The following is a summary of “Impact of Menarche on Hippocampal Mechanisms of Severity of Psychotic-Like Experiences in the ABCD Study,” published in the January 2024 issue of Psychiatry by Damme et al.

Accumulating evidence underscores the pivotal role of estrogens in modulating the pathogenesis of psychosis, with a specific focus on the dynamic interplay of these hormones within the context of emerging psychopathology and neurodevelopment. In this vein, estradiol, the primary form of estrogen, is posited to exert a direct or indirect influence on psychosis lability, particularly through its neurodevelopmental impact on estrogen-sensitive regions such as the hippocampus. This study, involving 4,422 female participants aged 8-13 from the Adolescent Brain Cognitive Development (ABCD) study, examined baseline and year 2 data, categorizing participants based on estradiol availability (pre-menarche, post-menarche, pre- and post-menarche timepoints). The analysis revealed a significant association between estradiol availability and the severity of psychotic-like experiences (PLE), both as a direct effect and interactively with hippocampal connectivity, factoring in menarche status (pre/post) in a multilevel model. Individuals experiencing early menarche demonstrated the highest PLE severity, underscoring the critical role of developmental timing. 

Despite an overall decrease in PLE severity over the 2 years, it remained clinically relevant. Notably, lower hippocampal connectivity correlated with heightened PLE severity, with this effect being moderated by estradiol. Pre-menarche reduced hippocampal connectivity significantly contributed to PLE severity, whereas post-menarche estradiol availability mitigated the impact of hippocampal dysconnectivity on PLE severity. This moderation implies that estradiol’s influence on hippocampal plasticity diminishes the mechanistic role of the hippocampus in PLE severity. Moreover, the absence of a significant direct reduction in PLE severity post-menarche suggests an augmented role for other interacting factors contributing to psychosis lability during this crucial developmental period. This investigation provides valuable insights into the intricate interplay between estrogen, hippocampal function, and psychosis lability, shedding light on potential mechanisms underlying these phenomena.

Source: sciencedirect.com/science/article/abs/pii/S0306453024000052