Sensorimotor gating deficits in schizophrenia: Advancing our understanding of the phenotype, its neural circuitry and genetic substrates

Swerdlow, Neal R.; Light, Gregory A.

doi:10.1016/j.schres.2018.02.042

Cited by 35 publications

(13 citation statements)

References 81 publications

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“…As PPI reflects the level of inhibitory function of the forebrain, our findings suggest that this dysfunction, which is shown in patients with schizophrenia, already exists in young people with clinical risk for psychosis. Our findings suggest that PPI deficits which were reported in patients with schizophrenia (Swerdlow & Light, ) begin in the earlier phases of the psychosis spectrum, as in line with the results of previous studies in UHR groups (De Koning et al, ; Quednow et al, ; Ziermans et al, ; Ziermans et al, ). We found that PPI in UHR was also lower than the FHR group.…”

Section: Discussionsupporting

confidence: 93%

Lower prepulse inhibition in clinical high‐risk groups but not in familial risk groups for psychosis compared with healthy controls

Togay

Çıkrıkçılı

Bayraktaroğlu

et al. 2019

Early Intervention Psych

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Aim Although the lower level of prepulse inhibition (PPI) of the startle response is well known in schizophrenia, the onset of this difference is not clear. The aim of the present study was to compare PPI in individuals with clinical and familial high risk for psychosis, and healthy controls. Methods We studied PPI in individuals within three groups: ultra‐high risk for psychosis (UHR, n = 29), familial high risk for psychosis (FHR, n = 24) and healthy controls (HC, n = 28). The FHR group was chosen among siblings of patients with schizophrenia, whereas UHR was defined based on the Comprehensive Assessment of At‐Risk Mental States (CAARMS). We collected clinical data using the BPRS‐E, SANS and SAPS when individuals with UHR were antipsychotic‐naïve. A cognitive battery that assessed attention, cognitive flexibility, working memory, verbal learning and memory domains was applied to all participants. Results PPI was lower in the UHR group compared with both the FHR and HC groups. Those with a positive family history for schizophrenia had lower PPI than others in the UHR group. There was no difference in PPI between the FHR and HC groups. We found no relationship between PPI and cognitive performance in the three groups. Startle reactivity was not different among the three groups. Positive and negative symptoms were not related to PPI and startle reactivity in the UHR group. Conclusions Our findings suggest that clinical and familial high‐risk groups for psychosis have different patterns of PPI.

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Section: Discussionsupporting

confidence: 93%

Lower prepulse inhibition in clinical high‐risk groups but not in familial risk groups for psychosis compared with healthy controls

Togay

Çıkrıkçılı

Bayraktaroğlu

et al. 2019

Early Intervention Psych

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“…Rather than suggesting that noise exposure should not be used for neurotherapeutic purposes, however, we would urge continued investigation into this subject. For one, sensorimotor gating measured by PPI is impaired in some neuropsychiatric disorders, most notably schizophrenia (Swerdlow et al, 2000; Swerdlow and Light, 2018). Noise-induced map expansion could thus be a way to target and reverse this specific preattentional deficit (Braff and Light, 2004).…”

Section: Discussionmentioning

confidence: 99%

Evidence of Hyperacusis in Adult Rats Following Non-traumatic Sound Exposure

Thomas

Guercio

Drudik

et al. 2019

Front. Syst. Neurosci.

