Stress in early childhood

Early childhood is a critical period in a child's life that includes ages from conception to five years old.[1][2] Psychological stress is an inevitable part of life. Human beings can experience stress from an early age. Although stress is a factor for the average human being, it can be a positive or negative molding aspect in a young child's life.[3]

A certain amount of stress is normal and necessary for survival. A few stressors can be manageable for young children; stress can be beneficial by helping children develop skills needed to adapt to a new set of circumstances and deal with dangerous and intimidating situations. Some experts have theorized that there is a point where prolonged or excessive stress becomes harmful and can lead to serious health effects.[4] When stress builds up in early childhood, neurobiological factors are affected.[1] In turn, levels of the stress hormone cortisol exceed normal ranges.[1] This theory however is based on animal studies and cross-sectional studies in humans, and the proposed impacts on brain centers have not been found in a landmark twin study[5] and studies where neurobiological factors were measured in humans prior to stress or trauma exposure.[6][7]

Researchers have proposed three distinct types of responses to stress in young children: positive, tolerable, and toxic.[8] These labels are based on theorized differences in lasting physiological changes occurring as a result of the intensity and duration of the stress response.[9]

Stress is caused by internal or external influences that disrupt an individual's normal state of well-being.[10] These influences are capable of affecting health by causing emotional distress and leading to a variety of physiological changes.[4] Internal stressors include physiological conditions such as hunger, pain, illness or fatigue. Other internal sources of stress consist of shyness in a child, emotions, gender, age and intellectual capacity.[3] Childhood trauma has lifelong impact.

Exposure to adverse childhood experiences can include separation from family, home violence, neighborhood violence, mental illness or substance use disorder of caregiver, physical/sexual abuse, neglect divorce, a new home or school, illness and hospitalization, death of a loved one, poverty, natural disasters, and adults’ negative discipline techniques (e.g. spanking).[3] Additional external stressors include prenatal drug exposure, such as maternal methamphetamine use, other maternal and paternal substance abuse, maternal depression, posttraumatic stress and psychosis.[3][11][12]

Levels of stress

Researchers have proposed three different levels of stress seen in children during early childhood; positive, tolerable and toxic.[1][9]

Positive stress is necessary and promotes resilience, or the ability to function competently under threat.[13] Such stress arises from brief, mild to moderate stressful experiences, buffered by the presence of a caring adult who can help the child cope with the stressor.[9] This type of stress causes minor physiological and hormonal changes to the young child; these changes include an increase in heart rate and a change in hormone cortisol levels.[4] The first day of school, a family wedding or making new friends are all examples of positive stressors.[4] Such experiences can promote healthy development within an environment of supportive relationships, giving children the chance to observe and practice healthy responses to stressful events.[9]

Tolerable stress comes from adverse experiences that are more intense in nature but short-lived and can usually be overcome.[4] The body's stress response is more intensely activated due to severe stressors.[14] Some examples of tolerable stressors are family disruptions, accidents or a death of a loved one. It is important though to realize that such stressors are only tolerable when managed the correct way. Tolerable stress can turn into positive stress.[14] With appropriate care from adults, young children can easily cope with tolerable stress and turn it into positive stress. However, if adult support is deficient in a child's coping stages, then tolerable stress can become detrimental.[4]

Toxic stress can occur when experiences are long in duration and intensity.[14] Children need caring and supportive adults to help them because it is difficult for children to handle this type of stress on their own.[4] Therefore, the stress response may be activated from weeks to months or even years.[4] Prolonged stress leads to adverse effects such as permanent emotional or developmental damage.[4] If sufficient support is not available, this type of stress can result in permanent changes in brain development.[4] Research has found that children experiencing severe and long-term abuse have smaller brain sizes.[15] If the situation is not as severe, toxic stress will still alter the stress response system; these changes will cause children to react to a wider variety of stressors.[15] However, with sufficient care and support from adults, children can return their stress levels to tolerable or good.[4] Examples of toxic stress are abuse, neglect, violence and overall hardship without adult support.[14] Toxic stress can have a cumulative effect on physical and mental health.

