Emerging findings of glutamate–glutamine imbalance in the medial prefrontal cortex in attention deficit/hyperactivity disorder: systematic review and meta-analysis of spectroscopy studies

Vidor, Marcos Vinícius; Panzenhagen, Alana Castro; Martins, Alexandre Ribeiro; Cupertino, Renata B.; Bandeira, Cibele Edom; Picon, Felipe Almeida; Silva, Bruna Santos da; Vitola, Eduardo S.; Rohde, Luís Augusto; Rovaris, Diego Luiz; Bau, Claiton Henrique Dotto; Grevet, Eugênio H.

doi:10.1007/s00406-022-01397-6

Cited by 12 publications

(7 citation statements)

References 99 publications

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“…Using magnetic resonance spectroscopy (MRS), the studies comparing IGD and ADHD have focused on altered levels of brain metabolites such as N-acetylaspartate (NAA), and combined glutamate and glutamine (Glutamate + Glutamine) in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate brain regions. The altered metabolites in patients with ADHD were comparable to those observed in patients with IGD ( 9 – 12 ). The DLPFC and anterior cingulate are well known candidate brain regions in patients with ADHD and patients with IGD ( 13 , 14 ).…”

Section: Introductionsupporting

confidence: 63%

“…Glutamine and glutamate are thought to be associated with neural pruning and neurotrophic activity, which are increased in adolescents with ADHD ( 12 ). The participants in the previous study were adolescents, including ADHD patients ( 10 ), while the participants in this study were healthy adults.…”

Section: Discussionmentioning

confidence: 99%

“…In a meta-analysis of spectroscopy for patients with ADHD, Vidor et al ( 12 ) reported that children with ADHD showed higher concentrations of Glutamate + Glutamine in the right medial frontal area, which they suggested may be associated with cortical thinning. The ratio of N-acetylaspartate/creatine (NAA/Cr) measured by proton magnetic resonance spectroscopy ( 1 H-MRS) within the DLPFC was associated with learning problems.…”

Section: Introductionmentioning

confidence: 99%

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Proton magnetic resonance spectroscopy (MRS) in individuals with internet gaming

McGlade

Han²,

Kim³

et al. 2022

Front. Psychiatry

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BackgroundVarious comorbid psychiatric diagnoses, including attention deficit hyperactivity disorder (ADHD), have been reported in individuals with internet gaming disorder (IGD). Prior research has shown alterations in brain metabolites, including N-acetylaspartate (NAA), and combined glutamate and glutamine in patients with ADHD that were similar to those observed in patients with IGD. We hypothesized that the decreased NAA levels in the IGD group would be associated with a history of ADHD.MethodsForty adults participated in this study. Participants were classified as having a high risk for IGD if they had a total score higher than 21 on the IGD Scale-short form. Proton magnetic resonance spectroscopy (1H-MRS) and high-resolution structural magnetic resonance imaging (MRI) data were acquired using a 3 Tesla Siemens Prisma scanner system.ResultsLevels of NAA within the right prefrontal cortex were lower in the IGD group than those observed in the control group. In a multiple linear regression analysis, internet addiction test scores and history of ADHD were shown to predict increased game play. In addition, history of ADHD predicted lower levels of NAA within the right prefrontal cortex.ConclusionThe preliminary results of current study suggest a mediating effect of ADHD on the severity of internet game play as well as the levels of NAA within the dorsolateral prefrontal cortex (DLPFC). The inclusion of ADHD in IGD research is important and deserving of further consideration.

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Section: Introductionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proton magnetic resonance spectroscopy (MRS) in individuals with internet gaming

McGlade

Han²,

Kim³

et al. 2022

Front. Psychiatry

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“…The results of a series of studies by Mortaza SM et al that found a signi cant correlation between mobile phone use and attention de cit were consistent [8, 28]. Attention de cit is related to the abnormal structure and function of the prefrontal cortex circuit in the brain [29,30]. Aalto et al found that when mobile phone use was close to the human head, local blood ow near the prefrontal cortex of the brain was affected, which may be due to an increase in the incidence of attention de cit symptoms caused by mobile phone use [31].…”

Section: Discussionmentioning

confidence: 75%

The causal associations between screen exposure time and attention deficit hyperactivity disorder: a two-sample Mendelian randomization

