Deficits in prepulse inhibition and habituation in never-medicated, first-episode schizophrenia.

BACKGROUND: Prepulse inhibition (PPI) is the normal suppression of the startle reflex when an intense startling stimulus is preceded by a barely detectable prepulse. Habituation of the acoustic startle reflex is decrement in response when the same stimulus is presented repeatedly. These factors have been proposed as neurophysiologic measures of sensorimotor gating or filtering and discussed as trait-linked markers for information-processing deficits in schizophrenia-spectrum disorders. The aim of this study was to examine whether first-episode schizophrenia patients also exhibit deficits in PPI and habituation. METHODS: Never-medicated male schizophrenic and schizophreniform patients in their first psychotic episode (n=24) were compared with age-matched healthy men (n=21) in an acoustic startle paradigm assessing PPI (30-, 60-, 120-, 240-, and 2000-msec interstimulus intervals) and habituation. RESULTS: Compared with control subjects, first-episode patients exhibited significant deficits in both PPI in the 60-msec prepulse condition and startle habituation. Patients also exhibited less facilitation in the 2000-msec prepulse condition. CONCLUSIONS: In combination with other studies, these findings indicate that PPI and habituation may be sensitive intermediate phenotypic markers for information-processing deficits in schizophrenic patients.     

Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication

BACKGROUND: Prepulse inhibition of the startle reflex response refers to the ability of a weak prestimulus to transiently inhibit the response to a closely following strong sensory stimulus. This effect represents an operational index of sensorimotor gating and is found to be deficient in schizophrenia. Prepulse inhibition deficits in schizophrenia seem to be partially normalized by typical antipsychotics and more fully by some atypical antipsychotics. Early onset of schizophrenia, particularly in men, has been associated with abnormal brain maturation, profound neuropsychological deficits, and less responsiveness to antipsychotic medication. We evaluated the effects of the age of onset of illness, current positive and negative symptoms, and the type of medication (typical vs atypical) on prepulse inhibition of the startle response in schizophrenia. METHODS: Thirty-eight male schizophrenic patients and 20 healthy male controls underwent testing for prepulse inhibition of the acoustic startle response. RESULTS: Earlier onset of illness was associated with reduced prepulse inhibition, while adult onset of illness was not. No significant relationships occurred between current symptoms and prepulse inhibition. Patients given typical, but not atypical, antipsychotics exhibited less prepulse inhibition compared with healthy controls. CONCLUSION: Early onset of illness is associated with profound deficits in prepulse inhibition of the startle response in men with schizophrenia.     

Sex differences in prepulse inhibition deficits in chronic schizophrenia

Recent years have seen a dramatic growth in the number of studies using prepulse inhibition (PPI) paradigms to index information processing deficits in schizophrenia. There are, however, robust sex differences in PPI in healthy subjects, with women exhibiting less PPI than men in the absence of any psychopathology. To investigate the role of sex in prepulse modification deficits in the long-term course of schizophrenia, we assessed PPI (response inhibition with the prepulse preceding the pulse by 30-150 ms) and prepulse facilitation (PPF; response facilitation with the prepulse preceding the pulse by 1000 ms) of the acoustic startle response in 42 chronic schizophrenia patients (27 men; all 42 on typical antipsychotics) and 35 controls (15 men). The results revealed that healthy women showed less PPI than healthy men. Men with schizophrenia showed less PPI compared to healthy men, but women with schizophrenia did not differ in PPI from healthy women. Age of illness onset negatively correlated to PPI in male patients. There was no significant effect of sex in PPF, and although patients (regardless of sex) showed less PPF relative to controls, this effect was abolished when the current age was co-varied for. These findings indicate sex differences in PPI deficits in schizophrenia. Future studies of schizophrenia patients need to take sex and age of subjects into account to optimise the investigation of PPI deficits, and their clinical, neural, and pharmacological correlates.     

