Lecture 1: Introduction to the course

Why should people learn about the long term consequences of childhood abuse and neglect?

Sceptics say we shouldn’t because:

• In adults negative childhood experiences took place a long time ago, and are irrelevant for current well-being.

• In adults numerous new experiences have overwritten the old, negative experiences.

• Focus on negative experiences in the past will inhibit positive feelings in the present.

• Personality/ emotional well-being has been programmed in the brain and cannot be easily changed.

Others say we should learn about the consequences. Freud for example said that the basis for neuroses lays in childhood and experiences in that time are of great importance. And Bowlby said the following: ‘The infant and young child should experience a warm, intimate and continuous relationship with his mother (or permanent substitute) in which both find satisfaction and enjoyment and not doing so may have significant and irreversible mental health consequences.'

DSM

The DSM is a classification system for psychological disorders based on standard criteria. When you compare the DSM IV and V there hasn’t changed much, the DSM still focuses on objective descriptions of symptoms with no theoretical framework. This means that there is no focus on the etiology of the disorders. The only disorder where the cause plays a role in the diagnosis is PTSD. There has to be a traumatic experience to develop PTSD. Symptoms of PTSD are: avoiding stimulants that may bring up memories from the traumatic event, reliving the event, overarousal and vigilance.

Research questions

There are two main questions in the research about child maltreatment:

1. What are the causes of mental health problems in adulthood?

Among the causes are recent stressors, genetic vulnerability and childhood abuse and/or neglect. Childhood abuse and/or neglect, and other negative childhood experienes can be associated with depressive symptoms in adulthood.

2. How can events that happened 25 years ago have such a pervasive impact on a person’s emotional, cognitive, social well-being?

The question here is: what makes the symptoms come up after such a long time? Research showed that child maltreatment can be associated with changes in the brain and changes in the stress response for example.

Definition

The definition of childhood maltreatment is: ‘any act of commission or omission by a parent or other caregiver that results in harm, potential for harm of threat of harm to a child. Harm does not need to be intended.’

The definition distinguishes between omission and commission. Omission is the failure to meet a child’s needs. Commission is actively doing something harmful. This form of maltreatment is mostly thought of when someone things about childhood maltreatment.

There are four forms of childhood maltreatment:

• Emotional neglect: ‘Failure to meet a child's emotional needs and failure to protect a child from violence in the home or neighborhood’

• Physical neglect: ‘Failure to meet a child's basic physical, medical/dental, or educational needs; failure to provide adequate nutrition, hygiene, or shelter’

• Emotional abuse: ‘Intentional behavior that conveys to a child that he/she is worthless, flawed, unloved, unwanted, endangered, or valued only in meeting another's needs’

• Physical abuse: ‘Intentional use of physical force or implements against a child that results in, or has the potential to result in, physical injury’

• Sexual abuse: ‘Any completed or attempted sexual act, sexual contact, or non-contact sexual interaction with a child by a caregiver’

These definitions are not the only ones. Definitions are influenced by cultural context, especially by emotional neglect of abuse.

Prevalence

Estimating the prevalence is difficult. Different studies find different prevalence numbers. The number depends on the measurement method and the population that is being investigated. There is a large dark number, and only the minority of the maltreatment is known.

Research

Ethical issues make research difficult. There are four types of research methods. First you can distinguish between observational and experimental research. With this type of research you can only find associations, not causal links. Forms of observational research are epidemiological research, longitudinal research (this takes a long time) and cross-sectional research. The research is based on self-reports, reports by parents and reports by professionals. It’s important to remember that self-report rates are 10 times as high when compared to informants. With experimental research you need to manipulate a factor. It is unethical to do this with humans, therefore animals are used in this type of research.

You can further distinguish between prospective and retrospective research. Prospective studies follow subjects over time. This way you can study a causal link between maltreatment and the consequences. A disadvantage is that there are ethical concerns when you don’t help a child who is being maltreated. In a retrospective study adults are being asked about their childhood. A disadvantage here is that the adult memory is erroneous. and the consequences and abuse are assessed at the same moment: you can’t say something about causality.

Results from research

The consequences of childhood maltreatment are broad. Many psychological disorders are linked to childhood maltreatment.

The NESDA study from 2010 shows us that every disorder is associated with maltreatment. Emotional neglect and psychological maltreatment form the greatest risk when you look at the different types of maltreatment. In more than 90% of these cases the perpetrator is a parent. With sexual abuse the perpetrator is someone outside the family most of the time.

When you control for demographic factors, comorbidity and adverse factors like emotional neglect are the only ones with links to psychological disorders and sexual abuse is associated with depression. When you control for emotional neglect there is no longer an association between psychological disorders and physical abuse. It is important to remember that not everyone who is maltreated during childhood develops a psychological disorder. So the question is: why do some people develop a disorder while others don't?

Heather et al. did a study about the link between childhood maltreatment, emotion regulation and depression. They formed a model about the different pathways that can lead to depression.  When doing research about the consequences of childhood maltreatment you have to take comorbidity into account. Not only the comorbidity of disorders, also the comorbidity of the different forms of maltreatment.

Guest lecture: Hameeda Lakho

In the guest lecture, they've showed a documentary: ‘ Hidden violonce.. then what?’  Lakho told about the reasons why children and adults don’t tell about the maltreatment:

• Shame about the situation

• Low self-esteem as result of the abuse

• Loyalty/love to the parents/partner

• Feelings of guilt

• Fear of the consequences of revealing the abuse

• A lack of trust in people.

Dissociation is disconnecting feelings and mind.  For victims it's important to talk about maltreatment. The maltreatment is a taboo and victims need to talk about it to break this taboo.

Lecture 2: Consequences of maltreatment

Child maltreatment can chronically increase the stress-sensitivity of a person. You can study this stress-sensitivity in two ways; on cognitive/emotional level and on neurobiological level. The cognitive/emotional level is about negative attitudes parents may hand to their children, which may become incorporated in his/her self-image. This may lead to a strong social sensitivity that may be evoked in new stressful situations. The neurobiological level is about alterations in brain function networks that are important for emotional reactivity, emotional memory, and emotion regulation. You can also look at alterations in de sensitivity of hormonal stress reactions, such as the HPA-as.

