scholarly journals Selective 5HT3 antagonists and sensory processing: a systematic review

2022 ◽  
Author(s):  
Eirini Tsitsipa ◽  
Jonathan Rogers ◽  
Sebastian Casalotti ◽  
Clara Belessiotis-Richards ◽  
Olga Zubko ◽  
...  
Keyword(s):  
Sensory Processing ◽  
Partial Agonist ◽  
Sensory Gating ◽  
Adjunctive Treatment ◽  
Future Studies ◽  
Novel Treatment ◽  
5Ht3 Antagonists ◽  
Potential Improvement ◽  
P50 Suppression ◽  
Healthy Participants

AbstractOndansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson’s disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.

The Influence of Background Auditory Noise on P50 and N100 Suppression Elicited by the Paired-Click Paradigm

2020 ◽  
Vol 34 (3) ◽  
pp. 171-178
Author(s):  
Samantha Major ◽  
Kimberly Carpenter ◽  
Logan Beyer ◽  
Hannah Kwak ◽  
Geraldine Dawson ◽  
...  
Keyword(s):  
Sensory Gating ◽  
Autism Spectrum ◽  
Inhibitory Response ◽  
Future Research ◽  
Typically Developing ◽  
Optimal Outcomes ◽  
Hyperactivity Disorder ◽  
Auditory Sensory Gating ◽  
Auditory Noise ◽  
P50 Suppression

Abstract. Auditory sensory gating is commonly assessed using the Paired-Click Paradigm (PCP), an electroencephalography (EEG) task in which two identical sounds are presented sequentially and the brain’s inhibitory response to the second sound is measured. Many clinical populations demonstrate reduced P50 and/or N100 suppression. Testing sensory gating in children may help to identify individuals at risk for neurodevelopmental disorders earlier, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which could lead to more optimal outcomes. Minimal research has been done with children because of the difficulty of performing lengthy EEG experiments with young children, requiring them to sit still for long periods of time. We designed a modified, potentially child-friendly version of the PCP and evaluated it in typically developing adults. The PCP was administered twice, once in a traditional silent room (silent movie condition) and once with an audible movie playing (audible movie condition) to minimize boredom and enhance behavioral compliance. We tested whether P50 and N100 suppression were influenced by the presence of the auditory background noise from the movie. N100 suppression was observed in both hemispheres in the silent movie condition and in the left hemisphere only during the audible movie condition, though suppression was attenuated in the audible movie condition. P50 suppression was not observed in either condition. N100 sensory gating was successfully elicited with an audible movie playing during the PCP, supporting the use of the modified task for future research in both children and adults.

Similarities and Differences between Performers and Observers in Processing Auditory Action Consequences: Evidence from Simultaneous EEG Acquisition

2020 ◽  
pp. 1-12
Author(s):  
Marta Ghio ◽  
Sophie Egan ◽  
Christian Bellebaum
Keyword(s):  
Social Environment ◽  
Sensory Processing ◽  
Action Observation ◽  
Methodological Approach ◽  
External Source ◽  
Similarities And Differences ◽  
The One ◽  
Physically Identical ◽  
Healthy Participants ◽  
Predictive Mechanisms

In our social environment, we easily distinguish stimuli caused by our own actions (e.g., water splashing when I fill my glass) from stimuli that have an external source (e.g., water splashing in a fountain). Accumulating evidence suggests that processing the auditory consequences of self-performed actions elicits N1 and P2 ERPs of reduced amplitude compared to physically identical but externally generated sounds, with such reductions being ascribed to neural predictive mechanisms. It is unexplored, however, whether the sensory processing of action outcomes is similarly modulated by action observation (e.g., water splashing when I observe you filling my glass). We tested 40 healthy participants by applying a methodological approach for the simultaneous EEG recording of two persons: An observer observed button presses executed by a performer in real time. For the performers, we replicated previous findings of a reduced N1 amplitude for self- versus externally generated sounds. This pattern differed significantly from the one in observers, whose N1 for sounds generated by observed button presses was not attenuated. In turn, the P2 amplitude was reduced for processing action- versus externally generated sounds for both performers and observers. These findings show that both action performance and observation affect the processing of action-generated sounds. There are, however, important differences between the two in the timing of the effects, probably related to differences in the predictability of the actions and thus also the associated stimuli. We discuss how these differences might contribute to recognizing the stimulus as caused by self versus others.

