Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Molecular Biology

Background:

• Cortical GABA deficits are consistently observed in schizophrenia, potentially stemming from impaired postnatal neurotransmitter maturation.
• Previous research indicated alterations in GABA(A) receptor alpha subunits in schizophrenia, but their developmental context remained unclear.

Purpose of the Study:

• To quantify GABA(A) receptor alpha-subunit mRNA expression during normal human dorsolateral prefrontal cortex (DLPFC) development.
• To compare these developmental patterns with expression in schizophrenia cases and controls.

Main Methods:

• Microarray and qPCR analysis of DLPFC tissue from 60 healthy individuals (6 weeks to 49 years) and 37 schizophrenia patients/37 matched controls.
• Quantification of GABA(A) receptor alpha subunit mRNA expression.

Main Results:

• Significant developmental changes observed: alpha5 mRNA decreased by 60%, while alpha1 mRNA doubled in the first few postnatal years.
• Schizophrenia patients showed decreased GAD67 (p=0.0012) and alpha5 mRNA (p=0.038) in DLPFC.
• No significant changes in alpha1, alpha2, or other alpha subunits were found in the schizophrenia cohort.

Conclusions:

• Confirms GABA deficits (reduced GAD67) as a feature of schizophrenia.
• Reports a novel down-regulation of alpha5 subunit mRNA in schizophrenia DLPFC.
• Suggests post-synaptic inhibitory receptor alterations are important in schizophrenia, with potential cohort variability.