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Long-interval intracortical inhibition (LICI) is a paired-pulse transcranial magnetic stimulation (TMS) paradigm mediated in part by gamma-aminobutyric acid receptor B (GABAB) inhibition. Prior work has examined LICI as a putative biomarker in an array of neuropsychiatric disorders. This review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) sought to examine existing literature focused on LICI as a biomarker in neuropsychiatric disorders. There were 113 articles that met the inclusion criteria. Existing literature suggests that LICI may have utility as a biomarker of GABAB functioning but more research with increased methodologic rigor is needed. The extant LICI literature has heterogenous methodology and inconsistencies in findings. Existing findings to date are also non-specific to disease. Future research should carefully consider existing methodological weaknesses and implement high-quality test-retest reliability studies.

Electronical Supplementary DocumentMethods: Genomic DNA was isolated from peripheral blood leukocytes by standard procedures.Whole exome target enrichment was performed with 0.5 µg of genomic DNA from patient 2 and with the Agilent SureSelectHuman All Exon 60 Mb Capture kit (Agilent Technologies, Santa Clara, CA), and 2 x 150 bp paired-end sequences were produced using an Illumina Hi-Seq4000 platform. Variants were identified in genes known to cause forms of congenital diarrheas using the SeattleSeq Annotation server (http://snp.gs.washington.edu/SeattleSeqAnnotation138/), and were filtered for autosomal recessive mode of inheritance, predicted effect on protein expression, and allele frequency of <0.005 in the Exome Aggregation Consortium (http://exac.broadinstitute.org/) database. The identified missense variant was evaluated in silico to estimate pathogenicity by PolyPhen-2 (http://genetics.bwh.harvard.edu/pph2), CADD (http://cadd.gs.washington.edu/score), and MutationTaster (http://www.mutationtaster.org/). A copy-number detection in targeted NGS data was performed using panelcn.MOPS (https://ml.jku.at/software/panelcnmops/). Sanger sequencing was used to determine the segregation of the EPCAM variant detected by exome sequencing. EPCAM variant designations are based on the NCBI reference sequence NM_002354.2.

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