Major Depressive Disorder: An Overview and a Discussion of Stigma

Depression is one of the most common mental disorders worldwide, appearing in all age groups and representing a major cause of disability. The DSM-5 states that the twelve-month prevalence of major depressive disorder is approximately 7% in the United States, yet our understanding of its mechanisms remains limited and our social acceptance of the disease remains lacking. In a general description, depression is characterized by the presence of a “sad, empty, or irritable mood” (American Psychiatric Association, 2013, Depressive Disorders section, p. 155), with irritability especially common among afflicted teenagers. In regards to depression in adolescents, the concept often brings to mind an image of a teen struggling in school, exhibiting mood swings, overusing drugs or alcohol, experiencing isolation, avoiding social situations, and in some cases enacting self-harm (Sawchuk, 2026). While these can all be accurate portrayals of depressive behaviors, the disorder may also manifest itself in those who do not fit the picturesque epitomization of someone suffering from disease. In a survey conducted by Yokoya and colleagues (2018), 54.5% of participants expressed the belief that “It is not necessary to worry about depression in a person behaving brightly” (Results section, p. 202). Although the results represent the understanding of the applicable population from eight years ago, it is nonetheless still the general phenomenon that while most possess awareness of the fact that someone with depression can still appear “happy”, we usually do not think to take concern in the mental health of seemingly cheerful individuals around us. Thus, it is absolutely crucial that we maintain the effort to continually destigmatize depression not just for the public, but also for those experiencing the disorder themselves so that they may recognize their struggles and seek professional help in a timely manner. 

 

It is without a doubt that our perception of depression has come a long way with the increase in societal awareness and medical improvements. The earliest accounts of the disorder came from Mesopotamian writings dating back to the second millennium B.C.E. Initial interpretations of depression attributed the condition to spiritual rather than physiological reasons, asserting that it was caused by “demons and by the anger of the gods” (Schimelpfening, 2026, Ancient Greek and Roman Philosophy section). Hippocrates proposed the idea that depression was the result of an imbalance in the four body fluids known as humours: yellow bile, black bile, phlegm, and blood. This consequently led to treatments such as bloodletting. Throughout the Middle Ages, inhumane treatments such as exorcisms and imprisonment were enacted as depression was viewed to be caused by demonic possession. The Age of Enlightenment then brought about a turn of beliefs in which depression was seen as a weakness in temperament, resulting in many individuals being locked up and shunned from society. In the 1890s, Sigmund Freud introduced the idea of talk therapy to relieve depressive symptoms, and by the late 1900s, cognitive theories such as learned helplessness (experiencing a lack of control and the perception that nothing can be done to make a difference) began to form the modern view of depression. This was followed by the development of medical models for mental disorders, leading to the rise of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) that aim to mediate serotonin levels in the brain. In the 1970s, the term Major Depressive Disorder was brought into the public eye by clinicians in the United States, and in 1980, the condition was officially documented into the DSM. Nonetheless, society still has a long way to go before the disorder is completely normalized. 

 

The DSM-5 (2013) provides the most recent diagnostic criteria for the spectrum of depressive disorders, of which Major Depressive Disorder (MDD) is focused on here. MDD is characterized by discrete, recurrent episodes lasting for at least 2 weeks, with careful consideration given to distinguish between MDD, grief, and other causes such as substance abuse. As per the DSM-5 diagnostic criteria, the main symptoms of MDD include: 

1. Depressed or irritable mood nearly every day

2. Significant decrease in interest or pleasure

3. Weight loss or weight gain

4. An increase or decrease in appetite

5. Fatigue 

6. Feelings of guilt, worthlessness, or taking exaggerated responsibility for unfortunate events 

7. Physical agitation

8. Markedly diminished cognitive abilities 

9. Indecisiveness

10. Recurrent thoughts of death or suicide attempts 

When seeking medical or psychological aid, many afflicted individuals tend to emphasize bodily discomfort such as muscle aches, insomnia, or chronic fatigue while denying any depressive feelings (Bains & Abdijadid, 2023). As a result, it is crucial that professionals are able to recognize the characteristics of depression from such somatic complaints and guide the patient to express out-of-the-ordinary emotional changes or feelings of sadness. 

