TY - JOUR
T1 - Decreased Neurotrophic Response to Birth Hypoxia in the Etiology of Schizophrenia
AU - Cannon, Tyrone D.
AU - Yolken, Robert
AU - Buka, Stephen
AU - Torrey, E. Fuller
N1 - Funding Information:
Dr. Cannon reports that he currently or in the past 5 years has received investigator-initiated research funding support from multiple not-for-profit entities including the National Institute for Mental Health, the Stanley Medical Research Foundation, the National Alliance for Research on Schizophrenia and Depression, the March of Dimes, and the Staglin Music Festival for Mental Health. Dr. Cannon reports that he has served as a consultant for Janssen Pharmaceuticals and Eli Lilly. Dr. Buka reports that he currently or in the past 5 years has received investigator-initiated research funding support from the National Institutes of Health, the Stanley Medical Research Institute, and the Flight Attendants Medical Research Institute. Dr. Torrey reports that he currently or in the past 5 years has received investigator-initiated funding from the Stanley Medical Research Institute. Dr. Yolken reports he currently or in the past 5 years has received investigator-initiated funding from the Stanley Medical Research Institute.
Funding Information:
This work was supported by grants from the Stanley Medical Research Institute, March of Dimes, and National Institute of Mental Health, as well as a gift from the Staglin Music Festival for Mental Health.
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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°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.
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°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.
KW - Brain-derived neurotrophic factor
KW - hypoxia
KW - neuroprotection
KW - schizophrenia
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U2 - 10.1016/j.biopsych.2008.04.012
DO - 10.1016/j.biopsych.2008.04.012
M3 - Article
C2 - 18486103
AN - SCOPUS:53249138261
SN - 0006-3223
VL - 64
SP - 797
EP - 802
JO - Biological psychiatry
JF - Biological psychiatry
IS - 9
ER -