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Lecture 1: Introduction, documentary, Questions & Answer session
All you need to know is that this course consists of self-study, mainly through scientific
papers but also by the book. The book of bruce perry (the boy who was raised as a dog)
includes case studies which give you insight in the scientific papers. Furthermore, there
is a discussion forum about the chapters of the book. Mainly focus on the reasoning,
main outcomes, and the conclusions in reading the research papers (don’t read too much
about the methods). However, in review papers you must focus on the theory, consensus
among other studies and the conclusion of these papers. In these review papers you do
not need to know the separate papers.
Background (terminology, Prevalence)
The role of the childhood has been discussed throughout all of psychology, for example
think about Freud, Bowbly or Harlow. In regular emotional interactions with the
caretakers are a fundament for later development (bowbly). It is important to form
attachment, establish sense of safety and security, to learn to regulate their own
emotions, to understand emotional states of others, to learn to trust others and to learn
empathy.
Based on a lot of research papers childhood abuse and neglect have pervasive
consequences for mental and physical health of an individual.
Terminology
Childhood maltreatment is any act of commission or omission by a parent or other
caregiver that results in harm, potential for harm, or threat of harm to a child. Harm does
not need to be intended by the caregiver. Whereas commission refers to a failure to meet
a child’s needs (physical, emotional neglect or denial of access to education). And
commission refers to actively doing something harmful (such as physical, emotional,
or sexual abuse).
- Emotional neglect: the failure to meet a child’s emotional needs and failure to
protect a child from violence in home or neighbourhood
- Physical neglect: the failure to meet a child’s basic physical, medical/dental, or
educational need. But also, the failure to provide adequate nutrition, hygiene, or
shelter.
- Emotional abuse: intentional behaviour 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 intentions aimed to a child by a caregiver
Psychological disorders after maltreatment
There are many different consequences of maltreatment, but only one has a direct
relation to the maltreatment. That is Trauma- and Stressor related disorders, while being
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maltreated is a big stressor. But it an indirect link is possible between maltreatment and
psychological disorders.
As you know we categorise disorders according to the following categories:
internalizing and externalizing disorders, personality disorders, psychotic symptoms,
and suicide & self-injury.
While a child is being maltreated, he or she has many different psychological
consequences, which can almost never be linked to one single psychological disorder.
Think about comorbidity, when one has one or more different psychological disorders
(there is an ~60% overlap between depression and anxiety)
Li et al:
Maltreatment in childhood substantially increases the risk of adult depression and
anxiety in prospective cohort studies. It was a systematic review (meta-analysis) of
English-speaking countries. The OR (odds ratio) is between 2-3 higher for maltreated
children compared to healthy controls.
Underlying mechanisms
It sounds strange that an event that happened 25 years ago has such a pervasive impact
on a person’s emotional ,cognitive and social well-being. The following are possible
underlying mechanisms:
- Cognitive schemata of self and others (attributional style): a negative way to
interpret the world.
- Emotion regulation styles: Stress system might be over activated, and you do not
know how to regulate this.
- (in)secure attachment: Emotional neglect is a big risk factor for insecure
attachment. The attachment to abusing parents occurs but is characterized by
unsafety. When biological parents are not available, children can still securely attach
to another person (resilience!) . All of this can influence the attachment in later
relationships.
- Hypervigilance to threat: When children are maltreated, they have a heightened
attention to angry faces. But they also give a hostile attribution when the stimuli are
ambivalent. This can be seen within the brain: in the activation of the amygdala. All
of this may lead to higher risk for anxiety disorders, aggressive reactions, or
avoidance.
- Low responsiveness to reward: This is very relevant during adolescence, since it
motivates and reinforces goal directed behaviour. The dopamine system (striatum)
is linked to this system. When there is low responsiveness this may lead to
depression or substance abuse.
- Neurobiological models:
Problems in emotion regulation can lead to problems in social interactions, rejection,
stress, and impulse control.
