Neuroendocrine, neuronal and behavioural peripartum adaptations are essential for the female`s successful adaptive response when becoming maternal. Despite these adjustive mechanisms, the period around birth represents a time with high risk for women to develop mood and anxiety disorders that include a severe confinement of mother-infant interactions. Unfortunately, the aetiology of postpartum mood and anxiety disorders is largely unknown. However, chronic stress during the peripartum period is one major risk factor of such mental illnesses. Therefore, my thesis centered on the premise that by assessing the consequences of peripartum stress, I can provide insight into the mechanisms underlying postpartum mood and anxiety disorders. In order to demonstrate the specificity of such effects to the peripartum period it is necessary to include controls such as males and, particularly, virgin females.
In this thesis, I demonstrated that chronic stress during either pregnancy or lactation prevented a number of the above mentioned peripartum adaptations.
Thus, I could show that chronic stress during pregnancy induces an increase in active maternal care with a concurrent increase in anxiety-related behaviour. Although, chronic stress and increased levels of anxiety are often associated with an increase in depression-like behaviour, I did not observe an effect of chronic stress in this direction. However, using the antidepressant imipramine, I revealed that chronic stress prevented the lactation-associated decrease in the noradrenergic system activity, which in general underlies the observed passive stress-coping behaviour in the FST. Furthermore, I could show that chronic pregnancy stress prevented the lactation-associated basal hypercorticism and the elevation in the OXT system within the PVN. Illustrating the specificity of the stress-induced changes to the peripartum period, most of the parameters were not affected in stressed virgin females. Given the fact that several postpartum psychiatric disorders have been linked to changes in basal ACTH and cortisol levels in humans, the results of the present thesis provide further important evidence that HPA axis dysregulation may be one major mechanism involved in the development of postpartum mood and anxiety disorders.
Naturally, males and females differ in their sensitivity to stress and their stress responsiveness to several stressors. Using chronic restraint as the stress paradigm and adult hippocampal neurogenesis as the readout parameter, I could demonstrate that sex differences do not only occur in the basal HPA axis activity and pattern of hippocampal neurogenesis, but moreover that cell proliferation, cell survival, cell differentiation and stem cell quiescence are differentially affected by chronic stress in male and female rats. These results are of importance for various reasons. First, there is a correlation between chronic stress, neurogenesis and depression and second, females have twice a higher risk to develop depressive disorders compared to males. Thus, the results provide evidence that sex differences in hippocampal neurogenesis may underlie the increased depression-susceptibility in females. Taking these findings, I next assessed the effect of this RS paradigm on the altered neurogenesis that occurs in the peripartum period. Here, I revealed that chronic stress during lactation prevents lactation-associated changes in cell proliferation and survival, but moreover, I showed for the first time that differentiation patterns and stem cell quiescence are altered after chronic lactation stress. The lactation period is a time when the bigger part of metabolic resources is needed to insure healthy survival of the offspring. Therefore, reducing growth processes like neurogenesis and simultaneously increasing efficiency might be an important adaptive mechanism of the lactation period.
Beside the effects of chronic stress on the mother, I provided a wide-ranging of basic knowledge about the effect of early life stress on the adult emotional and social behaviour in the offspring. Importantly, I demonstrated that not only the timing of the stressor plays a pivotal role, but moreover that postnatal maternal-infant interaction in the form of maternal care is seminal for the adult behavioural outcome of the offspring. While prenatal stress induced an anxiety-related and depression-like phenotype in adulthood, postnatal stress rather led to deficits in social behaviour. Although an increase in active maternal care was effective to restore the effect of postnatal stress on social behaviour, it did not restore prenatal induced stress effects. Thus, it seems that regulatory mechanisms that are fundamental for adult affective behaviour undergo a critical stage of development during the prenatal stage and a disruption of these processes might not be rescued by increased amounts of maternal care. However, a high quantity of maternal care might be able to restore deficits in social behaviour when occurring simultaneously with postnatal stress exposure. The neurobiological mechanisms underlying the observed time-dependent differences in behaviour have not been subject of investigation in this thesis. However, future studies will concentrate to identify mechanism that are involved in the regulation of adult affective and social behaviours that might also underlie psychopathologies like anxiety disorders, autism, attention deficit hyperactivity disorders and schizophrenia, which have all been associated with early life stress exposure
