Abstract
ObjectivesEndophenotypes in schizophrenia research is a contemporary approach to studying this heterogeneous mental illness, and several candidate neurophysiological markers (e.g. P50 sensory gating) and neuropsychological tests (e.g. Continuous Performance Test (CPT) and Wisconsin Card Sorting Test (WCST)) have been proposed. However, the clinical utility of a single marker appears to be limited. In the present study, we aimed to construct a diagnostic model incorporating P50 sensory gating with other neuropsychological tests in order to improve the clinical utility.MethodsWe recruited clinically stable outpatients meeting DSM-IV criteria of schizophrenia and age- and gender-matched healthy controls. Participants underwent P50 sensory gating experimental sessions and batteries of neuropsychological tests, including CPT, WCST and Wechsler Adult Intelligence Scale Third Edition (WAIS-III).ResultsA total of 106 schizophrenia patients and 74 healthy controls were enrolled. Compared with healthy controls, the patient group had significantly a larger S2 amplitude, and thus poorer P50 gating ratio (gating ratio = S2/S1). In addition, schizophrenia patients had a poorer performance on neuropsychological tests. We then developed a diagnostic model by using multivariable logistic regression analysis to differentiate patients from healthy controls. The final model included the following covariates: abnormal P50 gating (defined as P50 gating ratio >0.4), three subscales derived from the WAIS-III (Arithmetic, Block Design, and Performance IQ), sensitivity index from CPT and smoking status. This model had an adequate accuracy (concordant percentage = 90.4%; c-statistic = 0.904; Hosmer-Lemeshow Goodness-of-Fit Test, p = 0.64>0.05).ConclusionTo the best of our knowledge, this is the largest study to date using P50 sensory gating in subjects of Chinese ethnicity and the first to use P50 sensory gating along with other neuropsychological tests to develop a diagnostic model for schizophrenia. Further research to validate the predictive accuracy of this model by applying it on other samples is warranted.
Highlights
Schizophrenia, a complex psychiatric disorder, clinically encompasses heterogeneous syndromal presentations and pathogenetically involves complicated neurobiological process
A growing body of evidence has suggested several candidate endophenotypes in schizophrenia, including neurophysiological markers (e.g. auditory event-related potentials (ERPs), such as P50, P300 and Mismatch Negativity), and neuropsychological tests, some of which have been successfully linked to specific genetic components [1,2,3]
P50 gating ratio, derived from the S2 amplitude divided by S1 amplitude, is the most commonly used index for P50 sensory gating
Summary
Schizophrenia, a complex psychiatric disorder, clinically encompasses heterogeneous syndromal presentations and pathogenetically involves complicated neurobiological process. The lack of specific corresponding relationships between various phenotypes and neurobiological bases makes it difficult to elucidate the etiology of this mental illness, which is true based upon the phenomenological approach of the contemporary psychiatric classification system To address this issue, utilizing the concept of endophenotype, i.e. a state-independent intermediate marker, in schizophrenia research has been proposed and widely adopted [1]. It has been related to the high prevalence of cigarette smoking in schizophrenia patients, by which, as self-medication, psychiatric symptoms can be alleviated through improving P50 sensory gating deficits [9]. It remains unclear about the relationship between P50 sensory gating and long-term nicotine exposure. These findings support that P50 sensory gating may be qualified as an endophenotype for schizophrenia
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