Introduction to Depression

Depression has been historically reported as a disordered behaviour since the time of the ancient Egyptians who dubbed it melancholia. Depression as a mood disorder does not refer to a normal state of sadness that is an appropriate for the circumstances, though someone may refer to themselves as being depressed in such a state. Depression is further categorised according to more specific symptomology when diagnosed by a mental health professional with the most common being major depressive disorder, characterised by persistent low mood and loss of interest in pleasurable activities. Seasonal affective disorder is categorised as a sometimes occurring characteristic of major depressive disorder in the current revision of the diagnostic and statistical manual of mental disorders (DSM-5). Another common type of depressive diagnosis is persistent depressive disorder, or dysthymia which is a chronic state of low mood lasting more than two years.[1] Depression is more than twice as common in women than in men.[2]

Aaron Beck, who developed the cognitive theory of depression described the disorder as a negative triad of outlooks about the world, the self and the future. Beck described what he termed cognitive distortions in the way depressed people process stimulus. These cognitive distortions cause the affected individual to process stimulus as more negatively than what would be considered reasonable by a non-affected individual. Negative stimulus are perceived as more negative than they objectively are, and neutral and sometimes even positive stimulus may be interpreted as negative. A kind of downregulation of the interpretation of events can occur in which negative events are magnified and positive events are minimised. External events may be personalised inappropriately when it is consistent with the negative bias. Over-generalisation may occur whereby a single incident of a negative outcome is used to justify the assertion that all such attempts will lead to a negative outcome. Dichotomous thinking can occur when a person arbitrarily categorises experiences as either one extreme or another. One of the major assertions of cognitive psychology is that events are interpreted through schema that represent the thoughts, emotions, behaviours and motivations that make up a persons perspective. When that schema is negatively affected by depression it results in everything processed more negatively through the lens that is the schema of the individual.[3]

Causes of Depression

Heretability

Depression is believed to have a significant genetic component. Estimates of the heritability of major depression are typically in the range of 30 to 40%.[1] Research has found that close relatives of people with an affective disorder are more than ten times more likely to suffer from one themselves. Other research has found significantly increased likihood of monozygotic twins both experiencing a disorder compared with dizygotic twins. [2]

Much of the early research into a genetic basis for depression has not been replicated. Studies have identified some genes likely to be involved however. The RORA gene which is involved in regulation of circadian rhythms has been identified as having the strongest role in major depressive disorder. A second gene, GRM8 which is involved in the production of metabotrobic glutamate receptors also has evidence for its involvement.[2]

Environmental factors

Depression is a stress related disorder, which means a substantial number of possible environmental causes.[1] A far from exhaustive list of common potential environmental factors includes:

• Serious trauma
• Negative childhood and family experiences
• Drug use
• Drug withdrawal
• Poverty
• Unpleasant working environment

Psychological factors

How people respond to stress has a significant impact on the development of depression. Stress responses may be adaptive if they contribute to the overall improvement of a persons circumstance in response to a stressor, or maladaptive if they contribute to a worsening of it. Learned helplessness is a maladaptive stress response which causes an overall pessimistic response to circumstances. Because affected people do not think they can influence their circumstances, they often do not try to, which can in turn lead to further stressors and an increasingly pessimistic outlook.[4]

A common maladaptive response to stress and depression is illicit drug use. It is quite understandable that a depressed person would turn to drugs that provide immediate relief from the symptoms of depression, particularly when licit drug treatments of depression tend to provide results over longer periods of time and may be accompanied by undesirable side effects. The immediacy of relief may belie a detrimental impact of drug use on the development of the disorder. Common illicit drugs used to self-medicate depression, such as opioids, amphetamines, alcohol and cocaine lead to the rapid development of tolerance. The compensatory mechanisms of tolerance lead to withdrawal syndromes and a diminished capacity to experience relief from the substance after chronic use. These substances are also addictive and can lead to compulsive craving for the substance. The effects of tolerance, withdrawal and addiction present new stressors contributing to the development of depression.[5]