Allostatic load is "the wear and tear on the body" that accumulates as an individual is exposed to repeated or chronic stress.[16] It represents the physiological consequences of chronic exposure to fluctuating or heightened neural or neuroendocrine response that results from repeated or chronic toxic stress. The term was coined by Bruce McEwen and E. Stellar in 1993.[17]

Stages of stress

Stress is encountered in four different stages in early childhood.[3] In the first stage, stress usually causes alarm.[3] Next, in the second or appraisal stage, the child attempts to find meaning from the event.[3] Stage three consists of children seeking out coping strategies.[3] Lastly, in stage four, children execute one or more of the coping strategies.[3] However, children with lower tolerance for stressors are more susceptible to alarm and find a broader array of events to be stressful.[3] These children often experience chronic or toxic stress.[3]

Causes

Children from a lower socioeconomic status are more prone to exposure to all the early life stress listed above. Socioeconomic status can be measured by education and income level. A chronic exposure to stress will lead to the decline of physical health and increase susceptibility to diseases.[18]

Situations that may promote stress in childhood include:[4][14][19]

  • Disrupted homes: Divorce/separation, blended families, both parents working and parental incarceration
  • Lack of attention
  • Separation from parents
  • Exposure to violence: physical, mental and sexual abuse
  • Substance abuse
  • Being over-scheduled
  • Feeling pressured to perform or behave beyond their ability
  • Neglect: emotional and physical neglect
  • Meeting new people
  • Starting a new school
  • Death of a loved one
  • Illness: mental and physical
  • Difficulty with school work
  • Increased pressure/responsibility at home
  • Being bullied

Stress and brain development

Brain circuits and testosterone's systems are formed and activated in early life.[4] These neurobiological systems of the body help maintain viability and are necessary for survival in early childhood and along the course of life.[20] When a child or adult experiences a stressor, the body will attempt to regulate the stress through releasing hormones that pass through the body.[4] However, effects of the prolonged or frequent biological stress response may increase the risk for future physical and mental health problems in early childhood.[20] Since, brain circuits are vulnerable in early childhood, early stressors may impact the development of necessary brain connections.[4] Therefore, the theory of toxic stress is that stress might alter or impair brain circuit formation and essentially result in a small brain size in young children.[4] There are however no studies yet that have measured these brain circuits or volumes of brain centers prospectively in young children to prove this theory.

Stress response pathway in humans

In humans, the stress response pathway consists of the sympathetic-adrenomedullary (SAM) system and the hypothalamic-pituitary-adrenal axis (HPA).[20] The SAM system is a part of the sympathetic component of the autonomic nervous system.[20] These systems are responsible for releasing epinephrine and norepinephrine (NE), also known as the flight or fight response hormones.[20] When epinephrine is released it will bind to various receptors in various target organs; this will exhibit multiple roles in the fight or flight mechanism.[20] The HPA system is responsible for producing glucocorticoids from the adrenal cortex; the main glucocorticoid in humans is the steroid hormone cortisol.[20] In contrast to epinephrine, which takes a short amount of time for production, cortisol takes up to 25 minutes to reach peak levels.[20] Also, cortisol is able to penetrate the brain through the blood–brain barrier, unlike epinephrine.[20] Therefore, cortisol takes more time to form, but impacts the brain for a longer period of time.[20] In conjunction, the SAM and HPA systems work to regulate stress and unite at the hypothalamus, which in turn regulates behavior.[20]

