What can cause emotional disorders? - Chapter 9

Everyone sometimes goes through a period of stress, but for some this becomes so bad that they are no longer able to live a normal life. What factors are involved in developing such an emotional disorder? The American Psychiatric Association (APA) has released the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) , as a tool for classifying and diagnosing mental disorders. This manual contains five axes (I: clinical disorders, II: personality disorders and mental retardation, III: general medical conditions, IV: psychosocial and environmental problems. V: global assessment of functioning) that have a range of symptoms and characteristics of more than 200 mental contain disorders. The first three axes are always used, the fourth and fifth are optional and can be used if the specialist finds this necessary.

The problem with DSM-IV is that cultural differences are not taken into account, so it is primarily relevant in Western societies. In addition, it is a categorical classification, whereby people may or may not have a disorder, while many symptoms occur over a wide range of different disorders. These symptoms can also be experienced stronger or less strongly. A dimensional approach would therefore be more appropriate.

Emotional disorders are common in approximately 20% of the population. The prevalence (proportion of the population with a disorder) of mood disorders is higher in women, while other disorders (such as addiction) are more common in men. There is a high comorbidity between depression and anxiety disorders: nearly 90% of people with anxiety disorder experience at least one episode of clinical depression.

What are the risk factors for anxiety and depression?

The risk factors that make people more susceptible to emotional disorders are as follows:

• Stressful events in life or the environment
• Own temperament or personality traits
• Neurobiological factors, such as the decrease of certain neurotransmitters and receptors in the brain
• Certain cognitive processes and biases
• A genetic predisposition to emotional disorders

These factors are not independent of each other, they interact with each other to make someone more susceptible to a disorder. The cooperation of these factors is described by the diathesis-stress model of psychopathology . This model assumes that a disorder arises as a result of two things: a diathesis (predisposition to a certain disease or disorder; this can be both genetic and social) and stress (due to a serious event in the environment).

What is the role of environmental events on emotional disorders?

Very traumatic life events can play an important role in making people vulnerable to an emotional disorder. This link between environment and disorders is most evident in Post Traumatic Stress Disorder (PTSD / PTSD) . Almost everyone experiencing a traumatic event will experience symptoms of PTSD in the period immediately following. However, other factors must be present if the disorder is to continue in the long term.

Stress is an important factor associated with emotional disorders. It has a direct effect on the brain, which causes the loss of neurons (neuronal atrophy) in the hippocampus, among others. Children who experience stress (for example in the form of abuse or abuse) have a greater chance of having emotional disorders later in their lives. This also increases the chance of other serious disorders such as schizophrenia.

A lot of research is done with the Social Readjustment Rating Scale . Who examines which of 43 different life events someone has experienced in the past year. Each event has a score based on how much adjustment is needed (both positive events and negative events can be seen as stressful). Scores on this scale correlate strongly with the amount of anxiety and depression that someone experiences.

The question is how stressful life events cause vulnerability to disorders. It may be that the experience of stress (at a young age) affects the neurobiological mechanisms that normally help with coping . For example, people with anxiety disorder often have an overactive hypothalamic-pituitary-adrenal (HPA) system, most likely due to a lack of glucocorticoid receptors in the brain, which in turn is caused by a high level of stress during childhood. Chronic stress can also lead to a hyper-reactive state of the amygdala, causing it to be activated earlier.

Negative childhood experiences are also associated with a greater chance of developing a neurotic personality, which in turn is associated with developing a vulnerability to emotional disorders.

What is the influence of temperament and personality on emotional disorders?

There are four ways in which temperament can influence the development of clinical disorders such as anxiety or depression. These four models do not exclude each other; there is evidence for all of them.

1. The vulnerability or predisposition model: temperament plays a direct causal role.
2. The pathoplasty model: temperament influences the course of the disorder (for example via the social environment) without playing a direct causal role.
3. The scar or complication model: according to this model it is the other way around; the experience of an emotional disorder influences the temperament.
4. The continuity or spectrum model: temperament and emotional disorders reflect the same underlying processes; Emotional disorders are extreme manifestations of normal personality traits.

Are temperamental dimensions risk factors for emotional disorders?

