Neurobiological Determinants of Major Depression - Coursework Example

Neurobiological Determinants of Major Depression by Major depression or otherwise called clinical depression or unipolar disorder is a serious biological and psychological impairment that affects person`s emotional state, feelings, physical wellbeing, and behavior. Major depression is a long-term disorder during which the periods of normal state alternate with major depressive episodes. The frequency and recurrency of the episodes defines the seriousness of the disorder. There is some evidence that more than 25 million Americans experience major depression regardless of racial, sexual, and age differences. Larger part of patients with this impairment has single episodes throughout years but may suffer from pervasive recurrent episodes. Major depression is now recognized widely and most people can define its symptoms, however, only half of those suffering from depression would address for a medical help. According to DSM -5 if five or more symptoms must be present during 2 weeks it is possible to diagnose major depression: Anehdonia –inability to receive positive emotions from habitual activities. Significantly reduced interest in search for delight and pleasure through any activities during the day for a certain period of time marked by the patient himself or by close people; Change of eating habits: loss of appetite or unnatural appetite. Obvious weight loss not connected to dieting (e.g., a change of more than 5 percent of body weight in a month); Change of sleeping habits: permanent insomnia or hypersomnia ; Alternations in normal psychomotor activity: daily retardation or agitation (noticeable by others, not simply personal feelings); Exhaustion or permanent lack of physical energy; Permanent feeling of uselessness or unreasonable and excessive guilt (which can be not grounded) almost consistently (not connected to the present state of depression); Inability or reduced ability to concentrate and think critically, feeling of uncertainty, inability to take decisions, doubts (personal observation or testified by others); Suicidal thoughts (not simply fear of dying), persistent self-destructive ideas about the possibility of suicide without any particular arrangements, suicide attempts, particular arrangements for suicide All the articles chose by me concentrate on biological determinants of major depression and aim to provide the readers with plausible explanation of how biological factors can contribute to the development of depression. The articles regard not only biological theory but also take into account social and genetic determinants of major depression, however, most part is dedicated to thorough explanation of biological mechanisms. All three articles are peer-reviewed and were published in the reliable academic journals. In this essay I tried to summarize the main ideas regarding neurobiological determinants of major depression. There are different assumptions how neurobiological determinants provoke depression. The role of neuromodulators and neurotransmitters, such as serotonin, dopamine, norepinephrine, and epinephrine, in major depression is undisputable, however researches have not come to some to general and concrete conclusions regarding the exact mechanisms and factors. According to Rot et al., depression is most likely connected to the imbalance of serotonin. There is some evidence that people experiencing the symptoms of depression have disrupted serotonin synthesis. However, scientists claim that it is difficult to define the cause and effect factors: whether depression provokes changes in serotonin level or reduction of neurotransmitters cause the symptoms. Serotonin is responsible for mood regulation in the body. It influences social behavior, sleep, memory processes, sexual behavior, and digestion. The article by Rot et al., “Neurobiological mechanisms in major depressive disorder” examined different theories of major depression appearance and paid special attention to neurotransmitters deficiency. The study provides with experimental research which proves interconnection between the level of neurotransmitters ad the symptoms of depression. To define the exact influence of serotonin on depression experimental research with patients suffering from depression symptoms were conducted. Certainly, the manipulations with serotonin level and their effect on mood represented the main interest for the researchers. In the vast majority of these experiments subjects take a tryptophan-inadequate amino acid mixture that diminishes the neurotransmitter level in the cerebrum for a short period of time. Subjects ingesting pharmaceuticals at the time of study may experience a short relapse, particularly if they take antidepressants regularly. Those who do not take any pharmaceuticals are also prone to have a short relapse of depression symptoms when the level of tryptophan decreases. These findings allow concluding that serotonin imbalance is probably connected to depression. However, it is surprising that tryptophan depletion does not result in the symptoms of depression for all patients despite the fact that it changes the activity of amygdala responsible for mood. Those subjects who do not experience depression and do not have family history with this disorder demonstrated no concrete alternations in mood (Rot et al., 2009). Nevertheless, medicine therapy directed on normalization of neurotransmitters level is most often used in treatment of major depression along with psychotherapy. The article by Maletic et al. “Neurobiology of depression: an integrated view of key findings, International Journal of Clinical Practice” aimed to analyze the key discoveries of the clinical experiments in regards to the neurobiology of unipolar disorder and their suggestions for treatment results. According to Maletic et al., there is another hypothesis that links neurobiological mechanisms to depression that is called neurotropic hypothesis (2007). According to it stress and hereditary genetic predisposition increase the level