Cognitive/ emotional consequences of child maltreatment

An important model that describes cognitive and emotional consequences of child maltreatment is the Stress sensitization model of Beck. In this model cognitive vulnerability and life stressors are the causes of symptoms of depression and anxiety. Negative thoughts come up easily because of the cognitive vulnerability which increases the change of developing symptoms of depression and anxiety.

Van Hamelen shows in her study that emotional abuse is a strong indicator for negative thoughts about the self.  According to a study of Pollak, early childhood experiences can change the sensory threshold so that this can have negative consequences for effective emotion regulation. The results of the study show that children who have a history of abuse are more sensitive for identifying negative emotions.

Brain areas

The brain is plastic and sensitive for influences from the environment, especially in childhood when the brain is still developing. The idea is that the experience of childhood maltreatment alters neural networks that regulate emotions.

The amygdala is important for face identification, emotion regulation, emotional memories and classical conditioning. A study by van Hamelen shows that children who have been emotional abused have higher activity in the amygdala when seeing facial expressions, positive and negative expressions. The results from this study also showed that the abused children are more sensitive for identifying angry faces, they identify the expression sooner than the control group did. When a happy face was shown there was no difference between the abused and the control group.  The thought behind this is that the threshold for identifying negative emotions is lowered in children how have been abused. How this can be related to the amygdala is not know yet.  Soldiers who have been sent to a war zone also show more activity in the amygdala, but only with negative emotion expressions. Another difference is that after they have returned home the activity of the amygdala normalized.

People will not tell that they perceive faces more negative, but you can see it in the activity of the brain.

The medial prefrontal cortex is also important to study. This area is active when regulating stress. The mPFC of children who have been abused is smaller, even when they don’t develop a depression.

The mPFC is involved in regulation of affective states, emotional behavior, fear extinction, and self referential processes. The activity of mPFC attenuates fear responses by reducing the activity of the amygdala over time. Shin showed this in a study, there is a negative correlation between the activity of the amygdala and the mPFC. Dysfunctional mPFC activation is implicated in stress-related disorders such as PTSD and depression. In PTSD patients there is less activity in the PFC and the PFC is smaller in size.

Working memory

The working memory is responsible for inhibiting irrelevant information. This can be measured with the Sternberg Working memory task. First a couple of letters are shown, the maximum is 4 letters. Next a empty screen or a distracting image is shown. After this letters are shown again and you have to say which letter you have seen before. People who have experienced childhood maltreatment make more mistakes than do people who have no experience with abuse, when a distracting image has been shown. The amygdala is more active when the distracting image is shown and the activity of the amygdala inhibits the activity in the dorsolaterale prefrontale cortex. The dlPFC is responsible for updating information in the working memory. This can be an explanation for why the abused people do worse on this test.

People with borderline have a slower reaction time when doing this test in comparison with healthy people. But only when emotional images were used as distracting image. People with borderline judge neutral images sooner as negative in comparison with the control group.

Dissociation

Dissociation is a mental state. When people dissociate there are disturbances in the integration of consciousness, memory, identity, physical observations and the ‘self’. People who have experienced early or repeated trauma experience often dissociation. During dissociation there is a lowered activity in the amygdala and the insula and more activity in the mPFC and the anterior cingulated cortex. During a dissociation state nothing can be learned about the situation, so you cannot learn to deal with it. This can have negative effects later in life, for example during therapy.

Autonomic nerves system and the HPA-axis

The autonomic nerves system consists of the parasympathic and the sympathic nervous system. The autonomic nerves system releases adrenaline when you are stressed, in the body and the brain, especially in the amygdala and the PFC. The HPA-axis regulated stress hormones, such as cortisol. The effect of cortisol is much slower than the effect of adrenaline. Through the Trier social stress test you can measure the level of cortisol.

People who have experience childhood maltreatment and are depressed or have a social phobia show higher cortisolreactions and it takes longer until the cortisol level is back to normal. The higher level of cortisol is associated with the maltreatment because when you compare people who are depressed but have not experienced childhood maltreatment with people who have experienced childhood maltreatment and are depressed and a control healthy control group you see that there are no difference between the control group and the group who have not experienced childhood maltreatment.

Take home message

It is important to remember that a lot of the studies about this subject is cross-sectional. Another important thing to remember is that you have to distinguish patients with depression and/or anxiety who have and not have been abused as a child. People who are abused or maltreated as a child show more severe symptoms, more chronic symptoms, more comorbidity, different neurobiology and often have a poor reaction on therapy.

Lecture 3: Early Life Stress through animal models

Why do we use animal models of early life stress?

In research about early life stress animals are used for several reasons:

• Animals have a shorter life span, this makes longitudinal studies more easy.

• You can use more objective criteria. With humans self-reports are mostly used and this can contain biases.

• The possibility to experimentally induce early life stress. You can investigate cause and effect.

• Study the underlying hormonal and brain changes. With humans you can only use scanners and that is less precise.

• You can control for genetic background.

• Testing new biological treatments.

Establishing causality and defining underlying mechanisms is needed for preventive and therapeutic intervention.

Animal studies are translational research. The results from the studies can be translated to humans. You can investigate stress paradigms and you can measure the consequences of stress for example. It is important that the study is bi-directionally informed. There has to be some evidence that makes it possible to translate the results from animals to humans. The mostly used animals are mice, rats and primates.

Why do we use rats or mice?

Rats and mice are used because of their short life spans. A rat lives about 2,5 years and reaches puberty at 5-6 weeks and are mature at 3-5 months. Mice life about 2 years, reach puberty 4-6 week and are mature at 3-5 months. In studies the age of the animals are expressed in PND, post natal days.

Weaning is the natural separation from the mother. In humans the mother decides when this is, in animals the pup decides. Weaning is investigated a lot in animal studies.  Animal studies are based on natural variations in maternal care behavior. Maternal care behavior is licking , grooming and nursing. In studies they manipulate maternal care by maternal separation or deprivation, reducing maternal care, induce abusive behavior and fragmented maternal care.  You can separate the mother for 1 time or repeatedly for prolonged period of times. In this way you can induce single trauma or chronic early life stress. When the mother is separated from her pups for 24 hours it is called a severe stressor. You can also stress the mother by limiting the nesting availabilities. When the mother is stressed they show more abusing behavior and less maternal care behavior.  You can put the consequences of early life stress in a schema, for example:

Limited nesting material -> chronic stress in the mother -> fragmented dam-pup interaction -> chronic stress in pups -> lasting changes in HPA-axis activity and impaired cognitive functioning. Fragmented care is unorganized and unpredictable. This does not mean the more shows less caring behavior.

