title: Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium.
abstract: OBJECTIVE
  Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear.
  
  
  METHODS
  BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness.
  
  
  RESULTS
  Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia.
  
  
  CONCLUSIONS
  Small sample size in different episodes and drug-free patients was the limitation of thestudy.
  
  
  CONCLUSIONS
  Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia.
authors.affiliation: Dokuz Eylul University, Medical School, Izmir, Turkey. Electronic address: zeliha.tunca@deu.edu.tr.
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Tunca
authors.affiliation: Dokuz Eylul University, Medical School, Izmir, Turkey.
authors.forename: Aysegul
authors.initials: A
authors.lastname: Ozerdem
authors.affiliation: Dokuz Eylul University, Medical School, Izmir, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Ceylan
authors.affiliation: Dokuz Eylul University, Medical School, Izmir, Turkey.
authors.forename: Yaprak
authors.initials: Y
authors.lastname: Yalçın
authors.affiliation: Dokuz Eylul University, Medical School, Izmir, Turkey.
authors.forename: Güneş
authors.initials: G
authors.lastname: Can
authors.affiliation: Dokuz Eylul University, Medical School, Izmir, Turkey.
authors.forename: Halil
authors.initials: H
authors.lastname: Resmi
authors.affiliation: Dokuz Eylul University, Medical School, Izmir, Turkey.
authors.forename: Pınar
authors.initials: P
authors.lastname: Akan
authors.affiliation: Dokuz Eylul University, Medical School, Izmir, Turkey.
authors.forename: Gül
authors.initials: G
authors.lastname: Ergör
authors.affiliation: Celal Bayar University, Faculty of Medicine, Manisa, Turkey.
authors.forename: Omer
authors.initials: O
authors.lastname: Aydemir
authors.affiliation: Celal Bayar University, Faculty of Medicine, Manisa, Turkey.
authors.forename: Cengiz
authors.initials: C
authors.lastname: Cengisiz
authors.affiliation: Dokuz Eylul University, Medical School, Izmir, Turkey.
authors.forename: Doyuran
authors.initials: D
authors.lastname: Kerim
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage* / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D003863:Depression / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000097:blood*; D006801:Humans; D018020:Lithium Compounds / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008875:Middle Aged; D014635:Valproic Acid / Q000008:administration & dosage* / Q000097:blood
chemical_list: D018692:Antimanic Agents; D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018020:Lithium Compounds; D014635:Valproic Acid
keywords: BDNF (Brain-derived neurotrophic factor); Bipolar disorder; GDNF (glial cell line-derived neurotrophic factor); Lithium; Valproate