Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression

Sara Dallaspezia, Clara Locatelli, Cristina Lorenzi, Adele Pirovano, Cristina Colombo, Francesco Benedetti

Research output: Contribution to journalArticlepeer-review


Background Combined Total sleep deprivation (TSD) and light therapy (LT) cause a rapid improvement in bipolar depression which has been hypothesized to be paralleled by changes in sleep homeostasis. Recent studies showed that bipolar patients had lower changes of EEG theta power after sleep and responders to antidepressant TSD+LT slept less and showed a lower increase of EEG theta power then non-responders. A polymorphism in PER3 gene has been associated with diurnal preference, sleep structure and homeostatic response to sleep deprivation in healthy subjects. We hypothesized that the individual variability in the homeostatic response to TSD could be a correlate of antidepressant response and be influenced by genetic factors. Methods We administered three TSD+LT cycles to bipolar depressed patients. Severity of depression was rated on Hamilton Depression Rating Scale. Actigraphic recordings were performed in a group of patients. Results PER3 polymorphism influenced changes in total sleep time (F=2.24; p=0.024): while PER34/4 and PER34/5 patients showed a reduction in it after treatment, PER35/5 subjects showed an increase of about 40 min, suggesting a higher homeostatic pressure. The same polymorphism influenced the change of depressive symptomatology during treatment (F=3.72; p=0.028). Limitations Sleep information was recorded till the day after the end of treatment: a longer period of observation could give more information about the possible maintenance of allostatic adaptation. Conclusions A higher sleep homeostatic pressure reduced the antidepressant response to TSD+LT, while an allostatic adaptation to sleep loss was associated with better response. This process seems to be under genetic control.

Original languageEnglish
Pages (from-to)64-69
Number of pages6
JournalJournal of Affective Disorders
Publication statusPublished - Mar 1 2016


  • Antidepressant sleep deprivation
  • Bipolar depression
  • PER3 Gene
  • Sleep homeostasis

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology


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