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Pathophysiology of Depression Research Paper


Being understudied currently, the concept of depression remains rather elusive as far as its definition and pathophysiology are concerned. Using specific criteria for determining the presence of depression, therefore, does not seem useful currently due to the huge differences between the symptoms possessed by various patients. Wicks-Nelson summarizes the problem in the following way: “It is not possible at this point to make definitive statements about the ‘correct’ definition of depression” (Wicks-Nelson, 2015, p. 145). Therefore, the disorder is quite difficult to determine and diagnose, especially in children and adolescents.

To identify the changes in the patient’s well-being that may lead to the identification of the disorder, neuro-imaging tools along with post-mortem studies are typically used (Fekadu, Shibeshi, & Engidawork, 2016). The connection between the changes and the development of major depression, however, is yet to be explored in depth. Several approaches toward the explanation of the nature of the phenomenon currently exist. The neural circuitry of depression approach implies that the analysis of the brain processes involving the changes in the “mood, reward response, and executive functions” should be analyzed and used as the basis for diagnosing the problem.

The approach implying the identification and assessment of the stress response circuits is also viewed as a possible tool for determining the development of major depression in a patient. The biogenic monoamine theory, in turn, implies that the change in the number of monoamine neurotransmitters (serotonin and catecholamine) should be defined. Inflammation, neuropeptides, and hormones are also viewed as possible depression factors. Finally, changes in the circadian rhythm may also be deemed as possible ways in which depression manifests itself and, therefore, can be diagnosed (Fekadu, Shibeshi, & Engidawork, 2016).


At present, several options for treating depression exist, including pharmacology- and therapy-based ones. Pharmacotherapy, as a rule, implies the use of antidepressants, their severity depending on the stage of the disorder development, is required. As a rule, the following categories of antidepressants are mentioned when considering the treatment options: “Tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), selective serotonin noradrenaline reuptake inhibitors (SSNRIs)” (Depression: How effective are antidepressants?, 2017).

The use of the identified medications implies that the neurotransmitter transporters should be bound to the corresponding presynaptic neurons so that the process of producing serotonin and other hormones affecting the mood of the patient should not be inhibited (Depression: How effective are antidepressants?, 2017).

It should be noted, though, that, apart from using medications as the means of addressing major depression in patients, other tools are viewed as a possibility. For instance, the adoption of the somatic therapy framework is often deemed as a possible tool for managing the patients’ needs (). For instance, by selecting the electroniclusive approach toward addressing major depression, one will have to make sure that the patient’s mind and body are equally engaged in the process of treatment. The options for promoting active patient education and enhancing their independence should be viewed as the primary advantages of the approach (Guloksuz, Rutten, Arts, Os, & Kenis, 2014).

Finally, the use of psychotherapy must be viewed as an essential component of the major depression management process. Cognitive therapy tools such as psychodynamic psychotherapy coupled with interpersonal therapy approaches must be viewed as the foundation for addressing the patients’ needs. By incorporating the specified strategies, one will be able to promote active patient engagement and, thus, create the premise for a successful treatment process (Driessen et al., 2013).

Implications of the Age Continuum

When addressing the needs of patients with major depression, one must choose the appropriate frameworks based on the patient’s age as one of the crucial criteria for the treatment design. According to recent studies, children and adolescents require a combined treatment process implying the use of medications, cognitive behavior therapy, and the introduction of the elements of community care (Wicks-Nelson, 2015). The use of community support is bound to create the foundation for the further successful management of the problem.

Furthermore, the choice of the medications that will be used for addressing the issue of major depression hinges on the patient’s age to a considerable extent. According to the existing clinical studies, there is a propensity among older adults toward developing eating disorders leading to weight loss, as well as a rapid drop in interest toward the activities that used to seem exciting. Finally, adults tend to develop suicidal moods more often than a younger population (e.g., young adults, teenagers, adolescents, and children).

Therefore, it is crucial to make sure that the appropriate measures are taken to address the specified issues in older adults until the specified problems spin out of control. Among children and teenagers, the failure to make the expected weight gain as opposed to a rapid loss of weight can be viewed as the primary outcome of major depression (Wicks-Nelson, 2015).

