Using animal models to study post‐partum psychiatric disorders

Abstract

The post-partum period represents a time during which all maternal organisms undergo substantial plasticity in a wide variety of systems in order to ensure the well-being of the offspring. Although this time is generally associated with increased calmness and decreased stress responses, for a substantial subset of mothers, this period represents a time of particular risk for the onset of psychiatric disorders. Thus, post-partum anxiety, depression and, to a lesser extent, psychosis may develop, and not only affect the well-being of the mother but also place at risk the long-term health of the infant. Although the risk factors for these disorders, as well as normal peripartum-associated adaptations, are well known, the underlying aetiology of post-partum psychiatric disorders remains poorly understood. However, there have been a number of attempts to model these disorders in basic research, which aim to reveal their underlying mechanisms. In the following review, we first discuss known peripartum adaptations and then describe post-partum mood and anxiety disorders, including their risk factors, prevalence and symptoms. Thereafter, we discuss the animal models that have been designed in order to study them and what they have revealed about their aetiology to date. Overall, these studies show that it is feasible to study such complex disorders in animal models, but that more needs to be done in order to increase our knowledge of these severe and debilitating mood and anxiety disorders. LINKED ARTICLESThis article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi. org/10.1111/bph.2014.171.issue-20 Abbreviations BDNF, brain-derived neurotrophic factor; CORT, corticosterone; CRH, corticotrophin-releasing hormone; FSL, Flinders sensitive line; HAB, high anxiety-related behaviour; HPA axis, hypothalamus-pituitary-adrenal axis; HSP, hormone-simulated pregnancy; LAB, low anxiety-related behaviour; LH, learned helplessness; PPD, post-partum depression; PVN, paraventricular nucleus of the hypothalamus IntroductionThe post-partum period represents a time of profound physiological and emotional changes in all maternal organisms in order to ensure the well-being and nurturance of the offspring. These alterations are wide ranging and include the onset of maternal behaviour, lactogenesis, as well as increased calmness and a reduced response to stress. However, in a large subset of mothers, this phase also represents a risk period for the development of several psychiatric disorders. Such postpartum mood and anxiety disorders are particularly damaging because they not only affect the well-being of the mother but also disadvantage the development of the infant as well, increasing their likelihood of developing a psychiatric disorder in later life (Weinstock, 2001;Newport et al., 2002; Davalos et al., 2012). Several post-partum disorders have been described and include post-partum depression (PPD), postpartum anxiety and post-partum psychosis. A n...

The birth of new neurons in the maternal brain: Hormonal regulation and functional implications

“…Thus, while basal glucocorticoid levels are elevated, the response of the hypothalamic-pituitary-adrenal (HPA) axis is reduced postpartum (Slattery and Neumann, 2008; Perani and Slattery, 2014). New neurons have been implicated in the stress regulatory functions of the hippocampus by dampening the HPA response to stress (Snyder et al, 2011) and therefore may play a role in lowered stress responsiveness during the postpartum period.…”

“…Indeed, postpartum depression represents one of the most common complications following childbirth and has been estimated to affect up to 20% of new mothers (O’Hara and McCabe, 2013; Wisner et al, 2013; Agrati and Lonstein, 2015; Brummelte and Galea, 2015). A number of factors have been identified that may increase the risk of postpartum depression (Robertson et al, 2004; Stone et al, 2015), including stress during pregnancy and/or after birth which can be easily modeled in rodents (Perani and Slattery, 2014). For example, a growing body of research has revealed that repeated exposure to stress while pregnant can induce behavioral despair and impaired maternal care during the postpartum period (Smith et al, 2004; O’Mahony et al, 2006; Haim et al, 2014; Leuner et al, 2014), thus acting as a model of postpartum depression.…”

“…Across mammalian species, major hormonal shifts during pregnancy, parturition and the postpartum period coupled with experiential factors modify the brain and, as a result, the behavior of the female producing a high level of maternal responsiveness along with changes in maternal mood, cognition and stress regulation (Fleming et al, 1999; Numan and Insel, 2003; Lonstein, 2007; Slattery and Neumann, 2008; Macbeth and Luine, 2010; Numan and Woodside, 2010; Workman et al, 2012; Dulac et al, 2014; Galea et al, 2014; Hillerer et al, 2014; Perani and Slattery, 2014; Rilling and Young, 2014; Pereira and Ferreira, 2015). Together, these changes represent adaptive responses that are necessary to ensure the survival and well-being of the offspring.…”

Association of peripartum synthetic oxytocin administration and depressive and anxiety disorders within the first postpartum year

“…Despite negative impacts on both mother and child, the pathophysiology of postpartum depressive and anxiety disorders is poorly understood, with relatively few animal models (Perani & Slattery, 2014). Due to its role in the modulation of social behavior, especially affiliative bonding, oxytocin has been identified as a potential mediator of postpartum depression and anxiety (Sohye Kim et al, 2014)(Kim et al, 2014).…”

Maternal alterations in the proteome of the medial prefrontal cortex in rat

“…Maternal behaviors in postpartum rats include nest building, the retrieval of pups to the nest, the licking of pups, and the adoption of appropriate postures for suckling [2]. These behavioral alterations are accompanied with reduced anxiety-and depression-like behaviors, and increased aggressiveness towards intruders [3][4][5]. The highest, cortical control influencing maternal responses implies the involvement of the medial prefrontal cortex (mPFC) in maternal adaptations [6][7][8].…”