Effect of early stress on hippocampal gray matter is influenced by a functional polymorphism in EAAT2 in bipolar disorder

• EAAT2 influence the effect of early stress on hippocampal brain volume in bipolar disorder.
• Higher levels of early stress are associated with less hippocampal volume.
• G carriers show higher gray matter volumes than T/T homozygote.
• Differences between high and low exposure to stress are more relevant in G carriers.

Current views on the pathogenesis of psychiatric disorders focus on the interplay between genetic and environmental factors, with individual variation in vulnerability and resilience to hazards being part of the multifactorial development of illness. The aim of the study is to investigate the effect of glutamate transporter polymorphism SLC1A2–181A > C and exposure to Adverse Childhood Experiences (ACE) on hippocampal gray matter volume of patients with bipolar disorder (BD).Patients exposed to higher levels of ACE reported lower gray matter volume. The effect of SLC1A2–181A > C revealed itself only among patients exposed to lower levels of ACE, with T/T homozygotes showing the lowest, and G/G the highest, gray matter volume.The greatest difference between high and low exposures to ACE was observed in carriers of the G allele. Since the mutant G allele has been associated with a reduced transcriptional activity and expression of the transporter protein, we could hypothesize that after exposure to highest levels of ACE G/G homozygotes are more vulnerable to stress reporting the highest brain damage as a consequence of an excess of free glutamate.