The sympathetic adrenomedullary system

In humans, there are chromaffin cells in the adrenal glands (medulla) that get stimulated through the sympathetic nervous system during a stress response.[20] These cells release the hormones epinephrine and norepinephrine (NE).[20] Epinephrine and NE bind to receptors of target organs and instigate the fight or flight response.[20] As an example, epinephrine increases heart rate and causes blood vessels to dilate in muscles and blood vessels to constrict in the skin and gut.[20] This allows a sufficient amount of blood to access the brain and muscles.[20] Also, epinephrine initiates the breakdown of glycogen in the liver, in turn increasing blood glucose levels. This energy source allows humans to enact defensive responses due to stress.[20]

The hypothalamic-pituitary-adrenal system and cortisol

In the human body, the steps that lead to the release of glucocorticoids such as cortisol begin with the release of corticotropin releasing hormone (CRH) and arginine vasopressin (AVP).[20] These hormones travel through the blood vessels to the anterior pituitary gland of the brain.[20] At this location, adrenocorticotropic hormone (ACTH) is released.[20] ACTH binds to the receptors in the adrenal glands, which are located atop the kidneys, and this causes the release of cortisol.[20] Cortisol enters the cytoplasm of cells in the body, including the brain. The hormone then reacts with receptors inside of the cell.[20] The activated receptors reach the nucleus of the cells and regulate the transcription of genes. Eventually, the body experiences physiological and behavioral changes.[20] Because cortisol hormone enters the cell's nucleus, the effects of change take longer to occur, and last for a longer period of time, compared to the hormones of the SAM system.[20] The effect of cortisol depends upon the type of receptor that it interacts with inside of the cell.[20] There are two glucocorticoid receptors; one is the mineralocorticoid receptor (MR) and another is the glucocorticoid receptor (GR).[20] Normally, when cortisol is outside of the brain, it will bind to GRs. When cortisol is within the brain cells, it will bind to GRs and MRs.[20] However, cortisol and other glucocorticoids bind more readily to MRs.[20] Cortisol's varying affinity toward GR and MR plays an important role in distinguishing between normal and stress responses by the HPA system.[20] When cortisol is in its basal range, more MRs are bound to cortisol than GRs. GRs are predominantly bound when humans wake from sleep or experience stress.[20] Therefore, GRs arbitrate most of the stress effects of cortisol and glucocorticoids in other species, while MRs control most basal effects.[20] Often, cortisol and GR effects oppose the cortisol and MR effects. This leads many researchers to speculate that early childhood (and adult) stress resilience and weakness entail the ratio of MR to GR activation.[20] Research has found that GRs impair neural flexibility and the processes involved in learning and memory. In contrast, MRs increase the synaptic plasticity.[20] Therefore, the effects of frequent and prolonged stress responses from the HPA system may cause detrimental results.[20]

Infancy, early childhood, and stress

When the body undergoes a stressful situation, the stress hormone cortisol is released. Cortisol helps the body prepare for stressful and dangerous situation. It gives a quick burst of energy, heightened memory and lower sensitivity to pain, among other things.[21] When cortisol is present in the body at high levels and for extended periods of time, however, the body's immune response may be suppressed.[4] This leaves the developing bodies of children extremely vulnerable to damage and illness. Cortisol is usually bound to proteins in adults. The protein is called the corticosteroid-binding globulin (CBG).[20] In newborn babies, CBGs remain low and increase during the first six months after birth.[20] Therefore, as the amount of CBGs increase, more cortisol becomes bound to the CBGs. Due to this occurrence, plasma and total cortisol levels increase.[20] Although there are low levels of cortisol at birth, the levels are sufficient to have serious physiological effects.[20]

Newborns do not manifest typical adult circadian rhythms in cortisol production. Usually, newborns have peak cortisol levels every 12 hours and this does not depend on the time of day.[20] After three months of life, babies begin to experience the adult cortisol production patterns, an early morning cortisol peak and low evening levels of cortisol.[20] These cortisol rhythmic changes occur throughout infancy and early childhood, along with changes in sleep patterns.[20] The activity of the HPA stress system adapts by repeated exposure to stressful stimulation.[22]

