Scientists identify protein in brain that induces postpartum depression

Such depression has also been associated with infants’ developmental difficulties. Although stress has been identified as a significant risk factor for postpartum depression, this complex disorder is still poorly understood.

Scientists at Tufts University in the US have generated a novel preclinical model of postpartum depression and demonstrated involvement of the neuroendocrine system that mediates physiological response to stress, called the hypothalamic-pituitary-adrenal (HPA) axis, which is normally suppressed during and after pregnancy.

The findings in mice provide the first empirical evidence that disruption of this system engenders behaviours that mimic postpartum depression in humans.

The study, published in the Psychoneuroendocrinology journal, provides a much-needed research model for further investigation into the causes of and treatment for postpartum depression, which has largely relied on correlational studies in humans because of the scarcity of animal models.

Stress is known to activate the HPA axis, which triggers the fight or flight response seen in many species.

During and after pregnancy such activation is normally blunted — helping to insulate developing offspring from stress — and dysregulation of the HPA axis has been suggested as playing a role in the physiology of postpartum depression.

The effects of stress on postpartum behaviour are thought to be mediated by stress hormones because animal experiments show that stress and exogenous stress hormones can induce abnormal postpartum behaviours.

However, clinical data on stress hormones in women with postpartum depression has been inconsistent.

“Using a mouse model that we developed, our new study provides the first empirical evidence supporting the clinical observations of HPA axis dysfunction in patients with postpartum depression,” said Jamie Maguire, assistant professor at Tufts University.

“It shows for the first time that dysregulation of the HPA axis and a specific protein in the brain, KCC2, can be enough to induce postpartum depression-like behaviours and deficits in maternal care,” Maguire said.

“Pregnancy obviously involves great changes to a woman’s body, but we’re only now beginning to understand the significant unseen adaptations occurring at the neurochemical and circuitry level that may be important to maintaining mental health and maternal behaviour in the first few weeks to months following delivery,” said Laverne Camille Melon, postdoctoral fellow in the Maguire laboratory.

“We hope we have identified a potential molecular target for the development of a new class of compounds that are more effective for women suffering from postpartum depression and anxiety,” she said.

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