of glucocorticoid steroids and change the plasticity by decreasing the growth factors and receptor sensitivity. BDNF (brain-derived neurotrophic factor), which is the major neurotrophin of the hippocampus, plays a crucial role in supporting the health of glial-neuron interactions. BDNF is interconnected with nerve growth factor, and thus the decrease of such growth factors as BDNF, has a negative influence on important processes in the limbic system. Research suggests that major depression can lead to further atrophy and interruption in neurocircuitry. The experiments conducted in this field were aimed to test how BDNF dysregulation becomes a result of unipolar disorder. In the experiments with the animals it became evident that prolonged immobilization stress was accompanied by the decrease of BDNF. Additionally, animals exposed to the pain stimuli had the same alternation in brain activity. In the research which involved humans the hypothesis was also corroborated. Patients who did not undergo any medicine treatment from major depression had lower level of BDNF in comparison with the subjects exposed to treatment or healthy individuals. Moreover, the quantity of BDNS and neurotrophine were notably lower in people who committed suicide compared to the subject who died naturally. That is why it is possible to suggest that normal regulation of BDNF contributes to the healthy psychological state of a person, and treatment ad recovery from major depression is possible with the normalization of BDNF (Maletic et al., 2009). The article by Meyer et al. “Elevated monoamine oxidase A levels in the brain: an explanation for the monoamine imbalance of major depression” was to determine in the course of the experiment if MAO-A levels in the brain are increased if subjects do not undergo any treatment of unipolar disorder. As a result the theory was confirmed by the experiment. There is another scientific assumption which has grown into a theory that monoamines can also play a decisive role in depression establishment in a person. A low level of such monoamines as 5-HT and NE, provoke depression symptoms. A research examining this theory showed that subjects which did not undergo medical treatment had a “high global density of monoamine oxidase A (MAO-A)” which takes part in these neurotransmitters metabolism. Therefore it was suggested that long-term monoamine los because of this global MAO-A activity interacts with regional specific transporter densities (i.e. 5-HT, NE) leading to the depression outbreak. Both 5-HT and NE are interconnected with such parts of brain as brainstem nuclei and amygdala and are considered to play a role in mood regulation. Moreover, even the pain regulation is connected to the descending pathways that pass through dorsolateral spinal column. That is why the mechanisms of pain regulation and mood activation can be linked to the monoamines level. Regulation of this level will let influence the symptoms of depression correspondingly (Meyer et al., 2006). Depression has become a serious problem for the American society because major part of adults experiences from its symptoms. Depression with its constant bad mood, lack of energy, anxiety, insomnia, prevents a person from normal functioning in society and in personal relationships. There are different factors that provoke major depression, and scientists distinguish psychological, environmental, and biological among others. Neurobiologists on their part most often attribute major depression to imbalance and disorganization in the work of neurotransmitters, such as dopamine, serotonin, norepinephrine, and epinephrine. The article of Rot proves that the decrease of serotonin normal level is observed in patients with depression. Neurotrophic hypothesis decribed by Maletic et al., connects depression with the level of brain-derived neurotrophic factor, which is the major neurotrophin of the hippocampus. Thus, treatment of depression is possible only with BDNF restoration. Myer et al., in his article proves that monoamines play the decisive part in depression appearance in patients. The experiment proposed by me would also concentrate on determination of how neurobiological determinants can influence major depression appearance. As these three articles regard different assumptions of how misbalance in neurotransmitters, BDNF or monoamines presumably affect depression it would be interesting to learn what exact symptoms each of this components disorganization causes. For these purpose it is possible to create two groups of subjects one of which would be the target group with people suffering from depression and undergoing treatment with medicines while the other one will be control group with people having no medical history of this disorder. In the course of the experiment subjects will be exposed to different manipulations that would somehow influence the indexes such as neurotransmitters level, BDNF, and monoamines level. For example, to change the level of serotonin patients are provided with a tryptophan-inadequate amino acid mixture that diminishes the neurotransmitter level in the cerebrum for a short period of time. Further the exact symptoms of depression in people are marked. Later subjects undergo other manipulations that allow defining what symptoms appear with BDNF and monoamines change. This would allow treating particular symptoms in major depression with relevant medications and approaches. References Maletic, V., Robinson, M., Oakes, T., Lyengar, S., Ball, S. & Russel, J. (2007). Neurobiology of depression: an integrated view of key findings, International Journal of Clinical Practice, 61(12), 2030–2040. Meyer, J., Ginovart, N., Boovariwala, A., Sagrati, S., Hussey, D., Garcia, A., Young, T., (2006). Elevated monoamine oxidase A levels in the brain: an explanation for the monoamine imbalance of major depression, Archives of General Psychiatry, 63, 1209–16 Rot, M., Mathew, S., & Charney, D. (2009). Neurobiological mechanisms in major depressive disorder, Canadian Medical Association Journal, 180(3), 305-313. Read More