What are depression and mood disorders? - Chapter 7

What are depression and mood disorders?

Everyone experiences periods of sadness from time to time. This can be the result of various reasons, especially losses and failures, but most of us are able to shake it off after a short period of time. However, for some getting rid of these depressing feelings is much harder, and these feelings will affect other domains of their live, making depression a mood disorder affecting emotional, motivational, behavioral, physical, and cognitive domains. Mania is the emotion opposite of depression, and it is bound by boundless, frenzied energy and feelings of euphoria.

Depression affects the emotional domain as depressed individuals often report negative emotional experiences such as hopelessness and sadness. Those suffering from depression show several motivational deficits, like the lack of interests in activities they used to enjoy, not taking initiative anymore and reporting that they simply don't care anymore. Behavioral symptoms seen in depression are sleeping for long periods of time, no interest in leaving the house and reporting lack of energy. Depression can even be seen in the posture and movements of people, as are other physical symptoms such as a wide variety of sleeping problems, headaches, indigestion, constipation and several others. The most disabling feature of depression are its cognitive symptoms. The negative thoughts that arise from depression are negative views of themselves, the world around them and their own future. These pessimistic thoughts can give rise to new problems, such as impaired thinking, concentrating and decision-making, possibly leading to feelings of worthlessness, shame and guilt. These thoughts can lead to suicidal thoughts, because they might think the world is better off without them. The two main types of depression are major depression and bipolar disorder.

How is Major Depression diagnosed and what is its prevalence?

One of the two main types of depression is major depression. It is noted by relatively long periods of clinical depression causing significant suffering in the patient, and also impairing their social and/or occupational functioning. Another term used for major depression is unipolar depression. Due to changes in the DSM-5, major depression is now diagnosed only when a single major depressive episode has occurred, and the symptoms must have caused clinically significant impairment or distress in social, occupational, or other types of functioning. A major depressive episode consists of the presence of five (or more) depressive symptoms during a period of two weeks. Some of these symptoms include a depressed mood most of the time, significant weight changes unrelated to dieting, lack of energy, feelings of worthlessness or guilt,

Mood disturbances can also occur less intense but still impairing someone's life significantly, like when one is diagnosed with dysthymic disorder, where the person experiences a depressed mood on more days than not, for at least two years. These individuals often experience many symptoms of major depression, but these tend to be less severe.

Some disorders occur comorbid with depression: premenstrual dysphoric disorder, which is a condition suffered from by some women where severe depression is experienced some days prior to the start of their menstrual cycle, seasonal affective disorder (SAD), suffered by regularly feelings of depression in winter where a remission is seen the next spring or summer, and chronic fatigue syndrome (CFS), which is a disorder distinguished by depression and fluctuations of mood together with some physical symptoms such as muscle pain, chest pain, headaches, noise and light sensitivity , and extreme fatigue. Lastly, because anxiety is very comorbid with depression, many sufferers from depression are diagnosed as suffering from mixed anxiety/depressive disorder.

Depression occurs very often and is known to have a steady rise of incidence over the last 90 years. The prevalence rates differ however across different cultures, which may be due to many reasons:

• Different measurement methods used by different researchers
• The social stigma attached to depression especially in non-western countries
• The challenge in the measurement of the abstract concept of depression
• The tendency of the west to express psychological symptoms in physical symptoms (somatisation)

What is the aetiology of depression and mood disorders?

Genetics are thought to play an important role in the development of major depression. First-degree relatives of people suffering from major depression are seen to experience depression symptoms two to three times more often. Twin studies also suggest that depression is more likely to be due to shared genes instead of shared environment, with a heritability estimated to be between 30% to 40%. However, specific genes responsible for depression have yet to be found. Abnormalities in the levels of neurotransmitters have been shown to be associated with mood disorders. For instance, low levels of serotonin, norepinephrine, and dopamine are often linked to major depression. Medications prescribed in the 1950's for high blood pressure sometimes led to depression, this was found to be due to the lowering of serotonin levels in the brain by these medications. This led to the development of tricyclic drugs (TCA) and monoamine oxidase inhibitors (MAOI), both of which block the reuptake of both serotonin and norepinephrine. Tricyclic drugs work by blocking the reuptake (in the presynaptic neuron) of serotonin and norepinephrine, therefore leading to higher quantities of these neurotransmitters active in the synaptic cleft. A newer alternative are the selective serotonin reuptake inhibitors (SSRIs), which targets only the serotonin levels in the brain. The thought that specific neurotransmitter levels are responsible for depression is quite simplistic, and many theories suggest quite complex mechanisms. A recent theory is that depression is due to an imbalance between multiple neurotransmitters.

