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Depression

Major depression is one of the most prevalent mental disorders found in people of every age all over the world.
People experience different psychological issues induced by several factors.
Several factors such as genetic, environmental, social, demographic and psychological aspects play a pivotal role in the development of major depression (Schmaal et al., 2020).

(Source: Fleck and Richter, 2023)

Major depression is a widely suffered mental health issue that involves long-term depressed mood along with a loss of interest in different activities for a longer time (Gutiérrez-Rojas et al., 2020). The development of this mental disorder is multifaceted and quite complex as different factors contribute significantly to the initiation and maintenance of this critical psychological problem (Schmaal et al., 2020).
Several contemporary scientific research studies have highlighted that biological or genetic factors including neurobiology as well as environmental factors including society, substance abuse, life events and different childhood exposures cumulatively play a pivotal role in the development of depression in a person.
As per the research article by Monroe and Harkness (2022) Around 264 million people of different ages are currently diagnosed with depression. The World Health Organisation also identified major depression as the leading reason behind different physical and mental disabilities around the whole world which has also become a global burden (WHO, 2021).
Although this disorder is prevalent worldwide, the disparities in different generations and the severity of the disorder are diverse and often dependent on the socio-demographic details of the person (Gutiérrez-Rojas et al., 2020).
There are crucial symptoms that can help to identify and diagnose depression. Around 45% of the population of Sweden experiences mental health problems associated with anxiety, stress and depression (Fleck and Richter, 2023). Significant identifiers or symptoms are taken into consideration to administer necessary clinical intervention and provide requisite assistance. (237)

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Symptoms

18.5% of adults in the USA in 2019 showed symptoms of depression that lasted for at least two weeks (Villarroel and Terlizzi, 2020).
So, people with major depression experience a few common symptoms such as a lack of interest in previously involved activities, poor hygiene, worthlessness, helplessness and many more that are widely present in individuals of any age suffering from this mental health issue (Deng et al., 2021).

(Source: Richter, 2022)

While talking about this mental disorder, emphasising the fundamental identifiable symptoms need to be elucidated for better understanding. Among the popular symptoms, having a deep feeling of loss of interest or pleasure in different activities and regular mood swings are widely reported identifiers (Deng et al., 2021).
Besides, excessive guilt, poor self-worth, poor concentration, social withdrawal, poor executive functioning, hopelessness, robust change in the sleep cycle and appetite, lack of energy and suicidal thoughts and ideation are also visible symptoms of major depression (Ostinelli et al., 2021).
Mental healthcare workers diagnose any person with major depression only when it causes significant difficulty in the daily living of that person especially in the functioning of personal and professional life. The patterns or presence of depressive episodes can only be identified if 6 of the symptoms mentioned above are present for at least or more than 2 months in a person (Kennis et al., 2020).
In addition, the presence of recurrent depressive episodes such as a history of diagnosis with major depression with at least a couple of depressive episodes can be considered for serious clinical intervention and treatment. During the COVID-19 pandemic, 42.4% of the total US population has experienced both anxiety and depression (Richter, 2022).
Genetics is the primary key factor behind the development of depression as it highlights the presence of depression in the family. (227)

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Genetics

Genetic factors can be considered a major cause of developing major depression.
Genetic presence or family history of major depression is an essential predisposing factor for this mental disorder (Roberson-Nay et al., 2020).

(Source: Yao et al., 2022)

(Source: Roberson-Nay et al., 2020)

Genetics is an important contributing factor to the development of major depression which consists of different other sub-factors. Scientific studies have shown that people with a history of depression in their family are vulnerable to major depression. Even researchers identified that particular genes have influenced the biological pathways that contribute to mood regulation, neurotransmitter functions and stress response (Cai et al., 2020).
Major depression is also considered a polygenic disorder as multiple genes are responsible or can be considered the risk factors for developing this mental disorder (Mitchell et al., 2021). Contemporary family studies focused on twin studies significantly showed the influence of genetic factors contributes a lot to developing major depression (Roberson-Nay et al., 2020).
Although these can be considered an important environmental factor as well, the influence of genes escalates the proneness towards the development of major depressive disorder. However, genetic factors in association with different environmental components increase the potential chance of depression. In addition, epigenetic mechanisms regulate the expression of genes without changing the internal DNA sequence (Ortega et al., 2022).
Thus, genetic factors affect mood, behaviour, cognitive functioning, discharge of neurotransmitters, neuroplasticity and other determining factors for the development of depression. Consequently, genes are significantly associated with major depression as they produce neurotransmitters, transport important neural signals and activate necessary neurotransmitters (Kendall et al., 2021).
In addition, neurological explanation is also important to consider for evaluating the presence and severity of depression. (238)