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Lecture 2: Influence of maltreatment on a cognitive, emotional, and neurobiological level
Relatively new research has shown that symptoms you experience now may be the result of
something that happened a long time ago. People used to think that only thing in the here and
now influence your current symptoms.
Maltreatment can chronically increase stress-sensitivity:
1. Cognitive / emotional level: Parents may hand to the child negative attitudes, 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 (Beck, 2008)
2. Neurobiological level: This can be the result of altered brain functions in networks that
are important for emotional reactivity, emotional memory, and emotion regulation. But
also, by chronically altering the sensitivity of hormonal stress reactions, such as the
HPA-axis / adrenergic system.
Cognitive level (Beck’s cognitive model)
In general, cognitive vulnerability is the result of both heredity and early life adversities (such
as emotional maltreatment) that can interact with each other. What happens next is that when
one is exposed to stressors in life this leads to negative self-inferences, dysfunctional attitudes,
and low self-worth. All of this can result in symptoms of depression or anxiety.
1: Beck's cognitive model
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Emotional level
Maltreatment can chronically increase stress-sensitivity. One study shows that people with
emotional abuse are faster at implicitly categorizing depression and anxiety words with
themselves. Also, according to this study emotional maltreatment is the strongest predictor of
negative implicit self-associations. Another study tries to explain the mediation role between
childhood maltreatment and depression. Which had the same kind of conclusion as the study
named above. Furthermore, it showed that have a history of childhood maltreatment avoid close
relationships, which has influence on their severity of depression (also see week 5!).
Neurobiological level
Maltreatment can chronically increase stress-sensitivity by altering brain functions in networks
that are important for emotional reactivity, emotional memory, and emotion regulation. Or by
chronically altering the sensitivity of hormonal stress reactions, such as the HPA-as / adrenergic
system.
During childhood, the brain is of course not yet fully developed. The influence of maltreatment
depends on the age of the child. In early childhood the limbic system (threat & safety: “Am I
growing up in a stressful environment or not?”) is being developed, while later during puberty
the prefrontal brain (emotion regulation ) is being developed. As you know the brain of a child
can respond plastically to outside triggers.
During this course, the brain is seen as the following: The brain is seen as an anticipation
machine, that making a future is the most important thing it does. The ability to use past
experiences and information about our current state and environment to predict the future
allows us to increase the odds of desired outcomes while avoiding or bracing ourselves for
future adversity. If you translate this to maltreatment: Children would predict that the outcome
of “regular” interactions would be the same as the interactions with the person that maltreats
them.
Amygdala
What is happening in the brain when you see a stressful trigger? When you see a trigger, the
visual information goes to the thalamus, which can go immediately to the amygdala and can
trigger a reaction. But there is a second pathway that goes slower (through the visual cortex)
and makes you able to reconsider the what the immediate route told you. In brief: your first
reaction will be non-conscious while your second reaction adjust to what you know.
When you are exposed to a lot of stress during your childhood this system might be sensitised,
which means that you basically kind of learn to activate your amygdala stronger to triggers.
One study shows that when someone is emotionally maltreated the amygdala is more sensitive
to all facial expressions (yes, even a neutral or happy facial expression) of others. Right now,
there is not an explanation for this. A theory is that they might be suspicious for even happy
facial expression OR the amygdala is in general very sensitised. But further research must be
done to confirm this.
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Impact of abuse on face identification
One study looked at the way people perceive faces. A child which has been maltreated or abused
is better at identifying angry faces (they are also worse at identifying happy faces, but this
difference is non-significant). This shows that their implicit threshold of identifying angry faces
is low compared to a control group. Which makes sense, while these children need to anticipate
more to angry faces.
An interesting thing is that this study shows no difference in positive identification, while the
study named above this section does name a difference in positive facial expression
identification.
