Background of Postpartum Depression and Unmet Medical Need Sample Clauses

Background of Postpartum Depression and Unmet Medical Need. Postpartum depression (PPD) is defined as the occurrence of major depressive episode within 4 weeks of delivery (DSM-IV 1994) or up to a year after giving birth (Xxxx 2013). In Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the onset specifier includes the entire pregnancy as well as 4 weeks following delivery (DSM-5 2013). There are 2 entry criteria for the diagnosis of depression (depressed mood and/or loss of interest) and 7 associated symptoms of depression (appetite problems, sleep problems, motor problems, lack of concentration, loss of energy, poor self-esteem, and suicidality). To be diagnosed with severe PPD, women must present at least 5 symptoms of depression (DSM-5 2013). Most women experience onset of symptoms within the first 3 months following delivery, and PPD is most prevalent at 10 to 14 weeks following childbirth (Xxxx 2013). The overall incidence of PPD is estimated at around 15% to 20%, with up to 10% being considered severe (Edge 2007; O’Hara 2014). Although frequently recognized in the postpartum period, depressive episodes can also begin in the last trimester or earlier during pregnancy (Xxxxxxx-Xxxxx 2011). Converging preclinical and clinical evidence (Xxxxxxx 2011) implicates deficits in GABAergic neurotransmission in the pathophysiology of depressive disorders including PPD. Furthermore, several pieces of experimental data implicate deficiencies in the normal regulation of endogenous neuroactive steroid in depressive disorders (Xxxxxxx 2008; Xxxxxxx 2009). It is thought that the large increase in progesterone-derived neurosteroids during pregnancy and their precipitous decrease at parturition may have considerable effects on γ-aminobutyric acid-gated chloride channel (GABAA) receptors during pregnancy and postpartum leading to PPD. The dynamic trafficking of extrasynaptic (δ-containing) GABAA receptors may be an important compensatory mechanism to changing neurosteroid levels during healthy pregnancies, and this trafficking pattern may be disrupted in PPD (Xxxxxxx 2008; Xxxxxxx 2009). In a preclinical model of PPD, mice lacking GABAA receptor δ-subunits (Gabrd -/- mice) exhibit postpartum- specific phenotypes including reduced tonic inhibition, neuronal hyperexcitability, depressive- like behaviors, and profound deficits in maternal care (Xxxxxxx 2008; Xxxxxxx 2009). In this model, the onset of depression-like behaviors occurred only in the postpartum period and included a significant increase in pup mortality due...
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