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Neurobiology

Although genetic factors play a pivotal role in the development of major depressive disorder, they also contribute to the shaping and alteration of neurobiological Pathways which get significantly impaired while having depression (Jiang et al., 2022).
As the neurotransmitters get altered due to depression, epigenetic mechanisms help regulate gene expression and can easily modulate different neurological processes without changing the underlying sequence of DNA.

(Source: Kim et al., 2020)

(Source: Cui et al., 2024)

Different cortical systems such as the serotonin system, hypothalamic pituitary adrenal axis, dopamine system and brain-derived neurotrophic factors are some of the special neurobiological components that implicate major depression within a person (Trifut et al., 2020).
Considering the neurobiological perspective, concerning the genome-wide association studies (GWAS), brain structure, function of vital parts within the brain, neurotransmitters and other multiple neurological variants determine a person's susceptibility to major depression (Jiang et al., 2022).
Major depressive disorder is also identifiable by impairments in emotional regulation, cognition, motor functioning, memory neuro-vegetative symptoms and motivation. Along with the primary defects, this debilitating psychiatric issue showed that people with depression show altered dopaminergic, serotonergic, glutamatergic and noradrenergic systems, abnormalities in the HPA Axis, increased inflammation, decreased neurogenesis, vascular changes and alteration in neuroplasticity (Azizi, 2022).
Consequently, dysregulation of different neurotransmitter systems along with the HPA Axis is evident in individuals with major depressive disorder. Abnormalities in functional and structural aspects of the brain especially regions that focus on mood regulation like the amygdala, prefrontal cortex and hippocampus are evident in these people (Scheepens et al., 2020). Individuals with chronic stress exposure have reduced neuroplasticity and that influences the persistence of depressive disorders.
The inflammatory process within the brain due to stress impairs the functions of neurotransmitters, changes neuroendocrine pathways and facilitates the development of major depressive symptoms (Westfall et al., 2021). Besides, the environment has a significant influence on a person's development of major depression. (240)

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Neuroanatomy

The prefrontal cortex becomes shrank and activity gets reduced by MDD.
The amygdala becomes hyperactive and stress tolerance is reduced by MDD.
MDD regulates mood and alters communication as it impacts on the white matter integrity.

(Source: Thomas et al., 2021)

MDD can have major adverse effects on the neuroanatomy creating diverse impacts in various regions of the brain. The prefrontal cortex gets slowed as depression reduces the volume and activity of the individuals. As a result, people get slower in consecutively executive functioning responsible for decision-making, thinking, problem-solving and regulating emotions (Pizzagalli and Roberts, 2022).
The limbic system comprising the hippocampus and amygdala becomes hyperactive and lesser in volume, showing poor memory or stress tolerance (Siegel et al., 2021). In this way, MDD also impacts the HPA Axis, which elevates the level of stress hormones (cortisol) which worsens the mental health condition. Consequently, it leads to neuronal atrophy and lower density of the synapse resulting in a lesser level of neurotransmitters impacting mood and information processing.
MDD affects the white matter integrity, altering the communication process and other crucial cognitive functions (Thomas et al., 2021). Reduced neuroplasticity and poor effectiveness of clinical treatment are prevalent in people with MDD. In addition, the Default mode network (DMN), important for mind-wandering and self-referential thinking shows different and abnormal connectivity while having depression (Scalabrini et al., 2020).
Dysfunctional connectivity in DMN is a prevalent feature of depression. Thus, neuroanatomical changes are associated with the neurobiological issues that are highlighted with MDD and facilitate the development and recurrence of depressive symptoms. (216)

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Environment

Environmental factors consist of early life experiences, and cultural and social factors that cumulatively aggravate the chances of developing depression.
Environmental influence to develop chronic stress alters the functioning of different biological systems within the body, changing the mind and behaviour of an individual (Askeland et al., 2020).

