Neurobiology And Treatment Of Major Depressive Disorder Research Paper

Neurobiological of Major Depression Disorder

Areas of the brain are involved in MDD
As a result of Major Depression Disorder (MDD), there is a structural and synaptic alterations in various parts of the brain. These parts include hippocampus and the frontal cortex. According to the pathophysiological studies, these alterations are anticipated to prevent the brain from developing necessary adaptive reactions to the surrounding stimuli. These facts have raised concerns to the neuroscientists to develop a research of neurotrophins in depression. This is because there are neural survival factors of significant on maintenance and establishment of neural circuit during development in the adult patients. As a result, the right-hand side of the cerebral cortex of the depressed person shows thinning (Rot, Mathew & Charney, 2009). These influences attention, and mood among others.
In the brain, the derived neurotrophic factor is among the family of four different secrete growth factors in Neurotrophins. These factors sticks to the membrane receptors in the targeted neurons stimulates an intracellular cascade, which, as a result, promotes trophic effects and survival. The neurotrophins bind with high affinity to particular family members of the tyrosine kinase receptor. Additionally, low affinity is involved when neurotrophins are binding to p75. This receptor is responsible for transporting and storing neurotrophins, and also promotes death of neuronal cell to shape neuronal circuit in time of development (Villanueva, 2013). The raphe nuclei, a part of the brain that produces suprachiasmatic nucleus and serotonin is also affected by the MDD. As a result of depression, the raphe nuclei becomes unable to regulate the circadian rhythm in the brain. Additionally, a depressed person has lower activities in the ventral tegmental region, and hence unable to control their perception of pleasure effectively.
In the hippocampus, there are neurons which can regenerate and also replicate into new neurons by a process known as Neurogenesis. The hippocampus is the region of the brain that dominates other regions in terms of having numerous glucocorticoid receptors. As a result of stress, glucocorticoid such as cortisol are released in hippocampus, and the neurogenesis decreases its function. As the cortisol continues to be released subsequent to the toxic stress, it reduces the regulation of glucocorticoid receptor sensitivity in the hippocampus and also inhibits the regulation of the growth factors. In this case, growth factors include the Brain Derived Neurotropic Factor (BDNF). BDNF is extremely important protein in neurogenesis. Therefore, this theory suggests that depression is caused by toxic stress in individual’s life. Impaired neurogenesis results to depression, which can be treated with antidepressants that restore neurogenesis. The restoration process takes two weeks, and this explain why clinical effects exhibit after two weeks when a patient is given antidepressants. Another treatment mechanism involves inducement of BDNF factors. According to this theory, individuals with MDD have reduced hippocampal volume.

Principle neurotransmitters involved

In the human brain, different chemicals are utilized as messenger to spread the message within themselves and in the nervous system. These massagers are biologically known as neurotransmitters, which are received by the nerve cells in the brain called neurons. These neurons exchange the neurotransmitters to communicate with each other. For the patients suffering from MDD, the three principle neurotransmitters that are involved included norepinephrine, serotine, and dopamine. However, the evidence is in some way unavailable because it is challenging to measure the level of these chemical massagers in individual’s brain (Rot et al. 2009).
The neurotransmitter Serotonin is responsible for regulating the crucial physiological body functions such as eating, sexual behavior, aggression, sleep, and mood. This neurotransmitter is released by the serotonergic neurons. The contemporary research have indicated that when the serotonin production decreases, the neurons may result to depression in some people. Specifically, this effect can cause a mood condition that can make the patient develop a suicidal feeling. The depression is as a result of the shortage of the serotonin that provides inadequate reward and pleasure and hence depression (Villanueva, 2013).
According to the “catecholamine hypothesis,” the explanation of developing depression was associated with the deficiency of norepinephrine neurotransmitters also recognized as noradrenaline. Shortage of this neurotransmitter in a particular area of the brain develops depressed moods. Current research have strengthened this hypothesis by suggesting that there some depressed individuals who exhibit low amount of norepinephrine (Nemade, Reiss & Dombeck, 2007). For instance, according to the autopsy studies, people who have multiple depressive conditions have fewer norepinephrinergic neurons compared to the individuals who exhibit no depressive history. However, research suggests that not all mood experiences are developed as a result of deficiency in norepinephrine. For some depressed people, the hyperactivity exhibits in the neurons that produces norepinephrine and hence depression. There is also a relationship between the low level of serotonin and norepinephrine. Studies indicate that low amount of serotonin stimulates a decrease in norepinephrine amount, and hence depression. In order to reduce stressful situations in the human body, norepinephrine are used.
The other neurotransmitter that is associated with the depression is the dopamine. This is an important neurotransmitter that helps the body to regulate the ability to seek reward and acquire a sense of pleasure. Low levels of dopamine may explain why depressed people do not derive equal amount of pleasure from the activities they used to do prior to the depressive state. In addition, irregular feedback in the striatal dopamine system provides explanation to why depressed people often show unsuitable salience to even insignificantly negative stimuli. Current studies have shown that polymorphism existing in type 2 receptor gene of dopamine influences the impact of the past stressful conditions on the current mood. Therefore, the dopamine system may be adjusted to help the victim overcome MDD through environmental interaction (Nemade, Reiss & Dombeck, 2007).

