Mosaic trisomy 20 is a genetic condition in which three chromosomes 20 are found in some cells. Its clinical phenotype seems to be highly variable, with most features not reported across all individuals and not considered pathognomonic of the condition. Limited and recent evidence indicates that neuropsychiatric manifestations may be more present in the context of trisomy 20 than was once thought. Here, we present a case of a 14-year-old female adolescent of White/Caucasian ethnicity with mosaic trisomy 20, who was admitted twice to an inpatient Child and Adolescent Neuropsychiatry Unit for persisting self-injury and suicidal ideation. A severe and complex neuropsychiatric presentation emerged at the cognitive, emotional, and behavioral levels, including mild neurodevelopmental issues, isolation, socio-relational difficulties, depressed mood, temper outbursts, irritability, low self-esteem, lack of interest, social anxiety, panic attacks, self-cutting, and low-average-range and heterogeneous intelligence quotient profile. Particularly, the patient was considered at high risk of causing harm, mainly to self, and appeared to be only partially responsive to medication, even when polypharmacy was attempted to improve clinical response. Except for school bullying, no other severe environmental risk factors were present in the patient’s history. The patient received a diagnosis of disruptive mood dysregulation disorder.

Youth with Attention-Deficit Hyperactivity Disorder (ADHD) may suffer from comorbid difficulties, such as anxiety–depressive symptoms, social withdrawal, and somatic complaints. Although stimulants remain the ADHD cornerstone treatment, mental fatigue, school problems and low self-esteem may persist, often being the most unacceptable symptoms for these patients. We present two cases of adolescents (14 and 15 years old) with methylphenidate-treated ADHD, where cognitive fatigability, depressive thoughts, anxiety, irritability, and poor social relationships remained. Based on clinical observation and the completion of parent and child rating scales, the aforementioned manifestations appeared to progressively reduce by the time of the subsequent control visits planned 1, 3, and 5 months after, following the use of vortioxetine (up to 10 mg/day) as add-on therapy to methylphenidate. No significant side effects were reported in both cases in a follow-up period of 3 months, also supporting the stability of the observed clinical improvement. Vortioxetine monotherapy has already been tested for the treatment of anxiety–depressive symptoms in youth, as well as ADHD in adulthood. The cases presented here suggest that vortioxetine could also be an effective option for ADHD treatment in childhood and adolescence, warranting further investigation of its potential benefits as both a monotherapy and adjunctive therapy to stimulants.