As newborns progress through the early months of life, babies experience increased cortisol levels during medical examinations. This is physically characterized by the fussing and crying of babies.[20] After three months of life, babies do not respond to physical examinations with the HPA stress response system. However, babies can still respond to behavioral distress.[20] As another example, if blood is drawn from a baby, the baby experiences an increased cortisol level.[22] When this process is repeated 24 hours later, the same increase in cortisol is observed.[22] In addition, during the first year of life, it becomes difficult to induce cortisol level increases to some mild stressors. These stressors include the approach of a stranger, strange events, few-minute separations from parents, and more.[20] The decreased sensitivity of the HPA stress response may be due to physiological changes that occur in the system during early ages. The physiological changes that may occur include improved negative feedback regulation of the HPA system, and decreased sensitivity of the adrenal cortex to ACTH.[20] Also, the availability of adult support for young children helps safeguard the activity of the HPA stress system.[20]

Many experiences can cause structural changes in the HPA system.[22] The effects of repeated increases in cortisol levels have been researched in many animal studies, but these outcomes are also representative of humans, including young children.[22] It has been determined that when glucocorticoids, including cortisol, are placed into various parts of the brain for many days, CRH is produced in increased quantities.[22] In turn, this causes fear behaviors, increased caution, and activation of the SAM system. Eventually, these effects may cause posttraumatic stress disorder, in young children.[22] A more serious psychological symptom seen in children, PTSD manifests symptoms such as, heightened fear and anxiety, loss of interests, flashbacks, lacking some emotions, paranoia.[23] Other serious psychological symptoms of stress seen in children are depression, anxiety, low self-confidence and dysregulated aggression.[24][25]

Stress in children has the greatest effects on the developing brain. The brain is the primary stress organ because it controls all of the stress mechanisms.[26] Children's brains are constantly growing and developing. Therefore, their brains are very vulnerable and stressors can have great impacts on the brain that are irreversible.[27] Research has shown that children who have experienced extended periods of extreme stress have smaller brains and high difficulties in memory tasks. Cognitive functioning is greatly impaired.[28] Children who had experienced more intense and lasting stressful events in their lives posted lower scores on tests of spatial working memory.[27] They had more trouble navigating tests of short-term memory as well. The region of the brain that is most affected by increased levels of cortisol and other glucocorticoids is the hippocampus.[22]

Many times the physical structure of the hippocampus is altered with excessive amounts of cortisol. Dendrites in this section of the brain can shrink and this leads to cell or neuron death.[22] The shortening of dendrites and the loss of neurons in the hippocampus make a significant impact on the HPA stress response and on cognitive processes that involve the hippocampus.[22] In the HPA system, many of the glucocorticoid receptors become non-functional when there are increased levels of cortisol. If increased cortisol levels persist in a child's early years of life, the hippocampal damages will produce collective and detrimental effects over the life of the individual.[22] Stress has an outstanding effect on cognition, particularly memory.[22] Episodic memory, or memory associated with remembering specific events, is mostly affected.[22] When levels of glucocorticoids or cortisol increase, some cells in the hippocampus do not die. Instead, the activity of the neurons is changed. This creates problems with memory.[22]

Research has found that infants and young children with higher cortisol levels produce smaller electrical changes in their brain when they are forming memories.[22] This impairs new memory formation.[22] In addition, children who have increased levels of cortisol, during daycare or nursery school time, experience extreme hardship upholding attention.[22] Maintaining attention is a part of self-regulation, and these children are not able to regulate their behaviors due to the high cortisol levels.[22] Therefore, memory, attention-span, and self-regulation are influenced by cortisol production.[22]

