Focus on GABA_A receptor function

Summary

Impairment of GABA_A receptor function is increasingly recognized to play a major role in the pathophysiology of neuropsychiatric diseases including anxiety disorder (AD), major depressive disorder (MDD) and schizophrenia (SZ). Patients, method: We conducted a PUBMED search, which provided a total of 23 in vivo investigations with PET and SPECT, in which GABA_A receptor binding in patients with the primary diagnosis of AD (n = 14, 160 patients, 172 controls), MDD (n = 2, 24 patients, 28 controls) or SZ (n = 6, 77 patients, 90 controls) was compared to healthy individuals. Results: A retrospective analysis revealed that AD, MDD and SZ differed as to both site(s) and extent(s) of GABAergic impairment. Additionally, it may be stated that, while the decline of GABA_A receptor binding AD involved the whole mesolimbocortical system, in SZ it was confined to the frontal and temporal cortex. Conclusion: As GABA is known to inhibit dopamine and serotonin, GABAergic dysfunction may be associated with the disturbances of dopaminergic and serotonergic neurotransmission in neuropsychiatric disorders.

Zusammenfassung

In zunehmendem Maße wird erkannt, dass eine Fehlfunktion der GABA_A-Rezeptoren eine Bedeutung für die Pathophysiologie von neuropsychiatrischen Erkrankungen wie Angststörung, unipolarer Depression und Schizophrenie haben könnte. Patienten, Methode: Eine PUBMED-Recherche ergab insgesamt 23 In-vivo-Untersuchungen mit PET oder SPECT, in denen die GABA_A-Rezeptorbindung bei Patienten mit der primären Diagnose Angststörung (n = 14, 160 Patienten, 172 Kontrollen), unipolare Depression (n = 2, 24 Patienten, 28 Kontrollen) oder Schizophrenie (n = 6, 77 Patienten, 90 Kontrollen) mit gesunden Probanden verglichen wurde. Ergebnisse: Unsere retrospektive Analyse zeigte, dass sich Angststörung, unipolare Depression und Schizophrenie hinsichtlich des Ortes und des Ausmaßes der Beeinträchtigung unterscheiden. Außerdem betrifft die Abnahme der GABA_A-Rezeptorbindung bei der Angststörung das gesamte mesolimbokortikale System, während sie sich bei der Schizophrenie auf den frontalen und temporalen Kortex beschränkt. Schlussfolgerung: Da GABA Do- pamin und Serotonin inhibiert, steht die GABAerge Fehlfunktion wahrscheinlich in Zusammenhang mit den Störungen der dopa- minergen und serotonergen Neurotransmission bei neuropsychiatrischen Erkrankungen.

Keywords

Anxiety disorder - major depressive disorder - schizophrenia - GABA_A receptor - PET - SPECT

Schlüsselwörter

Angststörung - Depression - Schizophrenie - PET - SPECT - GABA_A-Rezeptor

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