(Source: Barrett et al., 2021)

(Source: Askeland et al., 2020)

Different environmental factors exacerbate major depression that initiates from an early age and continues till adulthood. Adverse early life experiences like abuse, negligence, broken home, parental loss, and trauma significantly enhance the possibility of developing major depression. consequently, childhood stressors impair and disrupt the development of requisite neural circuits for effective emotional regulation and alter the function of neurobiological systems (Dagnino et al., 2020).
In addition, specific life events especially job loss, dispossession, divorce, and death of a loved one are also key factors making any person susceptible to major depressive episodes (Askeland et al., 2020). Societal factors such as loneliness, being quarantined, socialisation, financial difficulties, housing instability, unemployment, dislocation, urbanisation, pollution and poor access to requisite administrative and healthcare services elevate the chances of developing major depression (Remes et al., 2021).
Moreover, cultural and social norms, stigma, racism, inequality and expectations regarding mental health disorders also impact the recognition or expression of different depressive symptoms. As a result, systemic oppression, discrimination, societal judgements and equality increase the level of stress along with increasing the chances of developing major depression (Barrett et al., 2021). Thus, considering the environmental factors is crucial to identifying the fundamental reasons behind the disorder.
Environmental reasons behind developing MDD especially socioeconomic status, sexual orientation and race or ethnic groups can help mental healthcare workers to administer proper intervention and treatment. Apart from, this, various essential elements are perceived as the perpetuating factors behind the persistence of this mental health issue. (245)

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Maintenance of Major Depression

Major depressive disorder is sustained by substance abuse, personality and behavioural issues and the presence of other mental disorders.
Different biological, personal, environmental, and other important perpetuating factors cumulatively play a pivotal role in the maintenance of major depression within a person (Achterbergh et al., 2020).

(Source: Achterbergh et al., 2020)

The crucial perpetuating factors enhance the chances of not only the development but also maintenance of the mental illness. In the case of major depression, personal vulnerabilities such as poor self-confidence, lower self-esteem, being self-critical, dependence, substance abuse, unemployment, pessimism and distorted thinking are some significantly important perpetuating factors (Smith et al., 2021).
The cumulative impact of these factors increases the psychological disorder severity and sustenance in a person. Environmental stressors are also important to consider while analysing the perpetuating elements of major depression. In this case, unemployment and access to proper education, educational qualification, financial burden, traumatic life experiences, sexual or physical or psychological abuse, negligence from childhood, social exclusion, and persistent exposure to chronic stress are important components of the environment that engenders the persistence of mental disorders (Gotlib et al., 2020).
In addition, biological perpetuating factors such as brain chemistry and neurotransmitters, family history, and genetics are inevitable to maintain major depressive disorder (Narmandakh et al., 2021). Thus, the integrated influence of these three perpetuating elements is significantly important to consider and eliminate to reduce the severity and persistence of depression.
Additionally, poor nutrition, pregnancy, major physical illnesses, loss of parents at an early age and a difficult postnatal period are also crucial perpetuating factors (Achterbergh et al., 2020). Even with the presence of these factors, various treatment procedures can be applied and incorporated to reduce the severity of major depression and derive psychological stability. (238)

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Treatment

Psychotherapy is a beneficial treatment major to improve mental health conditions and reduce the severity of depressive symptoms.
Medications such as selective serotonin reuptake inhibitors, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are crucial medicines to increase coping within patients with psychological health issues (Morris et al., 2021).
Inducing self-care or effectively changing the lifestyle by staying connected or social interaction with people, regularly exercising, sublimating negative emotions in productive ways, avoiding substance abuse, and maintaining a particular eating and sleeping behaviour can derive stability within the mind and reduce major depressive disorder.

