Timing Matters: Leveraging Positron Emission Tomography Imaging and Hormonal Cycles for Precision Psychiatry in...

Fluctuations in behavior across the menstrual cycle have been observed in several psychiatric disorders, particularly those affecting mood. Cycle-specific conditions, such as premenstrual dysphoric disorder (PMDD), and cycle-responsive conditions, in which changes in symptoms are tied to the menstrual cycle, including attention-deficit/hyperactivity disorder (ADHD), exemplify this pattern with an increase in symptoms during the luteal phase. Growing evidence indicates that within-cycle ovarian hormone fluctuations and withdrawal, along with associated neurotransmitter changes, shape symptom trajectories. In PMDD, serotonergic tone is associated with mood changes, providing direct evidence of a link between hormonal fluctuations and psychiatric symptoms. Advanced quantitative neuroimaging techniques, such as positron emission tomography (PET), offer a unique opportunity to investigate how neurotransmitter systems, particularly serotonin, GABA (gamma-aminobutyric acid), dopamine, and norepinephrine, interact with hormonal shifts to influence psychiatric symptoms. In this review, we explore the potential of PET neuroreceptor imaging to elucidate the neurobiological mechanisms underlying hormone-related mood changes. With PMDD as a model, we provide a conceptual framework and highlight directions of mechanistic understanding for ADHD and other psychiatric conditions across the relatively brief, yet consistently cyclical intervals, thereby identifying windows for targeted, menstrual phase-informed interventions. By integrating hormonal and cycle variability into psychiatric research and treatment, we aim to advance precision medicine approaches for mood disorders.