The prefrontal cortex is known to be important for the representations of goals and the means to achieve them. Lower activity in this area is seen in depressed people, and this may lead to a lack of the ability to anticipate incentives, which is commonly seen in those suffering from depression. Activity in the anterior cingulate cortex (ACC) is seen when behavior requires effortful emotional regulation in order to achieve an outcome. Lower activity in this region may represent the lack of will to change, also seen in those who are depressed. One of the functions of the hippocampus is to learn the context of affective reactions, and a lack in this function might lead to dissociating negative affect from their contexts, making people feel sad independently from the context. The hippocampus also plays an important role in the adrenocorticotropic hormone secretion, which will be mentioned in more detail later. Finally, the amygdala is crucial for direction attention to emotionally salient stimuli, for instance when your attention is needed for a potential threat. Increased activity in the amygdala, which is seen in depression, may lead to the person prioritizing threatening information and associating it with negative thoughts.

Cortisol is an adrenocortical hormone and is known to be secreted in times of stress. The before mentioned hippocampus is important in the adrenocorticotropic hormone secretion, and a dysfunction in the hippocampus might therefore lead to high levels of cortisol. Another big influence in the regulation of cortisol is the hypothalamic-pituitary-adrenocortical (HPA) network, which is our biological system managing and reacting to stress and triggering the secretion of cortisol when stress is experienced. A lack of inhibitory control over this network is linked to depression, and about 80% of hospitalized sufferers from depression show a poor regulation of this HPA network. An increase of cortisol might enlarge the adrenal glands, which results in a lowered level of serotonin neurotransmitters.

It is clear that depression has an inherited component, and that levels of brain neurotransmitters play a crucial role in the maintenance of depression. Specific brain areas are also known to be important in the aetiology of depression, and neuroendocrine factors are seen to be associated with it. However, not everything can be explained with biological factors. Biological factors may be the direct cause of symptoms, but psychological processes could be the trigger to those biological factors.

The most used psychodynamic view of depression is the one of Freud and Abraham, which states that depression is a person's response to loss, and especially the loss of a loved one. The first stage is introjection, which states that a person in the introjection stage regresses to the oral stage of their development, which allows them to integrate the identity of the person they have lost. Regression to the oral stage also allows the person to direct the feelings they hold of the loved one towards themselves, which can be feelings such as anger or guilt. The individual can start to experience self-hatred, which quickly develops into low self-esteem, resulting in feelings of hopelessness and depression. A problem with this view is that not all depressed people have lost a loved one, to which Freud coined the concept symbolic loss, in which other types of losses are viewed by the person as equally important as losing a loved one. This can lead to regression to the oral stage and trigger potential memories of bad parental support during their youth. Now we view poor parenting as a more likely cause of depression, and parental loss is not a prerequisite anymore. There is a link between depression and having experienced affectionless control, which is a type of parenting where there is a lack of warmth combined with high levels of overprotection.

Depression is highly characterized by a decrease of motivational and initiative-taking behaviour, together with a lack of positive feelings about their future. Based on these characteristics of depression, some theorists suggest that depression results from a lack of reinforcement of positive and adaptive behaviors, leading to a decrease of the existing behaviors, which is illustrated by the inactive and withdrawn behavior seen in depression.

Depressed individuals tend to be less skilled at communicating with others and tend to transfer their negative mood to others, resulting in the reinforcement of depression. This social reinforcement is because people will respond more negatively towards depressed individuals, because of the poor social skills depressed people often show. This also led to interpersonal theories, which argue that the maintenance of depression is because of the reassurance that depressed individuals keep on seeking that is subsequently not given by family and friends, because they are approached in such a negative way by the sufferer. This reassurance is often given, but because depression makes one doubt the reassurance, they keep on trying to confirm the reassurance, which is why family and friends might end up rejecting the reassurance at some point.

Beck's cognitive theory about depression is very influential, and it states that depression might be caused by biases in the way we think and process information. Beck claims that depressed people have developed many negative schemata, which are beliefs that tends to make someone view the world and themselves more negatively. These negative views have a big influence on the selection, encoding, categorization and evaluation of information that we encounter, and this is often long lasting. Beck also states that this negative approach of interpreting everything around us develops because of negative childhood experiences and can start again in adulthood due to some stressful experience. The negative triad is a theory stating that depressed people hold negative views of themselves, their future and the world. These negative beliefs result in self-fulfilling prophecies, making the people interpret events negatively because they believe they are negative. There is evidence that these cognitive biases indeed exist as:

• Attentional biases to negative stimuli, especially if they are depression related
• Memory biases, where depressed individuals recall more negative words than positive, again this applies mostly to depression-relevant material
• Interpretational biases, making them interpret ambiguous events more negatively

Research suggests two types of negative schema. The first one is focused on dependency and the second one on criticism. Depression triggered by losses is characteristic of dependency self-schemas, and depression triggered by failure is seen with criticism self-schemas. Pessimistic thinking (the thinking that nothing can improve in situations) is often thought of to be characteristic of depressed individuals, but research has shown that people suffering from depression are actually much more accurate at evaluating control over situations and evaluating the impression they made on others.

