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1.  A Reproductive Subtype of Depression: Conceptualizing Models and Moving Toward Etiology 
Harvard review of psychiatry  2009;17(2):72-86.
The lifetime risk for major depression in women is well known to be twice the risk in men and is especially high during the reproductive years between menarche and menopause. A subset of reproductive-age women experience depressive episodes that are triggered by hormonal fluctuations. Such “reproductive depressions” involve episodes of depression that occur specifically during the premenstrual, postpartum, and perimenopausal phases in women. These reproductive subtypes of depression can be conceptualized as a specific biological response to the effects of hormonal fluctuations in the brain. The different types of reproductive depressions are associated with each other, have unique risk factors that are distinct from nonreproductive depression episodes, and respond to both hormonal and nonhormonal interventions. This review uses a PubMed search of relevant literature to discuss clinical, animal, and genetic evidence for reproductive depression as a specific subtype of major depression. Unique treatment options, such as hormonal interventions, are also discussed, and hypotheses regarding the underlying biology of reproductive depression—including interactions between the serotonergic system and estrogen, as well as specific effects on neurosteroids—are explored. This review will provide evidence supporting reproductive depression as a distinct clinical entity with specific treatment approaches and a unique biology that is separate from nonreproductive depression.
PMCID: PMC3741092  PMID: 19373617
estrogen; major depression; neurosteroids; perimenopause; postpartum; premenstrual; reproductive; serotonin
2.  Antidepressant Use During Pregnancy: Current Controversies and Treatment Strategies 
The treatment of depression during pregnancy is both a common and complex clinical challenge. The decision to expose the fetus to antidepressant medication during pregnancy must be weighed against the risks of untreated maternal depression to both mother and fetus. Maternal depression during pregnancy has been associated with increased rates of preterm birth and maternal substance use. The safety of antidepressant use during pregnancy appears to be largely reassuring but there remain two areas of controversy including neonatal withdrawal syndrome and primary pulmonary hypertension of the newborn (PPHN). Individualized treatment recommendations based on the patient's history are essential in order to optimize outcomes.
PMCID: PMC2749677  PMID: 19661762
Depression; pregnancy; antidepressants; safety; PPHN; neonatal withdrawal syndrome
3.  Premenstrual mood symptoms: study of familiality and personality correlates in mood disorder pedigrees 
Archives of women's mental health  2009;12(1):10.1007/s00737-008-0043-4.
We sought to determine whether premenstrual mood symptoms exhibit familial aggregation in bipolar disorder or major depression pedigrees. Two thousand eight hundred seventy-six women were interviewed with the Diagnostic Interview for Genetic Studies as part of either the NIMH Genetics Initiative Bipolar Disorder Collaborative study or the Genetics of Early Onset Major Depression (GenRED) study and asked whether they had experienced severe mood symptoms premenstrually. In families with two or more female siblings with bipolar disorder (BP) or major depressive disorder (MDD), we examined the odds of having premenstrual mood symptoms given one or more siblings with these symptoms. For the GenRED MDD sample we also assessed the impact of personality as measured by the NEO-FFI. Premenstrual mood symptoms did not exhibit familial aggregation in families with BP or MDD. We unexpectedly found an association between high NEO openness scores and premenstrual mood symptoms, but neither this factor, nor NEO neuroticism influenced evidence for familial aggregation of symptoms. Limitations include the retrospective interview, the lack of data on premenstrual dysphoric disorder, and the inability to control for factors such as medication use.
PMCID: PMC3845804  PMID: 19137238
Premenstrual; Bipolar; Major depression; Genetics
4.  Fes-Cre Targets Phosphatidylinositol Glycan Class a (Piga) Inactivation to Hematopoietic Stem Cells in the Bone Marrow 
A somatic mutation in the X-linked phosphatidylinositol glycan class A (PIGA) gene causes the loss of glycosyl phosphatidylinositol (GPI)-linked proteins on blood cells from patients with paroxysmal nocturnal hemoglobinuria. Because all blood cell lineages may be affected it is thought that the mutation occurs in a hematopoietic stem cell. In transgenic mice, germline transmission of an inactive Piga gene is embryonic lethal. To inactivate the murine Piga gene in early hematopoiesis we therefore chose conditional gene inactivation using the Cre/loxP system. We expressed Cre recombinase under the transcription regulatory sequences of the human c-fes gene. FES-Cre inactivated PIGA in hematopoietic cells of mice carrying a floxed Piga allele (LF mice). PIGA− cells were found in all hematopoietic lineages of definitive but not primitive hematopoiesis. Their proportions were low in newborn mice but subsequently increased continuously to produce for the first time mice that have almost exclusively PIGA− blood cells. The loss of GPI-linked proteins occurred mainly in c-kit+CD34+Lin− progenitor cells before the CFU-GEMM stage. Using bone marrow reconstitution experiments with purified PIGA− cells we demonstrate that LF mice have long-term bone marrow repopulating cells that lack GPI-linked proteins, indicating that recombination of the floxed Piga allele occurs in the hematopoietic stem cell.
PMCID: PMC2195941  PMID: 11535627
hematopoiesis; stem cell; c-fes; paroxysmal nocturnal hemoglobinuria; conditional gene inactivation

Results 1-4 (4)