The effects of sertindole on sensory gating, sensorimotor gating, and cognition in healthy volunteers

2011 ◽  
Vol 25 (12) ◽  
pp. 1600-1613 ◽  
Author(s):  
Dominique H Holstein ◽  
Philipp A Csomor ◽  
Mark A Geyer ◽  
Theo Huber ◽  
Nicole Brugger ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Healthy Subjects ◽  
Spatial Working Memory ◽  
Memory Task ◽  
Sensorimotor Gating ◽  
Sensory Gating ◽  
Schizophrenia Spectrum Disorders ◽  
High Baseline ◽  
Schizophrenia Spectrum ◽  
P50 Suppression

Sensory gating, indexed by P50 suppression, and sensorimotor gating, indexed by prepulse inhibition (PPI), are impaired in schizophrenia spectrum disorders. There is considerable evidence that schizophrenia patients treated with atypical antipsychotics exhibit relatively less gating deficits than do other patients with schizophrenia. Some recent studies have investigated the effects of antipsychotic medications on gating in healthy volunteers exhibiting low levels of gating, rather than in patients. Therefore, the current study investigated the influence of sertindole versus placebo in two separate experimental sessions, on PPI, P50 suppression, and cognition in 30 male volunteers stratified for low and high baseline gating levels. Sertindole increased PPI and P50 suppression in healthy subjects exhibiting low baseline PPI and low baseline P50 suppression, respectively, while sertindole attenuated gating in subjects exhibiting high baseline gating. Furthermore, subjects exhibiting low PPI chose worse strategies in a spatial working memory task. These findings suggest that mixed D2/5-HT2 receptor antagonists enhance both PPI and P50 suppression in a way that enhances it in healthy subjects exhibiting low baseline gating. Furthermore, the results militate in favor of the concomitant assessment of PPI, P50 suppression and cognitive measures while investigating the effect of antipsychotic medication in healthy subjects.

scholarly journals Brexpiprazole: A review of a new treatment option for schizophrenia and major depressive disorder

2017 ◽  
Vol 7 (5) ◽  
pp. 207-212 ◽  
Author(s):  
Lauren A. Diefenderfer ◽  
Courtney Iuppa
Keyword(s):  
Clinical Trials ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Partial Agonist ◽  
Adjunctive Treatment ◽  
Inadequate Response ◽  
Major Depressive ◽  
Two Phase ◽  
New Treatment

Abstract Brexpiprazole is an atypical antipsychotic that works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. It has US Food and Drug Administration approval for monotherapy treatment of schizophrenia and adjunctive treatment to antidepressants for major depressive disorder. Two phase-3 clinical trials demonstrated efficacy and relatively fair tolerability with regard to adverse effects for each indication. Akathisia was frequently reported in the major depressive disorder trials but less so in the schizophrenia trials. Significant increases in body weight and triglycerides were seen across all studies. Brexpiprazole appears to be a viable option for treating an acute exacerbation of schizophrenia requiring hospitalization or adjunctive treatment of major depressive disorder in patients who showed an inadequate response to 1 to 3 antidepressants. Further clinical trials are warranted to determine the long-term efficacy of brexpiprazole, and comparison trials would be beneficial to establish its place in therapy.

Brexpiprazole in the treatment of schizophrenia and agitation in Alzheimer’s disease

2020 ◽  
Vol 10 (4) ◽  
pp. 205-217 ◽  
Author(s):  
Lauren Stummer ◽  
Marija Markovic ◽  
Megan Maroney
Keyword(s):  
Daily Living ◽  
Partial Agonist ◽  
Treatment Options ◽  
Unmet Need ◽  
Adjunctive Treatment ◽  
Metabolic Disturbances ◽  
Major Depressive ◽  
The Us ◽  
Us Fda ◽  
The Eu

Schizophrenia is a disabling psychiatric disorder marked by progressive loss of functionality in activities of daily living with each relapse. Antipsychotics, the mainstay of therapy for schizophrenia, treat hallucinations and delusions but may have intolerable side effects, including metabolic disturbances and extrapyramidal symptoms. Brexpiprazole, a second-generation antipsychotic with dopamine partial agonist properties, was approved by the US FDA in 2015 for the treatment of schizophrenia and adjunctive treatment of major depressive disorder and by the EU in 2018 for adults with schizophrenia. Additionally, brexpiprazole has recently been studied for the treatment of agitation in Alzheimer’s dementia, an area of largely unmet need. Overall, well-tolerated brexpiprazole expands the armamentarium of treatment options available for these conditions.

