In vivo gamma-aminobutyric acid-A/benzodiazepine receptor availability and genetic liability in asymptomatic individuals with high genetic loading of schizophrenia: A [11C]flumazenil positron emission tomography study.

Abstract

OBJECTIVES:

Whilst reduced signalling and gene expression related to gamma-aminobutyric acid (GABA) play a role in the presumed pathophysiology of schizophrenia, its origin is unclear. Studying asymptomatic individuals with high genetic liability to schizophrenia (AIs) would provide insights. Therefore, this study aimed to investigate the role of genetic liability in GABAergic dysfunction of schizophrenia by exploring in vivo GABA-A/benzodiazepine receptor (GABAR) availability in AIs.

METHODS:

A total of 10 AIs with multiple relatives diagnosed as schizophrenia and 11 healthy controls underwent [11C]flumazenil positron emission tomography and neurocognitive function tests.

RESULTS:

There was no significant difference in [11C]flumazenil availability based on the groups. GABAR availability in caudate nuclei had positive correlations with genetic liability of AIs. GABAR availability in caudate nuclei and verbal memory measures of AIs revealed positive correlations. Only the correlation between right caudate and short-term verbal memory survived multiple-comparison correction (p = 0.030).

CONCLUSIONS:

This study, for the first time, reports correlations between the genetic liability of schizophrenia and GABAR availability. Correlations between [11C]flumazenil binding in caudate of individuals with high genetic liability to schizophrenia suggests that the GABAergic dysfunction may arise from shared genetic factors and also that it may be responsible for cognitive impairment of AIs.

• Authors: Junhee Lee, Youngwoo Bryan Yoon, Kang Ik Kevin Cho, Seongho Seo, Jae Sung Lee, Jae Min Jeong, Euitae Kim, Minah Kim, Tae Young Lee, Jun Soo Kwon
• Journal: Human psychopharmacology (Hum Psychopharmacol) Vol. 36 Issue 2 Pg. e2766 (03 2021) ISSN: 1099-1077 [Electronic] England
• PMID: 33184922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 John Wiley & Sons Ltd.

Chemical References

• Carbon Radioisotopes
• Carbon-11
• Receptors, GABA-A
• Flumazenil
• gamma-Aminobutyric Acid

Topics

• Brain (diagnostic imaging, metabolism)
• Carbon Radioisotopes
• Flumazenil
• Humans
• Positron-Emission Tomography
• Receptors, GABA-A (genetics)
• Schizophrenia (diagnostic imaging, genetics)
• gamma-Aminobutyric Acid