Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder.

摘要: Bipolar disorder (BD) is a serious mood associated with circadian rhythm abnormalities. Risk for BD genetically encoded and overlaps systems that maintain rhythms. Lithium an effective stabilizer treatment BD, but only minority of patients fully respond to monotherapy. Presently, we hypothesized lithium-responsive (Li-R) would show characteristic differences in chronotype cellular rhythms compared lithium non-responders (Li-NR). Selecting from prospective, multi-center, clinical trial monotherapy, examined morning vs. evening preference (chronotype) as dimension function 193 Li-R Li-NR patients. From subset 59 patient donors, measured skin fibroblasts longitudinally over 5 days using bioluminescent reporter (Per2-luc). We then estimated parameters (amplitude, period, phase) the pharmacological effects on cells donors. Compared Li-NRs, Li-Rs showed difference chronotype, higher levels morningness. Evening was increased symptoms at baseline, including depression, mania, insomnia. Cells were more likely exhibit short linear relationship between period phase, shortening lithium. Common genetic variation IP3 signaling pathway may account some individual conclude influence response maintenance BD.