(Source: Cuijpers et al., 2020)

Treatment of depression can be administered with a combination of various procedures including psychotherapy, lifestyle changes, medication and different therapeutic interventions. The mental healthcare workers administer necessary treatment depending on the severity of the major depression. Psychotherapy is a widely used treatment measure that is applied to people with psychological disorders as it cultivates coping strategies, and self-awareness resolves interpersonal conflicts and increases acceptance (Cuijpers et al., 2021).
Different types of therapies like cognitive behavioural therapy, psychodynamic therapy, interpersonal therapy, rational emotive behavioural therapy and mindfulness or meditation are some prevalently used psychotherapeutic measures. Concerning the severity of major depression, psychiatrists often prescribe anti-depressant and anti-anxiety medicines to alleviate depressive symptoms and effectively restore neurotransmitters within the brain (Morris et al., 2021).
Clinicians while suggesting specific medicines for people with MDD, focus on increasing the level of neurotransmitters. Scientific studies have shown that higher levels of dopamine, epinephrine, noradrenaline and serotonin can work efficiently to culminate the increased risk of MDD. Mental health care assistance providers also help individuals suffering from major depression to make significant changes in their lifestyle.
They recommend incorporating a healthy diet, promoting regular exercise, maintaining sleep hygiene and following stress-reducing techniques. As a result, the integrated impact of all these treatment factors improves the quality of life of that person diagnosed with major depression or having mild depressive symptoms (Galindo-Vázquez et al., 2020). (228)

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Treatment

Electroconvulsive therapy and transcranial magnetic stimulation are also crucial therapeutic measures for people with treatment-resistant and higher critical mental health conditions (Li et al., 2021).
Regional therapies like meditation, yoga and acupuncture are also popular treatment procedures applied to people with major depressive disorder (Zhao et al., 2023).

(Source: Zhao et al., 2023).

Involvement of society especially support from family and friends, no judgments of society towards people with mental disorders, and availability and accessibility of practical psychotherapeutic assistance can help people to develop a sense of belongingness in society (Ustun, 2021). Even other treatment procedures like electroconvulsive therapy and transcranial magnetic stimulation are also recommended treatment processes to help individuals with severe major depressive symptoms (Li et al., 2021).
In addition, people who are resistant to treatment can be helped with these stimulating interventions as these make various regions within the brain excited that are necessary to provide relief to a person with major depressive disorder (Frid et al., 2023). Mental healthcare workers mainly recommend psychological treatments and self-care procedures as medications do have significant side effects that also hamper the functioning of other body systems.
Even some regional or alternative treatments, such as the consumption of herbal supplements, meditation, aromatherapy, acupuncture, yoga, and other relaxing techniques complement the psychiatric and psychotherapy treatment procedure (Zhao et al., 2023). Individuals experiencing social taboos or avoiding the side effects of medications are keen to incorporate these relaxing measures to reduce the severity of depressive symptoms. In fact, with the acceptance of mental health issues and awareness about MDD, people have become more vocal about their psychological health issues.
As a result, considering the advanced society and technology, people with or without a diagnosis of MDD are taking digital intervention, online or offline psychotherapy or using mental health protecting apps. Even though, there are several psychotherapeutic assisting means, 76% to 85% of the total population of lower or middle-income countries either become hesitant to take or do not get adequate mental health treatment (WHO, 2020). (280)

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Conclusion

The symptoms of major depressive disorder can be abated by proper clinical intervention and treatment ranging from psychotherapy to acupuncture.
Genetic, neurobiological and environmental factors individually and cumulatively contribute and determine the extent of the severity of the disorder.

(Source: Zhao et al., 2023)

While considering individuals with major depressive disorder it is essential to identify and analyse the genetic, neurobiological and environmental factors that increase the potential chances of getting worse. Additionally, developing incisive knowledge about the impact of these factors on the individual and deducing the ways to address these factors can help the individual to control the severity of the depressive symptoms and thoroughly culminate a wide range of hazards experienced by the individual in every sector of their lives.
While associating with genetic factors, the role of family and the history of depression running in the family plays a pivotal role in developing depression in any person from an early age. In addition, while a person suffers from prolonged sadness or social withdrawal, significant changes occur within the brain that escalate the propensity of developing and suffering from major depressive disorder. In this context, serotonergic and dopaminergic systems are affected.
The vicious cycle occurs between mental impairment and neurotransmitters. They are intertwined and vice-versa. Among the important environmental factors, early exposure to abuse, traumatic events, social discrimination, unemployment, social isolation and many more are significantly responsible. Various causes such as substance abuse, postpartum, loss of a loved one, accidents, and physical and sexual abuse can be considered important contributing factors behind the maintenance or persistence of major depressive disorder.
Different treatment procedures including psychotherapy, medication, ECT, TMS, mindfulness, and self-care techniques are recommended by mental healthcare workers to reduce the severity of the symptoms. (244)

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