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Manipulations that enhance neuroplasticity may inadvertently create opportunities for maladaptation. We have previously used passive exposures to non-traumatic white noise to open windows of plasticity in the adult rat auditory cortex and induce frequency-specific functional reorganizations of the tonotopic map. However, similar reorganizations in the central auditory pathway are thought to contribute to the generation of hearing disorders such as tinnitus and hyperacusis. Here, we investigate whether noise-induced reorganizations are accompanied by electrophysiological or behavioral evidence of tinnitus or hyperacusis in adult Long-Evans rats. We used a 2-week passive exposure to moderate-intensity (70 dB SPL) broadband white noise to reopen a critical period for spectral tuning such that a second 1-week exposure to 7 kHz tone pips produced an expansion of the 7 kHz frequency region in the primary auditory cortex (A1). We demonstrate for the first time that this expansion also takes place in the ventral auditory field (VAF). Sound exposure also led to spontaneous and sound-evoked hyperactivity in the anterior auditory field (AAF). Rats were assessed for behavioral evidence of tinnitus or hyperacusis using gap and tone prepulse inhibition of the acoustic startle response. We found that sound exposure did not affect gap-prepulse inhibition. However, sound exposure led to an improvement in prepulse inhibition when the prepulse was a 7 kHz tone, showing that exposed rats had enhanced sensorimotor gating for the exposure frequency. Together, our electrophysiological and behavioral results provide evidence of hyperacusis but not tinnitus in sound-exposed animals. Our findings demonstrate that periods of prolonged noise exposure may open windows of plasticity that can also be understood as windows of vulnerability, potentially increasing the likelihood for maladaptive plasticity to take place.

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“…53 Notably, the expression of Cdh23 in the subthalamic and pontine regions is conserved across the species, as shown in mouse and marmoset in this study, and those regions are known to form the neural circuitry that regulates PPI. 41,[54][55][56] Interestingly, deep brain stimulation (DBS) in the subthalamic region has been shown to improve PPI in rodent models and to ameliorate psychosis symptoms in individuals with Parkinson's disease. 57,58 In this study, a homologous variant of mouse Cdh23 c.753G>A in humans (rs769896655) showed a nominally significant enrichment, with overrepresentation of the A allele in Japanese population.…”

Section: Discussionmentioning

confidence: 99%

Role of an Atypical Cadherin Gene,Cdh23in Prepulse Inhibition and Implication ofCDH23in Schizophrenia

Balan

Ohnishi

Watanabe

et al. 2020

Preprint

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We previously identified quantitative trait loci (QTL) for prepulse inhibition (PPI), an endophenotype of schizophrenia, on mouse chromosome 10 and reported Fabp7 as a candidate gene from an analysis of F2 mice from inbred strains with high (C57BL/6N; B6) and low (C3H/HeN; C3H) PPI levels. The extremely high logarithm of odds (LOD) score of the chromosome-10 QTL suggests the presence of additional causative gene(s). Here, we reanalyzed the previously reported QTLs with increased marker density. The highest LOD score (26.66) peaked at a synonymous coding and splice-site variant, c.753G>A (rs257098870), in the Cdh23 gene on chromosome 10; the c.753G (C3H) allele showed a PPI-lowering effect. Bayesian multiple QTL mapping also supported the same variant with a posterior probability of 1. Therefore, we examined the roles of Cdh23 and c.753G>A in PPI. The Cdh23 gene was shown to be expressed in brain regions relevant for sensorimotor gating. We engineered the c.753G (C3H) allele into the B6 genetic background, which dampened PPI without affecting hearing acuity. An e-QTL (expression-QTL) effect imparted by the c.753G>A variant for the Cdh23 transcript in the brain was also revealed. The syntenous variant (c.753G>A; rs769896655) in CDH23 showed a nominally significant enrichment in individuals with schizophrenia. We also identified multiple potentially deleterious CDH23 variants in individuals with schizophrenia. Collectively, the data in the present study reveal a PPI-regulating Cdh23 variant and a possible contribution of this gene to schizophrenia susceptibility.

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Sensorimotor gating deficits in schizophrenia: Advancing our understanding of the phenotype, its neural circuitry and genetic substrates

Cited by 35 publications

References 81 publications

Lower prepulse inhibition in clinical high‐risk groups but not in familial risk groups for psychosis compared with healthy controls

Lower prepulse inhibition in clinical high‐risk groups but not in familial risk groups for psychosis compared with healthy controls

Evidence of Hyperacusis in Adult Rats Following Non-traumatic Sound Exposure

Role of an Atypical Cadherin Gene,Cdh23in Prepulse Inhibition and Implication ofCDH23in Schizophrenia

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