Startle gating in antipsychotic-naïve first episode schizophrenia patients: One ear is better than two

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Abstract

Prepulse inhibition (PPI) of the startle reflex to binaural prepulse stimuli is reliably reported to be reduced in patients with schizophrenia. Monaural acoustic prestimuli produce more inhibition of the eye blink reflex than binaural prestimuli in healthy people. The effect of monaural prestimulation on reflex inhibition in patients with schizophrenia is not known. In this study, inhibition of the acoustic startle response by monaural and binaural acoustic prestimuli was assessed in 20 antipsychotic-naïve first episode schizophrenia patients and compared with 20 age and sex-matched healthy subjects. The results revealed less PPI, especially with binaural prestimuli, in patients than healthy subjects but both groups showed more PPI with monaural than binaural prestimuli. It is concluded that first episode schizophrenia patients show deficient sensorimotor gating but they are not impaired in the mechanism underlying stronger PPI with monaural than binaural prepulses.

Introduction

The magnitude of the human eye blink reflex to a strong startle–eliciting sensory stimulus, the pulse, is reduced if this is preceded shortly by a weak prestimulus, the prepulse (Graham, 1975). This effect, known as prepulse inhibition (PPI), has been shown to be reliably reduced in schizophrenia patients (Braff et al., 1978, review, Braff et al., 2001, Kumari et al., 2005a, Ludewig et al., 2003, Meincke et al., 2004) especially in the presence of thought disorder (Perry and Braff, 1994, Perry et al., 1999). Monaural acoustic prestimuli produce more inhibition of the blink reflex than binaural prestimuli in healthy people (Marsh et al., 1976, Kumari et al., 2005b) and unaffected relatives of patients with schizophrenia (Kumari et al., 2005b). The effect of monaural prestimulation on startle inhibition in schizophrenia is not known.

Schizophrenia has been considered to involve left hemisphere dysfunction (Crow, 1995, Gruzelier, 2002). Empirical studies have shown deficient left hemisphere M50 gating (Thoma et al., 2003), normal functioning of the right auditory cortex but abnormalities of the left auditory cortex in an auditory paired-stimuli paradigm (Clementz et al., 2003), disturbed P300 topography with right ear stimulation (Bolsche et al., 1996), failure of dominant left-hemisphere activation to right ear stimulation (Rockstroh et al., 1998), and smaller right ear advantage for dichotic fused words (Bruder et al., 1995, Loberg et al., 1999). Furthermore, a number of studies have demonstrated that normal brain asymmetry at the structural and functional level is lost or even reversed in patients with schizophrenia (e.g. Bilder et al., 1999, Petty, 1999, Sharma et al., 1999, Aydin et al., 2001, Rockstroh et al., 2001, Kircher et al., 2002, Jin et al., 2003). Importantly, the regions found to show abnormal lateralization in this population include the hippocampus and the temporal lobes (e.g. DeLisi et al., 1989, Russell et al., 1997, Maher et al., 1998, Shirakawa et al., 2001, Hanlon et al., 2005) which are known to be involved in PPI from both animal (review, Swerdlow et al., 2001) and human studies (Kumari et al., 2003a, Kumari et al., 2005c).

In this study, we examined the effect of monaural and binaural prestimuli on startle inhibition in antipsychotic-naïve first-episode schizophrenia patients and matched controls. We hypothesised that patients, compared to controls, would show reduced PPI and, given previous data indicating left hemisphere dysfunction, this deficit might be most pronounced with right ear prestimulation. The use of antipsychotic-naïve patients allowed us to examine these issues free from effects that antipsychotics might exert on PPI (e.g. Kumari et al., 1999, Kumari et al., 2000, Kumari et al., 2002, Kumari et al., 2006, Leumann et al., 2002, Oranje et al., 2002, Oranje et al., 2004, Quednow et al., 2006) and functional lateralization of certain brain regions (Merrin et al., 1988, Bertolino et al., 2004).

Section snippets

Subjects

Participants, all right-handed, included 20 patients diagnosed with schizophrenia (SCID-P; First et al., 1996; re-confirmed after 1 year) and within three months of their first psychotic episode and 20 sex- and age-matched healthy subjects screened for exclusion of mental illness and neurological abnormalities. No participant had current alcohol and drug abuse, a positive history of alcohol and drug dependence in the last year or lifetime history of 5 years of alcohol or drug abuse/dependence,

Amplitude and habituation

There was a strong habituation over five blocks of pulse-alone trials (Block: F = 8.01, df = 4, 152, P < 0.001) with a linear trend (F = 18.17, df = 1, 38, P < 0.001) in both groups [Group × Block: F = 0.98, df = 4, 52, non-significant]. The two groups also showed similar response amplitudes over the entire session [Group: F = 0.75, df = 1, 38, non-significant].

PPI

The ANOVA on monaural PPI scores revealed a trend for the main effect of Group (F = 3.15, df = 1, 38, P = 0.08) and a marginally significant Group × Trial Type

Discussion

This study revealed, as expected, less PPI in antipsychotic-naïve first-episode schizophrenia patients relative to healthy controls. This observation confirms previously reported PPI deficit in this early stage of the illness (Mackeprang et al., 2002, Ludewig et al., 2003). Both the patient and control groups showed greater PPI with monaural relative to binaural prepulses and there was no evidence of a more pronounced PPI deficit in patients with right ear prestimuli. In fact, patients showed

Conclusions

This study demonstrates that first-episode schizophrenia patients show deficient sensorimotor gating, especially with binaural prestimuli, but they are not impaired in the mechanism underlying stronger PPI with monaural than binaural prepulses.

Acknowledgement

VK is supported by a Wellcome Trust Senior Research Fellowship (Grant 067427/z/02/z).

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