 

Although research has identified an abundance of brain regions and physiological changes associated with depression, no laboratory test has been developed correlating MDD with biological markers that may be used as a diagnostic tool (American Psychiatric Association, 2013). This has led to the diagnosis of MDD being dependent on subjective reports from the patient or from those close to the patient, as well as behavioral assessments based on set criteria (Bains & Abdijadid, 2023). Depression is further not a simple matter of an excess or deficit in particular neurotransmitters, nor can it be accurately pinpointed in an individual without a holistic examining of activity in the functioning of nerve circuits, between individual nerve cells, and in different brain regions. Nevertheless, it is still useful to gain a general understanding of the biological changes and processes involved with the condition. The limbic system is closely linked to depression as well as other emotional disorders. It is a group of structures deep within the brain responsible for regulating emotions, memory, and basic bodily processes, consisting of four main structures: the thalamus, hypothalamus, amygdala, and hippocampus (Cleveland Clinic, 2024). The amygdala is primarily associated with emotions such as fear and anger, as well as driving the fight-or-flight response in situations of arousal. Activity in the amygdala has been shown to be higher in individuals suffering from depression–with heightened activity continuing after recovery, even causing the amygdala to enlarge in some cases (Harvard Health Publishing, 2022). The hippocampus plays a crucial role in the processing and storing of long-term memory, and this structure has been shown to be smaller in depressed individuals due to continuous exposure to stress hormones and the diminished growth of neurons (Harvard Health Publishing, 2022). Furthermore, the frontal lobe has been shown to be the most common region reflecting anatomical abnormalities in those with MDD, including changes in the volume of frontal lobe regions, and reductions in the volume of gray matter (Zhang et al., 2018). 

 

The most modern treatment of MDD takes on a multidimensional, holistic approach, often combining medical treatment with cognitive-behavioral therapy (CBT) and talk therapy. This is reflective of the multifactorial etiology of depression, combining “biological, genetic, environmental, and psychosocial factors” (Bains & Abdijadid, 2023). Earlier approaches to treating MDD were reflective of the belief that abnormalities in neurotransmitter levels comprised the main cause of the disorder, with the widespread use of antidepressants. Selective serotonin reuptake inhibitors (SSRIs), for example, prevent the reabsorption of serotonin from the synaptic cleft, prolonging the effects of serotonin for mood improvement (Cleveland Clinic, 2025). Yet those who receive such medications experience delayed effects, where they only begin to feel better after several weeks or longer, illuminating the fact that depression is more complex than a simple neurotransmitter deficiency (Harvard Health Publishing, 2022). Treatments for MDD now take into account a more comprehensive understanding of its causes. Combination treatment of both medication and psychotherapy has been demonstrated to be more effective than either treatment by itself (Bains & Abdijadid, 2023). Psychotherapy, also known as talk therapy, involves sharing personal experiences and related feelings with a mental health professional. It includes methods such as cognitive behavioral therapy (CBT) and mindfulness-based cognitive therapy (MBCT). Brain stimulation therapies are another form of treatment. In electroconvulsive therapy (ECT), electrical currents are administered to the brain, which in turn influence brain chemistry and neurotransmitter activity (Sawchuk, 2026). In transcranial magnetic stimulation (TMS), brief magnetic pulses sent to the brain help to stimulate nerve cells (Sawchuk, 2026). Lifestyle modification such as incorporating moderate exercises into an individual’s daily routine has also been shown to be effective in improving mild to moderate depression (Bains & Abdijadid, 2023). Often, affected individuals would benefit from trying a variety of treatments and combinations before settling on the most successful one. This can be a frustrating process, as certain medications may need several weeks or longer to take effect, and the body also needs time to adjust. Genetic influences can play a crucial role in the effectiveness of antidepressants; however, other factors similarly influence an individual’s full response to medication. Thus, it is important that patients are offered support both from medical professionals as well as family members and close friends. 

 

The prevalence of depression in women is approximately double that in men as a result of uncontrollable biological disparities in gender, including hormonal differences and the effects of childbirth (Bains & Abdijadid, 2023). This highlights the importance of a thorough public understanding and acceptance of depression as a mental disorder and not the result of common stereotypes such as the perception that women are weaker and more emotionally fragile. Depressive individuals often suffer from a sense of worthlessness or guilt from the perception that they have imparted inconvenience onto the lives of others, in some cases not because of any particular past failings, but as a result of the mental and physiological changes brought about by the disorder itself (American Psychiatric Association, 2013). The presence of stigmas or simply a lack of awareness of hallmark depressive symptoms may thus further exacerbate feelings of self-blame, dragging the individual further and further down the “bottomless pit” that many use as a metaphor for the disorder. Finally, it is crucial that grief is appropriately distinguished from depression. Grief in response to a significant loss is often tied to specific thoughts that are directly related to the loss itself, and self-esteem is generally intact (American Psychiatric Association, 2013). On the other hand, the depressed mood is much more persistent and not tied to any specific preoccupations, and feelings of worthlessness is a defining characteristic. Depression should not be dismissed as a simple matter of feeling sad, nor should any grieving individual be assumed to have depression and seen as someone in need of curing.