慢性精神分裂症男性患者听觉刺激惊跳反射的初步研究

目的 探讨汉族人群精神分裂症患者是否存在听觉惊跳反射缺陷及抗精神病药的影响.方法 第1代药物组:服用第1代抗精神病药的慢性精神分裂症男性患者25例;氯氮平组:服用氯氮平的慢性精神分裂症男性患者25例;对照组:身体健康的男性25名;3组的年龄和受教育年限均匹配.对上述3组进行听觉刺激惊跳反射检测,并使用阳性和阴性症状量表(PANSS)评定精神分裂症患者的临床精神病理症状.结果 (1)第1代药物组惊跳反射的反应波幅(SR)[(553.6±516.9)mV]明显低于对照组[(942.0±447.3)mV,P=0.009],氯氮平组的SR[(755.9±439.4)mV]介于上述2组之间,但与2组间的差异均无统计学意义(P＞0.05);(2)第1代药物组惊跳反射的适应性(HAB)[(17.8±35.8)%]明显低于对照组[(44.9±28.9)%,P=0.027],氯氮平组的HAB[(22.9±34.1)%]介于上述2组之间,但与2组间的差异均无统计学意义(P＞0.05);(3)当时间间隔(LI)为120 ms时,第1代药物组的惊跳反射弱刺激抑制(prepulse inhibition,PPI)显著小于对照组(P=0.024),氯氮平组的PPI值介于上述2组之间,但与2组间的差异均无统计学意义(P＞0.05);LI为30 ms或60 ms时,3组间PPI的差异无统计学意义(P＞0.05);(4)第1代药物组和氯氮平组患者不同LI的PPI与其临床病理症状可能不存在相关(P＞0.05).结论 精神分裂症患者可能存在听觉惊跳反射弱刺激抑制的缺陷;氯氮平可能能部分改善精神分裂症患者对惊跳反射的脱抑制.     

Normalization of information processing deficits in schizophrenia with clozapine.

OBJECTIVE: The authors tested the hypothesis that the use of an atypical drug, clozapine, for patients with schizophrenia is related to less impairment in information processing deficits (assessed by prepulse inhibition of the startle response) than is the use of typical antipsychotics. METHOD: Two groups of schizophrenic patients--receiving either clozapine or a range of typical antipsychotics--were tested for prepulse inhibition (a reduction in response to a starting stimulus, if preceded briefly by a weak, nonstartling stimulus; measured at prepulse-to-pulse intervals of 30 msec, 60 msec, and 120 msec) of the acoustic startle response and compared with a group of healthy volunteers. RESULTS: Patients receiving typical antipsychotics showed less prepulse inhibition with 30-msec and 60-msec prepulse trials than did comparison subjects. Clozapine-treated patients showed normal levels of prepulse inhibition. CONCLUSIONS: Clozapine is superior to typical antipsychotics in normalizing prepulse inhibition, presumably because of its pharmacological effects on prefrontal regions of the brain or its effects on a broader range of neuroreceptors.     

Stability of the acoustic startle reflex, prepulse inhibition, and habituation in schizophrenia

Prepulse inhibition (PPI) of the acoustic startle reflex has been proposed as a neurophysiological measure of sensorimotor gating. There is high test-retest reliability of both startle magnitude and PPI in non-psychiatric subjects. The present study examined the stability of the acoustic startle reflex and its modulation in patients with schizophrenia. Startle measurements were performed in 19 chronic schizophrenic patients on stable medications and 24 healthy control subjects, three times at one-month intervals. PPI trials with various intervals between the prepulse and the startle stimulus (30, 60. 120, 240, and 2000 ms) were used. Intraclass correlation coefficients (ICC) were computed to assess stability. There was a good test-retest reliability of PPI in both schizophrenic patients (Mean ICC: 0.75) and control subjects (Mean ICC: 0.71). Acoustic startle magnitude was the most stable measure across sessions (Mean ICC schizophrenics: 0.89; Mean ICC controls: 0.89). In both groups, a good test-retest reliability was found in the startle latencies. Habituation and prepulse-induced shortening of latencies exhibited moderate stability. Schizophrenic patients exhibited significantly less PPI than control subjects in the 60 ms prepulse condition. This PPI deficit was evident in all three sessions. These results indicate that PPI is a stable neurobehavioral measure in chronic schizophrenic patients in the absence of changes in clinical state.     

Effects of antipsychotics on prepulse inhibition of the startle response in drug-na?ve schizophrenic patients.