When the mom is separated from her pups for a short period of time and then reunited, the mom shows more maternal care behavior.  In class they showed an experiment that induced chronic stress in mother rats. A male rat was put in the cage with the mom and the pups, this caused stress in the mother. In some cases it was only one time and in other cases the male rat was put in the cage for 1 hour every day. The level of maternal care, aggressive behavior, the preference for milk from the mother and physiological outcomes were measured. The results were not discussed.

HPA-axis

The HPA-axis consists the hypothalamus, pituary gland and adrenal gland. The HPA-axis is the stresssystem en releases the stress hormones adrenaline and cortisol. Adrenaline is released quick in the body en is responsible for the fight and flight mechanism. Cortisol released slower en has long term effects.

As told in lecture 2 a heightened cortisol level is shown as a reaction on a stressor in people who experienced early life stress. The stress system in rats and mice look like the system in humans, with a hypothalamus, pituary gland and adrenal gland. Rats are also sensitive for stress when they were neglected as pups. Pups are less sensitive for stress and adults more.

Effects on brain area’s

When brain area’s are investigated the amygdala, hippocampus and neurogenicis are the most investigated subjects.

As told in lecture 2, the amygdala is sensitive for early life stress and this is also the case with rats. Cohen et al. investigated de activity of the amygdala in rats in comparison with humans. In the experiment with humans, people had to press a button when seeing an neutral face en not press the button when a face with a expression came up. The rats had to walk into a new cage. People who experienced early life stress reacted slower on the task and the activity of the amygdala was higher. The rats who experienced early life stress were slower in entering the cage.  The hippocampus has a larger volume in children who had a normal childhood without early life stress. The hippocampus is important for learning, memory and it delivers negative feedback to the HPA-axis. It is an important structure for regulating behavioral measures of anxiety. The hippocampus is plastic because it is one of the few area’s that forms new neurons during life. Abnormal hippocampal development may underlie some of the adverse early-life induced behavioral difference. When looking at the hippocampus the dendritic complexity is something you can look at. The more complex it is , the better the hippocampus functions and the more can be memorized. More dendritic complexity stand for a more interconnected area.

Rats who fragmented care as a pup had less dendritic complexity. So the hippocampus is also sensitive for early life stress.

Cognition

Long-term potentation (LTP) is related to hippocampus dependent learning. When a neuron from the hippocampus is stimulated the activity of that neuron increases for a short period of time. Rats who experienced low maternal care showed less activity after stimulation. And neural survival is reduced in rats who experienced low maternal care.

In an experiment to measure hippocampus dependent learning rats were put in a pool and had to swim to a platform. Rats who received less maternal care did not learn were the platform was en took much more time the than rats who received normal amount of maternal care the second time they were put in the pool. They also stayed more distant from the platform while searching. Rats who receive more maternal care than normal were better at finding the platform.

Emotion

Studies with rodents show:

• more depressive behavior when they received less maternal care. The pups had a decreased preference for sucrose (milk from the mother)

• increased startle responses, facilitation of fear memories

• more aggressive behavior

• a heightened preference for alcohol and cocaine

• anxiety can be measured quite well because of the physical arousal.

PAR hypothesis

So far we have seen that early-life adversity is associated with an adult. But, early-life stress might program the brain such that it optimally responds to stressful contexts encountered later in life. Whit might be adaptive programming of the brain. The predictive adaptive response hypothesis: in response to a change in early-life environment the offspring makes adaptations to improve its chance of survival in the anticipated future environment.

Stress hormones, such as cortisol, program the brain in early development, and thereby allow adaptation to the present situation and the future environment.  When a future environment matches the early life environment, there are no problems and the changes in the brain are adaptive. When the future environment doesn’t match the early life environment there is a mismatch and problems can arise.  An experiment with rats shows that when you treat the rats with cortisol the LTP is increased in rats that had low maternal care as pups. This may indicate stronger fear memory after stress and this can be relevant for survival. These rats also had a higher contextual fear conditioning.  The general idea of PAR is that early life experiences may modulate optimal cognitive functioning in environments varying in demand in later life, with offspring experiencing adverse early life environment showing enhanced learning under contexts of high stress.

Sensitive periods

There has been a lot of research about the sensitive periods in humans. They found that the timing of placement in foster care is important, before the age of two years is associated with improved outcome. The timing of trauma is related to depression risk and brain changes.

An experiment with mice showed that it took two weeks before the mice responded on a mild stressor. It is not clear why it took two weeks.  The stress hypo-responsive period in infants develops between 6 and 12 months, lasting till about 4 years of age. There is little reaction on stress at this age. The development in this period is depend on the psychosocial context and due to maltreatment this period can end early. Vulnerable groups are toddlers and young preschoolers. It is probably a protective mechanism for brain development. When an adult, the kid is attached to, is present there is some kind of cortisol buffering.  Early stages of attachment in infancy emphasizes proximity seeking. This can explain why abuse by the caregiver is tolerated and why children attach to their abusing caregiver. The caregiver is a threat and biologically based an expected source of comfort.  Regina Sullivan did a research in rats and found that the infant brain supports approach responses, independent of the valence of the stimulus. In infants, adversity is approached and in adulthood adversity is avoided.  In the sensitive period cortisol is involved in the learning to avoid negative stimulus in rats.  In another experiment, rat pups got chocked when smelling an odor, but the pups didn’t avoided the smell when their mom was nearby. Avoiding would be more logic. The mom buffers the cortisol reaction.

Ethics

Animal studies are only allowed when the purpose of the experiment justifies the use of animals and when the harm done to the animals is outweighed by the benefits of the research.