Many children experience stress for prolonged amounts of time.[22] Usually these factors are toxic stress and can be due to internal or external stressors.[4] If a child has a sufficient support system, then he or she can display resilience.[22] Often, children do not have skills to be resilient themselves, and they do not have adults for constant loving care. In these situations, children experiencing stress exhibit persistent effects of varying cortisol levels. Some children manifest low levels of cortisol production, and some experience high cortisol levels. The children with higher levels of glucocorticoids are prone to have the most problems with physical, social, mental, and motor development.[22] Research has not yet determined whether these effects are permanent, however, it has been found that children experiencing stressful situations after the first four to six months of life endure from intellectual and social problems.[22] Also, persistent stress in young children makes the stress regulation mechanisms deviate from normal coping mechanisms.[1] For children experiencing good or tolerable stress, stress instigates an increase in cortisol levels. When the situation is resolved, cortisol levels will return to normal.[1]

Toxic stress

Toxic stress is a term coined by pediatrician Jack P. Shonkoff of the Center on the Developing Child at Harvard University to refer to chronic, excessive stress that exceeds a child's ability to cope, especially in the absence of supportive caregiving from adults.[29]

Learning to cope with mild to moderate stress is a part of normal development in children; however, extreme, long-lasting stress in the absence of supportive relationships to buffer the effects of a heightened stress response can produce damage and weakening of bodily and brain systems, which can lead to diminished physical and mental health throughout a person's lifetime. Extreme exposure to such toxic stress can result in the stress response system becoming more highly sensitized to stressful events, producing increased wear and tear on physical systems through over-activation of the body's stress response. This wear and tear increases the later risk of various physical and mental illnesses.[15]

In children experiencing persistent toxic stress, functioning occurs in a fear state and this becomes habitual.[1] Many times, cortisol levels do not reach basal ranges after the situation has been mitigated.[1] With chronic toxic stress, children undergo long term hyper-arousal of brain stem activity.[1] This includes an increase in heart rate, blood pressure, and arousal states.[1] Also, these children may experience a change in brain chemistry, which leads to hyperactivity and anxiety.[1] Therefore, it is evident that chronic stress in a young child's life can create significant physical, emotional, psychological, social and behavioral changes.[22]

Other symptoms and effects of stress on children

Physical

Stress may make the body more susceptible to infections, cardiovascular problems such as heart disease and high blood pressure, obesity, slower healing, viruses and gastrointestinal problems.[4][30] Stress can affect children's growth and development, including the onset of puberty.[30] Some of the physical cues that may be indicative of stress in children are rashes on skin and skin diseases such as eczema, acne and hair loss, worsening asthma, insomnia or hypersomnia, frequent headaches, muscle aches, vomiting, constipation and diarrhea.[30] Extreme fatigue, chest pain, racing heartbeat, shaking, cold and clammy hands and feet, frequently ill, and even ulcers are some other physical symptoms manifested due to stress.[30]

Emotional

When children cannot handle stress they may begin to develop emotional problems. They may become severely depressed, lacking in energy and motivation.[30] They may develop strange personality traits such as violence and disobedience.[30] Personality disorders may arise as well. Posttraumatic stress disorder may come about in children who have experienced stressors that are traumatic such as abuse or neglect.[23]

Psychological
Main article: Psychological stress § Psychological stress and disease

Changes in mood or personality, increased irritability or aggressiveness are some psychological symptoms indicative of stress in children. Frustration, feelings of guilt or confusion, isolating themselves from family and friends. Children may also exhibit symptoms of anxiety. They may begin to have new fears and nightmares or even paranoia.[19] They may lie to others to avoid situations to cover up their feelings.[31] Most often anxiety in children stems from academic stressors and being overwhelmed with responsibilities with workload.[31] However, anxiety also stems from more serious stressors as well.

