Can adaptive hyperactivation result in a positive score on the Mood Disorder Questionnaire? Evidence from a case-control study over a community survey

Michela Atzeni¹Michele Fornaro²Massimo Tusconi^3*Cesar Ivan Aviles Gonzalez⁴Elisa Cantone¹Elisa Pintus¹Serdar M Dursun⁵Antonio E Nardi⁶Federica Sancassiani¹Mauro Giovanni Carta^1,7,8

• ¹Department of Medical Sciences and Public Health, University of Cagliari, Monserrato Blocco I (CA), 09042 Cagliari, Italy, Cagliari, Italy
• ²Department of Neuroscience, Reproductive Science and Odontostomatology Federico II University of Naples, 80131 Naples, Italy, Naples, Italy
• ³University Hospital of Cagliari, Cagliari, Italy
• ⁴Department of Medicine and Surgery, University of Kore, Piazza dell'Università, 94100 Enna EN, Italy, Enna, Italy
• ⁵Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB, Canada, Edmonton, Canada
• ⁶Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro, 22290-140 Rio de Janeiro, RJ, Brazil, Rio de Janeiro, Brazil
• ⁷PhD Program in Tropical Medicine, Universidad Popular del Cesar, Valledupar, 200001, Colombia, Valledupar, Colombia
• ⁸Department of Nursing, Universidad Popular del Cesar, Valledupar 200001, Colombia, Valledupar, Colombia

Background: Bipolar Disorder (BD) remains challenging to identify, and the Mood Disorder Questionnaire (MDQ) may capture heterogeneous forms of hyperactivation, including adaptive patterns unrelated to psychopathology. 2 Objectives: To determine whether MDQ-positive individuals include a subgroup with adaptive hyperactivation— characterized by high quality of life (QoL) and minimal psychiatric morbidity—and to examine whether MDQ positivity also identifies diagnoses beyond BD. Methods: Using data from a large Italian community survey with DSM-IV clinical interviews and MDQ screening, we conducted a case–control analysis. MDQ-positive individuals were stratified by SF-12 QoL scores (>40 vs. ≤40), and matched MDQ-negative controls were selected by age and sex. Psychiatric diagnoses were compared using ANOVA and chi-square tests. Results: Among 91 MDQ-positive participants, 33% showed high QoL and exhibited markedly fewer psychiatric diagnoses than those with low QoL (χ²=15.529, p<0.0001). High-QoL MDQ-positive individuals displayed psychiatric morbidity comparable to MDQ-negative controls, whereas low-QoL MDQ-positive individuals showed excess anxiety, obsessive–compulsive, and eating disorders. Conclusions: MDQ positivity identifies a heterogeneous population, including individuals with adaptive hyperactivation and preserved functioning. These findings highlight the need for more refined instruments capable of distinguishing adaptive from pathological hyperactivation and caution against over-pathologizing MDQ positivity in clinical and public health settings.