Prolonged functional cerebral asymmetry as a consequence of dysfunctional parvocellular paraventricular hypothalamic nucleus signaling: An integrative model for the pathophysiology of bipolar disorder

Approximately 45 million people worldwide are diagnosed with bipolar disorder (BD). While there many known risk factors and models of the pathologic processes influencing BD, exact neurologic underpinnings BD unknown. We attempt to integrate existing literature create a unifying hypothesis regarding pathophysiology hope that concrete model may potentially facilitate more specific diagnosis, prevention, treatment in future. hypothesize dysfunctional signaling from parvocellular neurons paraventricular hypothalamic nucleus (PVN) results clinical presentation BD. Functional damage this its pathways be mediated by myriad (e.g. immune dysregulation auto-immune processes, polygenetic variation, interhemispheric connections, impaired or overactivated axes) which could help explain wide variety presentations along spectrum. The PVN regulate ultradian rhythms, observed cyclic variations healthy individuals, mediate changes functional hemispheric lateralization. Theoretically, prolonged dominance. In model, right dominance leads depressive symptoms, whereas left correlated picture mania. Subsequently, physiologic increase through (hypothalamic-pituitaryadrenal axis, hypothalamic- pituitary-gonadal hypothalamic-pituitary-thyroid axis activity, suprachiasmatic pathways) as well as, neuro-endocrine induced excito-toxicity, inflammatory flairs induce mood episodes susceptible individuals. Potentially, rhythms slowing age, combination axes maturation neural circuitry, accounts for clinically presenting frequently young adulthood than later life.