What can’t we learn from animal studies

We can’t learn about subjective emotions, negative self-inferences and mental health. We can’t induce sexual abuse of emotional abuse. We also can’t test behavioral interventions.  The reason we use animal studies is because of the large similarities between the animals and humans, the greater possibility to experiment, animals have a shorter life span, translation can be valuable, mechanism can be studies and biological interventions can be tested.  It is a bi-directional collaborations, you can translate findings and design new paradigms.

Lecture 4: Genetics

Introduction to genetics

There are some basic concepts in genetics that are important for this lecture. First the difference between genotype and phenotype is important. Genotype is the genetic information in your DNA. DNA is stored in the nucleus of cells and consists of four different nucleotides (G, C, T, A) which forms base pairs. The phenotype is the expression of your genes and it and differs from the color of your eyes till your behavior. There is also the endophenotype, this is the measurable aspects of the phenotype like brain activity. The endophenotype is what psychologist study.

Genes consist of chromosomes and alleles. Alleles are parts of the chromosomes and store specific information like eye or hair color. For some traits there are different alleles and that makes people differ from each other.

Humans consists of animal cells. Animal cells have a nucleus and in the nucleus you can find the DNA. Every cell stores the same DNA and still every cell has a different function. In every cell a different part of the DNA is active, that’s way they have different functions. The active part of the DNA is transcribed to form mRNA (messenger RNA).This process takes place in the ribosomes in the cell. The information on the mRNA is translated to form an protein. This protein can vary from enzymes, cells in the immune system, stress hormones, neurotransmitter, receptors and many other things. The transcription determines when, how long and how active the protein is. The transcription of the DNA starts at the promoter region. This is the start of the gene. The protein gives feedback, this way the transcription stops when there is enough of the protein.

There is variation in genes, through the multiple alleles. The variances develop through mutations or polymorphisms. A polymorphism is a change in the nucleotide chain. There are different types of polymorphisms, like SNP, repeats, deletions, inserts, inversions, or copy a number of variants. A SNP is a single nucleotide polymorphism, this means that 1 nucleotide is changed and not the whole chain. It is important to remember that not every SNP influences transcription or translation. This depends on the place of the SNP on the gene. When the SNP is on an inactive place of the DNA had no consequences for example.

Genetic material is collected by taking a blood or saliva sample. DNA can be abstracted from the white blood cells.

Genetic vulnerability

Genes are becoming more and more important in psychology. The big question is: can genes explain differences between people?

There have been a lot of studies about variations in genes that can be associated with hormones and neurotransmitters that play a role in growth, developments, stress and psychopathology. Some studies show that some psychological disorders, like depression and anxiety have a genetic component. The influence of serotine, cortisol, dopamine and oxytocine are mostly studies in relation to psychopathology. Within psychology a lot of studies are about the causes of disorders and the role genetics play in that process. An example of these studies are the studies about a possible genetic component in the development in depression and anxiety disorders. When there is a genetic component, specific medication can be developed for treatment.

There has been little success in finding specific genes that can be related to specific disorders. It is possible that there or no specific genes, but a combination of genes or even multiple genes that influence the development of disorders. The latter is the most plausible. Influence of the environment is also something that is thought of.

Experiencing trauma plays a big role in developing psychopathology. Not everyone who experiences a trauma develops a disorder. Why is this? The question can probably be answered with concepts like vulnerability and resilience. We can’t learn about subjective emotions, negative self-inferences and mental health. We can’t induce sexual abuse of emotional abuse. We also can’t test behavioral interventions.

The reason we use animal studies is because of the large similarities between the animals and humans, the greater possibility to experiment, animals have a shorter life span, translation can be valuable, mechanism can be studies and biological interventions can be tested. It is a bi-directional collaborations, you can translate findings and design new paradigms.

People with a resilience genotype have a lower chance of developing a disorder than people who have a vulnerable genotype. Remember, this is not a 1-1 relation, there are other factors involved, like the care of the mother, personal factors and prenatal stress.

Genetic vulnerability for developing depression is located at the serotin system. There are two alleles for serotin transporters, a short and a long one. So people can have two short ones ,two long ones and a long and a short one. This transporter regulated the release and re-uptake of serotine. The long alleles is responsible for 3 times more mRNA than the short alleles, so 3 times more activity in de cell. Capsi studies the two alleles in people in relation with depression. His study showed that people with the short alleles reported more depressive symptoms when there was a lot of stress than people with the long alleles. So it seems that the gene for serotin transporters can be related to sensitivity of stress. It seems related to stress reaction, depression- and anxiety measurements of behavrior, depressive fenotypes and negative affectivity. But only in stressful environments. So there is a gene-environment interaction.

Gene-environment interaction

When gene-environment interactions are studied, people look at the endofenotype. Bodgan et al have studied amygdala reactivity and sensitivity for threat. They looked at the role of genes that regulate the HPA-axis. They studies two MR-alleles, the val-allel and the iso-allel. The study shows that val-carriers show a stronger amygdala reaction that iso-carriers. This amygdala reactivity is measured while participant filled out the Childhood Trauma Questionnaire Emotional Neglect subscale. The higher the score on this subscale the more reactivity of the amygdala. And the reactivity was even higher in val-carriers.

The effect of neglect was only expressed in iso-MR polymorphisme. The reactivity of val-carriers didn’t get higher when there was more stress, in iso-carriers it did.

As said before, people with short alleles for serotin transporters report more depressive symptoms when there is a lot stress. These people report less depressive symptoms when there is no stress in comparison with the people with long alleles. A possible explanation is that the people with short alleles do not have a bad stress system but that they are more sensitive for the environment. Bakermans-Kranenburg and van IJzendoorn made a model about this.

Epigenetics

Epigenetics is about the effect of the environment on the expression of genes. There are no changes in the order of the nucleotides, but changes in the regulation of the genes. Epigenetics influences transcription, so the forming of mRNA.

DNA binds to histones that keep the DNA together. Closed DNA is fully wrapped around itself and can’t be transcripted. DNA has to actively be opened before transcription can take place. Methylation, a form of epigenetics, influences the opening of DNA. When a methylgroup is bound to the DNA, the DNA is closed. When this methylgroup are taken of the DNA the DNA can be opened. This process can be permanent and temporary.

There are several hypotheses about the way methylation influences the specialization or activity of cells:

• Trauma may impact regulation of the DNA via epigenetics

• It may impact activity of different cells, tissues, organs and systems.

