PROJECT ABSTRACT - Paediatric Bipolar Disorder (BD) with comorbid attention deficit hyperactivity (ADHD)

 Methylphenidate (MPH, a psychostimulant) plus quietapine (an antipsychotic) are needed to treat anti-social traits in youth. MPH taps dopamine transporter (DAT), quietiapine acts in part via serotonin (5-HT) 7 receptor; we propose an auto-immune role played by auto-antibodies (aAbs) targeting these proteins. In rats (Dr. Carli), we will induce attention/executive-control deficits, and glutamate/GABA imbalance, by focal NMDA blockade, to examine effect of MPH, quietapine, and 5-HT7 agonism. We will validate 5-HT7 -/- compared to +/+ mice as models of mania and/or inattention: they will be treated (MPH and/or quietapine, as adolescent/adult) and behaviorally phenotyped. In blood of paediatric patients (ADHD, BD, comorbid BD+ADHD, healthy controls; Prof. Masi), we will verify presence of: (a) serum aAbs targeting DAT or 5-HT7; (b) lymphocyte level of DAT or 5-HT7 protein. We will validate these biomarkers for prompt translation into clinics.

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