To investigate the direction of the causal relationship between risk factors and the development of an emotional disorder, years of longitudinal studies are needed in a group of people who do not yet have a disorder. Studies of this kind often reveal the affective dimensions neuroticism-negative affectivity (N-NA) and extraversion-positive affectivity (E-PA) as factors that play a role in the development of emotional disorders.

What is neuroticism-negative affectivity (N-NA)?

N-NA is an important dimension of personality with effects on mood, cognition, neurobiological processes and behavior. It also has a clear genetic component. N-NA is connected to the behavioral inhibition system (BIS) , which in turn is connected to behaviorally inhibited temperament. These constructs are strongly associated with neurobiological circuits related to the avoidance of damage. Many measuring instruments for anxiety and depression measure to a large extent the more general construct N-NA, which can partly explain the co-morbidity of anxiety and depression.

N-NA plays therefore an overcharging role in both types of disorders. Behavior-inhibited temperament is in itself a good predictor of emotional disorders. 30% of behavior-inhibited children develop a range of anxiety disorders. These children showed a strong amygdala response on unfamiliar faces in adolescence. A relatively large proportion of these young people were diagnosed with social anxiety disorder.

Although N-NA and behavioral inhibition are risk factors, it is important to remember that the majority of children in the risk groups do not develop a disorder.

Continuity models state that N-NA and anxiety and depression are causally related, but on the same continuum. It is therefore possible that a person's position on this continuum changes over time, bringing this person closer to depression or an anxiety disorder. This model predicts that shared genetic factors for all these aspects are associated with both temperament and emotional disorder.

There is evidence that N-NA influences the likelihood that a disorder will develop, that it predicts how long the disorder will last and how likely it is that someone will respond well to treatment.

What is extraversion-positive affectivity (E-PA)?

E-PA is connected to the behavioral approach system (BAS) , which in turn is connected to the uninhibited temperament that is observed in children. There is evidence that E-PA is related to dopamine-rich neurobiological circuits, including the amygdala and the nucleus accumbens (NAcc) and the ACC and dlPFC.

E-PA is not associated with multiple emotional disorders, but appears to be specifically associated with depression (and perhaps social anxiety disorder). The fact that a depressed person can no longer enjoy life or experience pleasure led to the theory that depression has to do with an abnormality (deficiency) in the E-PA system. Depressed people also respond less to rewards, this can also be seen as a lack of left frontal activity in the brain as a result of a reward. This suggests that this group has a deviation in the approximation system that is underlying E-PA.

There is some evidence that a high level of E-PA can act as a protective factor for developing depression, rather than a low level of E-PA being a risk factor.

Tripartite model of personality psychopathology relationships

The tripartite model was developed to explain the high comorbidity between anxiety and depression. It states that a general factor of adversity (in the form of N-NA) occurs in both depression and anxiety. However, low levels of E-PA are specific to depression, while hyper-excitement of the autonomic nervous system is specific to anxiety disorders. In addition, there is a third factor called anxiety sensitivity , which involves a high degree of fear about the physical symptoms of their anxiety (such as accelerated heartbeat, lack of breath, etc.). This would be a significant risk factor for developing an anxiety disorder.

What is the influence of neurobiological factors on emotional disorders?

Many studies show that anxiety disorders are associated with an increase in activity in the amygdala. However, it is not clear whether this is the result of the anxiety disorder or its cause.

What is the relationship between frontal brain asymmetries and emotional disorders?

Many studies found that damage to the left hemisphere often results in a depressed mood, while damage to the right hemisphere results in a euphoric mood. In particular, damage to the left PFC leads to depression more often. The closer the damage is to the front of the cortex, the more severe the depression. Often people with a diagnosis of depression have a reduced blood supply in the left PFC, with an increase in activity in the right PFC.

The judge PFC is probably primarily concerned with the coordination of vigilance, which is a clear feature of anxious moods. So, when there is extreme right asymmetry in the PFC, this is an indication of anxiety disorders. However, it is sometimes found that anxiety is related to greater activity in the left PFC. These confusing results are explained by the valence model of frontal asymmetries and anxiety . According to this model, anxiety consists of two processes: anxious apprehension and anxious arousal . Greater left PFC activity points to anxious apprehension, larger right activity to anxious arousal. People with social phobia exhibit greater right frontal activation when anticipating a social threat. 

Frontal asymmetry therefore makes people more vulnerable to both depression and anxiety disorders.

