Glutamatergic function in a genetic high-risk group for psychosis: A proton magnetic resonance spectroscopy study in individuals with 22q11.2 deletion

Rogdaki, Maria; Hathway, Pamela; Gudbrandsen, Maria; McCutcheon, Robert; Jauhar, Sameer; Daly, Eileen; Howes, Oliver

doi:10.1016/j.euroneuro.2019.09.005

Cited by 8 publications

(8 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Four studies 31,32,75,78 measured Glx in the thalamus in 113 2). There were insufficient studies of glutamate alone to meta-analyze.…”

Section: Glutamate Function In Genetic High-risk Subjectsmentioning

confidence: 99%

“…Five studies 31,74,[78][79][80] measured Glx in the basal ganglia in 138 GHR individuals and 145 controls (see Table 2). There were insufficient studies of glutamate alone to meta-analyze.…”

Section: Glutamate Function In Genetic High-risk Subjectsmentioning

confidence: 99%

“…A number of 1 H-MRS, PET and SPECT studies have investigated dopamine and glutamate functioning in CHR and GHR groups [25][26][27][28] , but to our knowledge no meta-analyses of the dopamine findings has been undertaken, and an earlier meta-analysis of the glutamate findings 29 is now outdated, since six new studies have been published after it was conducted [30][31][32][33][34][35] , increasing the sample size by 574 subjects. Moreover, variability has never been investigated for either dopamine or glutamate studies.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Dopamine and glutamate in individuals at high risk for psychosis: a meta‐analysis of in vivo imaging findings and their variability compared to controls

2021

Self Cite

View full text Add to dashboard Cite

Dopaminergic and glutamatergic dysfunction is believed to play a central role in the pathophysiology of schizophrenia. However, it is unclear if abnormalities predate the onset of schizophrenia in individuals at high clinical or genetic risk for the disorder. We systematically reviewed and meta-analyzed studies that have used neuroimaging to investigate dopamine and glutamate function in individuals at increased clinical or genetic risk for psychosis. EMBASE, PsycINFO and Medline were searched form January 1, 1960 to November 26, 2020. Inclusion criteria were molecular imaging measures of striatal presynaptic dopaminergic function, striatal dopamine receptor availability, or glutamate function. Separate meta-analyses were conducted for genetic high-risk and clinical high-risk individuals. We calculated standardized mean differences between high-risk individuals and controls, and investigated whether the variability of these measures differed between the two groups. Fortyeight eligible studies were identified, including 1,288 high-risk individuals and 1,187 controls. Genetic high-risk individuals showed evidence of increased thalamic glutamate + glutamine (Glx) concentrations (Hedges' g=0.36, 95% CI: 0.12-0.61, p=0.003). There were no significant differences between high-risk individuals and controls in striatal presynaptic dopaminergic function, striatal D2/D3 receptor availability, prefrontal cortex glutamate or Glx, hippocampal glutamate or Glx, or basal ganglia Glx. In the meta-analysis of variability, genetic high-risk individuals showed reduced variability of striatal D2/D3 receptor availability compared to controls (log coefficient of variation ratio, CVR=-0.24, 95% CI: -0.46 to -0.02, p=0.03). Meta-regressions of publication year against effect size demonstrated that the magnitude of differences between clinical high-risk individuals and controls in presynaptic dopaminergic function has decreased over time p=0.025). Thus, other than thalamic glutamate concentrations, no neurochemical measures were significantly different between individuals at risk for psychosis and controls. There was also no evidence of increased variability of dopamine or glutamate measures in high-risk individuals compared to controls. Significant heterogeneity, however, exists between studies, which does not allow to rule out the existence of clinically meaningful differences.

show abstract

“…Four studies 31,32,75,78 measured Glx in the thalamus in 113 2). There were insufficient studies of glutamate alone to meta-analyze.…”

Section: Glutamate Function In Genetic High-risk Subjectsmentioning

confidence: 99%

Section: Glutamate Function In Genetic High-risk Subjectsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Dopamine and glutamate in individuals at high risk for psychosis: a meta‐analysis of in vivo imaging findings and their variability compared to controls