Genomic Issue and Depression

What is Known

At present, a comparatively small amount of the information associated with the genomic factors determining the development of major depression is known. The existing studies [point to the fact that genome-wide significant risk variants are common for major depression (Power et al., 2017). Power et al. (2017) report that the age at onset (AOO) phenotype has been proven to be one of the heterogeneities in the genetic associations between the development of the disorder and the factors that ostensibly contribute to it. The results of the research point to the fact that there is a considerable genetic risk when it comes to the effects of AAO on the genetic architecture of major depression (Power et al., 2017).

Genetic-wide association studies (GWAS) also point to the fact that the gene desert on chromosome 12 can be viewed as one of the factors leading to the development of the premise for the major depression syndrome (Power et al., 2017). The following genes are believed to cause the development of major depression specifically: “5HTTP/SLC6A4, APOE, DRD4, GNB3, HTR1A, MTHFR, and SLC6A3” (Flint & Kendler, 2014, p. 487).

The authors mention that the identified candidates for the gene that spurs the progress of the disorder are commonly believed to trigger an equally large number of risks for the patients (Flint & Kendler, 2014). It should be borne in mind, though, that the disease progress is believed to be affected by a much greater number of genes, including TGFBR3, PVRL1, SNRPD3, APOBEC3G, PTPN4, KLRK1, DYSF, TNFRSF10C, NCALD, and C14orf (Jansen et al., 2015).

What Is Unknown

One must bear in mind that the degree to which clusters of genes express themselves hinges on a range of factors, some of which have not been studied thoroughly enough yet. Therefore, there are quite a lot of gray areas that need further exploration. For instance, the degree to which the genes listed above affect the development of major depression could be scrutinized closer. As a result, the basis for developing a comprehensive treatment approach based on the genetic factors determining the development of major depression could be designed.

The choice of the candidate gene selection and, thus, the biological factors that underlie the progress of major depression in patients, therefore, remains a mystery. When considering the reasons for the gaps in knowledge to exist, one must mention the fact that a genotyping platform used to be considered the foundation for a comprehensive analysis of the subject matter and the development of the assumptions regarding the genetic expression, variabilities, etc.

Nowadays, however, the incorporation of the whole-genome sequencing (WGS) approach is being promoted as a superior method in studying the problem and identifying the available solutions. Building the basis on which private genetic variations can be defined and scrutinized, the WGS strategy is likely to serve as the essential tool for filling in the current knowledge gaps.

Nevertheless, the development of major depression in patients as a result of specific genomic expression still needs further clarification. While the general picture is quite clear at present, a more detailed analysis of the factors that serve as catalysts for major depression development in patients needs to be conducted. As a result, a more efficient treatment strategy can be designed, with better approaches in both pharmacological and therapeutic aspects of major depression management.

Literature Review

Despite the blank areas in the current understanding and interpretation of the disorder, its causes, and effects, major depression has been explored extensively over the past few years. Apart from an all-embracive analysis of the nature of major depression, the existing works address the issue of comorbidity, thus, pointing to the fact that numerous complexities are likely to follow the development of major depression. For instance, Rhee, Gustafson, Ziffra, Mohr, and Jordan (2015) list anxiety, substance abuse, hypertension, asthma, and many more conditions as comorbid disorders that a patient may develop along with major depression.

The occurrence of the identified disorders, however, hinges on the adequacy of the selected treatment to a considerable degree (Rhee et al., 2015). At this point, one must bring up the fact that the existing guidelines do not detail the number of antidepressants that a nurse must provide to the patient so that the problem of major depression could be addressed. As a result, the lack of understanding of the patient’s needs may lead to the creation of a range of comorbid conditions that will have to be addressed along with depression.

The combined treatment of medications and psychotherapy should be deemed as one of the tools for preventing the incidences of comorbid issues development (Rhee et al., 2015). Particularly, by appealing to the patient’s independence and willingness to recover, a healthcare expert is likely to contribute to the development of the habits that will help either prevent the emergence of anxiety, substance abuse, etc., or handle the comorbid disorders successfully. Patient education must be promoted actively along with independence. Thus, the target population will be enabled to acquire the essential skills and manage the disorders successfully. For instance, the development of the patient’s control over substance abuse will become a possibility with the promotion of the identified strategies (Rhee et al., 2015).