Which cortical-subcortical circuits play a role in emotional disorders?

It is important to find out which connections between cortical and subcortical structures are involved in the development of emotional disorders. The structures involved in psychopathologies related to N-NA and E-PA are the cortical structures orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC, and the subcortical structures amygdala, hippocampus and nucleus accumbens.

The circuit related to N-NA is mainly in the right hemisphere, the circuit related to E-PA in the left hemisphere. Anxiety and depression are associated with an increase in amygdala and hippocampal activity, with the PFC failing to inhibit this activity. Successful regulation of negative affective state therefore rests on a well-functioning inhibitory effect of the PFC on the amygdala.

It is therefore not the case that the brain regions associated with emotional disorders are responsible for their development. It is more likely that the cause lies in a malfunction of the connections between these areas. However, it seems that the hyperactivity of the amygdala is a characteristic of both anxiety disorders and depression. The differences between the disorders have more to do with the functioning of the PFC areas and the development of disorder-specific neural circuits.

What is the role of neurotransmitter systems regulation in emotional disorders?

The HPA axis is the most important system that ensures interactions between genetic and environmental factors that play a causal role in emotional disorders. In particular, the neurotransmitters noradrenaline (also called norepinephrine, NE), serotonin (5-HT), dopamine (DA) and gamma-aminobutyric acid (GABA) play a major role in depression and anxiety disorders. Medications for anxiety and depression therefore act on these neurotransmitters.

A decrease in NE, 5-HT and DA is seen as a major cause of depression, while an increase in it leads to euphoria. Medications that cause higher concentrations of these neurotransmitters in the brain help to combat depression.

Research on anxiety focuses in particular on GABA, the most common inhibitory neurotransmitter in the brain. Medications that are used to fight anxiety disorders make GABA receptors more sensitive, allowing GABA to bind better and therefore work better in the brain. There are also drugs that have both antidepressant and anti-anxiety effects. These do not act on GABA, but in particular on the 5-HT receptors and the amounts of NE and DA present. This also shows that there is a large overlap between the two types of disorders.

A problem with research into the relationship between neurotransmitters and emotional disorders (especially anxiety) is that this research is often done in rats. Rats do not have the same cognitive biases as humans, so models based on animal studies often lack important components.

What is the influence of cognitive factors on emotional disorders?

An important characteristic of emotional disorders is the presence of distorted, irrational beliefs and thoughts. Four general classes of 'thinking' are seen as important for emotional disorders. These are worry, negative automatic thoughts, intrusive thoughts (or obsessions) and over-general memories .

Worry

The definition of worry (worry) is a set of thoughts and images, loaded with negative affect and relatively uncontrollable. Worries represent an attempt to mentally solve problems of which the outcome is uncertain, but where there is a possibility of one or more negative outcomes. Worries are strongly related to anxiety processes.

Worrying is mainly related to generalized anxiety disorder (GAD), but also other anxiety and depressive disorders. People are particularly concerned about social evaluation and the possibility of physical injury or illness. In the case of disorders, continuous and repeated concerns are often reported. Worries are often seen as a form of cognitive avoidance of the actual problems.

One of the consequences of worrying excessively is that there is constant vigilance for threatening cues, so that the subject of the concerns remains present in the mind.

Negative automatic thoughts

These thoughts arise involuntarily in someone and are often provoked by a certain situation. For example, a person with social anxiety in a social situation might automatically think things like "I am unattractive." These thoughts are very difficult to control and constantly repeat themselves. They come up so quickly that the person is often not even aware of their occurrence. The difference with worry is that these automatic thoughts are more compressed and less consciously mediated.

Obsessions

Clinical obsessions are defined as "repeated thoughts, images, or impulses that are unacceptable and unintended". They often go together with subjectively experienced discomfort. These obsessions constantly interrupt current activity, have an internal cause and are difficult to control. They are often perceived by the person as meaningless and unacceptable.

Over-general memory

When a depressed person is asked to recall a happy, safe, interesting, painful or angry event, they tend to recall very general memories ("I walked the dog every day"). Someone without a disorder would give a much more specific example of a memory.

Over-generalized memory does not seem to occur in anxiety disorders, indicating that it may be a specific characteristic of depression rather than a general characteristic of emotional disorders.

What are the different cognitive biases?

