Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation

The putative effects of early-life stress (ELS) on later behavior and neurobiology have been widely investigated. Recently, microglia have been implicated in mediating some of the effects of ELS on behavior. In this review, findings from preclinical and clinical literature with a specific focus on microglial alterations induced by the exposure to ELS (i.e., exposure to behavioral stressors or environmental agents and infection) are summarized. These studies were utilized to interpret changes in developmental trajectories based on the time at which the stress occurred, as well as the paradigm used. ELS and microglial alterations were found to be associated with a wide array of deficits including cognitive performance, memory, reward processing, and processing of social stimuli. Four general conclusions emerged: (1) ELS interferes with microglial developmental programs, including their proliferation and death and their phagocytic activity; (2) this can affect neuronal and non-neuronal developmental processes, which are dynamic during development and for which microglial activity is instrumental; (3) the effects are extremely dependent on the time point at which the investigation is carried out; and (4) both pre- and postnatal ELS can prime microglial reactivity, indicating a long-lasting alteration, which has been implicated in behavioral abnormalities later in life.

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Early life stress and trauma: developmental neuroendocrine aspects of prolonged stress system dysregulation

HORMONES ◽

10.1007/s42000-018-0065-x ◽

2018 ◽

Vol 17 (4) ◽

pp. 507-520 ◽

Cited By ~ 20

Author(s):

Agorastos Agorastos ◽

Panagiota Pervanidou ◽

George P. Chrousos ◽

Gerasimos Kolaitis

Keyword(s):

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Stress System ◽

Prolonged Stress

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Early Life Stress and Pediatric Posttraumatic Stress Disorder

Brain Sciences ◽

10.3390/brainsci10030169 ◽

2020 ◽

Vol 10 (3) ◽

pp. 169 ◽

Cited By ~ 2

Author(s):

Panagiota Pervanidou ◽

Gerasimos Makris ◽

George Chrousos ◽

Agorastos Agorastos

Keyword(s):

Posttraumatic Stress Disorder ◽

Posttraumatic Stress ◽

Life Stress ◽

Early Life ◽

Stress Disorder ◽

Early Life Stress ◽

Traumatic Experiences ◽

Stress System ◽

Critical Periods ◽

Physical And Mental Health

Traumatic stress exposure during critical periods of development may have essential and long-lasting effects on the physical and mental health of individuals. Two thirds of youth are exposed to potentially traumatic experiences by the age of 17, and approximately 5% of adolescents meet lifetime criteria for posttraumatic stress disorder (PTSD). The role of the stress system is the maintenance of homeostasis in the presence of real/perceived and acute/chronic stressors. Early-life stress (ELS) has an impact on neuronal brain networks involved in stress reactions, and could exert a programming effect on glucocorticoid signaling. Studies on pediatric PTSD reveal diverse neuroendocrine responses to adverse events and related long-term neuroendocrine and epigenetic alterations. Neuroendocrine, neuroimaging, and genetic studies in children with PTSD and ELS experiences are crucial in understanding risk and resilience factors, and also the natural history of PTSD.

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Positive memory specificity reduces adolescent vulnerability to depression

10.1101/329409 ◽

2018 ◽

Cited By ~ 1

Author(s):

Adrian Dahl Askelund ◽

Susanne Schweizer ◽

Ian M. Goodyer ◽

Anne-Laura van Harmelen

Keyword(s):

At Risk ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Stress System ◽

Low Mood ◽

Memory Specificity ◽

Morning Cortisol ◽

One Year ◽

Positive Memories

Depression is the leading cause of ill health and disability worldwide1. A known risk factor of depression is exposure to early life stress2. Such early stress exposure has been proposed to sensitise the maturing psychophysiological stress system to later life stress3. Activating positive memories dampens acute stress responses with resultant lower cortisol response and improved mood in humans4 and reduced depression-like behaviour in mice5. It is unknown whether recalling positive memories similarly reduces adolescent vulnerability to depression. Here we used path modelling to examine the effects of positive autobiographical memory specificity on later morning cortisol and negative self-cognitions during low mood in adolescents at risk for depression due to early life stress (n = 427, age: 14 years)6. We found that experimentally assessed positive but not negative memory specificity was associated with lower morning cortisol and less negative self-cognitions during low mood one year later. Moderated mediation analyses demonstrated that positive memory specificity reduced later depressive symptoms through lowering negative self-cognitions in response to negative life events reported in the one-year interval. Positive memory specificity actively dampened the negative effect of stressors over time, thereby operating as a resilience factor reducing the risk of subsequent depression7. These findings suggest that developing methods to improve positive memory specificity in at-risk adolescents may counteract vulnerability to depression.

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Stress-system activation in children with chronic pain: A focus for clinical intervention

Clinical Child Psychology and Psychiatry ◽

10.1177/1359104519864994 ◽

2019 ◽

Vol 25 (1) ◽

pp. 78-97 ◽

Cited By ~ 1

Author(s):

Peter M McInnis ◽

Taylor A Braund ◽

Zhi Kai Chua ◽

Kasia Kozlowska

Keyword(s):

Heart Rate ◽

Chronic Pain ◽

Psychological Distress ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Stress System ◽

Identification Task ◽

System Activation ◽

Elevated Heart Rate

Accumulating evidence indicates that psychological and neurophysiological processes interconnect and interact to activate the body’s stress system and to trigger and maintain functional somatic symptoms. This study used the Early Life Stress Questionnaire, Depression Anxiety Stress Scales and biological markers (heart rate, heart rate variability, skin conductance, C-reactive protein (CRP) titre, respiratory rate, and accuracy and reaction time in an emotion-face identification task), to examine childhood adversity, psychological distress and stress-system activation in 35 children and adolescents (23 girls and 12 boys, 9–17 years old) disabled by chronic pain (vs two groups of age- and sex-matched healthy controls). Patients reported more early-life stress ( U = 798.5, p = .026) and more psychological distress ( U = 978, p < .001). They showed activation of the autonomic system: elevated heart rate ( U = 862.5, p = .003), elevated electrodermal activity ( U = 804.5, p = .024) and lower heart rate variability in the time domain ( U = 380.5, p = .007) and frequency domain ( U = 409.5, p = .017). The group showed an upward shift of CRP titres (with 75th and 90th CRP percentiles of 4.5 and 10.5 mg/L, respectively), suggesting the activation of the immune–inflammatory system. Elevated CRP titres were associated with elevated heart rate ( p = .028). There were no differences in respiratory rate or in accuracy and reaction time in the emotion-face identification task. The results indicate that interventions for children and adolescents with chronic pain need a multidisciplinary mind–body approach that concurrently addresses psychological distress, physical impairment and stress-system dysregulation.

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