The adolescent brain and age-related behavioral manifestations

Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.

Effects of stress throughout the lifespan on the brain, behaviour and cognition

Childhood maltreatment has been linked to a variety of changes in brain structure and function and stress–responsive neurobiological systems. Epidemiological studies have documented the impact of childhood maltreatment on health and emotional well–being. After a brief review of the neurobiology of childhood trauma, we use the Adverse Childhood Experiences (ACE) Study as an epidemiological “case example” of the convergence between epidemiologic and neurobiological evidence of the effects of childhood trauma. The ACE Study included 17,337 adult HMO members and assessed 8 adverse childhood experiences (ACEs) including abuse, witnessing domestic violence, and serious household dysfunction. We used the number of ACEs (ACE score) as a measure of cumulative childhood stress and hypothesized a "doseresponse" relationship of the ACE score to 18 selected outcomes and to the total number of these outcomes (comorbidity). Based upon logistic regression analysis, the risk of every outcome in the affective, somatic, substance abuse, memory, sexual,and aggressionrelated domains increased in a graded fashion as the ACE score increased (P <0.001). The mean number of comorbid outcomes tripled across the range of the ACE score. The graded relationship of the ACE score to 18 different outcomes in multiple domains theoretically parallels the cumulative exposure of the developing brain to the stress response with resulting impairment in multiple brain structures and functions.

https://traumasensitiveschools.org/wp-content/uploads/2013/06/Anda-Article-Enduring-Effects-of-Abuse.pdf

The enduring effects of abuse and related adverse experiences in childhood: A convergence of evidence from neurobiology and epidemiology

Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A–inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.

/pdf/epigenetic-regulation-of-the-glucocorticoid-receptor-in-42c0o5px64.pdf

Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(08)61706-7.pdf

Burden and consequences of child maltreatment in high-income countries

http://www.arts.uwaterloo.ca/%7eraha/CogSci600_web/Readings/wainwright4.pdf

Trajectories of brain development: point of vulnerability or window of opportunity?

The neurobiological consequences of early stress and childhood maltreatment

Stress, sensitive periods and maturational events in adolescent depression.

Volumetric MRI scans from 26 women with repeated episodes of childhood sexual abuse and 17 healthy female comparison subjects (ages 18-22 years) were analyzed for sensitive period effects on hippocampal and amygdala volume, frontal cortex gray matter volume and corpus callosum area. Hippocampal volume was reduced in association with childhood sexual abuse at ages 3-5 years and ages 11-13 years. Corpus callosum was reduced with childhood sexual abuse at ages 9-10 years, and frontal cortex was attenuated in subjects with childhood sexual abuse at ages 14-16 years. Brain regions have unique windows of vulnerability to the effects of traumatic stress.

/pdf/preliminary-evidence-for-sensitive-periods-in-the-effect-of-37ggznkp61.pdf

Susan L. Andersen

Papers

Trajectories of brain development: point of vulnerability or window of opportunity?

The neurobiological consequences of early stress and childhood maltreatment

Stress, sensitive periods and maturational events in adolescent depression.

Preliminary Evidence for Sensitive Periods in the Effect of Childhood Sexual Abuse on Regional Brain Development

Developmental neurobiology of childhood stress and trauma