Finally, the importance of social support, including the help of the community members, needs to be addressed as one of the primary factors contributing to the successful management of the disorder and the enhancement of patient independence. While often underrated compared with the significance of family support the assistance of the community is crucial to the further management of major depression and the successful integration of the patient into the community (Bellinger et al., 2014). At this point, the positive effect of encouraging the patient to engage in religious practices and experiences need to be mentioned.

According to the research conducted by Bellinger et al. (2014), in case a patient has a propensity toward exploring or adhering to a specific religious practice, a therapist may consider encouraging them to use their spiritual practice as the source of emotional strength (Bellinger et al., 2014). As a result, the foundation for managing the disorder successfully can be created. Particularly, the positive emotional experiences that the patient will have the opportunity to enjoy being bound to motivate them to engage in the active acquisition of the knowledge and skills that will help them handle the depression successfully (Bellinger et al., 2014).

Approach to Collecting the Data


The process of data collection was quite intricate since it required gathering information regarding different aspects of the disorder. Therefore, a different combination of keywords was used for every stage of the data collection process. Table 1 below shows the keywords that were used for every stage of the study.

Table 1. Keywords.

Information Keywords
  • major depression definition DSM-V;
  • major depression pathophysiology;
  • major depression symptoms;
  • major depression treatment;
  • major depression medications;
  • major depression cognitive therapy;
  • major depression age continuum;
  • major depression adults children difference
Genomic issues
  • major depression genomic issues;
  • major depression gene expression;
  • major depression genomic factors;
  • major depression GWAS;
  • major depression candidate gene.
Literature review
  • major depression comorbidity;
  • major depression treatment options;
  • major depression patient education;
  • major depression patient independence;
  • major depression emotional support.

The choice of the keywords was defined to a considerable extent by the results of the previous search. For example, the term “gene expression” was used after it had appeared in the results for the “major depression genomic issues” search. Thus, an all-embracive analysis of the available literature could be carried out.


For the most part, online databases were used to obtain articles on the topic of major depression. The NCBI site was used as the database for the available articles. Seeing that the site is owned by the National Institute of Health, it was deemed as a trustworthy resource for credible articles.

Additionally, the ResearchGate site was utilized to locate the articles on the issue of major depression. Being a repository of peer-reviewed articles, ResearchGate was also considered the location of credible, peer-reviewed journals and articles.

The identified databases were accessed from Google Scholar. While the latter also contains the resources that cannot be defined as fully credible, it was viewed as the medium for accessing peer-reviewed articles. Thus, trustworthy information could be retrieved.

The validity of the information obtained for the analysis was determined by the publishing date and the authors’ credentials. The articles published by professional nurses and scholars were incorporated into the analysis so that valid tools for diagnosing major depression in patients and treating them successfully could be identified. Furthermore, the publishing date was checked carefully; the articles that were published in 2012 and earlier were not included in the analysis due to possibly invalid data.

As a result, the validity and credibility of the information acquired in the course of the analysis were increased significantly. Consequently, the premise for building a comprehensive strategy that could help meet the needs of patients with major depression successfully was built. Particularly, the opportunities for including the strategies that will allow taking diversity issues into account were provided.

Electronic Tools

Apart from Google scholar as an electronic search tool and electronic databases as the sources of articles, no electronic devices were used. Incorporating Electronic Health Records (EHR) (EHR) of the patients was not viewed as an option because of the nature of the research. Without a trial that would require quantitative analysis, the use of EHR was unnecessary, which was the reason for not including the identified tool into the study.

Clinical Guidelines

The prescription of antidepressants must be viewed as the first step toward addressing the needs of the target population. Adult patients must be provided with antidepressant-based treatment for a total of at least six months, though twelve months is the preferable length of treatment (Rhee et al., 2015). Afterward, the target population should be given therapy options as a follow-up therapy process. The incorporation of cognitive-behavior-based approaches must be considered a necessity in the identified scenario. Finally, the supervision of nurses must be offered to the patients that show signs of recovery.