• DNA-methylation due to trauma could also be limited to certain brain areas.

Measuring methylation is possible in brain tissues (post-mortem), blood and in the future maybe in saliva.

We know that trauma influences the HPA-azis. But is this mediated by epigenetic changes in HPA-axis related genes? To answer this question people look at GR-genes (glucocorticoide receptor genes). Studies with people who committed suicide showed that the people who have a history with abuse had a heightened methylation level in the GR-genes in the hippocampus. Studies about this look at the hippocampus and DNA in white blood cells.

They also look at prenatal stress, and the presence of methylation GR-genes in the children. Because during the development of cell, changes can be quite permanent. Epigenetics in PTSD is a subject in studies. They don’t always look a specific genes, sometimes they do genome-wide studies and look at the whole genome.

Epigenetics can also be studies as a mechanism. The studies are about the environment influences us, biologically. They also investigate if some polymorphisms are more sensitive to methylation than others. It is important to remember that hardly any genes are found to directly cause psychiatric disorders.

Lecture 5: Psychiatric disorders, abuse and behavior

There was a guest speaker in this lecture and he told us about delinquency, behavior and psychological consequences. In this lecture he mainly talked about the consequences for girls.

At the start of the lecture the lecturer showed us a fragment of the documentary Alexandra. And during the lecture he showed us 3 other fragments. Each of these fragments showed the story of a girl who lived in house Alexandra. This is part of a detention centre in the Netherlands. The fragments showed us that one factor, house Alexandra, can have different effects on different people. Each of these girls lead different lives. On blackboard there is a link to the whole documentary.

Every child is unique and the combination of the following four factors makes every child unique: genes, environment, development and intergenerational factors (what a generation transfers to the next generation). All these factors are needed to understand and treat patients, and girls like the ones from the documentary.

It is also important to remember that adolescents can’t be treated like young adults. During adolescence people are emotionally vulnerable, with progression and regression in the development. They are quite unstable, in comparison with adults.

Psycho-social problems with youth delinquents

The delinquent group of girls is relative small, in comparison with the delinquent group of boys. The girls show more severe problematic behavior. The consequences are more severe, and there are more intergenerational consequences (the effects of the problematic behavior are passed on to their children). Delinquent girls are more emotional en had more traumatic experiences. Some say these emotions and trauma are the cause of the delinquent behavior.

More delinquent girls than boys have PTSD en show more antisocial behavior. There is also more substance abuse among delinquent youth than in the normal population. Substance abuse has a high predictive value for antisocial behavior.

Girls are more sensitive for relapses, especially when they are confronted with old behavioral patterns. A good treatment can help and prevent relapse. It differs per person what a good treatment is. Girls who have been receiving treatment have better outcomes.

Both delinquent boys and girls often live in an unstable home. They have divorces parents, one of the parents is unemployed, or both, and they often moved in the last year. They often belong to a minority group. They also have more often PTSD, depression, anxiety and somatic symptoms. This all is in comparison with the normal population. =

Girls who have been in detention are more often pregnant and at a younger age. Their children are often under supervision by child protection services. They often have violent relationships, didn’t finish school and have no job.

In the Pittsburgh girls study, mothers were interviewed about themselves and their children. The children were also interviewed. The study looked at what are the most important aspects of the mother that can be related to problematic behavior of children. They also looked at the cumulative effect of the factors. They distinguished between early and current factors. Early factors are for example maternal psychopathology or prenatal substance abuse. Current factors are for example demographic factors of the family and parenting practices. The results show that early motherhood, demographic factors, low education, substance abuse, psychopathology and parental practices play a role in the development of behavioral problems. There is a cumulative effect, when there are more risk factors the chance of developing behavioral problems is higher.

The brain

The brain is also important when you look at development. Not only genes, but also the environment influences the development of the brain. Nowadays there are a lot of studies about epigenetics. This is discussed in the previous lecture en is not further discussed here. Examples of influences from the environment are stress, drugs but also the population group you belong to. Stress triggers genes, drugs increase the chance at developing psychoses in adolescence and minorities have a higher change at developing psychopathology.

Childhood is a crucial period for developing. Therefore it is important to treat children/youngsters with psychopathology. Treatment can undo of lessen the negative effects. For example think about the hippocampus. The hippocampus shrinks as a consequence of experiencing trauma. When someone is treated for this traumatic experience the hippocampus normalizes in size. Meylinisation strengthens connections in the brain and this is a good thing when this are connection we want, but in happens also with bad connections.

Development in adolescence

Adolescents only see risks on the long term and think they can handle everything that crosses there path. They are more self-centered than children and adults. The brain is not fully developed as parts like the prefrontal cortex are still developing.

Adolescents have great learning capacities, but are very impulsive. They are very vulnerable for risks. A study of Blakemore showed that when adolescents have to estimate the risk of a car accidents they do even well as adults. But when there are peers present they react different, they perform worse.

The reward centre in the brain is very sensitive and the inhibitory circuit is still developing (PFC), this explains the impulsiveness and the risky behavior.

ild unique: genes, environment, development and intergenerational factors (what a generation transfers to the next generation). All these factors are needed to understand and treat patients, and girls like the ones from the documentary.

It is also important to remember that adolescents can’t be treated like young adults. During adolescence people are emotionally vulnerable, with progression and regression in the development. They are quite unstable, in comparison with adults.

Lecture 6: Childhood abuse, impact and neglect on health and ageing

Descartes (1596-1650) had the idea that body and mind are separated from each other, like a dichotomy. The body is, according to Descartes, subordinate to the mind. Now we know this is not the case. The mind influences the body. In this lecture the central question is: how can childhood maltreatment influence physical health?

Bad experiences and the influence on health

Experiences influence the perception of body and mind. The subjective health is how healthy you think you are. Adults who have experienced child abuse, report more physical complaints (headaches, stomachaches for example). The question is whether the body is weaker or the subjective health?

Diseases of aging are diseases that come with aging. Examples are cardiovascular disease or coronary heart disease, but also asthma, migraine, diabetes and cancer. The duration of a disease and the risks of a disease differ for people who have experienced child abuse. The risk for diseases of aging is higher for those people and the duration is shorter, they die sooner.