Receptor subtype that has been implicated in MDD

According to various studies the main receptors subtype that has been associated with MDD are the postsynaptic 5-HT1A and somatodendritic receptors. These receptors help to explain why people suffering from MDD or any other related disorder may exhibit blunted hormonal or endocrine responses to 5-HT1A receptor agonist. The patient may also exhibit reduced postsynaptic and somatodendritic 5-HT1A and decreased 5-HT1A receptor bonded in the hippocampus, prefrontal cortex, and raphe. The reduction of this receptor has been observed in the post-mortem cases of the suicide cases. Therefore, the studies indicate that there is a possibility that 5-HT1A receptor provide a potential mechanism to explain the MDD and other stress-related disorders (Savitz, Lucki, & Drevets, 2009).

Treatment of MDD

Major Depressive Disorder Treatment
Major Depressive Disorder is a condition that is frequently and highly manageable. There are many potential treatment modalities for MDD. But the paper will address key treatment types that are known to be empirical support and most relevant to primary care. Psychotherapies and psychotic medication are essential treatment types with effectiveness of about 80% of MDD disorder (Trivedi et al. 2004). After the patient going under one of the treatment, they usually report having experienced significant benefits in a 4-6 weeks’ time. Patients with more severe forms of clinical depression for example MDD, antidepressants are used as the first line of treatment. Most of the antidepressants have a comparable rate of time to onset of helpfulness and efficacy overall, for instance, they require 4-6 weeks for patients to achieve maximum therapeutic benefits. In addition, treatment depends on the factors such as subtype of MDD, cost considerations, age of the patient and the practitioner’s preferences.

Tricyclic antidepressants (TCAs)

TCAs are among the earliest antidepressant developed and first generation of antidepressants and have known to be effective in many of well-designed and randomized controlled trials. However, they have been replaced by antidepressant that has fewer side effects (Moy, & Elkassabany, 2013). Reviews suggest that TCAs are the solution and option for people suffering from severe MDD and MDD with melancholic. This is because, 50-70% of patients treated with this TCAs medication respond favorably. TCAs medication group include; doxepin (Adapin, Sinequan), amitriptyline (Elavil, Endep), Desipramine (Norpramin), clomipramine (Anafranil), and nortriptyline (Pamelor, Aventyl). TCAs work by easing depression by affecting neurotransmitters that are used to communicate between brain cells (Moy, & Elkassabany, 2013). TCAs prevent the reuptake of the neurotransmitters serotonin and norepinephrine that make these chemicals available in the brain. As a result, boosts the patients’ mood. TCAs require more care, since they are more risky when it comes to matters of overdose. Also, the side-effect profile can be difficult to manage in some patients.

