GABAergic System Dysfunction and Challenges in Schizophrenia Research

Abstract

Despite strenuous studies since the last century, the precise cause and pathology of schizophrenia are still largely unclear and arguably controversial. Although many hypotheses have been proposed to explain the etiology of schizophrenia, the definitive genes or core pathological mechanism remains absent. Among these hypotheses, however, GABAergic dysfunction stands out as a common feature consistently reported in schizophrenia, albeit a satisfactory mechanism that could be exploited for therapeutic purpose has not been developed yet. This review is focusing on the progress made to date in the field in terms of understanding the mechanisms involving dysfunctional GABAergic system and loops identified in schizophrenia research.

FN1, Collagen, MMP-2, and Lumican Associated with ECM Organization with Multiple Signaling Pathways Dysfunction in Schizophrenia Pathogenesis by Network Biology Approaches

“…Though complicated biological mechanisms but linked, hypotheses for SZ pathology include GABAergic system and EMC remodeling hypotheses are being proposed here. Abnormalities in the ECM would affect GABAergic synaptic transmission, which is essential in the pathophysiology of neuropsychiatric disorders, including SZ 90 . It has been reported that the enhanced and persistent GABA activity that balances the reduced density of parvalbumin neurons might be connected to changes in the ECM mediated by gene-environment interactions 91,92 .…”

“Too Soon on Earth”: A Biophilosophical Model of Schizophrenia. Some Implications for Humanoid Robots

“…For example, GABA (gamma amino butyric acid)-ergic receptors on astrocytes perform this inhibitory, or boundary-setting and rejecting function in glial-neuronal interactions. If non-splicing of GABA receptor mRNA changes the structure of GABA receptors, they cannot be occupied by GABAtransmitters appropriately and the inhibitory or rejection function of GABA is disturbed or lost [24]. Depending on the brain areas affected by mutations in the splicing controlling genes, a "borderless" generalization of functional units (neuronal groups) [25] results in the inability to reject information on the behavioral level.…”

Real‐world effectiveness of mood stabilizer use in schizophrenia

“…In addition, lithium has anti‐suicidal and anti‐aggressive effects and it may be targeted for persons with these symptoms 10 . Alternatively, GABA‐ergic drugs such as valproate and lamotrigine have a potential role in the treatment of schizophrenia, since they may alleviate the GABA deficit and dysfunctional glutamatergic transmission shown to be a part of the pathogenesis of schizophrenia as well as down‐regulate dopamine 11–13 . Mesolimbic dopamine hyperactivity is considered to be one of the possible mechanisms for the development of positive symptoms in schizophrenia 9 …”

“…10 Alternatively, GABA-ergic drugs such as valproate and lamotrigine have a potential role in the treatment of schizophrenia, since they may alleviate the GABA deficit and dysfunctional glutamatergic transmission shown to be a part of the pathogenesis of schizophrenia as well as down-regulate dopamine. [11][12][13] Mesolimbic dopamine hyperactivity is considered to be one of the possible mechanisms for the development of positive symptoms in schizophrenia. 9 Mood stabilizers are rarely recommended for patients with schizophrenia in clinical care guidelines, mainly due to a lack of high quality evidence for their efficacy.…”