The Ace Study is a big study with 17.000 participants. The study investigated the consequences of child abuse on physical and psychological health.

The pyramid shows the risks (from the Ace Study). A lower level on the pyramid increases the risk of a consequence on a higher level of the pyramid. So when you look at the pyramid, social and cognitive impairment increase the risk for developing health-risk behavior. The caps between the levels are scientific caps and they stand for the relation between the levels. They are caps because the don’t know what the relation between the levels is. From this study we know that people who have experienced child abuse have a higher risk for developing a disease and a lot of academic papers have been released about these different diseases.

Animal research

Animal research found the same results. An example of such a study is the study Ader et al. They placed tumors in rats who have experienced early life stress. There rats had more chance of dying from the tumor than the rats who didn’t experience early life stress. This effect applies also for ulcers. Conclusion: early life stress increased the risk for health problems. But does stress lead to a poor immune system or is there a different mechanism?

The influence of stress

There are four pathways in which abuse can influence health which will be explained here:

1. Behavioral pathway

   When you look at the behavioral pathway you see that people who have been abused show more harmful behavior. There is more substance abuse, obesities, suicide, risky sexual behavior, smoking en sleeping problems in this group of people. Generally, there can be said that these people show more risky behavior. When looked at the substance abuse there are two explanation people think off. On the one hand they think that the substance abuse is used to numb feelings/emotions. On the other hand they think the inhibition circuitry is impaired. It is also known that people who have been abused are more impulsive.

2. Social pathway

   Revictimisation: the risk of being abused is higher for people who have experienced child abuse. People who have experienced child abuse are also more sensitive for interactions. Especially for hostility, vigilance and distrust. This effect is also visible in the brain. The activity of the amygdala is increased and the cortisol reaction is stronger in people who have been maltreated. This heightened reaction is also visible in children who grew up in war zones and have been separated from their parents.

   People with a history of abuse/maltreatment have more problems with interpersonal relations. They have an increased risk for an avoidance style and an intrusive style. During the lecture examples are shown of behavioral acts for these interpersonal styles. Both of the interpersonal styles lower the chance of getting social support. And social support plays a big role in physical health. People who experience social support live longer and are better able to deal with disease. A study of Eisenberger showed that the cortisol reaction of people who experience little social support is stronger. This is also visible in the activity of the brain. In an experiment about playing catch. This game of catch was online and the participant was excluded from the game at some point by the other players. Being excluded has been related tot dACC activity. People who felt little social support showed more activity in de dACC when excluded than people who feel supported. Both of these experiments are about the feeling of support, there was no one in the room who could offer social support during the experiment.

   There has also been research about sex differences. In men, the cortisol reaction decreases when they’re feeling supported by their spouse or by a strange woman. Women only show a decreased cortisol reaction when there is physical contact with their spouse. When they were verbally supported there was an increased cortisol reaction.

   Oxytocine has also a decreasing effect on stress reactions. The idea is that manual therapies, like massage, may have a stress relieving effect. Because oxytocine is released with pleasant physical contact, like hugs, kisses and massage.

3. Cognitive pathway

   Research has found a relation between social support, optimism in childhood and health in later life. Cognition about the self and others can increase the stress reaction. The Nun study has investigated this relation. Nuns had to hand in an autobiography when they started living in the monastery. This autobiography was graded on optimism. The more optimistic the autobiography was the longer that nun lived in comparison with the nuns who had written a more negative autobiography. The conclusion that was drawn from this study is that optimism plays a big role in health. It is important to remember that in this study there were no physical masseuses, so we can only talk about associations and no relations.

4. Emotional pathway

   In the emotional pathway it is about the relation between psychological disorders and diseases. For example if there is a relation between depression and an increased risk for diseases. From research we learned that depression causes an increased risk for cardiovascular disease. The mechanism behind this is not clear yet. Maybe the underlying mechanism is the HPA-axis, immune system of maybe the sleeping problems or poor self regulation that is seen in people with depression.

   During the lecture they showed us a documentary about Sapolsky and his research with monkeys. This research stress in apes from different levels in the hierarchy they live in. The apes who were lower in the hierarchy were more stressed and had more plaques in their veins. They were also more vulnerable for plaques attaching to their veins.

Child abuse and physical health

There are two main questions in this field of research:

1. How does childhood stress gets under the skin, at the level of tissues and organs, to affect risk for later diseases?

2. How does childhood stress incubates in the body, manifesting in disease several decades later?

There are three possible underlying mechanisms: chronic inflammation, the childhood adversity model and telomeres.

Chronic inflammation

Chronic inflammation is the reaction of the immune system and the related stress reaction of the HPA-axis. Chronic inflammation can happen through the immune system you are born with. This system developed during evolution. A mechanism of this system is epigenetics. The reactions of this system can be strengthened by risky behavior and hormonal dysregulation.

Chronic inflammation can also be programmed in your immune system through experiences. The immune system reacts when xenobiotics enter the body. It remembers them and when they enter again the immune system can react faster en better. It fights them using macrophages that destroy the xenobiotics.

The Biological pro-inflammation model of early life stress says that early life stress influences the programming of the macrophages. The immune system becomes less sensitive to inhibitory hormones like cortisol and reacts less adaptive on xenobiotics.

Cortisol is a stress hormone that inhibits the immune system during stressful situations. This is an adaptive response. This way the body can use all the energy in the flight/fight reaction. This way it protects the body from damage. But when the stress system is constantly active the immune system is constantly inhibited. This is harmful for the body. This is possible explanation for the many somatic complaints of the victims of child abuse.

The childhood adversity model

This model, described by Miller, explains that stress in sensitive periods can alter bodily systems. Every bodily systems has its own sensitive period. The body tries to change the systems so it can react in the best way possible in this type of situation, stressful situations, in the future. This is called a Predictive Adaptive Response (PAR). The idea is that this mechanism, the Predictive Adaptive Response (PAR), is to make sure the body can respond in the best way possible in the ecosystem it lives in. PAR’s enable the organism to protect itself, make optimal use of recourses and reproduce more successfully.

