Medication status affects the relationship of symptoms to prepulse inhibition of acoustic startle in schizophrenia

Duncan, Erica; Bollini, Annie M.; Lewison, Barbara; Keyes, Megan; Jovanović, Tanja; Gaytan, Osvaldo; Egan, Glenn; Szilágyi, Sándor; Schwartz, Marion; Parwani, Arti; Chakravorty, Subhajit; Rotrosen, John

doi:10.1016/j.psychres.2006.04.006

Cited by 20 publications

(8 citation statements)

References 40 publications

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“…Less consistent findings across recent single-site studies, as well as the present multi-site study, include the relationship between smoking and the magnitude of PPI deficits among SZ patients (Hong et al, 2008; Moriwaki et al, 2009), and the associations between PPI and either clinical symptoms (Braff et al, 1999; Duncan et al, 2006; Light et al, 2012; Martinez-Gras et al, 2009; Meincke et al, 2004; Quednow et al, 2010; Swerdlow et al, 2006a; Wang et al, 2013; Xue et al, 2012) or neurocognitive measures (Bitsios and Giakoumaki, 2005; Kishi et al, 2012) in SZ patients. Perhaps such variability should not be surprising: studies vary widely in the precision with which nicotine use and levels are documented, and many studies – including our own – use very blunt self-report measures of current and lifetime smoking history.…”

Section: Discussionsupporting

confidence: 62%

Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

Swerdlow

Light

Sprock

et al. 2014

Schizophrenia Research

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Background Startle inhibition by weak prepulses (PPI) is studied to understand the biology of information processing in schizophrenia patients and healthy comparison subjects (HCS). The Consortium on the Genetics of Schizophrenia (COGS) identified associations between PPI and single nucleotide polymorphisms in schizophrenia probands and unaffected relatives, and linkage analyses extended evidence for the genetics of PPI deficits in schizophrenia in the COGS-1 family study. These findings are being extended in a 5-site “COGS-2” study of 1800 patients and 1200 unrelated HCS to facilitate genetic analyses. We describe a planned interim analysis of COGS-2 PPI data. Methods Eyeblink startle was measured in carefully screened HCS and schizophrenia patients (n=1402). Planned analyses of PPI (60 ms intervals) assessed effects of diagnosis, sex and test site, PPI-modifying effects of medications and smoking, and relationships between PPI and neurocognitive measures. Results 884 subjects met strict inclusion criteria. ANOVA of PPI revealed significant effects of diagnosis (p=0.0005) and sex (p<0.002), and a significant diagnosis × test site interaction. HCS > schizophrenia PPI differences were greatest among patients not taking 2nd generation antipsychotics, and were independent of smoking status. Modest but significant relationships were detected between PPI and performance in specific neurocognitive measures. Discussion The COGS-2 multi-site study detects schizophrenia-related PPI deficits reported in single-site studies, including patterns related to diagnosis, prepulse interval, sex, medication and other neurocognitive measures. Site differences were detected and explored. The target COGS-2 schizophrenia “endophenotype” of reduced PPI should prove valuable for identifying and confirming schizophrenia risk genes in future analyses.

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Section: Discussionsupporting

confidence: 62%

Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

Swerdlow

Light

Sprock

et al. 2014

Schizophrenia Research

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“…Our findings suggest that schizophrenia (5/13 neuroleptic naïve) and SPD patients (12/13 neuroleptic naïve) exhibit dysfunction in dorsolateral, caudate, putamen, and mediodorsal nucleus regions during an attention-to-prepulse paradigm and that group differences are not due to current medication. Medicated patients failed to show the expected PPI vs. symptom severity correlations shown in unmedicated patients (Duncan et al 2006). Evidence from a double-blind study where schizophrenia patients were randomized to either 8-week treatment with amisulpride or olanzapine suggest that that the PPI-restoring effect of antipsychotics is likely attributed to a dopamine D2 receptor blockade (Quednow et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Frontal–striatal–thalamic mediodorsal nucleus dysfunction in schizophrenia-spectrum patients during sensorimotor gating

