Fragmentation and Unpredictability of Early-Life Experience in Mental Disorders

Abstract

Maternal sensory signals in early life play a crucial role in programming the structure and function of the developing brain, promoting vulnerability or resilience to emotional and cognitive disorders. In rodent models of early-life stress, fragmentation and unpredictability of maternally derived sensory signals provoke persistent cognitive and emotional dysfunction in offspring. Similar variability and inconsistency of maternal signals during both gestation and early postnatal human life may influence development of emotional and cognitive functions, including those that underlie later depression and anxiety.

Early-Life Experience, Epigenetics, and the Developing Brain

“…Reduction in neurotropic factors in the prefrontal cortex is also observed in pups that have experienced abusive caregiving in infancy (Roth et al, 2009). Similar to the case of attachment in humans, fragmentation of mother-infant interactions may be a common pathway in many of these models of adversity and serve a mediating role in predicting long-term outcomes in offspring (Baram et al, 2012). This unpredictability of care can be achieved through removal of bedding material from the home-cage (Rice et al, 2008), and lead to reduced nurturing and increased abusive maternal interactions (eg, stepping on pups, aggressive grooming, and transporting of pups by a limb) with offspring, as well as increased basal corticosterone and impaired learning/ memory, likely mediated through forebrain corticotropin releasing-factor receptor 1 signaling (Rice et al, 2008;Roth et al, 2009;Wang et al, 2011).…”

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

“…Notably, there is little evidence of physical stress of the pups, with no hypothermia and minimal weight changes . Thus, the early-life stress that is engendered seems to be a direct result of the fragmented, unpredictable sensory signals from the mothers (Moriceau et al 2009;Baram et al, 2012;Molet et al, 2014Molet et al, , 2015a. These seem to provoke chronic early-life stress, including persistent elevation of plasma corticosterone and adrenal hypertrophy (Gilles et al, 1996;Rice et al, 2008).…”

“…Decades of research in the neuroscience and neuroendocrine fields have therefore focused on identifying the mechanisms by which early-life stress regulates brain development. In mammals, including humans, monkeys, and rodents, maternal input has perhaps the most significant influence on the type of environment experienced during development (Bowlby, 1950;Seay, 1962;Baram et al, 2012;Rincón-Cortés and Sullivan, 2014;Kundakovic and Champagne, 2015). In accordance, most animal models of early-life stress have targeted maternal interaction, disturbing either the quantity or quality of maternal care early in life (for recent reviews, see Molet et al, 2014;Nishi et al, 2014).…”

Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation

“…The set point of HPA axis activity, and possibly also of neurogenesis regulation, is, on the one hand, programmed by genotype, but can be further modified by early development and epigenetic changes (Lucassen et al 2013b). In humans, early life stressors (ELS) are among the strongest predisposing factors for developing psychopathology and cognitive decline later in life (Heim et al 2008;Loman et al 2010;Maselko et al 2011;Baram et al 2012;Teicher et al 2012). In experimental conditions, ELS has been shown to affect emotional and cognitive functions as well.…”

“…In experimental conditions, ELS has been shown to affect emotional and cognitive functions as well. Indeed, stress reactivity is elevated and cognitive functions are impaired in rats exposed to ELS (Brunson et al 2005;Aisa et al 2007;Ivy et al 2010;Oomen et al 2010;Baram et al 2012).…”