The proposed project aims to investigate how maternal stress during pregnancy, maternal inflammation during pregnancy and fetal hypoxia (lack of oxygen to the fetus) influence the risk of symptoms of depression during adolescence in offspring. A secondary aim is to map trajectories of how these prenatal risk factors result in a cascade of events, leading to altered developmental trajectories in emotional, cognitive, and behavioral outcomes during childhood and subsequent depression during adolescence. The proposed project is based on a large birth cohort study, the Child Health and Development Study (CHDS), that followed women prospectively throughout their pregnancies from 1959-1966 and acquired detailed information on the mothers'experiences, health-risk behaviors, and medical complications during pregnancy and delivery. This information included maternal responses to open-ended questions about concerns or worries within the past year and feelings about the pregnancy. Multiple sera samples were collected from mothers throughout their pregnancies and archived at -20oC. Offspring were administered cognitive, behavioral, and psychological assessments at ages 5, 9, and 15. The present study will include 750 mothers and their offspring who have complete data at each time point. Serological analyses will be conducted on archived prenatal sera from the first and second trimesters of pregnancy in order to measure biomarkers of maternal stress during pregnancy (i.e. cortisol), maternal levels of inflammatory proteins, termed cytokines, (the soluble receptors for IL-1? and TNF-? and the cytokines IL-8 and IL-6), and markers of fetal hypoxia (VEGF). Further, prospectively collected labor and delivery information will be used for additional measures of fetal hypoxia. In addition, the present study will qualitatively code stress-related themes from narratives acquired in response to the aforementioned open- ended questions and geocode neighborhood-level contextual factors for each subject.
The specific aims are as follows: 1) to investigate the contributions of fetal exposure to maternal stress and stress hormones to risk of depression in adolescent offspring, 2) to investigate whether there are intermediate childhood emotional and behavioral phenotypes, as well as altered cognitive trajectories between fetal exposure to maternal stress during pregnancy and subsequent depression in adolescence, and 3) to investigate whether fetal exposure to elevated levels of maternal stress adds to or interacts with other pre- and perinatal complications to increase risk for neurodevelopmental sequelae and adolescent psychopathology. The proposed study is uniquely positioned to answer key questions about how prenatal risk factors operate within the neurodevelopmental course of depression. The present study has the potential to influence the development of early intervention and prevention strategies, as well as to identify early risk markers for subsequent difficulties in adolescence.

Public Health Relevance

The proposed project aims to investigate how maternal psychosocial and neuroendocrine indicators of stress during pregnancy, maternal inflammation during pregnancy and fetal hypoxia (lack of oxygen) contribute to the neurodevelopmental course of depression in adolescent offspring.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH096478-03
Application #
8596852
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Zehr, Julia L
Project Start
2012-03-15
Project End
2016-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
3
Fiscal Year
2014
Total Cost
$407,931
Indirect Cost
$69,950
Name
Temple University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Maxwell, Seth D; Fineberg, Anna M; Drabick, Deborah A et al. (2018) Maternal Prenatal Stress and Other Developmental Risk Factors for Adolescent Depression: Spotlight on Sex Differences. J Abnorm Child Psychol 46:381-397
Gibson, Lauren E; Cooper, Shanna; Reeves, Lauren E et al. (2018) Attentional biases and trauma status: Do psychotic-like experiences matter? Psychol Trauma :
Espinosa, Adriana; Tikhonov, Aleksandr; Ellman, Lauren M et al. (2018) Ethnic Identity and Perceived Stress Among Ethnically Diverse Immigrants. J Immigr Minor Health 20:155-163
Gibson, Lauren E; Reeves, Lauren E; Cooper, Shanna et al. (2018) Traumatic life event exposure and psychotic-like experiences: A multiple mediation model of cognitive-based mechanisms. Schizophr Res :
Cooper, Shanna; Kring, Ann M; Ellman, Lauren M (2018) Attenuated positive psychotic symptoms and the experience of anhedonia. Early Interv Psychiatry 12:1188-1192
Ered, Arielle; Cooper, Shanna; Ellman, Lauren M (2018) Sleep quality, psychological symptoms, and psychotic-like experiences. J Psychiatr Res 98:95-98
Murphy, Shannon K; Fineberg, Anna M; Maxwell, Seth D et al. (2017) Maternal infection and stress during pregnancy and depressive symptoms in adolescent offspring. Psychiatry Res 257:102-110
Ered, A; Gibson, L E; Maxwell, S D et al. (2017) Coping as a mediator of stress and psychotic-like experiences. Eur Psychiatry 43:9-13
Gibson, Lauren E; Cooper, Shanna; Reeves, Lauren E et al. (2017) The association between traumatic life events and psychological symptoms from a conservative, transdiagnostic perspective. Psychiatry Res 252:70-74
Fineberg, Anna M; Ellman, Lauren M; Schaefer, Catherine A et al. (2016) Fetal exposure to maternal stress and risk for schizophrenia spectrum disorders among offspring: Differential influences of fetal sex. Psychiatry Res 236:91-97

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