!! One problem with all these studies is that you need to ask participants to look
retrospectively at their childhood, which might be influenced by all kinds of factors. It is
merely subjective !!
A brief conclusion:
➔ Early childhood experiences can change the sensory threshold ( Pollak, 2005)
➔ Maltreated children / adults show increased sensitivity in amygdala response to faces
(Pollak, 2005 ; van Harmelen, 2012)
➔ Enhanced sensitivity may be associated with impaired emotion regulation (O’Mahen ,
2015) and on the long term (in response to new stressful experiences) with development
of psychological symptoms.
➔ Emerging evidence points to sensitive periods and specificity of type of abuse in the
development of neurobiological sensitisation.
mPFC volume
Things that are the most interesting in maltreatment are functional changes in the brain. One of
them is a decrease in mPFC volume in individuals reported a history of emotional maltreatment.
This reduction is consistently observed in both males and females and it cannot be explained
by psychopathology, neuroticism, or recent life events.
The role of the mPFC is that it is involved in regulation of affective states emotional behaviour,
fear extinction and self-referential processes. The activity lowers fear responses by reducing
the amygdala activation over time. Furthermore, the mPFC is involved in modulation
neuroendocrine and autonomic stress response. A dysfunctional mPFC activation is implicated
in stress-related disorders (including PTSD and depression).
Amygdala-prefrontal circuity and vulnerability in stress related psychopathology
One study shows the influence of emotional distractors on working memory (by using a
working memory delay task). When one is presented with an emotional distractor the individual
has more problems with remembering a certain stimulus. This means that an emotional
distractor can be a great influence on working memory.
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A different study tried to replicate this with a different approach (letters instead of faces, but
still negative emotional distractors). The studies used borderline personality disorder patients.
They struggle with affect and have an enhanced amygdala reactivity towards emotional stimuli.
Frequently they have a history of childhood abuse (either sexual or emotional). In general, these
patients have no problems with working memory, but there are disruptive results when
presented with negative emotions on their cognition. There is evidence for bias towards
processing of emotional information at the detriment of neutral information.
Furthermore, these patients react slower when presented with a negative distraction. This hints
that they have struggle with ignoring these emotional distractors. In the amygdala there is no
increase of amygdala activation in a baseline test, but when presented with a neutral or
negative emotional distraction their activation increases.
Dissociation
They used the same study as named above to investigate dissociation. People who are extremely
sensitized during childhood are prone to dissociate. Dissociation has different aspects
(depersonalization or derealisation) , but in general it is the feeling that you are not connected
to either yourself or the environment. This is often seen in people after repeated and early
trauma. It might be a de-attachment of the traumatic experience and result into memory and
emotional problems
The study shows that in the borderline patients there are two groups. One whom experienced
dissociation and one who did not. The group that did not had an association had an above
average amygdala response at the neutral and negative picture. What is striking is that the
people who dissociated had a blunted amygdala activation to all stimuli, basically the same as
the control group. This kind of confirms the thought that dissociations help with taking distance
from a traumatic experience.
Therefore, some researchers suggest that there are two forms of PTSD:
1. Emotion under-modulation: which results into re-experiencing of the trauma because
the regions implicated in regulation of emotion and arousal (mPFC) decrease and the
regions implicated in awareness of bodily states (anterior insula) increase. Furthermore,
the amygdala activation is increased in this form of PTSD.
2. Emotion over-modulation: which results into dissociation because the regions
implicated regulation of emotion and arousal increase, and the regions implicated in
awareness of bodily states (anterior insula) decreases. Furthermore, the amygdala
activation is decreased in this form of PTSD.
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Lecture 3: Animal models of early life stress impact of ELS on the HPA-axis
Note that the article of Nemeroff (2016) is a compact overview of most topics within this
course!
