PMID- 18486103
OWN - NLM
STAT- MEDLINE
DCOM- 20090408
LR  - 20211020
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 64
IP  - 9
DP  - 2008 Nov 1
TI  - Decreased neurotrophic response to birth hypoxia in the etiology of 
      schizophrenia.
PG  - 797-802
LID - 10.1016/j.biopsych.2008.04.012 [doi]
AB  - BACKGROUND: Obstetric complications, particularly fetal hypoxia, are associated 
      with increased risk for schizophrenia later in life. Such factors are also 
      related to increased severity of certain neuropathological features of 
      schizophrenia, including hippocampal and cortical gray matter reduction, among 
      individuals with a genetic susceptibility to the disorder. However, the molecular 
      mechanisms underlying these associations are unknown. Here, we sought to 
      determine whether neurotrophic factors, which are stimulated as part of a 
      neuroprotective response to fetal distress, are differentially expressed in cord 
      blood samples at the time of birth following fetal hypoxia, maternal 
      hypertension/small for gestational age status, and/or prematurity among 
      individuals who developed schizophrenia as adults, as compared with control 
      subjects. METHODS: One hundred eleven cases with psychotic disorders (70 with 
      schizophrenia) and 333 control subjects matched for gender, race, and date of 
      birth were drawn from the Philadelphia cohort of the National Collaborative 
      Perinatal Project in a nested case-control study. Brain-derived neurotrophic 
      factor (BDNF) was assayed from cord and maternal blood samples taken at delivery 
      and stored at -20 degrees C for 45 to 50 years. RESULTS: Among control subjects, 
      birth hypoxia was associated with a significant (10%) increase in BDNF in cord 
      samples, while among cases, hypoxia was associated with a significant (20%) 
      decrease in BDNF. This differential response to fetal hypoxia was specific to 
      schizophrenia and was not explained by other obstetric complications or by the 
      BDNF valine (val) to methionine (met) polymorphism at codon 66 (val66met). 
      CONCLUSIONS: These findings provide serologically based prospective evidence of 
      disrupted neurotrophic signaling in response to birth hypoxia in the molecular 
      pathogenesis of schizophrenia.
FAU - Cannon, Tyrone D
AU  - Cannon TD
AD  - Department of Psychology, University of California Los Angeles, Los Angeles, 
      California 90095-1563, USA. cannon@psych.ucla.edu
FAU - Yolken, Robert
AU  - Yolken R
FAU - Buka, Stephen
AU  - Buka S
FAU - Torrey, E Fuller
AU  - Torrey EF
CN  - Collaborative Study Group on the Perinatal Origins of Severe Psychiatric 
      Disorders
LA  - eng
GR  - RL1 MH083269/MH/NIMH NIH HHS/United States
GR  - RL1 MH083269-02/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080516
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/*genetics/*metabolism
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Female
MH  - Fetal Hypoxia/*complications
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Methionine/genetics
MH  - Middle Aged
MH  - Risk Factors
MH  - Schizophrenia/*etiology/*metabolism/pathology
MH  - Valine/genetics
PMC - PMC2655104
MID - NIHMS74199
FIR - Goldstein, J
IR  - Goldstein J
FIR - Seidman, L
IR  - Seidman L
FIR - Tsuang, M
IR  - Tsuang M
FIR - Hadley, T
IR  - Hadley T
FIR - Bearden, C
IR  - Bearden C
FIR - Rosso, I
IR  - Rosso I
FIR - Dhavale, D
IR  - Dhavale D
EDAT- 2008/05/20 09:00
MHDA- 2009/04/09 09:00
PMCR- 2009/11/01
CRDT- 2008/05/20 09:00
PHST- 2008/01/25 00:00 [received]
PHST- 2008/03/27 00:00 [revised]
PHST- 2008/04/11 00:00 [accepted]
PHST- 2008/05/20 09:00 [pubmed]
PHST- 2009/04/09 09:00 [medline]
PHST- 2008/05/20 09:00 [entrez]
PHST- 2009/11/01 00:00 [pmc-release]
AID - S0006-3223(08)00434-4 [pii]
AID - 10.1016/j.biopsych.2008.04.012 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2008 Nov 1;64(9):797-802. doi: 10.1016/j.biopsych.2008.04.012. 
      Epub 2008 May 16.