Inhibitory Gating of an Evoked Response to Repeated Auditory Stimuli in Schizophrenic and Normal Subjects

Freedman, Robert; Adler, Lawrence E.; Myles-Worsley, Marina; Nagamoto, Herbert T.; Miller, Christine L.; Kisley, Michael A.; McRae, K.A.; Cawthra, Ellen; Waldo, Merilyne

doi:10.1001/archpsyc.1996.01830120052009

Cited by 230 publications

(129 citation statements)

References 46 publications

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“…For instance, schizophrenia patients and their first-degree relatives exhibit a smaller reduction in the startle response or, in other words, show reduced PPI (Cadenhead et al, 2000;Geyer and Braff, 1987;Swerdlow et al, 1994;Swerdlow and Geyer, 1998). In addition, investigators have also developed protocols to assess auditory gating directly in the brain by using surface electrodes or, in animals, intracranial electrodes, and have found similar results (Adler et al, 1982;Boutros et al, 1991;Clementz et al, 1997;Connolly et al, 2003;Erwin et al, 1991;Freedman et al, 1996;Judd et al, 1992;Stevens et al, 1996).…”

Section: Introductionmentioning

confidence: 96%

Sensorimotor Gating Deficits in Transgenic Mice Expressing a Constitutively Active Form of Gsα

Gould

Bizily

Tokarczyk

et al. 2003

Neuropsychopharmacol

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Schizophrenia is a complex disorder characterized by wide-ranging cognitive impairments, including deficits in learning as well as sensory gating. The causes of schizophrenia are unknown, but alterations in intracellular G-protein signaling pathways are among the molecular changes documented in patients with schizophrenia. Using the CaMKIIα promoter to drive expression in neurons within the forebrain, we have developed transgenic mice that express a constitutively active form of G s α (G s α*), the G protein that couples receptors such as the D 1 and D 5 dopamine receptors to adenylyl cyclase. We have also generated mice in which the CaMKIIα promoter drives expression of a dominant-negative form of protein kinase A, R(AB). Here, we examine startle responses and prepulse inhibition of the startle reflex (PPI) in these G s α* and R(AB) transgenic mice. G s α* transgenic mice exhibited selective deficits in PPI, without exhibiting alterations in the startle response, whereas no deficit in startle or PPI was found in the R(AB) transgenic mice. Thus, overstimulation of the cAMP/PKA pathway disrupts PPI, but the cAMP/ PKA pathway may not be essential for sensorimotor gating. G s α* transgenic mice may provide an animal model of certain endophenotypes of schizophrenia, because of the similarities between them and patients with schizophrenia in G-protein function, hippocampus-dependent learning, and sensorimotor gating.

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Section: Introductionmentioning

confidence: 96%

Sensorimotor Gating Deficits in Transgenic Mice Expressing a Constitutively Active Form of Gsα

Gould

Bizily

Tokarczyk

et al. 2003

Neuropsychopharmacol

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“…[30][31][32] The P50 wave is generated in a conditioning-testing paradigm where the first stimulus activates or conditions the inhibition phenomenon, whereas the second tests its strength. Normally, individuals reduce the second (test) response relative to the first (condition) waves.…”

Section: Introductionmentioning

confidence: 99%

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

et al. 2012

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There is considerable evidence implicating the 15q13.3 region in neuropsychiatric disorders, with the a7 nicotinic receptor gene CHRNA7 the most plausible candidate. This region has multiple duplications and many copy number variants (CNVs). A common CNV involves a partial duplication of CHRNA7 (CHRFAM7A), which occurs in either orientation. We examined the distribution of these alternative genomic arrangements in a large cohort of psychiatric patients, their relatives and controls using the 2-bp deletion polymorphism as a marker for the orientation of CHRFAM7A. We investigated three common alleles for association with psychosis and with the P50 sensory gating deficit, which is strongly associated with psychosis and strongly linked to 15q13.3. We found significant within-family association with P50 (empirical P ¼ 0.004), which is robust to population stratification. Most of the effect came from the 2-bp deletion allele, which tags the variant of CHRFAM7A in the same orientation as CHRNA7. This allele is associated with the presence of the P50 sensory gating deficit (empirical P ¼ 0.0006). Tests comparing within-family and between-family components of association suggest considerable population stratification in the sample. We found no evidence for association with psychosis, but this may reflect lower power using this phenotype. Four out of six previous association studies found association of different psychiatric phenotypes with the same 2-bp deletion allele.

