Delineating psychological and biomedical profiles in a heterogeneous fibromyalgia population using cluster analysis

Abstract

The heterogeneity of patients meeting American College of Rheumatology (ACR) criteria for a diagnosis of fibromyalgia (FM) challenges our ability to understand the underlying pathogenesis and to optimize treatment of this enigmatic disorder. Our goal was to discern clinically relevant subgroups across multiple psychological and biomedical domains to better characterize the phenomenology of FM. Women meeting 1990 ACR criteria for FM (N = 107) underwent psychological (childhood trauma, mood, anxiety, and stress) and biomedical (neuroendocrine, immune, and metabolic) testing. Cluster analysis identified four distinct subgroups. Subgroups I, II, and III exhibited profiles that included high psychological distress. Subgroup I was further distinguished by a history of childhood maltreatment and hypocortisolism, and these women reported the most pain and disability. Subgroup II evinced more physiological dysregulation and also reported high levels of pain, fatigue, and disability. Subgroup III was characterized by normal biomarkers and reported intermediate pain severity with higher global functioning. Subgroup IV was distinguished by their psychological well-being, reporting less disability and pain. Our findings underscore the heterogeneity of both psychological and physiological features among FM patients presenting with nearly identical tender point counts. This subgroup categorization is compatible with hypothesized pathogenetic mechanisms of early trauma, stress system dysregulation, and pro-inflammatory bias, each prominent in some but not all FM patients. Appreciation of distinct FM subgroup features is invaluable for selecting the most appropriate treatment modalities.

Fig. 1

Psychological and biomedical profiles of FM subgroups. Cluster I (N = 19) was named Maltreated; Cluster II (N = 20), Dysregulated Biology; Cluster III (N = 36), Normal Biology; Cluster IV (N = 18), Positive Outlook. CTQ = Childhood Maltreatment Questionnaire; PSS = Perceived Stress Scale; Anx = General Distress from Anxiety Symptoms; PA/NA = the ratio of positive-to-negative affect; Chol = total cholesterol (mg/dL); HA_1c = Hemoglobin A_1c; CrCl = creatinine clearance; cort = cortisol; GH = growth hormone; Testo = testosterone; NK = natural killer cell counts; ESR = erthrocyte sedimentation rate (mm/hr); ANA = antinuclear antibody titers.

Fig. 2

Subgroup differences in the FM symptoms of subjective pain, measured by the Visual Analogue Scale, and Global Assessment of Functioning, assessed with a Structured Clinical Interview for DSM-IV.