GABAA dysregulation as an explanatory model for late-onset postpartum depression associated with weaning and resumption of menstruation.

It is well established that a subgroup of women are particularly vulnerable to affective dysregulation during times of hormonal fluctuation. One underrecognized reproductive transition may be late-onset postpartum depression (PPD) in the context of weaning from breastfeeding and the resumption of menstruation. The goal of this review is to propose a biologically plausible mechanism for affective dysregulation during these transitions. The relationship between affective symptoms and neurohormonal changes associated with weaning will be investigated through a hypothesis-driven review of relevant literature. Neurosteroids, like allopregnanolone (ALLO), are widely recognized for augmenting GABAergic inhibition and having a powerful anxiolytic effect (Belelli D and Lambert JL, Nature Reviews Neuroscience 6:565-575, 2005). However, when ALLO is administered after prolonged withdrawal, there may be a paradoxical anxiogenic effect (Smith et al., Psychopharmacology 186:323-333, 2006; Shen et al., Nat Neurosci 10:469-477, 2007). Weaning from breastfeeding is a physiologic example of fluctuating levels of ALLO after prolonged withdrawal. We propose that the complex hormonal milieu during weaning and resumption of menstruation may modify GABAA receptors such that ALLO may contribute to rather than ameliorate depressive symptoms in vulnerable individuals. The proposed model provides an initial step for understanding the mechanisms by which the changing hormonal environment during weaning and resumption of menstruation may contribute to an increased risk of depression in a subgroup of women who are hormonally sensitive. Future research investigating this model would be valuable both to identify women at increased risk for developing mood symptoms late in postpartum and to inform treatment for this and related reproductive depressive disorders.

Protection against hormone-mediated mood symptoms.

We present the case of a woman with bipolar I disorder with severe premenstrual mood instability, confusion, and psychosis resembling the clinical features of postpartum psychosis when estrogen levels are expected to be low, and hypomania when estrogen levels are expected to be elevated. While depressive symptoms across the menstrual cycle have been extensively documented in the literature, there is little information regarding manic and hypomanic symptoms. In addition, we describe the successful treatment of her menstrual-cycle related symptoms. Approaches to the management of menstrual psychosis have not been systematically studied, and clinical guidelines do not exist. Clinical experiences such as the one reported here, in which the clinical formulation of the patient was consistent with known neuroendocrine phenomena and in which the treatment approach was successful, are crucial to developing promising approaches that can be tested in controlled trials.

Selective serotonin reuptake inhibitors for depression in pregnancy.

Perinatal depression is associated with a high risk of morbidity and mortality and may have long-term consequences on child development. The US Preventive Services Task Force has recently recognized the importance of identifying and treating women with depression in the perinatal period. However, screening and accessing appropriate treatment come with logistical challenges. In many areas, there may not be sufficient access to psychiatric care, and, until these resources develop, the burden may inadvertently fall on obstetricians. As a result, understanding the risks of perinatal depression in comparison with the risks of treatment is important. Many studies of selective serotonin reuptake inhibitors in pregnancy fail to control for underlying depressive illness, which can lead to misinterpretation of selective serotonin reuptake inhibitor risk by clinicians. This review discusses the risks and benefits of selective serotonin reuptake inhibitor treatment in pregnancy within the context of perinatal depression. Whereas selective serotonin reuptake inhibitors may be associated with certain risks, the absolute risks are low and may be outweighed by the risks of untreated depression for many women and their offspring.

A simple, efficient tool for assessment of mice after unilateral cortex injury.

A refined battery of neurological tests, SNAP (Simple Neuroassessment of Asymmetric Impairment), was developed and validated to efficiently assess neurological deficits induced in a mouse model of traumatic brain injury. Four to 7-month old mice were subjected to unilateral controlled cortical impact or sham injury (craniectomy only). Several behavioral tests (SNAP, beam walk, foot fault, and water maze) were used to assess functional deficits. SNAP was unique among these in that it required no expensive equipment and was performed in less than 5 min per mouse. SNAP demonstrated a high level of sensitivity and specificity as determined by receiver-operator characteristics curve analysis. Interrater reliability was good, as determined by Cohen's Kappa method and by comparing the sensitivity and specificity across various raters. SNAP detected deficits in proprioception, visual fields, and motor strength in brain-injured mice at 3 days, and was sensitive enough to detect magnitude and recovery of injury. The contribution of individual battery components changed as a function of time after injury, however, each was important to the overall SNAP score. SNAP provided a sensitive, reliable, time-efficient and cost-effective means of assessing neurological deficits in mice after unilateral brain injury.