Targeting novel synaptic pathways in trauma-related psychiatric disorder: Clinical Research Priority Program 2019-2021
In today's turbulent world, psychological trauma and early-life adversity have emerged as major risk factors for various psychiatric disorders. Across the entire spectrum of trauma-related disorders, cognitive-behavioural psychotherapy, which seeks to modify aversive memories, is currently the recommended treatment by national and international guidelines. Yet, in clinical practice the majority of patients remain symptomatic. This has led to high-profile calls for developing adjunct pharmacological therapies. During the same time, our understanding of synaptic biology has increased exponentially, yielding a wide range of compounds that modify synapses themselves, the surrounding extracellular matrix that shapes their properties, and the daily rhythms of sleep and wake that govern their strength.
This CRPP connects these disparate strands and delivers a novel approach to alter aversive memories with a combination of psychotherapy and pharmacological agents. While previous models for pharmacological intervention targeted synapses indirectly via neurotransmitters, this CRPP focuses on directly targeting molecular pathways involved in degrading old, and shaping new, synaptic connections. In humans, the CRPP will use several candidate drugs already approved for other indications. Using in-vitro and animal models, the CRPP seeks to decipher signalling pathways and elucidate further drug targets.