Biological embedding of early trauma: the role of higher prefrontal synaptic strength

Early trauma is linked to stronger glutamatergic synaptic strength in people with PTSD, measured via a novel in vivo marker called energy per cycle (EPC). In a sample of 34 adults (16 with PTSD, 18 healthy controls), higher early trauma correlated with higher EPC only in the PTSD group. Greater synaptic strength was associated with reduced behavioral inhibition, and EPC mediated stronger links between reward responsiveness and early trauma. These findings suggest that trauma-induced changes in synaptic plasticity may underlie psychiatric risk and point to potential targets for treatments like ketamine and psilocybin.

Study at a glance

Abstract

Background: Early trauma predicts poor psychological and physical health. Glutamatergic synaptic processes offer one avenue for understanding this relationship, given glutamate's abundance and involvement in reward and stress sensitivity, emotion, and learning. Trauma-induced glutamatergic excitotoxicity may alter neuroplasticity and approach/avoidance tendencies, increasing risk for psychiatric disorders. Studies examine upstream or downstream effects instead of glutamatergic synaptic processes in vivo, limiting understanding of how trauma affects the brain.Objective: In a pilot study using a previously published data set, we examine associations between early trauma and a proposed measure of synaptic strength in vivo in one of the largest human samples to undergo Carbon-13 (13C MRS) magnetic resonance spectroscopy. Participants were 18 healthy controls and 16 patients with PTSD (male and female).Method: Energy per cycle (EPC), which represents the ratio of neuronal oxidative energy production to glutamate neurotransmitter cycling, was generated as a putative measure of glutamatergic synaptic strength.Results: Results revealed that early trauma was positively correlated with EPC in individuals with PTSD, but not in healthy controls. Increased synaptic strength was associated with reduced behavioural inhibition, and EPC showed stronger associations between reward responsivity and early trauma for those with higher EPC.Conclusion: In the largest known human sample to undergo 13C MRS, we show that early trauma is positively correlated with EPC, a direct measure of synaptic strength. Our study findings have implications for pharmacological treatments thought to impact synaptic plasticity, such as ketamine and psilocybin.