Fang,

Cai,

Kang

et al. 2024

Preprint

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Background Observational studies have showed that there was controversy over whether screen exposure could induce attention deficit hyperactivity disorder (ADHD). Therefore, a two-sample Mendelian randomization (MR) study was conducted to explore the potential genetic association between screen exposure time and ADHD. Methods This study selected genetic variations in screen exposure time as instrumental variables (IVs) that included relevant genotype data of European populations from 437,887 cases time spent watching television (TSWT), 456,972 cases length of mobile phone use (LMPU), and 360,895 cases time spent using computer (TSUC), respectively. Simultaneously 20,183 cases European ADHD populations were selected as genome-wide association study data. The inverse variance weighted (IVW) method was used as the primary approach for analysis. Results Research has shown that TSWT and LMPU have a positive and causal effect in increasing the risk of ADHD. According to the IVW analysis, the risk of ADHD with an odds ratio (OR) of 3.454631 [95% confidence interval (CI): 2.460256 - 4.850909], P = 8.17611E-13 in TSWT. The risk with OR of 2.0063796 (95%CI: 1.30737263 - 3.079121), P = 0.001440136 in LMPU. However, no causal effect of TSUC on ADHD was found in the analysis. Conclusion The MR analysis provided evidence of the causal role of TSWT and LMPU in increasing the risk of ADHD. This suggests screen exposure might be a potential environmental risk factor for the development of ADHD.

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“…Astrocytes are the main cells that recycle extracellular Glu and convert it into Gln via glutamine synthetase. We found that muscone enhanced the cycle of Glu-glutamine in astrocytes after injury (38,39). We have 3 hypotheses as to the possible mechanisms by which this occurs.…”

Section: Discussionmentioning

confidence: 87%

Protective role of muscones on astrocytes under a mechanical-chemical damage model

Li¹,

Gui²,

Yu³

et al. 2022

Ann Transl Med

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Background Traumatic spinal cord injury (SCI) is a major clinical concern and a life-changing neurological condition with substantial socioeconomic implications. The initial mechanical force applied to the spinal cord at the time of injury is known as the primary injury. After the primary injury, ischemia and hypoxia induce cell death and autolysis, which are associated with the release of a group of inflammatory factors and biologically active substances, such as superoxide dismutase (SOD), malonaldehyde (MDA), lactate dehydrogenase (LDH), and tumor necrosis factor-α (TNF-α). These processes are called the secondary injury, and may lead to an excess of extracellular glutamate (Glu), which in turn promotes the neuronal injuries. Muscone has been shown to have anti-inflammatory effects in the treatment of brain diseases and other diseases. However, to date, no study has examined the effects of muscone in the treatment of SCI. Methods Astrocytes were separated and purified by the method of short-term exposure combining with differential sticking wall. Astrocyte was identified by glial fibers acidic protein (GFAP) selecting cell immunochemical staining. A mechanical-chemical damage (MCD) model was established via the primary spinal astrocytes of rats, and treatment was administered with different concentrations of muscone. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) was detected at 6, 12, 24, 48 and 72 h. SOD, MDA, LDH, TNF-alpha and intracellular calcium was detected at 3, 6 and 12 h. Glu in supernatant was detected respectively at 3, 6 and 12 h by enzyme-linked immunosorbent assay (ELISA) method. Intracellular calcium was detected respectively at 3, 6 and 12 h by flow cytometry method. MRNA expression of excitatory amino acid transporters (EAATs) and GFAP were detected by the quantitative reverse transcription polymerase chain reaction (qRT-PCR) method and protein expression of those by western blot at 6 h. Results Muscone reduced the levels of LDH, TNF-α, and MDA after injury, and upregulated the level of SOD. Muscone also reduced the density of extracellular Glu and suppressed the intracellular calcium level. Additionally, it decreased the expression levels of EAATs and GFAPs. Conclusions Muscone has a protective effect on astrocytes in a MCD and inhibits astrocytes’ proliferation.

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Emerging findings of glutamate–glutamine imbalance in the medial prefrontal cortex in attention deficit/hyperactivity disorder: systematic review and meta-analysis of spectroscopy studies

Cited by 12 publications

References 99 publications

Proton magnetic resonance spectroscopy (MRS) in individuals with internet gaming

Proton magnetic resonance spectroscopy (MRS) in individuals with internet gaming

The causal associations between screen exposure time and attention deficit hyperactivity disorder: a two-sample Mendelian randomization

Protective role of muscones on astrocytes under a mechanical-chemical damage model

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