On the correlation between perceptual inundation caused by realistic immersive environmental auditory scenes and the sensory gating inventory in schizophrenia

2015 ◽  
Vol 30 (5) ◽  
pp. 606-614 ◽  
Author(s):  
A. El-Kaim ◽  
M. Aramaki ◽  
S. Ystad ◽  
R. Kronland-Martinet ◽  
M. Cermolacce ◽  
...  
Keyword(s):  
Population Group ◽  
Sensory Gating ◽  
Future Research ◽  
Control Group ◽  
Entire Group ◽  
Listening Tests ◽  
Schizophrenic Patients ◽  
On Line ◽  
Auditory Scenes ◽  
P50 Suppression

AbstractBackgroundIn schizophrenia, perceptual inundation related to sensory gating deficit can be evaluated “off-line” with the sensory gating inventory (SGI) and “on-line” during listening tests. However, no study investigated the relation between “off-line evaluation” and “on-line evaluation”. The present study investigates this relationship.MethodsA sound corpus of 36 realistic environmental auditory scenes was obtained from a 3D immersive synthesizer. Twenty schizophrenic patients and twenty healthy subjects completed the SGI and evaluated the feeling of “inundation” from 1 (“null”) to 5 (“maximum”) for each auditory scene. Sensory gating deficit was evaluated in half of each population group with P50 suppression electrophysiological measure.ResultsEvaluation of inundation during sound listening was significantly higher in schizophrenia (3.25) compared to the control group (2.40, P < .001). The evaluation of inundation during the listening test correlated significantly with the perceptual modulation (n = 20, rho = .52, P = .029) and the over-inclusion dimensions (n = 20, rho = .59, P = .01) of the SGI in schizophrenic patients and with the P50 suppression for the entire group of controls and patients who performed ERP recordings (n = 20, rho = −.49, P = .027).ConclusionAn evaluation of the external validity of the SGI was obtained through listening tests. The ability to control acoustic parameters of each of the realistic immersive environmental auditory scenes might in future research make it possible to identify acoustic triggers related to perceptual inundation in schizophrenia.

scholarly journals Anhedonia to Gentle Touch in Fibromyalgia: Normal Sensory Processing but Abnormal Evaluation

2020 ◽  
Vol 10 (5) ◽  
pp. 306 ◽  
Author(s):  
Rebecca Boehme ◽  
Helene van Ettinger-Veenstra ◽  
Håkan Olausson ◽  
Björn Gerdle ◽  
Saad S. Nagi
Keyword(s):  
Sensory Processing ◽  
Early Stage ◽  
Pain Catastrophizing ◽  
Brain Activity ◽  
Functional Brain Imaging ◽  
Opposite Pattern ◽  
Tactile Stimuli ◽  
Morphometry Analysis ◽  
The Right ◽  
Healthy Participants

Social touch is important for interpersonal interaction. Gentle touch and slow brushing are typically perceived as pleasant, the degree of pleasantness is linked to the activity of the C-tactile (CT) fibers, a class of unmyelinated nerves in the skin. The inability to experience pleasure in general is called anhedonia, a common phenomenon in the chronic pain condition fibromyalgia. Here, we studied the perception and cortical processing of gentle touch in a well-characterized cohort of fibromyalgia. Patients and controls participated in functional brain imaging while receiving tactile stimuli (brushing) on the forearm. They were asked to provide ratings of pleasantness of the tactile stimulus and ongoing pain. We found high distress, pain catastrophizing, and insomnia, and a low perceived state of health in fibromyalgia. Further, patients rated both slow (CT-optimal) and fast (CT-suboptimal) brushing as less pleasant than healthy participants. While there was no difference in brain activity during touch, patients showed deactivation in the right posterior insula (contralateral to the stimulated arm) during pleasantness rating and activation during pain rating. The opposite pattern was observed in healthy participants. Voxel-based morphometry analysis revealed reduced grey matter density in patients, in the bilateral hippocampus and anterior insula. Our results suggest anhedonia to gentle touch in fibromyalgia with intact early-stage sensory processing but dysfunctional evaluative processing. These findings contribute to our understanding of the mechanisms underlying anhedonia in fibromyalgia.

