Circadian activity rhythm abnormalities in ill and recovered bipolar I disorder patients


  • RJB is a consultant or research collaborator to, or has received research support from Auritec Labs., Biotrofix Labs., Eli Lilly & Co., IFI SpA, Janssen Pharmaceutica, JDS Labs., NeuroHealing Corp., Novartis Labs., and Solvay Corp. PS, SG, GZ, CDeP, SL and CM have no reported conflicts of interest.

Corresponding author: Dr Paola Salvatore, International Consortium for Bipolar Disorder Research, McLean Hospital, Center Building GO7B, 115 Mill Street, Belmont, MA 02478-9106, USA.
Fax: +1 617 855 3479;


Objectives:  Most physiological indicators of bipolar disorder (BPD) reflect current acute illness, and rarely have proved to be state-independent. Activity rhythms are highly abnormal in acute phases of BPD; we compared circadian activity rhythms in BPD I patients during ill and recovered states to those of normal controls to test the hypothesis that some abnormalities may persist.

Methods:  We compared 36 adult DSM-IV BPD I patients during acute mania or mixed states, and during full and sustained clinical recovery, to 32 healthy controls of similar age and sex distribution, using wrist-worn, piezoelectric actigraphic monitoring for 72 h and computed cosinor analysis of circadian activity rhythms.

Results:  We verified expected major differences between manic or mixed-state BPD I patients and matched normal controls, including phase advances averaging 2.1 h in ill BPD I patients and 1.8 h in recovered patients. Moreover, recovered BPD patients differed highly significantly from controls in several measures, including acrophase advance, higher percentage of nocturnal sleep, and lower average daily activity (mesor). Actigraphic measures among recovered BPD patients were independent of ratings of mania (on the Young Mania Rating Scale), depression (on the Hamilton Depression Rating Scale), or rating-scale scored subjective distress, as well as the type and dose of concurrent psychotropic medication.

Conclusions:  These findings suggest that abnormal activity rhythms, including sustained phase advances, may represent enduring (trait) characteristics of BPD patients even during clinical recovery. If verified, such indices may be useful in supporting diagnoses and as an objective phenotype for genetic or other biological studies.