BACKGROUND: Disturbances in sensorimotor gating measured by prepulse inhibition of the startle response (PPI) have frequently been reported in medicated and unmedicated schizophrenia spectrum patients and in their relatives, suggesting that the deficit represents a stable vulnerability marker for schizophrenia. Clinical data on the effects of antipsychotics on PPI disturbances are scarce, but from preclinical studies, antipsychotics have been shown to influence PPI. To differentiate pathogenetic mechanisms from drug related effects, longitudinal clinical studies on the effect of antipsychotic treatment on PPI in drug-naive first-episode schizophrenic patients are needed. METHODS: First-episode schizophrenic patients never previously medicated with antipsychotics were examined at inclusion and after 3 months of treatment with the atypical antipsychotic compound, risperidone, or the typical drug, zuclopenthixol. Healthy controls were used as a comparison group. RESULTS: The results confirm deficits in PPI in drug-naive first-episode patients. No effect of antipsychotic treatment on PPI dysfunction was observed in any of the treatment groups. CONCLUSIONS: The data are the first to show the possible effect of treatment with antipsychotic drugs on PPI disturbances in a longitudinal study of drug-naive schizophrenic patients. The data do not support any influence of treatment with antipsychotic drugs on sensorimotor gating deficits. Instead, the results point to the impairment in PPI as a stable vulnerability indicator.     

Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia

Schizophrenia patients have prominent deficits in information processing that can be detected by measures of prepulse inhibition (PPI) of the startle response. Deficient PPI in schizophrenia is thought to reflect a failure of brain-based information 'protective' mechanisms that normally inhibit responsivity for 30-500ms after a weak prepulse stimulus. The relationship between specific prepulse stimulus characteristics and PPI deficits in this study was examined in 31 schizophrenia patients and 34 normal comparison subjects. Schizophrenia patients had overall deficits in PPI across four conditions where the prepulse was either discrete (abrupt) or continuous (sustained) and consisted of either white noise or a pure tone. On inspection and analysis of the data, it appears that the white noise conditions, rather than tone conditions, account for the group differences. Thus, the discrete white noise prepulse was most effective in eliciting PPI deficits, resulting in a large effect size between groups (d=0.85; P<0.01). Deficits in information-protective mechanisms in schizophrenia may be differentially sensitive to specific stimulus characteristics; this observation may be relevant both to the neurobiology of information processing deficits in schizophrenia and to the methodologies for studying these deficits experimentally.     

Sensorimotor gating and habituation of the startle response in schizophrenic patients randomly treated with amisulpride or olanzapine.

BACKGROUND: Schizophrenic patients exhibit impairments in prepulse inhibition (PPI) and habituation of the acoustic startle response (ASR). Recent studies suggested that PPI deficits and habituation deficits are normalized after antipsychotic treatment. Despite clear evidence of gating and habituation mechanisms in animal models, it is still unknown which neurotransmitter systems are involved in schizophrenic patients. Thus, we compared the effects of a combined 5-HT2A/D2 and a pure D2/D3 antagonist on PPI and habituation of ASR in patients with schizophrenia. METHODS: The ASR was measured in 37 acute schizophrenic patients who were randomized and double-blinded as to treatment with amisulpride or olanzapine. Patients were assessed during the first week and after four and eight weeks of treatment. Twenty healthy matched control subjects were examined likewise. RESULTS: Schizophrenic patients showed a significant PPI deficit and significantly decreased startle amplitude at baseline. The gating deficit disappeared after antipsychotic treatment in both treatment groups. Amisulpride sensitized the startle amplitude, whereas startle amplitude was not changed by olanzapine. After correcting for startle amplitude, patients did not show a habituation deficit; however, amisulpride accelerated habituation, whereas olanzapine had no effect. CONCLUSIONS: Our findings suggest that the PPI-restoring effect of antipsychotics is probably attributed to a dopamine D2 receptor blockade.     

Impaired prepulse inhibition of acoustic startle in schizophrenia.

BACKGROUND: Schizophrenics show deficits in sensorimotor gating, as measured by prepulse inhibition of acoustic startle (PPI). The goal of this investigation is to further characterize PPI and habituation deficits in schizophrenia, and to examine whether differing subgroups of schizophrenics would show comparable PPI deficits. METHODS: PPI was measured in 24 male schizophrenic subjects (9 acutely decompensated inpatients and 15 stable outpatients) and in 20 age-matched normal control subjects. Schizophrenic subjects were rated for positive and negative symptoms at the time of testing. RESULTS: Schizophrenic subjects showed deficits in prepulse inhibition and habituation as compared to normal subjects. Similar latency facilitation was produced by the prepulse in both groups. Acutely decompensated inpatients and stable outpatients did not differ in percent PPI. PPI did not correlate with severity of positive or negative symptoms. CONCLUSIONS: These results suggest that schizophrenic subjects have impaired central inhibitory mechanisms as measured by PPI, and support the hypothesis that periods of relative clinical remission are not accompanied by normalization of sensorimotor gating.     

