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Startle Gating Deficits in a Large Cohort of Patients With Schizophrenia: Relationship to Medications, Symptoms, Neurocognition, and Level of Function
Abstract
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.
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“A weak tone initiates habituation of the reticular neurons’ response to a successive louder tone, leading to the phenomenon of prepulse inhibition (PPI) of the acoustic startle response (7, 8).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [7]
In the citing paper
“The deficit in PPI is most prominent in schizophrenia when the weaker tone precedes the startling sound by 60 msec (7).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [7]
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Metadata
- Authors
- Swerdlow, N. R., Light, G. A., Cadenhead, K. S., Sprock, J., Hsieh, M. H., & Braff, D. L.
- Affiliations
- University of California San Diego (US)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2006-12-01
- Volume
- 63
- Issue
- 12
- Pages
- 1325-35
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2169289621
- Cited by
- 339
- References
- 101
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 12 · 2022: 8 · 2021: 8 · 2020: 14 · 2019: 7 · 2018: 10 · 2017: 19 · 2016: 19 · 2015: 25 · 2014: 17 · 2013: 16 · 2012: 26
- FWCI
- 16.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH069589, MH65571, MH69589, MH42228, MH 01436, MH60720, K02MH001436, R01MH060720, R01MH065571)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, prepulse inhibition, sensorimotor gating, acoustic startle response, neurocognitive function, functional disability, sex differences, atypical antipsychotics, smoking, antipsychotic effects
- MeSH terms
- Acoustic Stimulation, Adolescent, Adult, Aged, Auditory Perception, Cognition Disorders, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Neural Inhibition, Neuropsychological Tests, Psychiatric Status Rating Scales, Reaction Time, Schizophrenia, Schizophrenic Psychology, Sex Factors, Smoking, Reflex, Startle, Antipsychotic Agents, Cohort Studies
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