Preface

In the last few years, evidence has been found to demonstrate that child maltreatment is associated with the risk of developing major psychological disorders in adulthood. These disorders include: depression, bipolar disorder, post-traumatic stress disorder (PTSD), substance -and alcohol abuse. Another consequence of child abuse is getting medical illnesses, such as: asthma, diabetes and cardiovascular disease. For children that experienced abuse in their childhood, the course of a mental disorder is more severe. Therefore, the biological substrates of the diathesis of psychiatric and medical morbidity were studied. In the current review, these studies were summarized. The focus is on the biological alterations and brain alterations associated with mental -and physical disease caused by childhood maltreatment.

What are the psychological effects of child maltreatment?

Sexual, emotional -and physical abuse can lead to a significant increase in mood -and anxiety disorders, but also substance -and alcohol abuse and some medical disorders. According to a recent study 78.3% of children referred to the department of health and services suffered from neglect, which is the failure of a parent or caretaker to comply with the responsibility for providing shelter, safety, medical care, supervision and well-being. It is important to consider he majority of neglect is unreported, and that sexual abuse is most reported happening at a very young age.

The researchers of this study measured adverse childhood experiences (ACE) and found that 64% of participants experienced at least one ACE. The risk of developing a medical -or mental illness is significant for persons with more than three experiences of childhood abuse. Moreover, children with experiences of neglect and abuse were more likely to develop comorbid disorders. When exposed to sexual abuse, the risk for the development of the disorders: depression, PTSD, eating disorders, sleep disorders and suicide effects was bigger. Bullying is not included as a form of child abuse by most studies. However, the untoward effects of verbal aggression between the age of 18-22 were the same as those when witnessing non-familial sexual abuse or domestic violence. Bully victims showed larger rates of panic disorder, agoraphobia in women -and suicidality in men.

Another finding is that early life stress (ELS) is a major risk factor in the risk for suicide of which sexual -and physical abuse had the most effect. In general, childhood trauma is associated with both suicidal ideation and depressive symptoms. The effects of ELS on vulnerability to other disorders has not been studied as often. It was found that ELS increases the risk for bipolar disorder and substance abuse. Patients with bipolar disorder combined with childhood adversities show higher rates in suicide attempts compared to patients without ELS. There is considerable evidence that ELS and childhood trauma can cause a more severe course of depression.

What are the neurobiological consequences of child maltreatment?

The biological consequences of ELS change the role of hypothalamic pituitary-adrenal (HPA) and extra-hypothalamic corticotropin-releasing factor (CRF) in handling effects of stress. These circuits mediate endocrine behaviour, immune and autonomic effects of stress. Maternal deprivation causes deprivation of neural activity in the response to CRF. Furthermore, there is an effect of repeated stress during the first postnatal week which influences the dendritic development in the cingulate -and prelimbic cortex. Lastly, it is repeatedly demonstrated that ELS has both neuroendocrine and neurotransmitter effects in non-human primates. Maternally deprived subjects display greater regional glucose metabolism in sensory -and emotional processing areas (thalamus, inferotemporal cortex) in response to moderate stress.

The role of the HPA axis in the regulation of stress is potentially affected by early life trauma. Both increased and decreased HPA axis activity can be the consequence of child maltreatment. For example, in depression, hyperactivity of the HPA axis was reported for people that experienced ELS. They also showed increased ACTH and cortisol responses in the Trier Social Stress Test (TSST). However, the findings are discordant and currently an active avenue of investigation. The effects of child abuse and neglect on HPA axis activity are impacted by the following factors:

1. The nature of ELS, this can be sexual, physical, emotional or neglect. Also, the number of episodes, chronicity and the age of first abuse/neglect is important.

2. The presence of psychosocial support.

3. The existence of traumatic events during childhood.

4. Whether there is a family history in psychiatric disorders.

5. Genetic and epigenetic factors.

Besides changes in the HPA-axis, evidence was found that oxytocin plays a critical role in mediating social affiliation, attachment, intimacy, trust and maternal behaviour. This neural system is also affected by ELS. Furthermore, the hormones progesterone, oestrogen and testosterone are affected by ELS.

What are the risks of child maltreatment in developing a medical disorder?