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

Inhibition of the acoustic startle response by a smaller preliminary nonstartling stimulus is termed prepulse inhibition (PPI). Schizophrenia patients have impairments in PPI that may not fully normalize even when they are clinically stable on medication, particularly typical antipsychotics. There is evidence that more severe symptoms are associated with more severe PPI abnormalities, but the effect of antipsychotics on this relationship is not clear. Seventy-three male schizophrenia patients underwent acoustic startle and PPI testing. Symptom ratings were performed using the Brief Psychiatric Rating Scale (BPRS) and its subscales. Fifty-two subjects were treated with antipsychotic medication at time of testing; 21 were unmedicated. For all subjects, PPI was negatively correlated with the BPRS psychological discomfort subscale but not with BPRS total symptoms, BPRS positive symptoms or BPRS negative symptoms. For medicated subjects analyzed separately, there were no correlations with BPRS total scores or any subscales. For the unmedicated subjects analyzed separately, there were significant correlations of lower PPI with greater severity of BPRS total symptoms, positive symptoms and the psychological discomfort subscale. These data indicate that more severe symptoms are associated with lower PPI, but that medication status is an important factor in the relationship between symptom severity and sensorimotor gating.     

Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects

Prepulse inhibition (PPI) of the startle reflex refers to the ability of a weak prestimulus, the prepulse, to inhibit the response to a closely following strong sensory stimulus, the pulse. PPI is found to be deficient in a number of psychiatric and neurological disorders associated with abnormalities at some level in the limbic and cortico-pallido-striato-thalamic circuitry. We applied whole-brain functional magnetic resonance imaging to elucidate the neural correlates of PPI using airpuff stimuli as both the prepulse and the pulse in groups of (i) healthy subjects and (ii) schizophrenic patients. Cerebral activation during prepulse-plus-pulse stimuli with stimulus-onset asynchronies of 120 ms was contrasted with activation during pulse-alone stimuli. In healthy subjects, PPI was associated with increased activation bilaterally in the striatum extending to hippocampus and thalamus, right inferior frontal gyrus and bilateral inferior parietal lobe/supramarginal gyrus, and with decreased activation in the right cerebellum and left medial occipital lobe. All activated regions showed significantly greater response in healthy subjects than schizophrenic patients, who also showed a trend for lower PPI. The findings demonstrate involvement of the striatum, hippocampus, thalamus, and frontal and parietal cortical regions in PPI. Dysfunctions in any of these regions may underlie observations of reduced PPI in schizophrenia.     

Gating and habituation of the startle reflex in schizophrenic patients.

Schizophrenic patients exhibit impairments in both sensorimotor gating and habituation in a number of paradigms. Through human and animal model research, these fundamental cognitive deficits have well-described neurobiologic bases and offer insights into the neuroanatomic and neurotransmitter abnormalities that characterize patients with schizophrenic spectrum disorders. In this context, the startle response is particularly interesting, because it is a cross-species response to strong stimuli that is plastic or alterable using experimental and neurobiologic manipulations. Thirty-nine medicated schizophrenic patients and 37 normal control subjects were studied in a new electromyography based startle response paradigm in which both prepulse inhibition (an operational measure of sensorimotor gating) and habituation (the normal decrease in response magnitude to repeated stimuli over time) can be separated and assessed in one test session. The results indicate that schizophrenic patients have extensive deficits in both intramodal and cross-modal sensorimotor gating and a trend to show acoustic startle habituation deficits. The deficit in prepulse inhibition of startle amplitude exhibited by schizophrenic patients was evident when an acoustic prepulse stimulus preceded either an acoustic or a tactile startle stimulus. No deficit was observed in the prepulse-induced facilitation of startle latencies, indicating that the failure of gating was not due to a failure of stimulus detection. These findings suggest centrally mediated deficits in sensorimotor gating in schizophrenic patients.     

