Elsevier

Biological Psychiatry

Volume 64, Issue 9, 1 November 2008, Pages 766-773
Biological Psychiatry

Archival Report
Impaired Sensorimotor Gating of the Acoustic Startle Response in the Prodrome of Schizophrenia

https://doi.org/10.1016/j.biopsych.2008.04.019Get rights and content

Background

Schizophrenia patients exhibit impairment in prepulse inhibition (PPI) of the acoustic startle response (ASR), which is commonly interpreted as a sensorimotor gating deficit. To date, it is unclear when these gating deficits arise. Results of animal studies and some human data suggest that PPI deficits are in part genetically determined, such that gating deficits could be present before the onset of a full-blown psychosis. To test this assumption, we investigated PPI of ASR in individuals with prodromal symptoms of schizophrenia and patients with first-episode schizophrenia.

Methods

Startle reactivity, habituation, and PPI of ASR, as well as a neuropsychological test battery, were assessed in 54 subjects with prodromal symptoms of schizophrenia (35 early and 19 late prodromal subjects), 31 first-episode schizophrenia patients (14 unmedicated, 17 medicated), and 28 healthy control subjects. Patients were also examined with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale.

Results

Prodromal subjects and unmedicated patients with first-episode schizophrenia showed significant PPI deficits, whereas schizophrenia patients treated with risperidone had almost normal PPI. Startle reactivity decreased with greater severity of symptoms (control subjects, early prodromal group > late prodromal group > unmedicated first-episode patients) but was almost normal in the medicated patients. With respect to habituation, prodromal subjects and schizophrenia patients did not differ from healthy control subjects.

Conclusions

PPI disruption is already present in a prodromal state of schizophrenia, but startle reactivity deficits seem to emerge with the onset of acute psychosis.

Section snippets

Participants

Subjects with symptoms suggestive of either early or late prodromal stages were recruited as described previously (31). In brief, subjects were screened by general practitioners, counseling services or secondary health care providers using the 17-item Early Recognition Inventory/Interview for the Retrospective Assessment of the Onset of Schizophrenia (ERIraos) checklist (31). Persons scoring six points or higher were referred to the Early Recognition and Intervention Center at the Department of

Demographic and Clinical Data

Demographic data and clinical data are shown in Table 1. Multiple and single comparisons with Chi-Square tests revealed no significant differences with respect to sex and smoking, and analysis of variance (ANOVA) showed no significant differences with respect to years of education or verbal IQ between the groups. However, an ANOVA revealed a significant group effect for age (p < .01). LSD post hoc tests showed that both EP and LP were younger than US (p < .05) and MS (p < .01). However, the

Discussion

This study is the first to investigate PPI, habituation, and startle reactivity of the ASR in individuals fulfilling research diagnostic criteria of a psychotic prodrome. The major finding is that prodromal subjects had a significant PPI deficit. This was true for both early and late prodromal subgroups. As expected, we could also demonstrate reduced PPI in unmedicated first-episode schizophrenia patients, whereas medicated schizophrenia patients did not differ from control subjects. Further

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      These results indicate that the startle habituation dysfunction in the RHA rats is only present in adulthood, similar to the results of PPI observed in male RLA rats, although the possibility of a floor effect cannot be dismissed regarding the absence of differences in the prepubescent and adolescent rats. These results seem consistent with some studies in humans that show that schizophrenia patients exhibit impaired startle habituation in the acute phase of the illness [23,24]. Nevertheless, some studies found this alteration [19,74,75], whereas in other reports this alteration was not found [76–80].

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