Human research methods
Almost all human research is retrospective (if you want to study the consequences of
maltreatment, you research adults who have been maltreated). The advantage of this that it is
practical in the case of long-term consequences, while the consequences are already there. But
there are many disadvantages like memory (which is erroneous), recall bias (when someone is
in a depressed mood, they remember more negative things), and the consequences and abuse
assessed at the same moment (therefore the causality regarding cause and effect are unclear).
But you can also do prospective research (if you want to study the consequences of
maltreatment, you start with maltreated children). The advantages of this study are that you
have a temporal order, and you can follow them over time. You also have an object
identification of abuse, there is no recall bias, and no selective inclusion based on outcome. Of
course, there are also disadvantages like: selective inclusion, on-ethical without intervening in
the situation, duration, costs, and drop-outs.
A combination of methods is the best method for human research.
All these studies are observational, which means that you do not manipulate the situation. It is
therefore impossible to randomize the groups. This kind of research can be:
- Epidemiological research
- Longitudinal research
- Cross sectional
In all these cases information is based on self-reports, reports by parents, or reports by
professionals. But research shows that self-report rates 10x as high as compared to informants.
Why use animal models of early life stress?
The professor lists a lot of reasons why they use animal models of early life stress, but the main
goal is to establish causality and defining underlying mechanisms that is needed for preventive
and therapeutic intervention on humans:
- Shorter life span
- Objective criteria: you can really abuse a mouse
- The possibility to experimentally induce early life stress, which give you the ability
to examine cause and effect. But also controlling for parental mental health and
genes
- Examine which factors of care are most detrimental (what kind of care works, and
there is less co-morbidity)
- Study the underlying hormonal and brain changes (intrusive measures)
- Examine gene by environment interactions independently
- Define biomarkers
- Testing new biological treatments
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How to study early life stress in animals?
The goal is always to do translation research, which means that we do research on animals that
we can translate to humans. Therefore, a stress paradigm is needed so we can measure the
consequences and it should be bi-directionally informed (see if it’s possible to test the same in
humans). It all starts with a choice of an animal: a mouse, rat, or a primate. Depending on the
research you want to do and the needed intelligence you choose an animal.
As stated before, animals have a shorter lifespan and therefore it’s easier to look at longitudinal
consequences. For example. A mouse lives about 2 years, hits puberty between week 4 and 6,
and is mature between 3 – 5 months.
Maternal separation and induced stress
The way they study early life stress (is seen as the same as maltreatment in humans) is based
on natural variations in maternal care behaviour ( licking and grooming, active nursing, or
passive nursing) or you can induce it experimentally (maternal separation / deprivation, reduced
maternal care, abusive behaviours, and fragmented maternal care). Most often to induce early
life stress is separation. With repeated stress it can induce a chronic early life stress, but if you
separate them longer for once the result might be a single trauma. But you can also stress the
mother by limiting nesting availabilities resulting into big life stressors for the mother and then
you can study what happens to the maternal behaviour in an impoverished environment. One
study researched this and concluded that it increases the abusive behaviour of the mother.
Augmented maternal care
There are also ways to better maternal care and research the effects of that. This is called
augmenting maternal care. You can take away the mother rat for 15 minutes a day, then the
maternal behaviour goes up. The translation that the professor makes of this is the following:
Small stressors are good, while the mother will compensate for her “being away”.
Translation effects of early life stress
HPA-Axis
Think about stress, ziekte en gezondheid. Cortisol is a
more long-term reaction (slower) to stress and
noradrenaline is a quicker, direct reaction to stress.
Mice have the same kind of feedback-loop as humans
do. In the previous lecture it is mentioned that there is
an effect on humans when one is maltreated and their
general stress responses (stronger stress reactivity).
Today we talk about the translation of finding in mice.
There were two groups of mothers: high or low in
licking and grooming. Results show that the effect on HPA-axis after maternal deprivation is
the following: when one is deprived, they have a higher cortisol level, but when they get older
it will be lower than usual (depletion). They see the same reaction in people with PTSD.
