Hyperarousal transdiagnostically dissected: different dimensions characterize mood, anxiety, insomnia, posttraumatic stress and attention deficit hyperactivity disorders.

Background: Hyperarousal is a common symptom key to the severity of insomnia-, depression-, anxiety-, posttraumatic stress- and attention deficit/hyperactivity disorders. Hyperarousal however remained a loosely defined construct assessed with different questionnaires in different disorders. Here we addressed the unresolved question whether hyperarousal may be one common transdiagnostic construct or rather has multiple, possibly disorder-specific, dimensions. Methods: In this cohort study, participants were recruited through media and from the Netherlands Sleep Registry between Dec 2023 and June 2024. We included 467 adults (mean age 58.3 years [range 21-89]; 77.6% female) with a wide range of psychiatric diagnoses and severities who completed all hyperarousal questionnaires and disorder symptom severity scales (Insomnia Severity Index, Rapid Measurement Toolkit-20, and ADHD Self-Report Scale). Factor analyses evaluated potential dimensions in hyperarousal assessed with 221 items from 18 questionnaires. Multiple regression models were used to reveal profiles of the most relevant hyperarousal dimensions associated with the symptom severity of insomnia disorder, major depressive disorder, generalized anxiety disorder, social anxiety disorder, panic disorder, posttraumatic stress disorder and attention deficit/hyperactivity disorders. We used 27 selected items representing the seven dimensions of hyperarousal to create the Transdiagnostic Hyperarousal Dimensions Questionnaire (THDQ). A second sample was recruited between March 2025 and April 2025 for confirmation and validation (n = 592; mean age 61.0 years [range 19-89]; 65.2% female), who completed the THDQ. To examine the possibility to estimate hyperarousal dimension factor scores using available UK Biobank items, we calculated the polychoric correlation between the 27 selected items and 22 UK Biobank items in 467 adults. Findings: Exploratory factor analysis identified 7 dimensions, explaining 50.2% of the variance and representing anxious-, somatic-, sensitive-, sleep-related-, irritable-, vigilant- and sudomotor hyperarousal. Multiple regression models showed that hyperarousal dimensions differentially correlated with the severity of insomnia, major depression, anxiety, panic, posttraumatic stress and attention deficit/hyperactivity disorder symptoms (standardized beta-coefficients = -0.10 to 0.70). We next developed and validated a 27-item THDQ, reliably assessing each dimension (CFI = 0.92, RMSEA = 0.05, Cronbach's alpha = 0.90). Finally, we showed that UK Biobank items can estimate anxious, irritable and sleep-related hyperarousal (r = 0.75-0.85). Interpretation: Distinguishing different hyperarousal dimensions, enabled by the THDQ, can propel our understanding of hyperarousal to provide clues for better treatment of multiple mental disorders. Funding: European Research Council (ERC) and ZonMw (partnership between Care Research Netherlands and Dutch Research Council).