Social

Children under extreme stress tend to withdraw from their family and friends.[30] They spend more time alone and lack motivation. Children may begin to struggle in school and on their assignments.[32] They may have difficulties in paying attention and act with anger and irritability towards others.[4]

Behavioral

Children may exhibit behavioral symptoms such as over-activity, disobedience to parental or caretaker's instructions. New habits or habits of regression may appear, such as thumb-sucking, wetting the bed and teeth grinding. Children may exhibit changes in eating habits or other habits such as biting nails or picking at skin due to stress.[30] They may become more accident-prone, cry more often, stutter, or get into fights.[32]

Long-term effects of stress on children
Main article: Adverse Childhood Experiences Study
The ACE Pyramid represents the conceptual framework for the ACE Study, which has uncovered how adverse childhood experiences are strongly related to various risk factors for disease throughout the lifespan, according to the Centers for Disease Control and Prevention.[33][34]

The landmark Adverse Childhood Experiences Study (ACE Study) conducted between 1995 and 1997 on 17,337 participants by Dr. Vincent Felitti from the Kaiser Permanente health maintenance organization and Dr. Robert Anda from the Centers for Disease Control and Prevention demonstrated the association of adverse childhood experiences (ACEs) with health and social problems as an adult.

Participants were asked about the following types of childhood trauma:

  • Physical abuse – US Hotline: 1-800-799-7233
  • Sexual abuse – US Hotline: 1-800-656-4673
  • Emotional abuse
  • Physical neglect
  • Emotional neglect
  • Violent treatment from mother
  • Household substance abuse – US Hotline: 1-800-662-HELP (4357)
  • Household mental illness
  • Parental separation or divorce
  • Incarcerated household member

The ACE study found that ACEs have a dose–response relationship with many health problems. As researchers followed participants over time, they discovered that a person's cumulative ACEs score has a strong, graded relationship to numerous health, social, and behavioral problems throughout their lifespan, including substance use disorders. Furthermore, many problems related to ACEs tend to be comorbid, or co-occurring.

Preventing stress in children

Recommendations offered to help prevent stress in children include:

  1. Helping children prepare for everyday stressful situations, such as traveling to new places or going to the doctor.
  2. Talking to children about the experience to help them understand that it is okay to be stressed and scared.
  3. Keeping communication open. This includes making sure that the child feels comfortable talking to a person. This may include being in a comfortable space, such as their bedroom, where they feel safe. The comfort level of the child is important because if a child is not comfortable, or feels forced to speak, they may not open up at all.
  4. Spending time together as a family so that no one's feelings go unseen; ensuring that a child knows that their feelings are valued, and should be expressed in healthy ways is very important ways. Reassuring children that they can come to you with whatever it is that is upsetting them is a valuable bond that will only grow as time goes on.
  5. Modeling healthy and successful coping mechanisms for children (such as going for a walk).
  6. Encouraging children to express themselves creatively (as an outlet or to help others to understand what is stressing the child). Some healthy outlets of stress relief include sports or running, writing, reading, art, as well as playing musical instruments.
  7. Teaching children to act and think positively when they are faced with a situation to manage the stress before it becomes overwhelming.
  8. Providing a safe and healthy home and environment for children.
  9. Providing children with proper nutrition and attention.
  10. Ensuring children are not exposed to substance abuse or violence.[35] When a healthy environment is provided, children are more likely to be emotionally and physically healthy.[35]

Helping children cope with stress

Recommendations offered to help children cope with stress include:

  1. Asking children if something is wrong or what is bothering them.
  2. Listening and trying to understand where the children are coming from (sometimes they may just need to talk).
  3. Listening to their side and not interjecting with things that they should have done or did wrong.
  4. Taking notice of the child's behaviors and feelings and expressing interest in hearing what is bothering them.
  5. Casually asking children why or what they are upset about, naming the emotion you feel they are experiencing. (e.g., "You seem to be mad about what happened after school yesterday.” “Are you still sad about that?”)
  6. Talking about solutions to stress with children (providing ideas and encouraging children to come up with a few on their own to help foster confidence in their own coping abilities).
  7. Helping the child to think and act positively.
  8. Encouraging the child to develop positive habits to deal with stress.
  9. Showing patience, as children may not be forthcoming with their emotions due to stress.[36]