Monoamine oxidase inhibitors (MAOIs)

These drug classes of medications have been shown as effective as TCAs. Mostly they are useful for patients with atypical Major Depressive Disorder. The drugs are also effective for the patients who do not respond to other classes of medication. Main drugs involve tranylcypromine (Parnate) and phenelzine (Nardil). Despite MAOIs’ efficacy, their drugs are rarely used due to their potential for severe and frequently life-threatening interaction with other constituents. Therefore, this calls for thorough instructions on the administration of medications to prevent cheese effect consequences (El-Ganzouri, Ivankovich, Braverman, & McCarthy, 1985). MAOIs are in charge of breaking down tyramine. Therefore, food containing amines are avoided in order to prevent life-threatening hypertensive predicament. Similar to TCAs, MAOIs have possibilities of overdose which in return can be severe for the patients. Due to their side-effects, MAOIs have relegated to a second line of defense in treatment planning.

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs are in the first line of treatment at the moment. It is newer class of medications that have been revealed to be effective antidepressants from other medications. SSRIs are used to ease symptoms of moderate to severe depression. This class of medications is relatively safe since they have fewer side effects than other types of medication. SSRIs affect naturally occurring chemical messengers hence easing the depression (Trivedi et al. 2004). SSRIs are used in blocking the reabsorption of the neurotransmitter serotonin in the brain. As a result, this alternates the balance of serotonin and hence helps the brain cells in sending and receiving of chemical messages, which in turn boosts patients’ mood. SSRIs are selective since they primarily affect serotonin, not other neurotransmitters.

Serotonin-norepinephrine reuptake inhibitor (SNRI)

SNRI are used to treat depression symptoms and other conditions for example nerve pain and anxiety. Examples of medications include Duloxetine (Cymbalta), Desvenlafaxine (Pristiq) and Duloxetine (Cymbalta). The treatments are approved effective for treating depression by the Food Drug Administration (American Psychiatric Association, 2010). Serotonin and norepinephrine reabsorption inhibitors are hence easing depression; as a result, this affects chemical messengers that are used to connect to the brain cells. SNRI function by altering the levels of one or more of naturally occurring chemicals. According to American Psychiatric Association (2010), drugs are used to block the absorption of the neurotransmitter in the brain and affect other neurotransmitters. Therefore, by altering the balance of these chemicals in the brain help the brain cells to send and receive messages hence boosting the mood.

References

American Psychiatric Association. (2010). PRACTICE GUIDELINE FOR THE Treatment of Patients With Major Depressive Disorder. Retrieved from http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf
El-Ganzouri, A. R., Ivankovich, A. D., Braverman, B., & McCarthy, R. (1985). Monoamine oxidase inhibitors: should they be discontinued preoperatively?. Anesthesia & Analgesia, 64(6), 592-596.
Moy, G., & Elkassabany, N. (2013). Tricyclic Antidepressants (TCAs). Pharmacology in Anesthesia Practice, 2.
Nemade, R., Reiss, N. S., & Dombeck, M. (2007, September 19). Biology of Depression – Neurotransmitters - Depression Resources, Education About Depression and Unipolar Depression. Retrieved from https://www.mentalhelp.net/articles/biology-of-depression-neurotransmitters/
Rot, M. A., Mathew, S. J., & Charney, D. S. (2009). Neurobiological mechanisms in major depressive disorder. Canadian Medical Association Journal, 180(3), 305–313. doi:10.1503/cmaj.080697
Savitz, J., Lucki, I., & Drevets, W. C. (2009). 5HT 1A receptor function in major depressive disorder. Progress in Neurobiology, 88(1), 17-31. doi:10.1016/j.pneurobio.2009.01.009
Trivedi, M. H., Rush, A. J., Crismon, M. L., Kashner, T. M., Toprac, M. G., Carmody, T. J., & Shon, S. P. (2004). Clinical Results for Patients With Major Depressive Disorder in theTexas Medication Algorithm Project. Archives of General Psychiatry, 61(7), 669-680.
Villanueva, R. (2013). Neurobiology of major depressive disorder. Neural plasticity, 2013. http://dx.doi.org/10.1155/2013/873278