2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Due to PRODH haploinsufficiency, glutamate neuroexcitotoxicity may occur more frequently in 22q11DS relative to healthy individuals, which might explain the reduced cortical brain volumes reported in these patients [ 19 ]. Nevertheless, recent studies did not reveal significant alterations in glutamatergic functioning, as assessed by proton magnetic resonance spectroscopy ( 1 H-MRS), in the ACC or the striatum of patients with 22q11DS compared to healthy controls [ 20 , 21 ]. However, increased hippocampal glutamate and Glx (glutamate and glutamine combined) concentrations were found in 22q11DS patients who developed schizophrenia compared to 22q11DS patients who did not [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…In summary, possible alterations in dopaminergic and glutamatergic systems in individuals with 22q11DS might explain the increased risk of developing a psychotic disorder, as well as the increased prevalence of cognitive impairments in these patients. Although previous studies have examined dopaminergic [ 9 , 10 , 32 ] and glutamatergic functioning [ 20 , 21 ] in individuals with 22q11DS, to the best of our knowledge, no study has examined whether cortical and striatal glutamatergic and dopaminergic measures are correlated in individuals with 22q11DS. Therefore, we investigated glutamate, glutamine, and Glx concentrations in the ACC and striatum in relation to frontal and striatal dopamine D 2/3 R availability in individuals with 22q11DS using 1 H-MRS and 18 F-fallypride PET, respectively.…”

Section: Introductionmentioning

confidence: 99%

The Relationships between Dopaminergic, Glutamatergic, and Cognitive Functioning in 22q11.2 Deletion Syndrome: A Cross-Sectional, Multimodal 1H-MRS and 18F-Fallypride PET Study

Hooijdonk

Tse

Roosenschoon

et al. 2022

Genes

View full text Add to dashboard Cite

Background: Individuals with 22q11.2 deletion syndrome (22q11DS) are at increased risk of developing psychosis and cognitive impairments, which may be related to dopaminergic and glutamatergic abnormalities. Therefore, in this exploratory study, we examined the association between dopaminergic and glutamatergic functioning in 22q11DS. Additionally, the associations between glutamatergic functioning and brain volumes in 22q11DS and healthy controls (HC), as well as those between dopaminergic and cognitive functioning in 22q11DS, were also examined. Methods: In this cross-sectional, multimodal imaging study, glutamate, glutamine, and their combined concentration (Glx) were assessed in the anterior cingulate cortex (ACC) and striatum in 17 22q11DS patients and 20 HC using 7T proton magnetic resonance spectroscopy. Ten 22q11DS patients also underwent 18F-fallypride positron emission tomography to measure dopamine D2/3 receptor (D2/3R) availability in the ACC and striatum. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery. Results: No significant associations were found between ACC or striatal (1) glutamate, glutamine, or Glx concentrations and (2) D2/3R availability. In HC but not in 22q11DS patients, we found a significant relationship between ACC volume and ACC glutamate, glutamine, and Glx concentration. In addition, some aspects of cognitive functioning were significantly associated with D2/3R availability in 22q11DS. However, none of the associations remained significant after Bonferroni correction. Conclusions: Although our results did not reach statistical significance, our findings suggest an association between glutamatergic functioning and brain volume in HC but not in 22q11DS. Additionally, D2/3R availability seems to be related to cognitive functioning in 22q11DS. Studies in larger samples are needed to further elucidate our findings.

show abstract

Meta-analysis and open-source database for in vivo brain Magnetic Resonance spectroscopy in health and disease

Gudmundson

Koo

Virovka

et al. 2023

Analytical Biochemistry

View full text Add to dashboard Cite

Glutamatergic function in a genetic high-risk group for psychosis: A proton magnetic resonance spectroscopy study in individuals with 22q11.2 deletion

Cited by 8 publications

References 57 publications

Dopamine and glutamate in individuals at high risk for psychosis: a meta‐analysis of in vivo imaging findings and their variability compared to controls

Dopamine and glutamate in individuals at high risk for psychosis: a meta‐analysis of in vivo imaging findings and their variability compared to controls

The Relationships between Dopaminergic, Glutamatergic, and Cognitive Functioning in 22q11.2 Deletion Syndrome: A Cross-Sectional, Multimodal 1H-MRS and 18F-Fallypride PET Study

Meta-analysis and open-source database for in vivo brain Magnetic Resonance spectroscopy in health and disease

Contact Info

Product

Resources

About