Sensitization and habituation of the acoustic startle reflex in patients with schizophrenia

Meincke, Ulrich; Light, Gregory A.; Geyer, Mark A.; Braff, David L.; Gouzoulis-Mayfrank, Euphrosyne

doi:10.1016/j.psychres.2004.01.003

Cited by 110 publications

(93 citation statements)

References 42 publications

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“…In the current study, no sensitization effect was found, as opposed to the study of Meincke et al (2004) (NB: although the effect of sensitization appears to reach towards significance in the current study, it was only based on the responses of three subjects, of which one was a considerable outlier (an increase in the response to trial 2 of 486% compared with trial 1)). The discrepancy between the current study and the study of Meincke et al (2004) regarding sensitization might be explained by the difference in subject population: in the current study, only males were included, whereas in the study of Meincke et al (2004) both males and females were included. As there are numerous reports in literature describing a gender difference in both PPI (Swerdlow et al, 1993Jovanovic et al, 2004;Kumari et al, 2004) and/or prepulse facilitation (Aasen et al, 2005), it is not inconceivable that gender differences might also exist in the processes of habituation and sensitization.…”

Section: Discussioncontrasting

confidence: 82%

“…As there are numerous reports in literature describing a gender difference in both PPI (Swerdlow et al, 1993Jovanovic et al, 2004;Kumari et al, 2004) and/or prepulse facilitation (Aasen et al, 2005), it is not inconceivable that gender differences might also exist in the processes of habituation and sensitization. Another explanation might be the difference in the intensity level of the background noise, which was slightly higher in the current study (70 dB) than in the study of Meincke et al (2004) (65 dB), which might have reduced the sensitization effect.…”

Section: Discussioncontrasting

confidence: 70%

“…Similarly, in animal studies, fluvoxetine (SSRI) reduced habituation in rats (Geyer and Tapson, 1988), whereas administration of the 5-HT1A/1B agonist RU24969 reduced habituation in mice (Dulawa and Geyer, 2000). In the current study, no sensitization effect was found, as opposed to the study of Meincke et al (2004) (NB: although the effect of sensitization appears to reach towards significance in the current study, it was only based on the responses of three subjects, of which one was a considerable outlier (an increase in the response to trial 2 of 486% compared with trial 1)). The discrepancy between the current study and the study of Meincke et al (2004) regarding sensitization might be explained by the difference in subject population: in the current study, only males were included, whereas in the study of Meincke et al (2004) both males and females were included.…”

Section: Discussioncontrasting

confidence: 40%

“…As two other studies from our laboratory, in which exactly the same habituation paradigm was used as in the current study, showed that the first four trials of the first habituation block displayed the most variation or decline in response amplitudes (similar to the current study, see Figure 3), a post hoc comparison between the startle amplitudes of trials 1 through 4 was performed with an ANOVA with factors 'treatment' and 'trial' (trial 1 through 4). In addition, a post hoc comparison was performed between the percentage magnitude of trial 2 relative to trial 1 (formula: 100 Â (amplitude trial 2/amplitude trial 1)) and the magnitude of trial 1 over both treatments, as previous research with a similar habituation paradigm had shown a sensitization in the response of healthy volunteers from trial 1 to 2 (Meincke et al, 2004). Analysis of blood pressure was carried out using ANOVA with factors 'treatment' and 'time' (t ¼ 0 h or t ¼ 210 or t ¼ 285 min) of systolic and diastolic blood pressure separately.…”

Section: Discussionmentioning

confidence: 99%

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The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

Jensen

Oranje

Wienberg

et al. 2007

Neuropsychopharmacol

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Sensorimotor gating is critical to normal brain functioning, and disruptions are associated with certain mental illnesses, such as schizophrenia. Prepulse inhibition of the acoustic startle reflex (ASR) (PPI) is an operational measure of sensorimotor gating, of which evidence for a serotonergic modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences between the two treatments were observed on PPI, although escitalopram was found to significantly delay habituation of the ASR. In the current study, escitalopram was found to delay habituation, but it did not affect PPI in healthy male volunteers. As escitalopram is a highly specific SSRI, the results suggest that an increased serotonergic activity disrupts habituation, but not PPI in healthy volunteers.

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Section: Discussioncontrasting

confidence: 82%

Section: Discussioncontrasting

confidence: 70%

Section: Discussioncontrasting

confidence: 40%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

Jensen

Oranje

Wienberg

et al. 2007

Neuropsychopharmacol

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“…Most notably, alterations in both paradigms have repeatedly been described in patients with schizophrenia and their firstdegree relatives (Adler et al, 1982;Cadenhead et al, 2000;Siegel et al, 1984). Furthermore, patients with schizophrenia show deficits in the habituation of the auditory startle reflex Meincke et al, 2004) and specific alterations in the AEP peak refractoriness paradigm (Shelley et al, 1999;Erwin et al, 1994).…”

Section: Introductionmentioning

confidence: 96%

Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

Bickel

Lipp

Umbricht

2007

Neuropsychopharmacol

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Cognitive deficits in schizophrenia include impairments at automatic, preattentive stages of sensory information processing. These deficits are evident in the prepulse inhibition-(PPI) and habituation of the auditory startle response paradigm, the paired tone paradigm in the EEG, and the peak recovery function of auditory evoked potentials (AEP). Administration of NMDA receptor antagonists reliably disrupts PPI and habituation of the startle, but not gating of AEPs in rodents. In the peak recovery paradigm, patients with schizophrenia and primates treated with NMDA receptor antagonists show reduced maximal response at long interstimulus intervals (ISI), but normal responses at short ISIs. Thus reduced NMDA receptor signalling may underlie alterations in these paradigms observed in schizophrenia. We tested the paradigms mentioned in mouse mutants with reduced expression of the NR1 subunit of the NMDA receptor (N ¼ 15) and their wild-type littermates (N ¼ 16). The NR1 mutant mice showed impaired habituation and PPI of the auditory startle response, as well as impaired gating in the paired tone paradigm. Deficits between the two gating measures did not correlate, corroborating previous evidence that these paradigms measure distinct processes. In the peak recovery paradigm, the NR1 mutants showed increased responses of the AEPs P1 and N1 at short ISIs but no difference between groups were observed at long ISIs. In conclusion, the NR1 hypomorphic mice modelled sensory and sensorimotor gating and startle habituation deficits observed in schizophrenia, but failed to model alterations in the peak recovery function.

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A Reverse-Translational Study of Dysfunctional Exploration in Psychiatric Disorders

Perry¹,

Minassian²,

Paulus³

et al. 2009

Arch Gen Psychiatry

178

280

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Context Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, raising the question of whether they are in fact the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these two disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. Objective We used a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM), to quantify exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Design Static group comparison. Setting Psychiatric hospital. Participants 15 bipolar mania and 16 schizophrenia subjects were compared to 26 healthy volunteers in the human BPM. The effects of amphetamine, the selective dopamine transporter (DAT) inhibitor GBR12909, and genetic knockdown of the DAT were compared to controls in the mouse BPM. Measures The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Results Bipolar manic subjects demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Schizophrenia subjects did not show the expected habituation of motor activity. Selective genetic or pharmacological inhibition of the DAT matched the mania phenotype better than the “gold standard” model of mania (amphetamine). Conclusion These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to identify neurobiological underpinnings of neuropsychiatric disorders.

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Sensitization and habituation of the acoustic startle reflex in patients with schizophrenia

Cited by 110 publications

References 42 publications

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

A Reverse-Translational Study of Dysfunctional Exploration in Psychiatric Disorders

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