This career development award proposal is a five-year plan that will enable the candidate to develop into an independent investigator in the genetics of affective disorders with an emphasis on hormonally-triggered symptoms in women. The candidate is an academic psychiatrist with training in mood disorders who now seeks further training in genetics and genetic epidemiology. Dr. J. Raymond DePaulo, Jr, director of the Affective Disorders Genetics Research Group and Chair of the Johns Hopkins Department of Psychiatry will mentor the candidate on conducting genetic research in the psychiatric patient. Dr. Terri Beaty, Professor at the Johns Hopkins School of Public Health, will mentor the candidate on using statistical methods and genetic epidemiology. Dr. David Rubinow, Professor and Chair of Psychiatry at the University of North Carolina and Dr. Peter Schmidt, Chief of the Unit on Reproductive Endocrinology Studies, will mentor the candidate in both the neurobehavioral effects of gonaldal steroids as well as clinical and phenotypic issues in women's mental health. The training program will be enhanced by a research plan based on the hypothesis that women with postpartum depressive episodes have a genetic vulnerability to times of normal hormonal change that consists of variation in a gene (or genes) that is estrogen responsive. The research plan will take advantage of previously collected family samples of bipolar disorder and recurrent major depression. Based on preliminary data demonstrating the familiality of postpartum depressive episodes in families with major depression and bipolar disorder, the candidate will complete the following three specific aims: 1) complete a linkage analysis for this trait;2) perform association studies, specifically examining genes in regions of interest which contain estrogen-response elements and thus may be susceptible to the hormone fluctuations that occur during the postpartum period;and 3) begin collection of a pilot sample of women with major depression with and without postpartum depression. The proposed research is significant because it will lead to a better understanding of the pathophysiology of postpartum depression in women with mood disorders as well as potentially contribute to understanding the increased rate of depressive episodes observed in women as a group.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH074799-05
Application #
8014933
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Desmond, Nancy L
Project Start
2007-02-01
Project End
2012-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
5
Fiscal Year
2011
Total Cost
$183,276
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Di Florio, A; Putnam, K; Altemus, M et al. (2017) The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale. Psychol Med 47:787-799
Osborne, Lauren M; Gispen, Fiona; Sanyal, Abanti et al. (2017) Lower allopregnanolone during pregnancy predicts postpartum depression: An exploratory study. Psychoneuroendocrinology 79:116-121
Clive, Makena L; Boks, Marco P; Vinkers, Christiaan H et al. (2016) Discovery and replication of a peripheral tissue DNA methylation biosignature to augment a suicide prediction model. Clin Epigenetics 8:113
Kimmel, Mary; Clive, Makena; Gispen, Fiona et al. (2016) Oxytocin receptor DNA methylation in postpartum depression. Psychoneuroendocrinology 69:150-60
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Osborne, Lauren; Clive, Makena; Kimmel, Mary et al. (2016) Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels. Neuropsychopharmacology 41:1648-58
Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium (2015) Heterogeneity of postpartum depression: a latent class analysis. Lancet Psychiatry 2:59-67
Kimmel, Mary; Hess, Edward; Roy, Patricia S et al. (2015) Family history, not lack of medication use, is associated with the development of postpartum depression in a high-risk sample. Arch Womens Ment Health 18:113-21
Kaminsky, Zachary; Payne, Jennifer (2014) Seeing the future: epigenetic biomarkers of postpartum depression. Neuropsychopharmacology 39:233-4
Guintivano, Jerry; Brown, Tori; Newcomer, Alison et al. (2014) Identification and replication of a combined epigenetic and genetic biomarker predicting suicide and suicidal behaviors. Am J Psychiatry 171:1287-96

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