Perinatal programming of emotional brain circuits: an integrative view from systems to molecules

Abstract

Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional “scars” in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of “stress inoculation” is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life.

The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming

“…During gestation, rapid growth and plasticity render the brain sensitive to the effects of environmental factors that can confer adaptive advantages or lasting vulnerability. As the fetal origins of disease hypothesis was pioneered four decades ago by Barker (1997) and Dörner (1973), substantial advances have been achieved in understanding the neurodevelopmental consequences of intrauterine challenges, including maternal psychosocial stress, infection, and metabolic dysfunction (Bock et al, 2014(Bock et al, , 2015Brown and Derkits, 2010;Markham and Koenig, 2011;Weinstock, 2008). Maternal stress during pregnancy, in particular, has been identified in autism spectrum disorders (ASDs), attention deficit/hyperactivity disorder (ADHD), and schizophrenia risk (Beversdorf et al, 2005;Khashan et al, 2008;Kinney et al, 2008a;Li et al, 2010;Ronald et al, 2010).…”

Untying the Gordian Knot: What We Do and Don't Know About Gender-specific Medicine-Keynote Address for the 2014Academic Emergency MedicineConsensus Conference

“…Roth and Sweatt 28 have shown that early adverse experiences are associated with methylation of the brain-derived neurotropic factor, which is released in response to activity and is vital for brain development and plasticity. In a comprehensive review of the effect of experience on brain development, Bock et al 29 refer to the interesting concept of "functional scars" in the prefrontal and limbic areas of the brain, which are regions involved in emotional control, learning, and memory. These are induced by what the authors call "stress inoculation": responses to stress early in life, with either adverse or positive adaptations of the brain to adverse experiences.…”

Prenatal stress and childhood asthma risk: taking a broader view

“…a "two hit" model of disease). Pioneering animal studies demonstrate that effects of prenatal stress and/or hormonal correlates on offspring development may be different from those related to postnatal stress [19]. Other evidence demonstrates that an adverse postnatal environment modulates the developmental consequences of prenatal stress in a sex-specific manner.…”

“…immune, autonomic, neuroendocrine and oxidation systems) hypothesised to be responsible for the association between maternal stress and child respiratory outcomes. Promising candidates that warrant focus include placental biomarkers [15], epigenetics [16][17][18] and developing neurobiological systems [19] that are responsive to stress as well as being implicated in respiratory health. Stress responsive mechanisms operating at the level of the placenta are only beginning to be elucidated and may provide markers of early risk [20].…”