title: Diurnal alterations in circadian genes and peptides in major depressive disorder before and after escitalopram treatment.
abstract: BACKGROUND
  Strong links exist between circadian disturbances and some of the most characteristic symptoms of clinical major depressive disorder (MDD). However, changes in the expression of clock genes or neuropeptides related to the regulation of circadian rhythm that may influence the susceptibility to recurrence after antidepressant treatment in MDD have not been investigated.
  
  
  METHODS
  Blood samples were collected at 4h intervals for 24h from 12 male healthy controls and 12 male MDD patients before and after treatment with escitalopram for 8 weeks. The outcome measures included the relative expression of clock gene mRNA (PERIOD1, PERIOD2, PERIOD3, CRY1, BMAL1, NPAS2, and GSK-3β), and the levels of serum melatonin, vasoactive intestinal polypeptide (VIP), cortisol, adrenocorticotropic hormone (ACTH), insulin-like growth factor-1 (IGF-1), and growth hormone (GH).
  
  
  RESULTS
  Compared with healthy controls, MDD patients showed disruptions in the diurnal rhythms of the expression of PERIOD1, PERIOD2, CRY1, BMAL1, NPAS2, and GSK-3β and disruptions in the diurnal rhythms of the release of melatonin, VIP, cortisol, ACTH, IGF-1, and GH. Several of these disruptions (i.e., PER1, CRY1, melatonin, VIP, cortisol, ACTH, and IGF-1) persisted 8 weeks after escitalopram treatment, similar to the increase in the 24h levels of VIP and decreases in the 24h levels of cortisol and ACTH.
  
  
  CONCLUSIONS
  These persistent neurobiological changes may play a role in MDD symptoms that are thought to contribute to the vulnerability to recurrence and long-term maintenance therapy.
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing 100191, China. Electronic address: li313@bjmu.edu.cn.
authors.forename: Su-Xia
authors.initials: SX
authors.lastname: Li
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Liu
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Xin-Fu
authors.initials: XF
authors.lastname: Wang
authors.forename: Jing-Tao
authors.initials: JT
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000187:drug effects / Q000235:genetics*; D015283:Citalopram / Q000494:pharmacology* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000097:blood; D009479:Neuropeptides / Q000097:blood*; D063189:Symptom Assessment; D014660:Vasoactive Intestinal Peptide / Q000097:blood
chemical_list: D056925:Circadian Rhythm Signaling Peptides and Proteins; D009479:Neuropeptides; D015283:Citalopram; D014660:Vasoactive Intestinal Peptide; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D008550:Melatonin; D006854:Hydrocortisone
keywords: Circadian rhythms; Clock genes; Escitalopram; Hormones; Major depressive disorder; Peptides