OBJECTIVE:The objective of the study was to assess depressive symptoms (DS) and difficulties in emotion regulation (ER) in adult people with epilepsy (PWE) and their correlation with quality of life and stigmatization feelings of patients. MATERIALS AND METHODS:We enrolled consecutively 110 PWE who completed the Beck Depression Inventory-II (BDI-II) questionnaire and, for the first time, the Italian translation of Difficulties in Emotion Regulation Scale (DERS) to evaluate DS and ER. They also fulfilled the Italian version of the Stigma Scale of Epilepsy (SSE), which allowed the quantification of the stigma perception by our cohort of patients and a 3-item Jacoby's Stigma Scale (JSS) and QOLIE-31 (Q31) for the evaluation of stigma and the quality of life. The results of BDI-II and DERS were correlated with clinical details of PWE, as well as the Q31 and SSE scores. Finally, a multiple stepwise regression analysis was applied to identify the main factors affecting DS and ER difficulties in these patients. RESULTS:About 30% of PWE evidenced DS, of which 17.3% showed a BDI-II score higher than 19, suggestive of moderate to severe DS. Several factors related to epilepsy (seizure frequency, number of antiepileptic drugs (AEDs)) as well as ER and quality of life/stigmatization perception resulted significantly correlated with DS. As a new finding, the main factors affecting DS in PWE turned out to be the difficulties in ER and quality of life and stigma perception (as evaluated through Q31 and JSS scores). CONCLUSIONS:Our findings evidenced that DS in PWE are highly prevalent and strongly correlated with ER difficulties that mostly influence DS together with quality of life and stigma perception. Depressive symptoms and emotion dysregulation are linked by a bidirectional relationship and are significantly associated with worse quality of life and higher stigmatization feelings.