The effects of chronic administration of established and putative antipsychotics on natural prepulse inhibition deficits in Brattleboro rats

We previously reported that vasopressin deficient Brattleboro (BRAT) rats exhibit deficits in prepulse inhibition (PPI) of the startle reflex that are consistent with PPI deficits exhibited by patients with schizophrenia and other neuropsychiatric disorders. Preliminary evidence indicates that this may be the basis of a predictive model for antipsychotic drug efficacy. Here we report the effects of acute and chronic administration of established and putative antipsychotics on these PPI deficits. BRAT rats, compared to their derivative strain, Long Evans rats, exhibited significantly decreased PPI and startle habituation consistent with patients with schizophrenia and other neuropsychiatric disorders. The second generation antipsychotics, risperidone and clozapine as well as a neurotensin agonist (PD149163) increased BRAT rat PPI, whereas saline, the typical antipsychotic, haloperidol, and a vasopressin analog (1-desamino-D-arginine vasopressin) did not. Similar to their effects in humans, chronic administration of antipsychotic drugs produced stronger effects than acute administration. These results further support the BRAT rat as a model of sensorimotor gating deficits with predictive validity for antipsychotics. The model appears to be able to differentiate first generation from second generation antipsychotics, identify putative antipsychotics with novel mechanisms (i.e., peptides) and reasonably model the therapeutic time course of antipsychotic drugs in humans.     

Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function

CONTEXT: Patients with schizophrenia exhibit deficits in automatic, preattentive sensorimotor gating (prepulse inhibition [PPI]) of the startle reflex. OBJECTIVE: To assess the relationships between PPI deficits and demographic, clinical, neurocognitive, and functional status in a large cohort of patients with schizophrenia. DESIGN: Cross-sectional comparison of patients with schizophrenia and normal comparison subjects. SETTING: University-based psychophysiology laboratory. PARTICIPANTS: Carefully screened patients with schizophrenia (n = 103) and normal comparison subjects (n = 66). MAIN OUTCOME MEASURES: Participants were assessed in structured clinical interviews and tested in measures of acoustic startle PPI and neurocognition. The level of functioning was assessed in patients using validated scales. Analyses first compared all of the patients vs normal comparison subjects. Patients were then divided based on sex, medications, smoking status, and levels of PPI. The associations of PPI to clinical, neurocognitive, and functional variables were assessed using both continuous and categorical analyses. RESULTS: Compared with normal comparison subjects, patients exhibited PPI deficits at 60-millisecond intervals but not at 30- or 120-millisecond intervals. In addition, patients exhibited deficits in neurocognition. Among patients, PPI levels were associated with sex (higher in men than in women), medication status (highest in patients treated with atypical antipsychotics), and smoking (higher in smokers than in nonsmokers). Compared with patients in the highest quartile of PPI, those in the lowest quartile of PPI were significantly more impaired on specific functional measures but did not differ in neurocognitive measures or symptom severity. The relationship between low PPI and functional impairment was most pronounced and orderly in male patients. CONCLUSIONS: These findings highlight several important factors (sex, medications, and smoking status) that strongly impact the study and interpretation of PPI deficits in patient populations. These results also support the concept that deficient PPI is associated with impaired functional status in schizophrenia.     

Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits

OBJECTIVE: Patients with schizophrenia spectrum disorders have been shown to have deficits in sensorimotor gating as assessed by prepulse inhibition of the startle response. The authors hypothesized that nonschizophrenic relatives of patients with schizophrenia would also have prepulse inhibition deficits, thereby reflecting a genetically transmitted susceptibility to sensorimotor gating deficits. METHOD: Twenty-five comparison subjects, 23 patients with schizophrenia, 34 relatives of the schizophrenic patients, and 11 subjects with schizotypal personality disorder were assessed in an acoustic startle paradigm. The eye-blink component of the startle response was assessed bilaterally by using electromyographic recordings of orbicularis oculi. RESULTS: The patients with schizophrenia, their relatives, and subjects with schizotypal personality disorder all had reduced prepulse inhibition relative to comparison subjects, and these deficits were more evident in measures of right eye-blink prepulse inhibition. Comparison subjects demonstrated greater right versus left eye-blink prepulse inhibition, whereas the probands, their relatives, and subjects with schizotypal personality disorder showed less asymmetry of prepulse inhibition. CONCLUSIONS: These data suggest a genetically transmitted deficit in prepulse inhibition (sensorimotor gating) in patients with schizophrenia spectrum disorders, including subjects with schizotypal personality disorder and relatives of patients with schizophrenia.     

