title: Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression.
abstract: 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 PER3(4/4) and PER3(4/5) patients showed a reduction in it after treatment, PER3(5/5) subjects showed an increase of about 40min, suggesting a higher homeostatic pressure. The same polymorphism influenced the change of depressive symptomatology during treatment (F=3.72; p=0.028).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute, San Raffaele, Milan, Italy. Electronic address: dallaspezia.sara@hsr.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Dallaspezia
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute, San Raffaele, Milan, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Locatelli
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute, San Raffaele, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lorenzi
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute, San Raffaele, Milan, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Pirovano
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute, San Raffaele, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute, San Raffaele, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedetti
mesh_terms: D056044:Actigraphy; D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000523:psychology / Q000628:therapy*; D003863:Depression / Q000235:genetics / Q000523:psychology / Q000628:therapy*; D005260:Female; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D056950:Period Circadian Proteins / Q000235:genetics*; D010789:Phototherapy; D011110:Polymorphism, Genetic; D011312:Pressure; D011569:Psychiatric Status Rating Scales; D012890:Sleep / Q000235:genetics*; D012892:Sleep Deprivation / Q000235:genetics* / Q000523:psychology; D016896:Treatment Outcome
chemical_list: C512644:PER3 protein, human; D056950:Period Circadian Proteins
keywords: Antidepressant sleep deprivation; Bipolar depression; PER3 Gene; Sleep homeostasis