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The brain
One of the studies of this week’s reading material shows the effect on the amygdala when one
is being maltreated. This study is one of the orphanage studies in Eastern Europe. The study
shows that the amygdala is higher after early life stress factors, which is the same as a study in
mice shows.
The hippocampus is important for the negative feedback loop of the HPA axis, but also for
memory. It is an important structure in regulating behavioural measures of anxiety and it is
fairly plastic. An abnormal hippocampal development may underlie some of the adverse early-
life induced behavioural differences. The human studies show that maternal support in early
childhood predicts larger hippocampal volumes, while in maltreated children the volume is
reduced. In mice they found that their hippocampal dendrites are more complex when they get
maternal supports.
Neurogenesis
Inside the hippocampus neurogenesis happens. This is the creation of cells while using stem
cells. Research showed that early life stress can affect the creation of new cells. While it is hard
to study in humans, this can be done in mice. The neuronal survival is reduced in rats
experiencing lower maternal sensory input (aka maltreatment).
Early life experience reduces hippocampal neurogenesis later in life and impairs hippocampus
dependent learning (next) in offspring experiencing adverse early life environments.
Effects on cognition
The effects on cognition are not totally clear yet, while we only know the cognitive styles who
depend on comorbid psychopathology. But long-term potentiation (a signal that shows that
something new is learned) is related to hippocampal dependent learning, it responds stronger to
those who had a good childhood. When animals that have augmented maternal care, they learn
quicker and memorize more...!
Emotions
After maternal deprivation mice show more freezing behaviour when being spooked. Stress
sensitisation is therefore higher in mice when they are maltreated.
PAR Hypothesis
Studies have shown that early-life adversity is associated with enhanced stress, responses,
changes in the brain , and impaired cognitive and emotion function. But why is this? The states
that early life stress might program the brain such that it optimally response to stressful context
encountered later in life, it is therefore an adaptive program. The predictive adaptive response
(PAR) hypothesis states that in response to a change in early-life environment the offspring
makes adaptations to improve its chance of survival in the anticipated future environment.
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Match-mismatch hypothesis
When the environment is very different then your environment as a child. This hypothesis asks
if the future environment match or mismatch the early life environment. If it matches, then you
might have an advantage over others. For example, early-life experiences can enhance cognition
under stressful conditions. Higher contextual fear condition in maternally deprived rates after
cortisol treatment showed that after cortisol the maternally deprived rats have a stronger
learning capability.
They showed a similar result in humans, but cumulative stress most likely leads to worse long-
term health outcomes.
Sensitive periods
In humans timing of foster care seems crucial. Placement before the age of two years is
associated with improved outcome. Furthermore, the timing of trauma is related to depression
risk and brain changes.
In animal research it is easier to see when maltreatment happens. One of the first studies in this
area is the stress hyporesponsive period. The first two weeks after birth are the most
insensitive in changing the cortisol levels. This has been translated a human study, this study
suggests that infants between 6 and 12 months have a period where they respond less to stressful
periods. During this time there is a lot of buffering in the presence of the adult (cortisol
fluctuation are suppressed). In vulnerable groups this period can disappear. The infant brain
supports approach responses, even negative approach responses. They are not naturally scared
for a lot of things. The lower cortisol is a moment of learning for avoidance. (the sooner one
has cortisol responses the sooner they learn what to avoid).
Ethics in animal studies
The purpose of the experiment should justify the use of animals. When harm is done to an
animal is should be outweighed by the benefits of the research. Or just use commons sense to
explain the ethical questions relating to animal studies.
What can(‘t) we learn from animal studies?
Think about things like subjective emotions, negative self-inferences and cognitions, sexual
abuse, and emotional abuse. But maybe even mental health in general is hard to study in
animals. Furthermore, testing behavioural interventions cannot be done in animals.
But we can learn a lot from them, while there are large similarities and gain the possibility to
experiment (investigate cause and effect)!