A large single ethnicity study of prepulse inhibition in schizophrenia: Separate analysis by sex focusing on effect of symptoms

Deficits in sensorimotor gating, as measured with prepulse inhibition (PPI), have been considered an endophenotype of schizophrenia. However, the question remains whether these deficits are related to current symptoms. This single site study aimed to explore clinical features related to the modulation of startle reflex in a large sample of Japanese patients with schizophrenia (DSM-IV). The subjects comprised 181 patients and 250 healthy controls matched for age and sex. Schizophrenia symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Startle reflex to acoustic stimuli was recorded using a startle stimulus of 115 dB and a prepulse of four different conditions (intensity: 86 dB or 90 dB; lead interval: 60 ms or 120 ms). Patients exhibited significantly reduced startle magnitude (p < 0.001), habituation (p = 0.001), and PPI (90 dB, 60 ms, p = 0.016; 90 dB, 120 ms, p = 0.001) compared with controls. Patients of both sexes exhibited significantly lower habituation and PPI (90 dB, 120 ms) compared with the same sex controls. We could not detect a significant correlation with any clinical variable in the entire patients, however, when men and women were examined separately, there was a negative correlation with the PANSS cognitive domain (ρ = −0.33, p = 0.008) in men, but not in women. Moreover, when patients were subdivided into four clusters, two clusters with high positive symptoms showed significant PPI deficits in men. Our results suggest that sensorimotor gating is impaired in schizophrenia of both sexes, and PPI deficits may be related to thought disturbance and disorganization in male patients with schizophrenia.     

Heterozygous reeler mice exhibit alterations in sensorimotor gating but not presynaptic proteins

Post mortem, reduced brain reelin is noted in schizophrenia. Accordingly, the reelin-haploinsufficient heterozygous reeler mouse (HRM) has been posited as a murine model of the illness. One study reported that HRM exhibit deficits in prepulse inhibition (PPI) of the acoustic startle reflex, a sensorimotor-gating behavior that is disrupted in schizophrenia, although this finding has not been reproduced. To extend the characterization of putative sensorimotor-gating deficits in HRM, these mice were subjected to a sophisticated series of PPI tests. Mice were tested in a cross-modal PPI protocol that combined an acoustic prepulse with a tactile startle stimulus and also in a protocol that included varying prepulse–pulse intervals and varying acoustic startle pulse intensities. Levels of acoustic startle habituation and cross-modal PPI were significantly lower in HRM, although unimodal PPI did not differ. The HRM also exhibited increased PPI compared to wildtypes at short interstimulus intervals between prepulse and pulse stimuli when the interval between the acoustic prepulse and pulse were varied, and were more reactive to higher intensity startle stimuli. Some of these deficits in sensorimotor gating parallel those of schizophrenia, a disease characterized by alterations in synaptic protein expression. Therefore, levels of presynaptic proteins were measured in multiple brain regions using ELISA in HRM. No significant alterations in presynaptic protein expression were found. Thus, HRM exhibit a complex pattern of changes in startle reactivity and sensorimotor gating, with both similarities to and differences from schizophrenia. However, it is unlikely that these behavioral differences may be accounted for by altered regional levels of presynaptic proteins.     

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

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-na?ve 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.     

Impaired prepulse inhibition and prepulse-elicited reactivity but intact reflex circuit excitability in unmedicated schizophrenia patients: a comparison with healthy subjects and medicated schizophrenia patients

Deficient sensorimotor gating as indexed by prepulse inhibition (PPI) of the startle response has been reported repeatedly in patients suffering from schizophrenia. According to the widely accepted "protective hypothesis," PPI reflects the protection of ongoing information processing against interference by other stimuli. Alternatively, it has been proposed that PPI might be regulated by startle reflex circuit excitability. In the present study, we evaluated these 2 conceptually divergent approaches underlying the regulation of PPI. To this end, we assessed sensorimotor gating as indexed by PPI, the reactivity to the prepulse-alone stimulus indexed as prepulse-elicited reactivity (PPER), and acoustic blink reflex excitability in terms of paired pulse suppression (PPS) within a single recording session in 13 unmedicated and 24 medicated (11 first break) schizophrenia patients in comparison to 43 healthy control subjects. The results showed that PPI was significantly reduced in unmedicated, but not in medicated schizophrenia patients. Furthermore, unmedicated patients could be distinguished from the medicated patients and control subjects in terms of PPER. In contrast to PPI, PPS did not differ between patients and control subjects. These findings are in line with the "protective hypothesis" of PPI and indicate that reduced sensorimotor gating in schizophrenia patients might be based on a reduced perception and/or processing of the prepulse stimulus. The extent to which PPER may or may not be causally associated with sensorimotor gating in schizophrenia has to be further investigated in human and animal studies.