Notes
  1. Poulsen, Marie K., and Karen M. Finello. "Foundations of Early Childhood Mental Health: Public Health & Life Course Perspectives." Preventive Medicine 583 Lecture. University of Southern California, Los Angeles. 25 Aug. 2011. Lecture.
  2. Lewis, Andrew James; Galbally, Megan; Gannon, Tara; Symeonides, Christos (2014). "Early life programming as a target for prevention of child and adolescent mental disorders". BMC Medicine. 12 (33). doi:10.1186/1741-7015-12-33. PMC 3932730.
  3. Jewett, Jan. "Childhood Stress." Childhood Education 73.3 (1997): 172-73. Web.
  4. Middlebrooks, J.S.; Audage, N.C. (2008). The Effects of Childhood Stress on Health Across the Lifespan (PDF). Atlanta, Georgia: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Archived from the original (PDF) on 2016-02-05.
  5. Gilbertson MW, Shenton ME, Ciszewski A, et al. (2002). "Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma." Nature Neuroscience 5(11):1242-1247
  6. DiGangi JA, Gomez D, Mendoza L, et al., (2013). "Pretrauma risk factors for posttraumatic stress disorder: A systematic review of the literature." Clinical Psychology Review 33:728-744.
  7. Schmidt U, Willmund GD, Holsboer F, et al., (2015). "Searching for non-genetic molecular and imaging PTSD risk and resilience markers: Systematic review of literature and design of the German Armed Forces PTSD biomarker study." Psychoneuroendocrinology 51:444-458
  8. "Key Concepts: Toxic Stress". Center on the Developing Child at Harvard University. Retrieved 3 April 2018.
  9. Shonkoff, J. P; Garner, A. S; Siegel, B. S; Dobbins, M. I; Earls, M. F; Garner, A. S; McGuinn, L; Pascoe, J; Wood, D. L (2011). "The Lifelong Effects of Early Childhood Adversity and Toxic Stress". Pediatrics. 129 (1): e232–46. doi:10.1542/peds.2011-2663. PMID 22201156.
  10. Effects of Stress on the Body | Lachina. (n.d.). Retrieved April 9, 2018, from https://lachina.com/blog/effects-stress-body/
  11. Schechter, Daniel S; Willheim, Erica; McCaw, Jaime; Turner, J. Blake; Myers, Michael M; Zeanah, Charles H (2011). "The Relationship of Violent Fathers, Posttraumatically Stressed Mothers and Symptomatic Children in a Preschool-Age Inner-City Pediatrics Clinic Sample". Journal of Interpersonal Violence. 26 (18): 3699–719. doi:10.1177/0886260511403747. PMID 22170456.
  12. Schechter, Daniel S; Willheim, Erica (2009). "Disturbances of Attachment and Parental Psychopathology in Early Childhood". Child and Adolescent Psychiatric Clinics of North America. 18 (3): 665–86. doi:10.1016/j.chc.2009.03.001. PMC 2690512. PMID 19486844.
  13. Davies, Douglas. "Chapter 3: Risk and Protective Factors: The Child, The Family, and Community Contexts." Child Development, A Practitioner's Guide. 2nd ed. New York: Guilford Press. Print.
  14. "Toxic Stress: The Facts". Center on the Developing Child at Harvard University.
  15. National Scientific Council on the Developing Child (2014). "Excessive Stress Disrupts the Architecture of the Developing Brain: Working Paper 3" (PDF). Center on the Developing Child, Harvard University.
  16. McEwen, Bruce S. (1998). "Stress, Adaptation, and Disease: Allostasis and Allostatic Load". Annals of the New York Academy of Sciences. 840 (1): 33–44. doi:10.1111/j.1749-6632.1998.tb09546.x. ISSN 1749-6632.
  17. McEwen, B.S.; Stellar, E. (1993). "Stress and the individual. Mechanisms leading to disease". Archives of Internal Medicine. 153 (18): 2093–2101. doi:10.1001/archinte.153.18.2093. ISSN 0003-9926. PMID 8379800.
