# Does hypothalamic CCN3 hypersecretion confer postpartum mood disorder risk?

## TL;DR

This paper proposes that excessive CCN3 protein secretion in the brain may contribute to postpartum mood disorders, offering a new explanation and potential treatment approach.

## Contribution

The paper introduces a novel hypothesis linking CCN3 hypersecretion to postpartum mood disorder risk.

## Key findings

- CCN3 hypersecretion from hypothalamic neurons may predispose to adverse postpartum mental health.
- Circulating CCN3 levels could correlate with mood symptoms in humans.
- CCN3 over-expression in animal models may induce behavioral abnormalities.

## Abstract

Postpartum mood disorders, of which postpartum psychosis is the most severe, occur shortly after childbirth in a proportion of mothers. These conditions can impact negatively and substantially on maternal health, mother-child bonding, and family dynamics, but their pathophysiology is poorly-understood, and treatment options are limited. Following recent research in a preclinical model, here, I propose that hypersecretion of the CCN3 protein from kisspeptin neurons of the hypothalamic arcuate nucleus in response to severe oestrogen depletion and/or abnormal calcium metabolism predisposes to adverse postpartum mental health. This novel idea reconciles many previous disparate theoretical, preclinical, and clinical findings with respect to postpartum psychopathology, and suggests that neuroendocrine and psychological processes act in combination to confer disorder risk. It also provides testable predictions: notably, that circulating CCN3 levels are positively-correlated with adverse postpartum mood symptoms in humans, and that CCN3 administration/over-expression in postpartum animal models induces relevant behavioural abnormalities. Empirical support for this hypothesis would indicate viable alternative therapeutic strategies e.g. pharmacological downregulation of CCN3.