Altered Expression of GABA-Related Genes in Schizophrenia: Insights from Meta-Analyses of Brain and Blood Samples and iPSC-Derived Organoids
Abstract
Background: Schizophrenia, one of the most disabling mental disorders, affects approximately seven per 1000 individuals worldwide and has an estimated heritability of around 80%; however, its pathophysiology remains incompletely understood. The disorder has been linked to dysregulation of multiple neurotransmitter systems, including dopamine, serotonin, γ-aminobutyric acid (GABA), and glutamate. GABA, the primary inhibitory neurotransmitter in the central nervous system, is synthesized by the enzymes glutamic acid decarboxylase 67 (GAD67) and glutamic acid decarboxylase 65 (GAD65), encoded by the GAD1 and GAD2 genes, respectively. The genes (SST) and parvalbumin (PVALB) encode somatostatin and parvalbumin, which are characteristic markers of specialized GABAergic interneuron subpopulations involved in maintaining excitatory-inhibitory balance and supporting cortical circuit function. While reduced GAD1 expression has been consistently reported in schizophrenia, findings regarding GAD2 expression have been inconsistent.
Methods: In this study, we examined the expression of GAD1, GAD2, SST, and PVALB across three biological levels: postmortem brain tissue, peripheral blood samples, and patient-derived induced pluripotent stem cell (iPSC)-derived brain organoids, compared with healthy controls. The meta-analysis of brain tissue included seven independent datasets (295 samples: 151 individuals with schizophrenia and 144 healthy controls) and was conducted in accordance with the…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,000 participants or records.
Read the paper
Related studies
- Preliminary Toxicity Analysis of 3DCRT versus IMRT on the High Dose Arm of the RTOG 0126 Prostate Cancer Trial
- Adaptive Radiotherapy for Head and Neck Cancer: Initial Clinical Outcomes from a Prospective Trial
- American Association of Physicists in Medicine Task Group 263: Standardizing Nomenclatures in Radiation Oncology
- Motion Management Strategies and Technical Issues Associated with Stereotactic Body Radiotherapy of Thoracic and Upper Abdominal Tumors: A Review from NRG Oncology
- High-dose-rate interstitial brachytherapy as a monotherapy for localized prostate cancer: treatment description and preliminary results of a phase I/II clinical trial
- Highly efficient training, refinement, and validation of a knowledge-based plan quality control system for radiotherapy clinical trials
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.