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“…Their results show that different brain structures are implicated in the reduction of the sensory gating ability studied by the P50 paradigm 5,8,10,15,16 . The sensory filter depends on complex brain circuits.…”

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confidence: 97%

“…The response to the first (conditioning) stimulus (S1) activates brain mechanisms that reduce the response to the second (test) stimulus (S2). The finding of a smaller ratio or a greater difference between stimuli indicates better inhibition or, in other words, a more effective gating of irrelevant stimuli [3][4][5][6][7][8][9][10][11][12][13] . Several studies have shown that the P50 evoked potential obtained using the paradigm of paired conditioning-test stimuli is a very effective method for the analysis of the functioning of the sensory filter.…”

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confidence: 99%

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Pattern of P50 suppression deficit in patients with epilepsy and individuals with schizophrenia

Becker

Filho

et al. 2011

Arq. Neuro-Psiquiatr.

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Objective: To identify P50 suppression in patients with epilepsy, to investigate the effect of seizure control on P50 suppression, and to compare epilepsy patients with individuals with schizophrenia and healthy volunteers. Method: P50 evoked potential parameters and P50 suppression were studied crossectionally in patients with uncontrolled or controlled epilepsy, in individuals with schizophrenia and in healthy volunteers. Results: Individuals with schizophrenia had significantly smaller conditioning stimulus (S1) amplitude, and patients with epilepsy had larger test stimulus (S2) amplitude. Mean S2/S1 ratio was 0.71±0.33 for patients with uncontrolled epilepsy; 0.68±0.36 for patients with controlled epilepsy; 0.96±0.47 for individuals with schizophrenia, and 0.42±0.24 for healthy volunteers. Conclusion: The sensory filter of patients with epilepsy is altered, and this alteration is not associated with seizure control. Also, it works differently from the sensory filter of individuals with schizophrenia. Key words: epilepsy, P50 auditory evoked potential, schizophrenia, sensory filter.Padrão do déficit de supressão do P50 em pacientes com epilepsia e em indivíduos com esquizofrenia RESUMO Objetivo: Identificar se existe déficit de supressão do P50 em pacientes com epilepsia, verificar a influência do controle das crises nesse déficit, comparando com pacientes com esquizofrenia e com voluntários saudáveis. Método: Os parâmetros do potencial evocado P50 e sua supressão foram estudados, com um corte transversal, em pacientes com epilepsia controlada ou não, esquizofrenia e em voluntários saudáveis. Resultados: Indivíduos com esquizofrenia apresentam uma amplitude de S1 significativamente menor que os demais, sendo que os pacientes com epilepsia apresentavam uma resposta S2 de maior amplitude. A média da razão S2/S1 foi de 0,71±0,33 nos pacientes com epilepsia não controlada; 0,68±0,36 naqueles com epilepsia controlada; 0,96±0,47 nos com esquizofrenia e 0,42±0,24 nos controles normais. Conclusão: O filtro sensitivo de pacientes com epilepsia é alterado, e essa alteração não está associada com o controle das crises. Além disso, ele funciona de forma diferente do filtro sensitivo dos indivíduos com esquizofrenia. Palavras-chave: epilepsia, potencial evocado auditivo P50, esquizofrenia, filtro sensitivo.

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Inhibitory Gating of an Evoked Response to Repeated Auditory Stimuli in Schizophrenic and Normal Subjects

Cited by 230 publications

References 46 publications

Sensorimotor Gating Deficits in Transgenic Mice Expressing a Constitutively Active Form of Gsα

Sensorimotor Gating Deficits in Transgenic Mice Expressing a Constitutively Active Form of Gsα

Association between the 2-bp deletion polymorphism in the duplicated version of the alpha7 nicotinic receptor gene and P50 sensory gating

Pattern of P50 suppression deficit in patients with epilepsy and individuals with schizophrenia

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