et al. 2008

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Prepulse inhibition (PPI) refers to a reduction in the amplitude of the startle eye-blink reflex to a strong sensory stimulus, the pulse, when it is preceded shortly by a weak stimulus, the prepulse. PPI is a measure of sensorimotor gating which serves to prevent the interruption of early attentional processing and it is impaired in schizophrenia-spectrum patients. In healthy individuals, PPI is more robust when attending to than ignoring a prepulse. Animal and human work demonstrate frontalstriatal-thalamic (FST) circuitry modulates PPI. This study used functional magnetic resonance imaging (fMRI) to investigate FST-circuitry during an attention-to-prepulse paradigm in 26 unmedicated schizophrenia-spectrum patients (13 schizotypal personality disorder (SPD), 13 schizophrenia) and 13 healthy controls. During 3T-fMRI acquisition and separately measured psychophysiological assessment of PPI, participants heard an intermixed series of high-and lowpitched tones serving as prepulses to an acoustic-startle stimulus. Event-related BOLD-response amplitude curves in FST regions traced on co-registered anatomical MRI were examined. Controls showed greater activation during attended than ignored PPI conditions in all FST regions--dorsolateral prefrontal cortex (Brodmann areas 46,9), striatum (caudate, putamen), and the thalamic mediodorsal nucleus (MDN). In contrast, schizophrenia patients failed to show differential BOLD responses in FST-circuitry during attended and ignored prepulses, whereas SPD patients showed greater-than-normal activation during ignored prepulses. Among the three diagnostic groups, lower left caudate BOLD activation during the attended PPI condition was associated with more deficient sensorimotor gating as measured by PPI. Schizophrenia-spectrum patients exhibit inefficient utilization of FST-circuitry during attentional modulation of PPI. Schizophrenia patients have reduced recruitment of FST-circuitry during task-relevant stimuli, whereas SPD patients allocate excessive resources during task-irrelevant stimuli. Dysfunctional FST activation, particularly in the caudate may underlie PPI abnormalities in schizophrenia-spectrum patients.

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“…BPRS total score was not significantly correlated to Fagerstrom score (r ¼ 0.33, p ¼ 0.23) or MNWS and QSU withdrawal/craving scores in either nicotine or placebo conditions (all rp0.28 in absolute values, all pX0.37). Duncan et al (2006) reported that for medicated schizophrenia patients, there were no significant correlations between PPI and BPRS total scores or any subscales. For unmedicated patients, there were significant correlations of PPI and BPRS total symptoms and positive symptoms.…”

Section: Clinical Symptoms and Nicotinic Effect On Ppimentioning

confidence: 95%

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

Hong

Wonodi

Lewis

et al. 2007

Neuropsychopharmacol

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Acoustic prepulse inhibition (PPI) is considered an important biomarker in animal studies of psychosis and a number of psychiatric conditions. Nicotine has been shown to improve acoustic PPI in some animal strains and in humans. However, there is little data on effects of nicotine on acoustic PPI in schizophrenia patients using a double-blind, placebo-controlled study design. The primary aim of the current study was to test the effect of nicotine nasal spray on acoustic PPI in schizophrenia patients. The secondary aim was to test nicotine effect on prepulse facilitation (PPF). The study included 18 schizophrenia patient smokers and 12 healthy control smokers, tested in a double-blind, placebo-controlled, crossover, randomized design immediately after nicotine or saline placebo nasal sprays. PPI was tested using 120 ms prepulse-pulse interval. PPF was tested using 4500 ms prepulse-pulse interval. The results showed a significant main effect of drug on PPI in that nicotine improved PPI compared to placebo (p ¼ 0.008) with no drug by diagnosis interaction (p ¼ 0.90). Improvement in PPI in response to nicotine was significantly correlated with the baseline severity of clinical symptoms (r ¼ 0.59, p ¼ 0.02) in patients. There was no significant drug or drug by diagnosis interaction for the 4500 ms prepulse-pulse interval condition. However, nicotine improved inhibition in a subgroup of subjects exhibiting PPF (p ¼ 0.002). In conclusion, the findings confirmed that nicotine transiently improves acoustic PPI in schizophrenia patients. Additionally, schizophrenia patients with more clinical symptoms may have benefited more from nicotinic effect on PPI.

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Medication status affects the relationship of symptoms to prepulse inhibition of acoustic startle in schizophrenia

Cited by 20 publications

References 40 publications

Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS

Frontal–striatal–thalamic mediodorsal nucleus dysfunction in schizophrenia-spectrum patients during sensorimotor gating

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

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