  18. Fagundes, Christopher P., and Baldwin Way. "Early-Life Stress and Adult Inflammation." Current Directions in Psychological Science 23.4 (2014): n. pag. Web. 11 Sept. 2014. <http://cdp.sagepub.com/content/23/4/277.full>.
  19. Tennant, V. (2005). School of Education at Johns Hopkins University-The Powerful Impact of Stress. Johns Hopkins School of Education - Home. Retrieved February 2013, from http://education.jhu.edu/PD/newhorizons/strategies/ Archived 2013-05-01 at the Wayback Machine topics/Keeping%20Fit%20for%20Learning/stress.html.
  20. Gunnar, Megan, and Karina Quevedo. "The Neurobiology of Stress and Development."Advance (2007): 145-65. Annual Reviews. Web. 8 October 2011. <www.annualreviews.org>.
  21. Cortisol and Stress: How Cortisol Affects Your Body, and How To Stay Healthy in the Face of Stress. Stress and Stress Management - Causes, Symptoms, Stress Relief Tips and Stress Tests. Retrieved from http://stress.about.com/od/stresshealth/a/cortisol.htm.
  22. Gunnar, Megan R., and Ronald G. Barr. "Stress, Early Brain Development, and Behavior." Inf Young Children 11.1 (1998): 1-14. Print.
  23. PTSD in Children. Dendrite Forest, Inc. Retrieved from http://www.forests.com/ptsdchil1.html.
  24. Schechter, Daniel S; Zygmunt, Annette; Coates, Susan W; Davies, Mark; Trabka, Kimberly A; McCaw, Jaime; Kolodji, Ann; Robinson, Joann L (2007). "Caregiver traumatization adversely impacts young children's mental representations on the MacArthur Story Stem Battery". Attachment & Human Development. 9 (3): 187–205. doi:10.1080/14616730701453762. PMC 2078523. PMID 18007959.
  25. Schechter DS, Willheim E (2009). The Effects of Violent Experience and Maltreatment on Infants and Young Children. In CH Zeanah (Ed.). Handbook of Infant Mental Health—3rd Edition. New York: Guilford Press, Inc. pp. 197-214.
  26. Wittmer, D. S., & Petersen, S. H. (2006). In Infant and toddler development and responsive program planning: A relationship-based approach (pp. 72-73). Upper Saddle River, N.J: Pearson/Merrill Prentice Hall.
  27. Hanson, J. L; Chung, M. K; Avants, B. B; Rudolph, K. D; Shirtcliff, E. A; Gee, J. C; Davidson, R. J; Pollak, S. D (2012). "Structural Variations in Prefrontal Cortex Mediate the Relationship between Early Childhood Stress and Spatial Working Memory". Journal of Neuroscience. 32 (23): 7917–25. doi:10.1523/JNEUROSCI.0307-12.2012. PMC 3375595. PMID 22674267.
  28. McEwen, B. S. Effects of Stress on the Developing Brain. The Dana Foundation. Retrieved from https://dana.org/news/features/detail_rop.aspx?id=33204.
  29. "How does the 'toxic stress' of poverty hurt the developing brain?". PBS NewsHour. 27 June 2015.
  30. WebMD. Stress Symptoms: Effects of Stress on the Body. WebMD - Better information. Better health. Retrieved from http://www.webmd.com/balance/stress-management/stress-symptoms-effects_of-stress-on-the-body.
  31. DeNoon, Daniel J. "Your Child and Anxiety: School Stress Starts Early". WebMD.
  32. Children and Stress: Caring Strategies to Guide Children - Home - Virginia Cooperative Extension. Publications and Educational Resources - Home – Virginia Cooperative Extension. Retrieved from http://pubs.ext.vt.edu/350/350-054/350-054.html.
  33. "The ACE Pyramid". Atlanta, Georgia: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, Division of Violence Prevention. May 2014. Archived from the original on 16 January 2016.
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