There are several medical disorders that can be caused by ELS. These include: chronic lung disease, cancer, heart disease, skeletal fractures, liver disease and autoimmune disorders. Sexual abuse was found to be associated with in increased risk for functional gastrointestinal (GI) disorders, psychogenic seizures and chronic pain. Also, rape was associated with an increased risk for fibromyalgia. Evidence has been found that the occurrence of many medical disorders is increased in people exposed to ELS. There are effects of child maltreatment on biomarkers of inflammation. Maltreated children exhibit a significant increase in C-reactive protein (CRP). This effect was independent of other life stressors. Prenatal adversity is also associated with higher levels of CRP. It is suggested such inflammation may contribute to the poor outcome in breast cancer patients with depression.

What are genetic and epigenetic consequences of child maltreatment?

Inflammation can reduce telomere length, which is associated with increased morbidity and mortality of age-related diseases. Telomeres are DNA-protein complexes that protect the genome from damages. Several studies have been done to assess the connection between childhood abuse and telomere shortening. It turns out greater adverse childhood experience cause reduced telomere length. In depressed participants, telomerase activity increased. In healthy volunteers there was no change in telomere length or telomerase activity during the experiment. Disorders including PTSD, major depression, schizophrenia and bipolar disorder are complex illnesses that are virtue to an environmental and genetic contributions. Child maltreatment accounts for a great environmental risk factor and it turns out that several candidate gene polymorphisms are modifiers for the development of PTSD and depression in victims of child abuse. The number of ELS events is associated with depressive symptom severity. Findings of genetic and epigenetic consequences of child abuse pave the way for the development of new anxiolytic and antidepressant agents.

The emerge of epigenetics in physiology and pathophysiology is considered a major advance in biomedical science. Epigenetics are the alterations in gene expression that is not a consequence of DNA-change, but of DNA methylation or acetylation, post-transitional histone modifications and non-coding RNA’s. There is evidence that early life experiences alter DNA expressions. A molecular model has emerged on how maternal care changes gene expressions by effecting DNA methylation.

What does brain imaging research conclude on the consequences of child maltreatment?

The long-lasting effects of child abuse can be researched using functional brain imaging. Different forms of childhood maltreatment produce distinct effects on brain areas, just like the heterogeneity of an individual’s past experiences. Polymorphisms of candidate genes are impactful on some provocative studies using fMRI. The responsiveness of the amygdala to fearful stimuli is one thing that can be shaped by childhood maltreatment. These MRI studies can be divided into two types:

1. The testing of specific hypothesis that are related to the effects of specific types of abuse and neglect on the brain.

2. The testing of effects of child abuse on grey and white matter volumes and their connectivity to different regions of the brain.

Besides the amygdala, the hippocampus is affected by child maltreatment and plays a significant role in the development of several mental illnesses. In patients with PTSD or major depression, the hippocampus has a reduced volume. The amygdala plays a critical role in mood-and anxiety related illnesses. Amygdala volume and its response to stressors have repeatedly been studied in non-human primates. It turns out, an increased amygdala volume can be the result of abuse and neglect. This can cause increased anxiety and depression. Finally, grey -and white matter volumes are affected by ELS. A reduction in grey matter in the prefrontal cortex, hippocampus and orbitofrontal cortex was found in subjects with ELS. Furthermore, childhood maltreatment was found to be associated with changes in the cortical network.

What are the implications for treatment?

There is also an effect of child maltreatment on treatment response of both mental and physical illnesses. The available evidence suggest that childhood maltreatment causes a poorer response to psychotherapy and pharmacotherapy in patients suffering from depression. Also, childhood sexual abuse was a negative predictor of response to cognitive behavioural therapy. In another study it was found that ELS predicts a poor response to antidepressants and people need a longer time for remission. Childhood abuse can not predict antidepressant response though. However, having a neglectful parent did predict a poorer antidepressant response. This evidence suggests that individuals with a history of child abuse have a fundamentally different biological endophenotype that cause corresponding differences in treatment.

What are suggestions for further research?

In the current review, evidence has been stated to support the claim that child abuse has devastating effects on the course -and risk for inflammation, mood -and anxiety disorders, depression and PTSD. Furthermore, child maltreatment has a negative effect on treatment of these disorders. However, some critical questions remain:

• How does the timing of adverse childhood experiences affect their impact?

• Which biological mechanisms are involved in the response to neglect and child abuse into vulnerability to disease?

• What interactions in gene-environment can mediate the effects of child maltreatment?

• How can treatment methods benefit from research on the effects of child maltreatment?

• Should there be therapeutic interventions directly after the recognition of child abuse to prevent the development of psychiatric syndromes?

• Are the biological effects caused by ELS reversible?

• What prevention programs for parental abuse and neglect should be implemented?

• What biological mechanisms are involved in mediation of the risk for obesity, cardiovascular disease and diabetes in patients that experienced childhood maltreatment?