Circadian rhythm disruption in bipolar disorder: Mechanisms, clinical significance, and rhythm-oriented interventions

Table 2 Some biomarkers of dysrhythmia that can provide basis for the diagnosis of bipolar disorder

Biomarker	Rhythmic change	Related variant clock gene	BD performance	Ref.
Sleep-wake cycle	Sleep phase delayed	CRY1	Sleep wake cycle CBT rhythm disordered, accompanied by changes in tryptophan metabolism and circadian rhythm disorder	Marchetti et al[57]; Panchal et al[58]; Scott and McClung[59]; Patke et al[60]; Yavuz Ataşlar and Altınbaş[61]
CBT	Decreased rhythm amplitude	BMAL1	CBT rhythm disordered	National Toxicology Program[62]; Liang et al[63]; Ma et al[64]
Cortisol	Rhythmic phase shifted	CLOCK, PER1, PER2, PER3, TIMELESS	Circadian rhythm disordered	Rathor and Ch[35]; National Toxicology Program[62]; Hasenmajer et al[65]
Melatonin	Differed in rhythm phase shift and rhythm interference sensitivity		Circadian rhythm disordered	Yang et al[68]
Peripheral clock	Reduced sensitivity and rhythm desynchronization	PER2, BMAL1	SCN level control is broken, and the whole-body rhythm is not synchronized	Woodie et al[69]; Palm et al[70]; Costello and Gumz[71]

BD: Bipolar disorder; CBT: Cognitive behavior therapy; SCN: Suprachiasmatic nucleus.