Seligman proposes that negative life experiences give rise to a 'cognitive set' which makes the person learn to become helpless, depressed and lethargic, this is known as the learned helplessness theory. The level of uncontrollability of these negative life events is important, and the more uncontrollable a situation, the more pessimistic beliefs the person will adopt. Battered woman syndrome is an example where learned helplessness of an abused woman's situation results in their belief that they are powerless, making them express symptoms of depression. The original learned helplessness theory does not explain why experience with negative events may actually help performance, and that passivity in battered woman syndrome may actually be a learned response to avoid abuse. Because of these difficulties,

Attribution theories state that people are more likely to become depressed because of certain attributional styles that consist of negative thinking, like attributing a negative event to factors that aren't easily changed, therefore thinking that they are powerless. There are multiple ways in which life events can be attributed:

• One can interpret an event as internal (personal cause) or external (environmental cause)
• An event can be seen as stable (lasting over time) or unstable (short lasting) factors
• Something can be global (relatable to many domains of life) or specific (only to a specific part of life)

Depressed people tend to think of negative life events as internal, stable and global, and think of positive events as external, unstable and specific. The repeated use of negative attributional styles will lead to more and more perceived helplessness over time.

Attributing negative events for global and stable reasons combined with negative life events is suggested to increase the level of vulnerability to symptoms such as retarded initiation of voluntary responses, lack of energy, apathy and psychomotor retardation, which are all symptoms of hopelessness. Hopelessness theory states that individuals show the expectation that positive outcomes won't occur, that negative outcomes will occur and that no change can be made about this. Hopelessness theory is quite similar to the previously mentioned attributional and helplessness theories, but hopelessness theory suggests that factors like low self-esteem also play a role. Hopelessness can therefore be predicted by a negative attributional style, negative life events and low self-esteem. Hopelessness can be used to predict suicidal tendencies and especially completed suicide. Some limitations to the hopelessness theory are:

• Many studies supporting it are carried out on healthy or mildly depressed individuals
• A majority of the studies conducted on the model cannot generate evidence for a causal role of hopelessness thoughts on the development of depression, because the studies are correlational in nature
• The model only explains symptoms related to hopelessness, and other DSM-5 required symptoms of depression are not explained
• Some evidence shows that the prevalence of negative attributional styles can decrease after one recover from depression

Rumination is an individual's tendency to repeatedly mull over the experience of depression and to find out its possible causes. Indulging too much in these ruminating activities can cause and predict depressive episodes and relapses. Rumination seems to be caused by meta-cognitive beliefs that it is necessary in order to resolve one's depression.

What is Bipolar Disorder?

A person suffering from bipolar disorder has extreme mood swings. On one side of the spectrum, one experiences a state of depression, and on the other side there's the manic state, which is characterized by forced speech, extreme energy, short attention span, excessive talking and shifting from topic to topic. Someone in a manic state can become angry when 'confronted' with their state, and irritability is quite common. A manic state can last for days or weeks, and the onset can be quite quick.

What is the diagnosis and prevalence of Bipolar Disorder?

The DSM-5 differentiates between bipolar disorder I and bipolar disorder II. The first, bipolar disorder I, is characterized by full alternating episodes of major depression and mania. Bipolar disorder II is slightly different, since it does contain major depression episodes, but then followed by hypomania episodes. A hypomania episode is a milder version of a mania episode, and an episode of hypomania does not have to be impairing the 'sufferer'. Prolonged episodes of hypomania can however lead to full blown mania. A milder form of bipolar disorder is cyclothymic disorder, where the individual suffers from mood swings for at least two years, and the mood swings consist of mild depression to hypomania symptoms like euphoria, happiness and excitement.

What is the aetiology of Bipolar Disorder?

Bipolar disorder has an inherited component, since it has been estimated that about 7% of first-degree relatives of those suffering from bipolar disorder, also have bipolar disorder themselves. Concordance studies have shown that on average, sharing all genes (as seen in monozygotic twins) more than doubles a person's risk of developing bipolar disorder compared to dizygotic twins.