A series of cognitive biases also plays a causal role in the development of emotional disorders. This often happens on an implicit, unconscious level. Many theories assume that mood-matching cognitive biases are an important characteristic of both the occurrence and the persistence of emotional disorders. However, it is also possible that the bias is caused by the disorder, or that the bias is caused by a third factor that also underlies the disorder.

Biases in attention

A bias towards the processing of negative information is an important characteristic of depression and also a vulnerability factor for the development of depression or anxiety. A depressed person therefore tends to absorb negative information faster, while positive information is much less noticed. This type of bias occurs in all major anxiety disorders such as PTSD, social anxiety, specific phobias, panic disorder, OCD and GAD. The effect also occurs when the information is offered subliminally. It therefore seems that the information is processed at an automatic level, making it difficult to check.

Anxiety therapy can help to eliminate the bias. A reduction in the bias in attention also leads to a reduction in worries . These results seem to indicate that attentional bias for threat is a characteristic of clinical anxiety disorders, rather than a characteristic of people who are vulnerable to these disorders. It also points out that the bias is probably not a consequence of the disorder.

The strength of the bias hardly varies across all different anxiety disorders, and it also doesn't matter if there is a clinical anxiety disorder or just a tendency to be more anxious than average. That bias is therefore probably related to a high degree of the overarching N-NA, which occurs in all anxiety disorders.

A vigilant-avoidant pattern is often found in people with anxiety disorder. This means that through the cognitive bias they first focus attention very quickly on the threatened stimulus, after which they almost immediately avoid this stimulus. Because of this avoidance no habituation (habituation) occurs, so that the fear persists.

In people with depression, more attention is given to negative stimuli that are offered for a longer period of time. Both people who are currently depressed and people who have been depressed in the past (the latter already being a risk factor for depression in the future) showed a focus bias for sad faces. This indicates that attentional bias is not a characteristic of a current depression, but rather an indication of a persistent characteristic of depression. However, it is also possible that the bias is a consequence of a period of severe depression.

What are the biases in judgment and interpretation?

Most theories agree that biased judgments and interpretations are common in all emotional disorders. Both anxious and depressed people estimate negative events as more likely for the future. Conversely, estimating positive events is less likely to be seen as a specific characteristic of depression. The latter corresponds to the idea that lower scores for E-PA do occur in depression, but not in anxiety disorders.

Both anxious and depressed people tend to interpret ambiguous situations in a negative way.

What are the biases in memory?

Depressed people remember more negative information, especially when this information is encoded in a way that is related to the self. There is some evidence that this explicit memory bias is a characteristic of vulnerability to depression; the strength of the bias is a good predictor of a subsequent depressive episode. The bias also still occurs in people who have recovered from depression, which seems to mean that the bias is a factor of predisposition to depression rather than current depression. When information needs to be retrieved, there is often talk of the over-generalized memory effect, which was discussed earlier.

Although it seems logical that information is better remembered when it receives more attention, as in the case of anxiety for negative information, no evidence has been found for a memory bias in anxiety disorders. It is possible that this is because fear is associated with the tendency to avoid extensive processing of threatening information.

Is a cognitive bias a risk factor for emotional disorders?

An important question is whether bias in cognitive processing a significant risk factor for the development of anxiety disorders and / or depression is. Both are strongly associated with these biases, although the specific type of bias (attention vs. memory) may differ. However, it is not clear whether this is a cause or a consequence of the disorder.

One way to find out is cognitive bias modification (CBM) . This causes a bias that is similar to the bias found in anxious people. If this bias is a cause of the disorder, the bias caused should reinforce emotional vulnerability. Conversely, reducing this bias should lower emotional vulnerability. In this way, various studies have found that attentional and interpretation bias play a causal role in the development of anxiety.

It was also found with the same method that cognitive bias can have a causal effect on the interpretation of new and ambiguous information. A bias can therefore lead to an increased anxious reactivity as a result of a stressful experience.

With CBM it was also found that attentional bias ensures that more stress is experienced with a stressful task. The findings therefore suggest that cognitive biases do indeed play a causal role in mediating fear responses. However, more research is needed to find out whether biases can also serve as a cause for depression.

What are cognitive theories of emotional disorders?

