Neurobehavioral Consequences of Circadian Rhythm Disturbances: Insights into Mood Disorders and Cognitive Decline

Abstract

Circadian rhythms are endogenous biological oscillations with an approximately 24-hour periodicity that synchronize behavioural and physiological processes with the environmental light–dark cycle. In humans, the circadian timing system regulates sleep-wake behaviour, hormonal secretion, neurotransmission, and higher cognitive functions. This system is hierarchically organised, with the suprachiasmatic nucleus (SCN) acting as the central pacemaker and coordinating peripheral clocks through transcription-translation feedback loops involving core clock genes such as CLOCK, BMAL1, PER, and CRY. Disruption of circadian rhythms, driven by light exposure, shift work, irregular sleep schedules, aging, and chronic stress, has emerged as a major contributor to neurobehavioral dysfunction. Growing evidence links circadian misalignment to mood disorders, including depression, bipolar disorder, and anxiety, as well as to cognitive decline. Mechanistically, circadian disruption impairs sleep-dependent memory consolidation, alters synaptic plasticity, dysregulates neuroendocrine pathways such as the hypothalamic-pituitary–adrenal axis, and disturbs the rhythmic release of neurotransmitters including serotonin, dopamine, glutamate, and GABA. At the molecular level, clock gene dysregulation, neuroinflammation, mitochondrial dysfunction, oxidative stress, and reduced neurogenesis collectively compromise emotional regulation and cognitive resilience. Age-related weakening of circadian rhythmicity further increases vulnerability to mood instability and neurodegenerative processes. This review integrates molecular, neurochemical, behavioural, and clinical evidence linking circadian rhythm disturbances to mood disorders and cognitive decline, and highlights emerging chronotherapeutic, light-based, pharmacological, and lifestyle interventions aimed at restoring circadian alignment and promoting brain health.