Symptoms & Types/Variations of Depression

• Persistent low mood
• Anhedonia (loss of interest in pleasurable activities)
• Weight loss or lack of appetite
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Fatigue or loss of energy
• Feelings of worthlessness and/or hopelessness
• Diminished ability to think or concentrate or indecisiveness
• Recurrent thoughts of death, suicide ideation or suicide attempt.[6]

Seasonal affective disorder

Seasonal affective disorder presents with the same types of symptoms as other depressive disorders, but the pattern of presentation of symptoms is linked to seasonal changes. Specifically it is linked to the level of sunlight. It typically occurs in winter months and in non-equatorial regions, but can also occur during summer months for some individuals.

Treatments of Depression

Natural

• Psychotherapy
• St Johns Wort[7]
• Physical exercise[8]
• Phototherapy (Light box therapy) (Seasonal affective disorder only)

Medical

• Selective serotonin reuptake inhibitors (SSRI) such as sertraline and fluoxetine
• Serotonin norepinephrine reuptake inhibitors such as venlafaxine and duloxetine
• Tryclyclic antidepressants such as amitriptyline
• Reversibible inhibitors of monoamine oxidase A (RIMA) such as moclobemide
• Monoamine oxidase A inhibitors (MAOI) such as tranylcypromine
• Norepinephine dopamine reuptake inhibitors such as bupropion
• Tetracylcic antidepressants such as mirtazapine
• Ketamine
• Atypical (second generation) antipsychotics such as quetiapine or olanzapine are sometimes used as an adjunct for depression but are not approved or shown to be effective on their own
• Symbyax (a combination drug with unique synergy comprised of fluoxetine and olanzapine)
• Amphetamines (Used prior to the discovery of newer antidepressants. Occasionally still prescribed off-label for depression that does not respond to other treatments)
• Electroconvulsive therapy (ECT)
• Transcranial magnetic stimulation
• Deep brain stimulation

Antidepressant efficacy controversy

Controversy over the efficacy of antidepressants has arisen in recent years. Media reports of meta-analysis were published stating that these antidepressants were no more effective than placebo. In at least one case the authors of the meta-analysis reported felt the media coverage misrepresented the findings. The meta-analysis found that antidepressants did in fact demonstrate efficacy over placebo in all but the mildest cases of depression as measured on the scale most commonly employed to demonstrate efficacy. The issue largely revolves around whether the efficacy above placebo reached the threshold for clinical significance. In order to reach the level of clinical significance an antidepressant needs to score a specific number of points more on the scale than placebo, and this was achieved in the most serious cases of depression, but fell short of the clinical significance threshold in less serious cases. This is not the same as saying antidepressants are no more effective than placebo however. The meta-analysis showed that antidepressants were more effective than placebo in most of the range of severity, reaching the level of clinical significance in serious cases.[9]

This graph summarises the results of the meta-analysis.

Neurobiological basis of Depression

It has been hypothesises that a region of the frontal cortex, called the subgenual ACC is a focal point in the development of depression. Deep brain stimulation of this area is an effective treatment for depressive symptoms. Brain imaging studies have found this area to be hyperactive in depressed individuals. Decreased activity in this area achieved through deep brain stimulation may affect connected structures involved in depression such as the prefrontal cortex, amygdala, hippocampus and nucleus accumbens.[2]

The monoamine hypothesis

The efficacy of MOAI's in the treatment of depression led to experiments with monoamine levels in an attempt to understand the neurobiological basis of the disorder. Studies found that low tryptophan (the serotonin precursor) levels led to increased depressive symptomology in depressed individuals, but had no effect on healthy individuals. The role of tryptophan is suggestive of serotonin being an important factor in depression. It is believed that a chain of events caused by serononinergic antidepressants administered chronically is responsible for their efficacy in treating depression, but a full understanding of exactly how that works has not yet been achieved.[2]

