Investigating Neurobiological Pathways Connecting PCOS, Neurodivergence, and Mood Disorders

Polycystic Ovary Syndrome (PCOS) is a complex endocrine condition affecting approximately 10% of women of reproductive age. Long considered to be a gynaecological and metabolic issue, recent advances indicate a robust linkage between PCOS and neuropsychiatric comorbidity such as attention deficit hyperactivity disorder (ADHD), Generalised Anxiety Disorder (GAD) and Major Depressive disorder (MDD). This review provides an interdisciplinary perspective spanning endocrinology and psychiatry by focusing on the Ovary Brain Axis and hormonal changes associated with PCOS, which contribute to brain structure and cognitive function. The discussion focuses on three principal biological mechanisms. First, hormonal programming as suggested by the Organisational Hypothesis, suggests that prenatal exposure to increased androgens may have an impact on fetal brain development, particularly dopamine pathways associated with ADHD. Secondly, chronic low-grade inflammation with raised CRP and interleukin-6 has the potential to compromise the BBB, activate microglia and increase anxiety through modulation of the amygdala. Lastly, metabolic failure, and in particular insulin resistance, could be associated with a lower production of brain-derived neurotrophic factor, altering neuroplasticity and working memory.