AbstractBipolar disorder is
a chronic and disabling psychiatric condition characterized by alternating
episodes of mania/hypomania and depression. Among the myriad of biological
disturbances implicated in its pathophysiology, circadian rhythm dysregulation
has emerged as a significant contributor, particularly in bipolar depression.
Circadian rhythms, orchestrated by the suprachiasmatic nucleus (SCN) in the
hypothalamus, govern sleep-wake cycles, hormonal release, body temperature, and
other physiological functions. Disruptions in these rhythms have been
consistently linked to mood instability, sleep disturbances, and increased
relapse risk in bipolar individuals.
This review
explores the intricate neurobiological relationship between circadian
dysregulation and bipolar depression, focusing on genetic, molecular, and neuroendocrine
pathways. Evidence from clinical and preclinical studies highlights
abnormalities in melatonin secretion, CLOCK gene polymorphisms, and altered
expression of circadian proteins in patients with bipolar disorder.
Furthermore, the bidirectional influence of circadian misalignment and mood
dysregulation is considered, demonstrating how lifestyle factors like shift
work, light exposure, and irregular sleep patterns exacerbate symptom severity.
Chronotherapeutic
interventions such as light therapy, interpersonal and social rhythm therapy
(IPSRT), and pharmacological agents like lithium and agomelatine provide
promising avenues to restore circadian balance and improve clinical outcomes.
This review underscores the importance of integrating circadian-focused
strategies into the treatment and management of bipolar depression and calls
for further translational research to elucidate causal mechanisms and optimize
therapeutic targets.