Neurogenesis

Neurogenesis in the hippocampus is an important mechanism in learning. Animal studies have found decreased neurogenesis in this area after stressful experiences that produce symptoms of depression. Administration of many types of treatments for depression increases neurogenesis in these models. At this time it is not possible to measure neurogenesis in the human brain so research into this area is necessarily limited.[2]

Circadian rhythms

One of the main symptoms of depression is sleep disruption. Sleep deprivation has been shown to improve the symptoms of depression. In particular, antidepressants commonly suppress REM sleep and selective deprivation of REM sleep also causes improved mood in depressed individuals. Slow wave sleep deprivation and total sleep deprivation are also positively correlated with improved mood in depressed individuals, however that needs to be understood in that these techniques also suppress REM sleep because REM sleep follows slow wave sleep in healthy (non-narcoleptic or similar disorder) individuals so it is not clear if the efficacy of those techniques is a consequence of REM sleep deprivation.[2]

Seasonal affective disorder is related to circadian rhythms, with affected individuals having a genetic abnormality related to the gene responsible for the production of melanopsin. Melanopsin is a retinal photopigment that detects light and is involved in the synchronisation of circadian rhythms.[2]

The Dangers & Health Risks of Depression

Depression is characterised by disrupted activity of the hypothalamus-pituitary-adrenal axis of the endocrine system which regulates hormones involved in the stress response. High cortisol levels are a common feature. This disruption can lead to compromised immune function and sleep problems.[4]

Depression can alter the perception of pain. Clinically depressed people regularly report higher levels of pain on pain scales, for sources of pain similar to those who are not depressed. Antidepressants are an accepted treatment option for chronic pain, as is psychotherapy with both options have demonstrated improvement on pain scales.[10]

Suicide is a significant risk for sufferers of depression. Around 15% of sufferers attempt suicide.[2]

Morbidity Rate

Depression is linked to a four to five times increased rate of premature death by both suicide and natural causes[11]

More Depression Sections

Recent threads about depression in the forums

References

1. ^ a b c dBurton, L., Westen, D., & Kowalski, R. (2015). Psychology: Australian and New Zealand edition (4th ed.). Milton, Australia: John Wiley & Sons.
2. ^ a b c d e f g h iCarlson, N. R. (2017). Physiology of behavior (12th ed.). Boston, MA: Allyn and Bacon.
3. ^Beck, A. T., & Weishaar, M. E. (2008). In R. J. Corsini & D. Wedding (Eds.). Current psychotherapies (8th ed.). Itasca, IL: Peacock.
4. ^ a bLehrer, P. M., Woolfolk, R. L., & Sime, W. E. (2009). Principles and practice of stress management (3rd ed.). New York, NY: Guilford.
5. ^Schafer, W. (2000). Stress management for wellness (4th ed.). Belmont, CA: Wadsworth Group/Thompson Learning.
6. ^American Psychiatric Association, & American Psychiatric Publishing. (2014). Diagnostic and statistical manual of mental disorders: DSM-5. Washington: American Psychiatric Publishing.
7. ^Kasper, S., Anghelescu, I., Szegedi, A., Dienel, A., & Kieser, M. (2006). Superior efficacy of St John's wort extract WS®5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298]. BMC Medicine, 4(1). doi:10.1186/1741-7015-4-14
8. ^MacKinnon, M. (2017, February 12). How Exercise Reduces Depression, Anxiety, Cynicism, & Anger. Retrieved from https://drugs-forum.com/ams/how-exercise-reduces-depression-anxiety-cynicism-anger.26984/
9. ^Johnson, B. T., & Kirsch, I. (2008). Do antidepressants work? Statistical significanceversusclinical benefits. Significance, 5(2), 54-58. doi:10.1111/j.1740-9713.2008.00286.x
10. ^Brannon, L., & Feist, J. (2010). Understanding and managing pain. In Health psychology: An introduction to behavior and health (10th ed., pp. 157–187). Belmont, CA: Wadsworth Cengage Learning
11. ^Hardy, P. (2009). [Severe depression : morbidity-mortality and suicide]. Encephale, 35(7), 269-271. doi:10.1016/S0013-7006(09)73484-0

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