Victims of child abuse have altered bodily systems for stressful environments. But most the these victims don’t live in a stressful environment for the rest of their life. There is a mismatch, the reactions of the bodily systems don’t match the environment. This causes problems, like behavioral, emotional and physical problems. 

Telomeres

Telomeres protect the endings of DNA. Every time a chromosome replicates the telomere gets shorter. This process is a normal aging process. But research showed that this process is also seen in children who have experienced child abuse. The lengthen of the telomeres decreased between the age of 5 and 10. The decrease was more when there were multiple traumatic experiences. There are individual differences, like genetic differences in this process.

The enzym telomerase can restore the telomeres. The experience of being socially supported strengthens this restoring process.

In every lecture a different aspect of the integrative model about the impact of child abuse on physical and psychological health is being explained.

1. ased risk for an avoidance style and an intrusive style. Both of the interpersonal styles lower the chance of getting social support. And social support plays a big role in physical health. People who experience social support live longer and are better able to deal with disease. A study of Eisenberger showed that the cortisol reaction of people who experience little social support is stronger. This is also visible in the activity of the brain. In an experiment about playing catch. This game of catch was online and the participant was excluded from the game at some point by the other players. Being excluded has been related tot dACC activity. People who felt little social support showed more activity in de dACC when excluded than people who feel supported. Both of these experiments are about the feeling of support, there was no one in the room who could offer social support during the experiment.

   There has also been research about sex differences. In men, the cortisol reaction decreases when they’re feeling supported by their spouse or by a strange woman. Women only show a decreased cortisol reaction when there is physical contact with their spouse. When they were verbally supported there was an increased cortisol reaction.

   Oxytocine has also a decreasing effect on stress reactions. The idea is that manual therapies, like massage, may have a stress relieving effect. Because oxytocine is released with pleasant physical contact, like hugs, kisses and massage.

2. Cognitive pathway

   Research has found a relation between social support, optimism in childhood and health in later life. Cognition about the self and others can increase the stress reaction. The Nun study has investigated this relation. Nuns had to hand in an autobiography when they started living in the monastery. This autobiography was graded on optimism. The more optimistic the autobiography was the longer that nun lived in comparison with the nuns who had written a more negative autobiography. The conclusion that was drawn from this study is that optimism plays a big role in health. It is important to remember that in this study there were no physical masseuses, so we can only talk about associations and no relations.

3. Emotional pathway

   In the emotional pathway it is about the relation between psychological disorders and diseases. For example if there is a relation between depression and an increased risk for diseases. From research we learned that depression causes an increased risk for cardiovascular disease. The mechanism behind this is not clear yet. Maybe the underlying mechanism is the HPA-axis, immune system of maybe the sleeping problems or poor self regulation that is seen in people with depression.

   During the lecture they showed us a documentary about Sapolsky and his research with monkeys. This research stress in apes from different levels in the hierarchy they live in. The apes who were lower in the hierarchy were more stressed and had more plaques in their veins. They were also more vulnerable for plaques attaching to their veins.

Lecture 7: Sexual abuse, consequences and treatment

Psychological consequences

Anxiety disorders and depression are most common in children. PTSD is a non-specific factor in the development of psychopathology. You can look at PTSD from different domains. There are often problems in emotion regulation, self image, cognitive problems (these problems keep existing after psychological treatment, like problems with concentrating), problems with interpersonal relationships, negative cognitions (like blaming the self for bad things happening), and somatization (like substance abuse, headaches, most of the time the symptoms are vague but have a lot of influence on daily life). De consequences of childhood abuse that are circled are related to PTSD. De consequences that are connected with a line are part of a subtype of PTSD.

Diagnostics

1. PTSD: a post traumatic stress disorders can develop after a traumatic experience.

2. There is a lot of comorbidity: besides PTSD people often have symptoms of other disorders and something meeting the criteria for a diagnosis. Most of the time the comorbidity is with depression (often the chronic type). Anxiety disorders, addictions, eating disorders, conversion and dissociation.

3. Complex PTSD is PTSD with extra symptoms. It is a category from the ICD-11. PTSD develops often after experiencing child abuse en the following symptoms are often seen in these patients: feeling trapped, fragmentation, los of feeling being secure, negative self image, fear of revictimization and a distorted attachment style.

In the DSM-V the following symptoms are being distinguished:

1. Traumatic event: a traumatic event is the cause of PTSD.

2. Reliving: reliving the trauma is an important symptom. Reliving can be through nightmares but also through flashbacks. Most of the time there is not much needed to trigger flashbacks.

3. Avoidance

4. Negative thoughts/mood

5. Hyperactivity: there is a distorted balance between stress and relaxation. People with PTSD have a heightened stress levels which can lead to concentration of sleeping problems.

There a two subtypes of PTSD: the subtype with dissociation symptoms and the subtype with delayed expression. Delayed expression means that people have no symptoms for a long time but at some point the symptoms start.

Predictors

The predictors of PTSD are divided in 3 groups: pre-trauma, peri-trauma and post-trauma factors. During the lecture the guest speaker told about DESNOS a category from the ICD-10. It offers no clarification about PTSD. This is not material for the test.

PTSD and personality disorders

When a patient with PTSD also has a personality disorders it looks a lot like complex PTSD. The difference is that the personality disorder comes with specific symptoms that is not seen in complex PTSD.

Borderline personality disorder: characterized by: fear of abandonment, unstable relationships, unstable self-image, impulsivity, self-harm, mood swings, feelings of emptiness, fits of anger, dissociation/paranoia. Patient with this disorder and PTSD are hard to treat, they often don’t do their homework, are impulsive and often have an addiction.

Avoidant personality disorder: patients have a avoidant lifestyle, often lead isolated lives, don’t have o job or relationships. Patients say they don’t need relationships to be happy. These patients are also difficult to treat. The idea of the therapy is to talk about the trauma and these patients often don’t want to talk at all.

Treatment: Trimbos guidelines

These guidelines are for therapists in the Netherlands. According this guidelines the first choice of therapy is CBT, followed by EMDR. These guidelines are not proves to be effective, but therapist are by law obligated to work with Trimbos.

A lot of studies about the effect of treatment related to trauma in later life. Treatment of chronic depression often stagnates in patients who have a history of child abuse. There is no consensus between investigators and clinicians. Trauma-oriented CBT is, according to the literature, the most effective treatment.

