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

<b>Background:</b> 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 <i>in vivo</i>, limiting understanding of how trauma affects the brain. <b>Objective:</b> In a pilot study using a previously published data set, we examine associations between early trauma and a proposed measure of synaptic strength <i>in vivo</i> 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). <b>Method:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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. Abnormalities in the strength of synaptic connections have been implicated in trauma and trauma-related disorders but not directly examined.We used magnetic resonance spectroscopy to investigate the association between early trauma and an <i>in vivo</i> measure of synaptic strength.For people with posttraumatic stress disorder, as early trauma severity increased, synaptic strength increased, highlighting the potential for treatments thought to change synaptic connections in trauma-related disorders. Abnormalities in the strength of synaptic connections have been implicated in trauma and trauma-related disorders but not directly examined. We used magnetic resonance spectroscopy to investigate the association between early trauma and an <i>in vivo</i> measure of synaptic strength. For people with posttraumatic stress disorder, as early trauma severity increased, synaptic strength increased, highlighting the potential for treatments thought to change synaptic connections in trauma-related disorders.