −0.7% point, 95% CI: −2.0, −0.03% point). The changes in glucose tolerance and serum lipids were not significantly different between groups. Conclusions Six weeks of fructose restriction per se led to a small, but statistically significant, decrease in IHL content in comparison with an isocaloric control group. This trial was registered at clinicaltrials.gov as NCT03067428.

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