Treatment: Final Selection

As stressed above, the nature of major depression as a clinical disorder has not been specified fully yet. As a result, the efficacy of certain treatment approaches needs to be tested, some being very innovative and needing further testing, while others have worn out their welcome. At present, the use of the treatment approach based on a combination of antidepressants as a part of the medication-based strategy and the adoption of Cognitive Behavior Therapy tools must be viewed as the most reasonable option. Contacting the nurse at least once a month is crucial for the prevention of relapse (Bellinger et al., 2014).

Follow-up Treatment

As stressed above, the follow-up treatment process will include visiting the therapist once a month. Thus, the possibility of recidivism will be addressed efficiently. The patient’s diet and lifestyle choices will also have to be shaped significantly so that the instances of depression could be avoided in the future. Particularly, the sedentary life and unhealthy food choices will need to be replaced with a well-balanced diet and the promotion of an active lifestyle. The identified changes will presumably help the patient accept the coping strategy developed in the course of the treatment procedures. As a result, the threat of a recurrent major depressive episode will be avoided successfully.


The patient must be provided with the services of a nurse and a therapist so that the incidence of major depression could be handled successfully. Furthermore, the essential tests such as the CAT scoring system should be applied to determine the presence of the disorder (Junior et al., 2014).


Bellinger, D. L., Berk, L. S., Koenig, H. G., Daher, N., Pearce, M. J., Robins, C. J.,… King, M. B. (2014). Religious involvement, inflammatory markers and stress hormones in major depression and chronic medical illness. Open Journal of Psychiatry, 4, 335-352. Web.

(2017). Web.

Driessen, E., Van, H. L., Don, F. J., Peen, J., Kool, S., Westra, D.,… Dekker, J. J. M. (2013). The efficacy of cognitive-behavioral therapy and psychodynamic therapy in the outpatient treatment of major depression: A randomized clinical trial. American Journal of Psychiatry, 170(9), 1041-1050. Web.

Fekadu, N., Shibeshi, W., & Engidawork, E. (2016). Major depressive disorder: Pathophysiology and clinical management. Journal of Depression and Anxiety, 6, 255-257. Web.

Flint, J., & Kendler, K. S. (2014). The genetics of major depression. Neuron, 81(3), 484-503. Web.

Guloksuz, S., Rutten, B., Arts, B., Os, J., & Kenis, G. (2014). The immune system and electroconvulsive therapy for depression. Journal of ECT, 30(2). Web.

Jansen, R., Penninx, B. W. J. H., Madar, V., Xia, K., Milanesch, Y.,… Sullivan, P. F. (2015). Gene expression in major depressive disorder. Molecular Psychiatry, 15, 1–9. Web.

Junior, J. L. R. S., Conde, M. B., Correa, K. S., Silva, C., Prestes, L. S., & Rabahibs, M. F. (2014). COPD Assessment Test (CAT) score as a predictor of major depression among subjects with chronic obstructive pulmonary disease and mild hypoxemia: a case–control study. BMC Pulmonary Medicine, 14(1), 186. Web.

Power, R. A., Tansey, K. E., Buttenschon, H. N., Cohen-Woods, S., Bigdeli, T., Hall, L. S., … Lewis, C. M. (2017). Genome-wide association for major depression through age at onset stratification: Major depressive disorder working group of the psychiatric genomics consortium. Biological Psychiatry, 81(4), 325-335. Web.

Rhee, Y. R., Gustafson, M., Ziffra, M., Mohr, D. C., & Jordan, N. (2015). Association of comorbidity with depression treatment adequacy among privately insured patients initiating depression. Open Journal of Depression, 4(1), 13-23. Web.

Wicks-Nelson, R. (2015). Abnormal child and adolescent psychology with DSM-V updates (8th ed.). New York, NY: Psychology Press. Web.

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IvyPanda. (2020) 'Pathophysiology of Depression'. 26 July.

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