Patients with comorbidity are often left out in studies because it is more difficult to treat them. Therefore there is not much known about this group of patients.

Phase –based vs trauma-focused treatment

There is a lot of debate about the question whether treatment should start with working on the trauma or first work on possible other problems like emotional problems. There is a lot of research needed for this question can be answered.

Satisfaction of patients

A research of the Dutch policy in 1996 showed that the treatment of PTSD was not rated very positive. Patients felt ashamed and had the idea that they were not allowed to talk about the trauma.

CBT as a treatment form for PTSD

1. Imaginary exposure treatment: with this treatment it is about the recall of events by talking about it in detail. At the start the symptoms will get worse but after a couple of sessions it will get better. There will also be exploration of the hierarchy of the events that are related to the trauma. The therapy will start with the events that are low in the hierarchy and end with the events that are high in the hierarchy. The final step is exposure in vivo. The window of tolerance is shown to the patient to help explain that it is important for the therapy that the highest level of arousal is reached. During therapy the patient can also point on this schema how the level of fear is at that moment when it is hard to talk about it.

2. Cognitive therapy: this therapy is based on the idea that feelings and emotions are influenced by your thoughts and that when these thoughts change the feelings change. In this therapy the patients have to work to change the negative thoughts they have.

3. Schema therapy: this will be explained in the next lecture.

4. EMDR.

Clinical practice

There is a lot of debate about whether the therapist should stabilize the patient before starting the treatment for the PTSD. According to Trimbos is pharmacotherapy not effective for treating PTSD. There is a lot of drop out during treatment, most of the time because people want to avoid the bad and negative thoughts they have to talk about in therapy.

Trimbos is not always being used as guideline and there are several reasons for this. Some say it is because of the frequent comorbidity, or because therapist are scared to treat the trauma, or because the therapist thinks he or she is uncomfortable with using CBT. Some say it is due to characteristics of the patient, like being disorganized or financial problems.

Dissociation

Dissociation is the feeling of being detached from the self. Black outs, flashbacks and amnesia are common with dissociation symptoms. A lot of therapists don’t use CBT in patients with dissociation, but dissociation shouldn’t be a an obstacle because it is just a symptom of PTSD and not another disorder. Research showed that CBT is effect for patients with PTSD and dissociation symptoms.

Innovative treatment

There are several innovative treatments like: intensive Exposure, (Group) schema therapy, virtual Reality Therapy ,E-health, serious gaming, narrative Exposure Therapy, mindfulness/Compassion

Lecture 8: Long-term effects of childhood maltreatment

Schema therapy

Schema therapy is developed in the 90s by Jeffrey Young. It is an integrative theory and treatment.

In schema therapy the basic idea is that the core emotional needs are not met. These needs are named by Young:

• Secure attachment

• Autonomy, competence, and sense of identity

• Freedom to express valid needs and emotions

• Spontaneity and play

• Realistic limits and self-control.

When these needs are not met, the child develops dysfunctional schemas.

Young: ‘ Early maladaptive schemas are self-defeating emotional and cognitive patterns that begin early in our development and repeat throughout life.’ In this model the negative cognitions are seen as a factor in the development of depression. According to the schema theory there is a specific schema that leads to the cognitive patterns. Schemas develop through an interaction with the environment. When the schemas are develop the schemas keep being confirmed throughout life and this way the schemas are being strengthened.  Schema therapy can be used in multiple ways. For example when treating depression the therapy is focused on finding the one schema that leads to the negative cognitions. For more information the guest speaker referred to the paper of Renner.

Modes

There are different modes:

• Child mode: in this mode the patient feels like the way he or she felt during childhood.

• Parent mode: in this mode it is like the patient hears the voice of his or her parent talking bad. In this mode it is about talking negative about the self.

• Coping mode: this mode is also called the protector mode. In this mode it is about the cognitions and behaviors that help the patient deal with emotions that are to intense.

• Healthy adult: in this mode the patient functions normal.

Modes are a lot like subpersonalities, the difference is that with modes the patient is still aware of the other modes. With subpersonalities the patient is not aware of the other subpersonalities. It is important to explain to the patient that he or she can shift between modes but that she or he first needs to recognize the different modes.

Goal

The goal of schema therapy is that patients learn to provide for their own basic emotional needs in healthy and adequate ways.

Treatment

(the following is also explained to the patient)

• First phase: diagnosis and information

Through schema questionnaires and conceptualizing the problem the schemas of the patient are identified. There will also be looked at the development of the schemas by looking at the life of the patient. There will also be giving information about schemas, modes and patterns before the therapy starts. This is important because when a patient is in a specific mode it can be hard to listen to the given information and to process it.

• Second phase: changing/processing

In this phase it is about the therapeutic relation, cognitive strategies, experiential strategies (this strategies focuses on the emotions during the modes and especially the feelings the patient had during the experiences that are important for forming the schemas), behavioral pattern- breaking (it is not enough to break cognitive patterns. For the patient to be able to stay away from the ‘bad’ schemas behavior patterns need to be changed. The therapeutic relation forms the base of the therapy. The trust in the therapist is important. A lot of patient have problems with trust due to child abuse. Here the therapy is explained like it is a step-wise therapy but in practice this is not the case. The different strategies are used mixed up.

DVD

At the end of the lecture the guest speaker shows a video fragment about a therapy session. The patient in this fragment just started the treatment. This video showed that the different techniques are being used interchangeably. When the patient is not opening up and keeping the therapist a distance, the therapist worked on the therapeutic relation so the patient would open up. When the patient opened up the therapist would talk about the mode the patient is in and the feelings the patient has.

Q and A for examination

For the test it is important that you get the overall idea of the papers and not the details. The overall results are important. The lectures of Tollenaar and Elzings are important for the test. The lectures of the guest speaker are less important when their material is not in line with the literature. The literature is more leading for the test for this lectures. The theory from How to raise a dog it important for the test. Methodological aspects are only important when they are covered in the lectures, like the problems in investigating long term consequences of child abuse. When there is question about what treatment would be the best there will always be more information about the case. There is no best treatment, it depends on the disorder and the patient which will be best.

Source

These lecture notes were written in 2015-2016.