The neurotransmitters norepinephrine and dopamine also play an important role in bipolar disorder, just like in depression. The role of serotonin however seems to be not that important in bipolar disorder. A commonly used medical treatment for bipolar disorder is the combination of the antipsychotic olanzapine and the antidepressant SSRI fluoxetine or Prozac.

The depression episodes in bipolar disorder seem to be triggered by many of the same triggers that are also seen in major depression, like the loss of a loved one or failures in life. The triggers for a manic episode vary, and often seem to be due to an increased reaction to rewarding situations, like a positive life event. Other triggers seem to be antidepressants, unusual circadian rhythms or disrupted sleep patterns, stressful life events, the exposure to intense expressions of emotions by family or caregivers, and seasonality, since manic episodes tend to increase in spring or summer.

How can Depression and Mood Disorders be treated?

Treating depression and mood disorders can be done with biological-based treatments, like electroconvulsive therapy (ECT), an old treatment where an electric current volt through the patients, or with the use of psychological therapies. Emphasizing the method of treatment according to the severity of the symptoms an individual is experiencing is often preferred. These stepped-care models are implemented to make sure that a treatment is effective and not too invasive when it's not necessary. An example of a stepped-care model could be:

• Not simply responding with medication right away, and assessing the individual properly
• Use  medication only when there is more evidence that it will be effective, in the case of depression this would count for moderate to severe depression
• Mild depression is best treated with short behavioral and cognitive interventions

What are biological treatments?

There are currently three main types of medications for the treatment of depression:

1. Tricyclic Antidepressants (TCAs)
2. Monoamine Oxidase Inhibitors (MAOIs)
3. Selective Serotonin Reuptake Inhibitors (SSRIs)

Tricyclic drugs and MAOIs elevates levels of both serotonin and norepinephrine, while SSRIs only work specifically on serotonin levels. Tricyclic drugs have been seen to work for 60-65% of individuals taking it, and this is 50% of those taking MAOIs. Tricyclic drugs and MAOIs are known to be quite effective, but the downside are that they come with many possible side effects. The newer SSRIs are known to be effective in 55-60% of the cases but come with much little side effects and are harder to overdose on. A downside to SSRIs is that they seem to take longer to have an effect, and they might increase the risk of suicide. Relapse is common when individuals quit drug therapy, and it is therefore advised to combine drug therapy with psychological therapies for the maximum result and the smallest risk of relapse.

Bipolar disorder is treated differently, with the traditional treatment being lithium carbonate. There are many theories as to the mechanisms of lithium on the symptoms of bipolar disorders, but a clear reason is unknown. The disadvantages of lithium treatment are that ending a treatment often increases the chance of a relapse, and since lithium is a toxic substance, the often-prescribed dosage tends to be close to the toxic level. An overdose can constitute delirium, convulsions, and occasionally death.

ECT consists of the passing of an electric current through the head of a patient for about half a second, which often results in a temporary relief from symptoms of severe depression. A serious side effect of electroconvulsive therapy is the possibility of both anterograde and retrograde amnesia which can last up to 7 months. Besides the possible serious amnesia, many people also tend to not be jolly about the fact that a strong electric current is being passed through their brains. The relief of depression often doesn't last long, since a relapse of depression has been seen after the small duration of only four weeks of relief. Some even state that any kind of direct trauma to the brain would give relief of depression for a considerable amount. Despite the criticisms, electroconvulsive therapy is still an effective treatment in some cases,

What are psychological treatments?

The psychodynamic view of depression; that depression develops out of anger projected inwards instead of toward a loss, is the basis of the psychoanalysis, where the goal is to achieve insight into an individual's anger and release the anger towards themselves. Finding the long-term source of one's depression is done with various techniques to explore conflicts and investigate problematic relationships with attachment figures (e.g., parents). An example is dream interpretation, which helps the person recall early experiences of (symbolic) loss, which may be a source of conflict. The efficacy of psychodynamic therapy is not clear, as it is hard to study because therapists often have a different view of psychodynamic principles. One study however showed that psychoanalysis may be as effective as CBT, but another study found no long-term efficacy.

Social skills therapy focuses on supporting the depressed individual with acquiring appropriate social skills and attempting to reduce the amount of maladaptive social skills, and assuming that it will help alleviate symptoms of depression. Social skills training has shown to improve social skills and decrease the amount of depression symptoms.

The loss or lack of pleasant rewards as the reason for depression is the main point in behavioral activation therapy. It focuses on increasing the access to pleasant rewards and events in a depressed individual's life, therefore taking the focus away from negative events. Behavioral activation therapy consists of monitoring daily events that are pleasant or unpleasant and behavioral interventions. Social skills training and time management are also taught in behavioral activation therapy. It has been shown that cognitive change is just as likely to occur from behavioral activation therapy as from cognitive interventions.

