by Anzalee Khan, PhD; Lora Liharska, MS; Philip D. Harvey, PhD; Alexandra Atkins, PhD; Daniel Ulshen, BA; and Richard S.E. Keefe, PhD

Dr. Khan is Senior Biostatistician at NeuroCog Trials and holds an appointment in the Psychopharmacology Research Program at the Nathan S. Kline Institute for Psychiatric Research in Orangeburg, New York. Ms. Liharska is a researcher at Columbia University Medical Center in New York, New York. Dr. Harvey is Professor of Psychiatry and Behavioral Sciences at the University of Miami School of Medicine in Miami, Florida. Dr. Atkins and Mr. Ulshen are employees of NeuroCog Trials. Dr. Keefe is an employee of NeuroCog Trials and Professor of Psychiatry and Behavioral Sciences at Duke University Institute for Brain Sciences in Chapel Hill, North Carolina.

Funding: This study is a secondary analysis of existing data, so it received no funding from any agency in the public, commercial, or non-profit sectors.

Disclosures: Dr. Khan currently or in the past three years has received funding support, received honoraria, served as a consultant, and served as a speaker for the National Institute of Mental Health, the Research Foundation for Mental Hygiene, Inc., the NY State Office of Mental Health, the Qatar Foundation at Weill Cornell Medicine, and eResearch Technologies. She also holds positions at NeuroCog Trials and at Manhattan Psychiatric Center Nathan S. Kline Institute for Psychiatric Research. Ms. Liharska has no conflicts of interest relevant to the content of this article. Dr. Harvey has served as a consultant to AbbVie, Allergan, Akili, Boehringer Ingelheim, Forum Pharmaceuticals, Genentech, Lundbeck Pharmaceuticals, Otsuka Digital Health, Roche Pharma, Sanofi, Sunovion, and Takeda Pharmaceuticals for the past three years. Dr. Atkins currently or in the past three years has received funding from the National Institute of Mental Health and the National Institute on Aging, and is a full-time employee of NeuroCog Trials. Mr. Ulshen is a full-time employee of NeuroCog Trials. Dr. Keefe currently or in the past three years has received investigator-initiated research funding support from the Department of Veteran’s Affairs, the Feinstein Institute for Medical Research, the National Institute of Mental Health, the Research Foundation for Mental Hygiene, Inc., and the Singapore National Medical Research Council. He currently or in the past three years has received honoraria, served as a consultant, speaker, or advisory board member for Abbvie, Acadia, Akebia, Akili, Alkermes, Astellas, Asubio, Avanir, AviNeuro/ChemRar, Axovant, Biogen, BiolineRx, Biomarin, Boehringer-Ingelheim, Cerecor, CoMentis, FORUM, Global Medical Education (GME), GW Pharmaceuticals, Intracellular Therapeutics, Janssen, Lundbeck, MedScape, Merck, Minerva Neurosciences Inc., Mitsubishi, Moscow Research Institute of Psychiatry, Neuralstem, Neuronix, Novartis, NY State Office of Mental Health, Otsuka, Pfizer, Reviva, Roche, Sanofi, Shire, Sunovion, Takeda, Targacept, University of Moscow, University of Texas Southwest Medical Center, and WebMD. He is also a shareholder in NeuroCog Trials, Inc., and in Sengenix.

Abstract: Objective: Recognizing the discrete dimensions that underlie negative symptoms in schizophrenia and how these dimensions are understood across localities might result in better understanding and treatment of these symptoms. To this end, the objectives of this study were to 1) identify the Positive and Negative Syndrome Scale negative symptom dimensions of expressive deficits and experiential deficits and 2) analyze performance on these dimensions over 15 geographical regions to determine whether the items defining them manifest similar reliability across these regions.

Design: Data were obtained for the baseline Positive and Negative Syndrome Scale visits of 6,889 subjects across 15 geographical regions. Using confirmatory factor analysis, we examined whether a two-factor negative symptom structure that is found in schizophrenia (experiential deficits and expressive deficits) would be replicated in our sample, and using differential item functioning, we tested the degree to which specific items from each negative symptom subfactor performed across geographical regions in comparison with the United States.

Results: The two-factor negative symptom solution was replicated in this sample. Most geographical regions showed moderate-to-large differential item functioning for Positive and Negative Syndrome Scale expressive deficit items, especially N3 Poor Rapport, as compared with Positive and Negative Syndrome Scale experiential deficit items, showing that these items might be interpreted or scored differently in different regions. Across countries, except for India, the differential item functioning values did not favor raters in the United States.

Conclusion: These results suggest that the Positive and Negative Syndrome Scale negative symptom factor can be better represented by a two-factor model than by a single-factor model. Additionally, the results show significant differences in responses to items representing the Positive and Negative Syndrome Scale expressive factors, but not the experiential factors, across regions. This could be due to a lack of equivalence between the original and translated versions, cultural differences with the interpretation of items, dissimilarities in rater training, or diversity in the understanding of scoring anchors. Knowing which items are challenging for raters across regions can help to guide Positive and Negative Syndrome Scale training and improve the results of international clinical trials aimed at negative symptoms.

Keywords: Schizophrenia, Positive and Negative Syndrome Scale, PANSS, negative symptoms, expressive deficits, experiential deficits

Innov Clin Neurosci. 2017;14(11–12):30–40

Category: Assessment Tools, Drug Development, Mental Disorders, Original Research, Past Articles, Patient Assessment, Psychiatry, Psychopharmacology, Scales, Schizophrenia, Study Protocol, Trial Methodology