Two Factors, Five Factors, or Both? External Validation Studies of Negative Symptom Dimensions in Schizophrenia

Author:

Ahmed Anthony O1,Kirkpatrick Brian2,Granholm Eric34ORCID,Rowland Laura M5,Barker Peter B67,Gold James M5,Buchanan Robert W5,Outram Tacina1,Bernardo Miguel891011,Paz García-Portilla María10121314,Mane Anna101516,Fernandez-Egea Emilio1718ORCID,Strauss Gregory P19

Affiliation:

1. Department of Psychiatry, Weill Cornell Medicine, White Plains, NY, USA

2. Department of Psychiatry, University of Nevada, Reno School of Medicine, Reno, NV, USA

3. Department of Psychiatry, University of California, San Diego, San Diego, CA, USA

4. Psychology Service, VA San Diego Healthcare System, San Diego, CA, USA

5. Department of Psychiatry and Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA

6. The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

7. FM Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA

8. Barcelona Clinic Schizophrenia Unit, Hospital Clinic of Barcelona, Neuroscience Institute, Barcelona, Spain

9. Department of Medicine, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain

10. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain

11. August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain

12. Department of Psychiatry, Universidad de Oviedo, Oviedo, Spain

13. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

14. Servicio de Salud del Principado de Asturias (SESPA), Oviedo, Spain

15. Institut de Neuropsiquiatria i Adiccions, Parc de Salut Mar, Barcelona, Spain

16. Fundació Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain

17. Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK

18. Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK

19. Departments of Psychology and Neuroscience, University of Georgia, Athens, GA, USA

Abstract

Abstract Objectives Negative symptom studies frequently use single composite scores as indicators of symptom severity and as primary endpoints in clinical trials. Factor analytic and external validation studies do not support this practice but rather suggest a multidimensional construct. The current study used structural equation modeling (SEM) to compare competing dimensional models of negative symptoms to determine the number of latent dimensions that best capture variance in biological, psychological, and clinical variables known to have associations with negative symptoms. Methods Three independent studies (total n = 632) compared unidimensional, two-factor, five-factor, and hierarchical conceptualizations of negative symptoms in relation to cognition, psychopathology, and community functioning (Study 1); trait emotional experience and defeatist performance beliefs (Study 2); and glutamate and gamma-aminobutyric acid levels in the anterior cingulate cortex quantified using proton magnetic resonance spectroscopy (Study 3). Results SEM favored the five-factor and hierarchical models over the unidimensional and two-factor models regardless of the negative symptom measure or external validator. The five dimensions—anhedonia, asociality, avolition, blunted affect, and alogia—proved vital either as stand-alone domains or as first-order domains influenced by second-order dimensions—motivation and pleasure and emotional expression. The two broader dimensions sometimes masked important associations unique to the five narrower domains. Avolition, anhedonia, and blunted affect showed the most domain-specific associations with external variables across study samples. Conclusions Five domains and a hierarchical model reflect the optimal conceptualization of negative symptoms in relation to external variables. Clinical trials should consider using the two dimensions as primary endpoints and the five domains as secondary endpoints.

Funder

National Institute of Health

Publisher

Oxford University Press (OUP)

Subject

Psychiatry and Mental health

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