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Objective To assess the psychometric properties of the Italian adaptation of the Hypomania-Check-List 32-item, second revision (HCL-32-R2) for the detection of bipolarity in major depressive disorder (MDD) treatment-seeking outpatients. Methods A back-to-back Italian adaption of the “Bipolar Disorders: Improving Diagnosis, Guidance, and Education” English module of the HCL-32-R2 was administered between March 2013 and October 2014 across twelve collaborating sites in Italy. Diagnostic and Statistical Manual Fourth edition (DSM-IV) diagnoses were made adopting the mini-international neuropsychiatric interview, using bipolar disorder (BD) patients as controls. Results In our sample ( n =441, of whom, BD-I=68; BD-II=117; MDD=256), using a cut-off of 14 allowed the HCL-32-R2 to discriminate DSM-IV-defined MDD patients between “true unipolar” (HCL-32-R2 − ) and “sub-threshold bipolar depression” (HCL-32-R2 + ) with sensitivity=89% and specificity=79%. Area under the curve was .888; positive and negative predictive values were 75.34% and 90.99% respectively. Owing to clinical interpretability considerations and consistency with previous adaptations of the HCL-32, a two-factor solution (F1=“ hyperactive / elated ” vs. F2=“ irritable / distractible / impulsive ”) was preferred using exploratory and confirmatory factor analyses, whereas items n.33 (“ I gamble more ”) and n.34 (“ I eat more ”) introduced in the R2 version of the scale slightly loaded onto F2 and F1 respectively. Cronbach׳s α=.88 for F1 and .71 for F2. Limitations No cross-validation with any additional validated screening tool; treatment-seeking outpatient sample; recall bias; no systematic evaluation of eventual medical/psychiatric comorbidities, current/lifetime pharmacological history, neither record of severity of current MDE. Conclusions Our results seem to indicate fair accuracy of HCL-32 as a screening instrument for BD, though replication studies are warranted. [ABSTRACT FROM AUTHOR]