Cognitive models assume that explicit deviations in thought processes are important characteristics of psychopathology. For example, irrational beliefs , especially when related to the self-concept, are an important characteristic of emotional disorders. Because these beliefs can easily be put into words, therapies such as cognitive behavioral therapy have been  developed. This is one of the most effective therapies for anxiety and depression. A bias is much harder to treat in therapy, but CBM might be the solution.

Beck's notion of ​​dysfunctional schemas

A diagram describes how we organize our beliefs and memory structures. The original definition is as follows: "functional structures of relatively long-term representations of previous knowledge and experience." Schemas work as cognitive 'cut-off paths', which means that we do not always have to process every detail of a situation again. If a part of the schema is activated, the entire schema is activated fairly automatically, so that the schema automatically fills in information that was not provided with the original input.

Schemas about social relationships and personal goals can be activated in the same way, making it easy for biases to be automatically recalled. The hypothesis is therefore that emotional disorders can develop if some important life event takes place that results in the activation of a dysfunctional schema. In the case of depression, this causes automatic (negative) thoughts about the self, the world and the future. In the case of fear, it causes automatic thoughts about the possibility of future injury and the inability to deal with it.

Cognitive abilities are focused on information that corresponds to the schema, so in depression this leads to selective processing of negative information, while in the case of anxiety mainly threatening information will be processed.

A problem with this theory is that the differences between depression and anxiety in terms of cognitive bias are much larger than would be expected based on the schema theory.

William's cognitive model of anxiety and depression

Williams made a distinction between integration and elaboration . Integration refers to cognitive processes that result in making a certain representation stronger. Elaboration, on the other hand, refers to the process that starts later with information processing, whereby a certain representation is linked to many other representations. The hypothesis is that anxiety mainly has an effect on the passive, automatic aspect of coding and retrieval (integration), while depression mainly has an effect on the more active, difficult aspects of encoding and retrieval (elaboration). This is confirmed by other studies that found that anxiety is related to attentional bias towards information corresponding to the anxiety, while these items are not better remembered. Depression, on the other hand, is characterized by being able to better retrieve negative information, while an attentional bias is not found.

The idea is that the valence of the stimulus determines the type of processing that must take place, so that attention can be directed towards the object or rather away from it. This is called the affective decision mechanism (ADM) . An anxious mood can influence the ADM, while an anxious personality has a more direct and stubborn influence on how to direct attention. Later studies show that this model exaggerates the role of personality traits in the allocation of attention. These characteristics only determine the threshold above which people become vigilant, but every threatening stimulus attracts attention regardless of personality traits.

Activation of a threatening stimulus can be improved by an emotional label . This label can arise from biological factors or from previous experience and ensures that the stimulus in question

What is the influence of genetic factors on emotional disorders?

There are four main approaches that address how gene variation is associated with the expression of emotional disorders.

1. The first approach assumes that there is a fairly direct, linear relationship between a specific genotype and a certain disorder.
2. The second approach connects genes with intermediate endophenotypes (for example temperament, neurophysiological systems, etc.). These phenotypes are said to have a more direct relationship with genes than the disorder itself.
3. The third approach assumes that the environmental factors (abuse, abuse) are the main cause of emotional disorders, but that genes influence susceptibility. So there is a dynamic interaction between genes and environment.
4. The fourth approach proposes an integration of the endophenotype approach and the gene-environment interaction approach. By looking at the effects of gene-environment interactions on specific neural circuits (endophenotype), it becomes clear how things work.

This fourth approach incorporates so many different factors that the alleles that a person carries have an increasingly smaller influence, as the behavior under investigation becomes more complex. The effects of the alleles are strong in specific neural systems and even stronger in individual cells.

Certain genetic polymorphisms can have a significant effect on the impact of life events on the development of emotional disorders. For example, carriers of the S-allele of the 5-HTT gene are more likely to become depressed if they experience more than four stressful life events.

Carriers of the S allele also have less gray matter in the ACC and the amygdala, and the connections between these two areas were also less present. As a result, the ACC can no longer perform its inhibitory function properly and there is therefore more activity in the amygdala. This seems to be mainly about an increased amygdala activity at rest, resulting in a higher baseline for arousal, increased vigilance, improved memory for affective material, reduced extinction of anxiety-related memories, etc. The difference in activity seems to be caused further due to reduced activity with neutral stimuli, instead of increased activity with negative stimuli.