Auto-aggressive behaviour, especially treatment refractory suicidality in adolescents with psychiatric disorders, may be challenging to clinicians. In search of therapeutic possibilities, we have integrated current opinions regarding causality and interdependency of suicidality and auto-aggressive behaviour across disorders within the HiTOP framework. We propose a developmental model regarding these unsettling behaviours in youths that may help to guide future directions for research and interventions. We argue that the interdependent development of biologic factors, attachment, moral reasoning and emotion regulation in an overprotective environment may lead to social anxiety and later during development to emotion dysregulation and severe internalizing behaviour disorders. To optimize treatment efficacy for both internalizing and externalizing behaviour, we emphasize the importance transdiagnostic interventions, such as addressing non-compliance, restoration of trust between parents and their child, and limitation of avoidance behaviour. These may be seen as higher order interventions within the HiTOP framework.