scholarly journals Opportunities for Overcoming Mycobacterium tuberculosis Drug Resistance: Emerging Mycobacterial Targets and Host-Directed Therapy

2019 ◽  
Vol 20 (12) ◽  
pp. 2868 ◽  
Author(s):  
Eveline Torfs ◽  
Tatiana Piller ◽  
Paul Cos ◽  
Davie Cappoen
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Antibiotic Susceptibility ◽  
Treatment Options ◽  
The Other ◽  
Adjunctive Treatment ◽  
Lung Pathology ◽  
Drug Resistant ◽  
Novel Treatment ◽  
Novel Targets

The ever-increasing incidence of drug-resistant Mycobacterium tuberculosis infections has invigorated the focus on the discovery and development of novel treatment options. The discovery and investigation of essential mycobacterial targets is of utmost importance. In addition to the discovery of novel targets, focusing on non-lethal pathways and the use of host-directed therapies has gained interest. These adjunctive treatment options could not only lead to increased antibiotic susceptibility of Mycobacterium tuberculosis, but also have the potential to avoid the emergence of drug resistance. Host-directed therapies, on the other hand, can also reduce the associated lung pathology and improve disease outcome. This review will provide an outline of recent opportunities.

A novel approach to evaluate the pharmacodynamics of a selective dopamine D1/D5 receptor partial agonist (PF-06412562) in patients with stable schizophrenia

2019 ◽  
Vol 33 (10) ◽  
pp. 1237-1247 ◽  
Author(s):  
Estibaliz Arce ◽  
Rita Balice-Gordon ◽  
Sridhar Duvvuri ◽  
Melissa Naylor ◽  
Zhiyong Xie ◽  
...  
Keyword(s):  
Working Memory ◽  
Partial Agonist ◽  
Monetary Incentive ◽  
Reward Processing ◽  
Adjunctive Treatment ◽  
Drug Mechanism ◽  
Significant Difference ◽  
Monetary Incentive Delay ◽  
Selective Dopamine ◽  
Back Task

Background: PF-06412562 is an orally bioavailable, selective dopamine D1/D5 receptor partial agonist with a non-catechol structure under evaluation for treatment of cognitive impairment in schizophrenia. Aims: This randomized, double-blind, placebo-controlled, parallel-group, Phase 1b study examined the pharmacokinetics and pharmacodynamics of three doses of PF-06412562 (3 mg, 9 mg, and 45 mg twice daily) over 15 days in patients with schizophrenia receiving antipsychotics. Methods: Primary endpoints included adjunctive safety/tolerability and effects on MATRICS Consensus Cognitive Battery Working Memory domain and reward processing (Monetary Incentive Delay) tasks. Exploratory endpoints included other behavioral/neurophysiological tasks, including the N-back task. Results: Among 95 subjects (78% male; mean age 34.8 years), baseline characteristics were similar across groups. The MATRICS Consensus Cognitive Battery Working Memory composite change from baseline on Day 13 improved in all groups, the smallest improvement was observed in the 45 mg group and was significantly smaller than that in the placebo group (two-sided p=0.038). For the Monetary Incentive Delay task (change from baseline in blood-oxygen-level-dependent functional magnetic resonance imaging activation in anterior ventral striatum for the contrast of cue gain>cue no gain on Day 15), no PF-06412562 dose was significantly different from placebo. No doses of PF-06412562 showed a significant difference on two-back task accuracy versus placebo. Conclusions: Adjunctive treatment with PF-06412562 was safe and well tolerated in patients with schizophrenia. PF-06412562 failed to show clinical benefit relative to placebo on assessments of cognition or reward processing in symptomatically stable patients over a 15-day treatment period. Numerous limitations due to the safety study design warrant further efficacy evaluation for this drug mechanism.

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