Supplementary data for a focused review and meta-analysis of 1H-MRS studies on cerebral glutamate and GABA levels in high-risk of psychosis states

Data (attached) for a focused review and meta-analysis of cerebral levels of glutamate, Glx, and GABA levels assessed with 1H-MRS in high-risk of psychosis states was collected and stored at covidence.org and extracted to The Cochrane Collaboration Review Manager software package (RevMan Version 5.3) for meta-analytical purposes. Meta-analyses were performed with a random-effects, inverse-variance weighted model to calculate the pooled effect size. Heterogeneity was measured using the I2 value. Significance was assessed using two-sided 95% confidence intervals. Potential publication bias was assessed by visual inspection of funnel plots. Supplementary to the co-submitted article are comprehensive meta-analyses of glutamate, Glx, and GABA, as well as the PRISMA flow diagram of included studies and a list of studies included in the review along with available measures and methodological variables. The attached data offers an insight into the included studies and the specified metabolite values for each study and offers possible further investigation for other researchers, as well as an insight into the review and meta-analyses performed. The supplementary material also serves to support findings and interpretations in the main article.

diagram of included studies and a list of studies included in the review along with available measures and methodological variables. The attached data offers an insight into the included studies and the specified metabolite values for each study and offers possible further investigation for other researchers, as well as an insight into the review and meta-analyses performed. The supplementary material also serves to support findings and interpretations in the main article.  Table   Subject Psychiatry and Mental Health Specific subject area Supplementary content to a focused review and meta-analysis of 1 H-MRS studies on cerebral glutamate and GABA levels in high-risk of psychosis states Type of data Value of the Data The provided data are useful for gaining insight into the data underlying the review and meta-analysis. The supplementary data are useful for supporting points made in the main article.
Researchers showing further interest in the available literature on glutamatergic and GABAergic disturbances in high-risk for psychosis states, as well as those who read the article and wish to gain further insight into the underlying analyses, will benefit from the raw data and supplementary material. Researchers wishing to perform additional analyses based on the available data, e.g., different subgroups will be able to extract and apply data to further research.

Data description
File I includes comprehensive meta-analyses for glutamate, Glx, and GABA as well as subgroup analyses according to the type of study (e.g., clinical or genetic high-risk; study performed on antipsychotic naïve participants or not). Fig. 1 depicts the PRISMA flow diagram of the included studies. Table 1 lists the studies included in the review as well as all available measures and methodological variables. Fig. 2 shows the meta-analysis and forest plot of all glutamate and Glx studies included in the review combined (including Glx measures for studies not reporting glutamate). Fig. 3 depicts the funnel plot of comparisons for studies included in the review for glutamate, Glx, and GABA, respectively, to assess signs of asymmetry reflecting possible publication bias.
File II includes raw data of glutamate, Glx, and GABA levels for all included studies as well as author information and a range of demographical and clinical data extracted from the studies.

Experimental design, materials, and methods
The associated review and meta-analysis [1]    or genetic high-risk states) compared to healthy controls as measured with 1 H-MRS (levels of cerebral glutamate (glutamate, glutamine, or Glx) and/or GABA measured by applying a voxel of interest in a cerebral region) where HR and healthy controls are being compared. High-risk states included clinical high risk as measured by clinical assessment tools (e.g., CAARMS, SIPS, or SOPS) as well as genetic high risk (having a relative with a psychotic disorder).
Embase and MEDLINE databases were searched for all relevant case/control studies without restrictions on language, year, or publication status. Studies fulfilling the search strategy were included search terms: (Ultra high risk or Genetic high risk or Clinical high risk or High risk) and (Glutamate* or GABA* or Neurotransmitter*) and (MRS or Spectroscopy or MR* or Magnetic resonance spectroscopy or 1 H-MRS). If more than one scan was done in the same population, we only included the baseline values.
Reference lists of included studies and reviews were searched manually for additional studies, and clinicaltrials.gov were searched for ongoing or unpublished studies, and the responsible researchers were contacted and asked to share potential unpublished data. We received no unpublished data.
We excluded studies with no comparison group or with the wrong comparison group (e.g., not healthy controls such as patients with schizophrenia or first-episode psychosis) as well as studies with previously published results.
The first search was performed on March 10th, 2019, and the final search was performed on April 9th, 2019, where no new eligible studies were found.