According to Beck's cognitive theory of depression, depression is maintained by dysfunctional negative beliefs, which turns into a negative schema which the individual uses to view itself, the world and the future. The most widely used therapies for treating depression are developed from this theory of Beck and are often named cognitive therapy or cognitive retraining. Cognitive retraining works in three steps, which are:

1. Assist the individual in identifying negative beliefs and thoughts
2. Challenge these beliefs and thoughts as dysfunctional, illogical or irrational
3. Help the person replace these negative thoughts with more adaptive and rational ones

Overgeneralization is often seen in depressed individuals, and these irrational patterns of thinking that one specific failure relates to one's ability in other domains are identified by the cognitive therapists and are challenged to be irrational. Asking the client to monitor negative automatic thoughts helps with the identifying them and possibly replacing them with more rational thoughts. Another method used to correct the individuals negative thinking is reattribution training, which is a technique which attempts to get individuals to relabel their difficulties in a more optimistic and constructive way, rather than in a negative way.

Cognitive therapy has been shown to be very effective in treating the symptoms of depression, and at least as effective as drug therapy. However, the chance of a relapse is smaller with cognitive therapy, compared to drug therapy. The combination of both drug therapy and cognitive therapy still appears to be the superior treatment of depression.

What is meant by nonsuicidal self-injury (NSSI)?

Direct and deliberate bodily harm without any suicidal intent is deliberate self-harm. It is now covered under the new DSM-5 category non-suicidal self-injury which describes intentional self-inflicted injury without suicidal intent. Deliberate self-harm is mostly seen in adolescents, and the motive is often when they are alone and experiencing negative feelings. It is often done as a means of soothing oneself or a way to seek help. Vulnerable groups include depressed adolescents, individuals with interpersonal crises (e.g., those suffering from substance abuse, eating disorders, psychosis) and those who have a history of previous self-harming. One of the few effective forms of preventing deliberate self-harm is with cognitive behavioral therapy and problem-solving therapy,

How can suicide be predicted?

The best predictor of suicide seems to be if someone matches the concept of hopelessness, which was described earlier. Women appear to be three times more likely than men to attempt suicide, but men 'complete' suicide four times more often than women. This is because men more often take a more lethal method (e.g., jumping or weapons) than women, which more often choose methods like attempting suicide with pills or cutting themselves. The prevalence rate of suicide in youth has risen a lot, for reasons unknown, although the following factors may be relevant:

• Nowadays, teenagers are exposed to more life stressors earlier, and often lack the coping mechanisms that adults have
• Suicide is also a sociological phenomenon, and media attention to suicide are known to increase suicide rates for teenagers
• The strong relationship between suicide, depression and substance abuse (and the fact that teenagers are more exposed to drugs and alcohol now) may influence the increasing suicide and self-harm rates

What are risk factors for suicide?

As mentioned before, the best predictor of self-harm or suicide, is a history of earlier self harm or attempted suicide. Yet these people only account for 20 to 30%, so other risk factor have been identified so we can more effectively prevent suicide. Risk factors are:

• A diagnosis of depression, borderline, panic disorder, schizophrenia, alcoholism, and substance abuse
• Hopelessness and low self-esteem
• Physical disability and poor physical health
• Low socio-economic status

Stress seems to be a very common predictor seen in suicide, and negative life events often precede suicide. Different types of life events are seen across different age groups. For teenagers and adolescents, relationship issues and interpersonal conflicts are often the trigger. Financial issues are most often the reason of suicide in middle age, and disability and (lack of) physical health for those in later life.

A genetic component exists in suicidal behaviour, as the inherited component may be up to 48%, according to twin and adoption studies. Low levels of serotonin metabolites in the brain have been associated with suicidal behaviour, and since this may partially be controlled by inherited components, which could explain the heritability of suicidal tendencies.

How is suicide identified and prevented?

Surveys suggest that 47% of those who attempted suicide, actually did not want to die, but that their attempt was a cry for help. Intercepting people who do not actually wish to die but find no other way of conveying their cry for help, is very important in the prevention of suicide. Approaches like educational programs or hotlines help some, but often only specific groups (young women in this case). Other approaches to suicide prevention are developed, and the most common ones are to train general practitioners to identify and treat suicidal intentions, improving the access to care for those at risk of suicide, and restricting the access to suicide. The latter might be hard in many cases but restricting locations for hanging in at-risk living facilities might be the way to go.