Prefrontal GABAA receptor α-subunit expression in normal postnatal human development and schizophrenia
Abstract
Cortical GABA deficits that are consistently reported in schizophrenia may reflect an etiology of failed normal postnatal neurotransmitter maturation. Previous studies have found prefrontal cortical GABA(A) receptor alpha subunit alterations in schizophrenia, yet their relationship to normal developmental expression profiles in the human cortex has not been determined. The aim of this study was to quantify GABA(A) receptor alpha-subunit mRNA expression patterns in human dorsolateral prefrontal cortex (DLPFC) during normal postnatal development and in schizophrenia cases compared to controls. Transcript levels of GABA(A) receptor alpha subunits were measured using microarray and qPCR analysis of 60 normal individuals aged 6weeks to 49years and in 37 patients with schizophrenia/schizoaffective disorder and 37 matched controls. We detected robust opposing changes in cortical GABA(A) receptor alpha1 and alpha5 subunits during the first few years of postnatal development, with a 60% decrease in alpha5 mRNA expression and a doubling of alpha1 mRNA expression with increasing age. In our Australian schizophrenia cohort we detected decreased GAD67 mRNA expression (p=0.0012) and decreased alpha5 mRNA expression (p=0.038) in the DLPFC with no significant change of other alpha subunits. Our findings confirm that GABA deficits (reduced GAD67) are a consistent feature of schizophrenia postmortem brain studies. Our study does not confirm alterations in cortical alpha1 or alpha2 mRNA levels in the schizophrenic DLPFC, as seen in previous studies, but instead we report a novel down-regulation of alpha5 subunit mRNA suggesting that post-synaptic alterations of inhibitory receptors are an important feature of schizophrenia but may vary between cohorts.
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In humans, mRNA for GABA receptor subunits and markers of inhibitory cell bodies change substantially across postnatal development, with some specific subunits and markers showing either positive or negative inflections around 10 years of age.
“In humans, mRNA for GABA receptor subunits (Duncan et al., 2010; Fillman et al., 2010) and markers of inhibitory cell bodies (Fung et al., 2010) change substantially across postnatal development, with some specific subunits and markers showing either positive or negative inflections around 10 years of age.”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Duncan et al., 2010
GABA receptors in frontal cortex demonstrate peripubertal changes that may influence cortical processing and plasticity.
“GABA receptors in frontal cortex also demonstrate peripubertal changes that may influence cortical processing and plasticity.”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Duncan et al., 2010
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Self-citation
- Authors
- Duncan, C. E., Webster, M. J., Rothmond, D. A., Bahn, S., Elashoff, M., & Shannon Weickert, C.
- Affiliations
- Schizophrenia Research Institute (AU)
- Stanley Medical Research Institute (US)
- University of Cambridge (GB)
- CardioDx (United States) (US)
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 44
- Issue
- 10
- Pages
- 673-681
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2033119682
- Cited by
- 169
- References
- 58
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 3 · 2022: 6 · 2021: 10 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 11 · 2016: 16 · 2015: 17 · 2014: 17 · 2013: 14 · 2012: 13
- FWCI
- 13.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Sydney
- National Health and Medical Research Council
- National Medical Research Council
- National Institute on Alcohol Abuse and Alcoholism
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, dorsolateral prefrontal cortex, postnatal brain development, GAD67, alpha5 subunit, alpha1 subunit, inhibitory neurotransmission, postmortem brain, transcript expression
- MeSH terms
- Adolescent, Adult, Analysis of Variance, Australia, Cadaver, Child, Child, Preschool, Humans, Human Development, Infant, Middle Aged, Receptors, GABA-A, Schizophrenia, Cohort Studies, Gene Expression, Polymerase Chain Reaction, Prefrontal Cortex, Age Distribution, Oligonucleotide Array Sequence Analysis, Young Adult
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