Sensorimotor Gating and Habituation of the Startle Response in Schizophrenic Patients Randomly Treated With Amisulpride or Olanzapine

Quednow, Boris B.; Wagner, Michael; Westheide, Jens; Beckmann, Katrin; Bliesener, N.; Maier, Wolfgang; Kühn, Kai‐Uwe

doi:10.1016/j.biopsych.2005.07.012

Cited by 102 publications

(106 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…According to the sensorimotor gating concept, PPI is considered as an example of mechanisms that limit sensory information overflow, facilitate selective attention, and enable efficient processing of relevant information. Reductions in PPI have been demonstrated with some consistency in schizophrenia (eg, Braff et al, 1978(eg, Braff et al, , 1992Ludewig et al, 2003a, b;Kumari et al, 2000;Parwani et al, 2000;Quednow et al, 2006), schizotypal personality disorder (Cadenhead et al, 1993(Cadenhead et al, , 2000, and psychotic bipolar mania (Perry et al, 2001). These results contributed to the view that schizophrenia patients suffer from a sensory inundation caused by a general inability to filter out relevant from irrelevant external stimuli automatically (Geyer and Braff, 1987).…”

Section: Introductionmentioning

confidence: 95%

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Vollenweider

Csomor

Knappe

et al. 2007

Neuropsychopharmacol

155

View full text Add to dashboard Cite

Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT 2A receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT 2A receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 mg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dosedependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

show abstract

Section: Introductionmentioning

confidence: 95%

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Vollenweider

Csomor

Knappe

et al. 2007

Neuropsychopharmacol

155

View full text Add to dashboard Cite

show abstract

“…However, another study failed to replicate this distinction, finding that typical and atypical medications were equipotent in reversing the PPI deficit in schizophrenia patients (Quednow et al, 2005). On the other hand, several studies have failed to show PPI-enhancing effects of either typical or atypical medication in schizophrenia patients (Duncan et al, 2003a, b;Perry et al, 2002;Mackeprang et al, 2002), even though Duncan et al (2003b) found an improvement of clinical symptoms with atypical medication.…”

Section: Introductionmentioning

confidence: 99%

Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels

Csomor

Stadler

Feldon

et al. 2007

Neuropsychopharmacol

102

View full text Add to dashboard Cite

Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D 2 -like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebocontrolled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D 2 -like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance.

show abstract

“…Diminished PPI has been consistently demonstrated in patients with schizophrenia [3,20,22,23,32] and schizotypal personality disorder [6,7]. The PPI deficit in schizophrenia is supposed to reflect a central abnormality underlying the disease; both neuroanatomical and neurochemical factors have been implicated on the basis of animal studies, which suggest contributions of diverse neurotransmitter systems, and particular functional association with multiple loci in the cortico-striato-pallido-thalamic (CSPT) circuitry, frontal and mediotemporal regions, ventral striatum, ventral pallidum, and pontine regions of the brainstem [12,37].…”

Section: Tcf4 and Sensorimotor Gatingmentioning

confidence: 99%

Impact of TCF4 on the genetics of schizophrenia

Lennertz

Quednow

Benninghoff

et al. 2011

Eur Arch Psychiatry Clin Neurosci

Self Cite

View full text Add to dashboard Cite

Mutations of the transcription factor 4 (TCF4) gene cause mental retardation with or without associated facial dysmorphisms and intermittent hyperventilation. Subsequently, a polymorphism of TCF4 was shown in a genome-wide association study to slightly increase the risk of schizophrenia. We have further analysed the impact of this TCF4 variant rs9960767 on early information processing and cognitive functions in schizophrenia patients. We have shown in a sample of 401 schizophrenia patients that TCF4 influences verbal memory in the Rey Auditory Verbal Learning Test. Contrary to expectations, carriers of the schizophrenia-associated allele showed better recognition, thus indicating that while TCF4 influences verbal memory, the TCF4-mediated schizophrenia risk is not determined by the influence of TCF4 on verbal memory. TCF4 does not impact on various other cognitive functions belonging to the domains of attention and executive functions. Moreover, in a pharmacogenetic approach, TCF4 does not modulate the improvement of positive or negative schizophrenia symptoms during treatment with antipsychotics. Finally, we have assessed a key electrophysiological endophenotype of schizophrenia, sensorimotor gating. As measured by prepulse inhibition, the schizophrenia risk allele C of TCF4 rs9960767 reduces sensorimotor gating. This indicates that TCF4 influences key mechanisms of information processing, which may contribute to the pathogenesis of schizophrenia.

show abstract

Sensorimotor Gating and Habituation of the Startle Response in Schizophrenic Patients Randomly Treated With Amisulpride or Olanzapine

Cited by 102 publications

References 76 publications

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Haloperidol Differentially Modulates Prepulse Inhibition and P50 Suppression in Healthy Humans Stratified for Low and High Gating Levels

Impact of TCF4 on the genetics of schizophrenia

Contact Info

Product

Resources

About