GABA and Schizophrenia

Kehne, John H.; Maynard, George D.

doi:10.1002/9781118309421.ch15

Cited by 3 publications

(1 citation statement)

References 184 publications

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“…In addition, based on anatomical and physiological evidences, the involvement of brain stem could be contributed by the widely-reported GABAergic deficiency in patients with schizophrenia. 51 52 The superior olivary complex (SOC) is consisted with two types of nuclei, i.e., lateral superior olive (LSO) and medial superior olive (MSO). These nuclei, anatomically located at lower brain stem, are positioned on the right and left sides within the brain stem.…”

Section: Discussionmentioning

confidence: 99%

Listening to Sentences in Noise: Revealing Binaural Hearing Challenges in Patients with Schizophrenia

Wahab

Zakaria

Rahman

et al. 2017

Psychiatry Investig

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ObjectiveThe present, case-control, study investigates binaural hearing performance in schizophrenia patients towards sentences presented in quiet and noise.MethodsParticipants were twenty-one healthy controls and sixteen schizophrenia patients with normal peripheral auditory functions. The binaural hearing was examined in four listening conditions by using the Malay version of hearing in noise test. The syntactically and semantically correct sentences were presented via headphones to the randomly selected subjects. In each condition, the adaptively obtained reception thresholds for speech (RTS) were used to determine RTS noise composite and spatial release from masking.ResultsSchizophrenia patients demonstrated significantly higher mean RTS value relative to healthy controls (p=0.018). The large effect size found in three listening conditions, i.e., in quiet (d=1.07), noise right (d=0.88) and noise composite (d=0.90) indicates statistically significant difference between the groups. However, noise front and noise left conditions show medium (d=0.61) and small (d=0.50) effect size respectively. No statistical difference between groups was noted in regards to spatial release from masking on right (p=0.305) and left (p=0.970) ear.ConclusionThe present findings suggest an abnormal unilateral auditory processing in central auditory pathway in schizophrenia patients. Future studies to explore the role of binaural and spatial auditory processing were recommended.

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Section: Discussionmentioning

confidence: 99%

Listening to Sentences in Noise: Revealing Binaural Hearing Challenges in Patients with Schizophrenia

Wahab

Zakaria

Rahman

et al. 2017

Psychiatry Investig

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GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia

Wong

2018

Acta Pharmacol Sin

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Schizophrenia is considered primarily as a cognitive disorder. However, functional outcomes in schizophrenia are limited by the lack of effective pharmacological and psychosocial interventions for cognitive impairment. GABA (gamma-aminobutyric acid) interneurons are the main inhibitory neurons in the central nervous system (CNS), and they play a critical role in a variety of pathophysiological processes including modulation of cortical and hippocampal neural circuitry and activity, cognitive function-related neural oscillations (eg, gamma oscillations) and information integration and processing. Dysfunctional GABA interneuron activity can disrupt the excitatory/inhibitory (E/I) balance in the cortex, which could represent a core pathophysiological mechanism underlying cognitive dysfunction in schizophrenia. Recent research suggests that selective modulation of the GABAergic system is a promising intervention for the treatment of schizophrenia-associated cognitive defects. In this review, we summarized evidence from postmortem and animal studies for abnormal GABAergic neurotransmission in schizophrenia, and how altered GABA interneurons could disrupt neuronal oscillations. Next, we systemically reviewed a variety of up-to-date subtype-selective agonists, antagonists, positive and negative allosteric modulators (including dual allosteric modulators) for α5/α3/α2 GABA and GABA receptors, and summarized their pro-cognitive effects in animal behavioral tests and clinical trials. Finally, we also discuss various representative histone deacetylases (HDAC) inhibitors that target GABA system through epigenetic modulations, GABA prodrug and presynaptic GABA transporter inhibitors. This review provides important information on current potential GABA-associated therapies and future insights for development of more effective treatments.

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Photopotentiation of the GABA _A receptor with caged diazepam

Sansalone

Bratsch-Prince

Tang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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As the inhibitory γ-aminobutyric acid–ergic (GABAergic) transmission has a pivotal role in the central nervous system (CNS) and defective forms of its synapses are associated with serious neurological disorders, numerous versions of caged GABA and, more recently, photoswitchable ligands have been developed to investigate such transmission. While the complementary nature of these probes is evident, the mechanisms by which the GABA receptors can be photocontrolled have not been fully exploited. In fact, the ultimate need for specificity is critical for the proper synaptic exploration. No caged allosteric modulators of the GABAA receptor have been reported so far; to introduce such an investigational approach, we exploited the structural motifs of the benzodiazepinic scaffold to develop a photocaged version of diazepam (CD) that was tested on basolateral amygdala (BLa) pyramidal cells in mouse brain slices. CD is devoid of any intrinsic activity toward the GABAA receptor before irradiation. Importantly, CD is a photoreleasable GABAA receptor-positive allosteric modulator that offers a different probing mechanism compared to caged GABA and photoswitchable ligands. CD potentiates the inhibitory signaling by prolonging the decay time of postsynaptic GABAergic currents upon photoactivation. Additionally, no effect on presynaptic GABA release was recorded. We developed a photochemical technology to individually study the GABAA receptor, which specifically expands the toolbox available to study GABAergic synapses.

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GABA and Schizophrenia

Cited by 3 publications

References 184 publications

Listening to Sentences in Noise: Revealing Binaural Hearing Challenges in Patients with Schizophrenia

Listening to Sentences in Noise: Revealing Binaural Hearing Challenges in Patients with Schizophrenia

GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia

Photopotentiation of the GABA _A receptor with caged diazepam

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GABA and Schizophrenia

Cited by 3 publications

References 184 publications

Listening to Sentences in Noise: Revealing Binaural Hearing Challenges in Patients with Schizophrenia

Listening to Sentences in Noise: Revealing Binaural Hearing Challenges in Patients with Schizophrenia

GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia

Photopotentiation of the GABA A receptor with caged diazepam

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Product

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Photopotentiation of the GABA _A receptor with caged diazepam