Major Depressive Disorder (MDD) is a common psychiatric illness characterized by marked and persistent low mood, which may lead to various changes in thought, behavior and bodily functions. It may present with symptoms such as diminished capacity to respond emotionally, loss of interest, lack of energy, appetite changes, sleep disturbances and guilt-related thoughts. The disorder not only affects mood but also negatively impacts social relationships, academic performance and occupational functioning.

Major depressive disorder may begin at any age, though it most commonly emerges during adolescence or early adulthood. The clinical course may be recurrent, and in some individuals may take on a chronic nature. According to the World Health Organization, MDD may be one of the leading causes of disability worldwide.

DSM-5 Criteria for Major Depressive Disorder

The diagnosis of major depressive disorder can be made based on the criteria defined in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders – Fifth Edition). For diagnosis, at least five of the following symptoms must be present nearly every day, for at least two weeks, and throughout most of the day:

• Depressed mood (feelings of sadness, emptiness, hopelessness)
• Markedly diminished interest or pleasure
• Significant weight loss or gain (without dieting) or appetite changes
• Insomnia or hypersomnia
• Psychomotor agitation or retardation
• Loss of energy or fatigue
• Feelings of worthlessness or excessive guilt
• Diminished ability to think, concentrate or make decisions
• Thoughts of death, suicidal ideation, plans or attempts

These symptoms must cause significant impairment in social, occupational or other areas of functioning and must not be attributable to another medical condition or substance use.

Major Depressive Disorder Symptoms

Symptoms of MDD may manifest on emotional, cognitive and physical levels. The individual may feel persistently sad, empty or restless. They may withdraw from previously pleasurable activities and experience social disconnection. Physiological symptoms such as appetite loss or overeating, insomnia or hypersomnia, fatigue and low energy may accompany the picture.

On the cognitive level, problems such as distractibility, forgetfulness and difficulty making decisions may develop. In some individuals, pervasive thoughts of guilt, inadequacy or worthlessness may intensify. These experiences may increase the risk of suicidal ideation or attempts. Since not all individuals present with identical symptoms, the individual distribution of symptoms must be taken into account in the diagnostic process.

What Are the Causes of Major Depressive Disorder?

The development of major depressive disorder may involve the interaction of biological, genetic, psychological and environmental factors. Due to this multidimensional structure, a single cause cannot usually be identified.

Genetic predisposition is a significant contributor to risk. Individuals with a family history of depression have a higher likelihood of developing MDD. Twin studies indicate that genetic transmission may account for 30–40% of the risk.

Neurobiological factors include imbalances in serotonergic, noradrenergic and dopaminergic systems. In particular, reduced serotonin levels are considered one of the core biochemical bases of depressive symptoms. Hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis is another physiological process linked to depression.

Psychosocial stressors such as childhood trauma, parental loss, history of abuse, unemployment, divorce and chronic stress may contribute to the onset of depression. Early adverse experiences may weaken coping mechanisms.

Cognitive theories emphasize the role of internal dialogue, negative schemas and distortions in reality appraisal. Aaron T. Beck’s cognitive triad (negative thoughts about the self, the world and the future) is a prime example of this perspective.

What Are the Risk Factors for Major Depressive Disorder?

Various risk factors have been identified that may facilitate the development of major depressive disorder. These factors provide guidance for preventive mental health strategies:

• Genetic predisposition
• Female gender (higher prevalence of depression has been observed in women)
• Early life loss and trauma
• Chronic medical conditions (for example diabetes, cancer, cardiovascular diseases)
• Substance use (especially alcohol, stimulants)
• Social isolation, loneliness and lack of support
• Low socioeconomic status and unemployment
• Hormonal changes (for example postpartum period, menopause)

The co-occurrence of these factors increases vulnerability, though none alone can definitively determine the disorder.

How Is Major Depressive Disorder Diagnosed?

The diagnostic process includes a detailed clinical interview and psychiatric evaluation of symptom history. DSM-5 diagnostic criteria serve as the basis for assessment.

Physical illnesses (such as thyroid dysfunction, anemia), neurological conditions and the effects of substances must be ruled out. Laboratory tests and, if necessary, neuroimaging methods may be used for this purpose.

Other conditions that may resemble depression include dysthymia (persistent depressive disorder), bipolar depression and seasonal affective disorder. Thus, careful differentiation of clinical pictures is essential.

Major Depressive Disorder Treatment

Major depressive disorder can largely be managed with appropriate treatment approaches. Treatment plans must be individualized according to the severity and duration of symptoms, as well as the individual’s life circumstances.

1. Pharmacotherapy

Antidepressant medications form the cornerstone of MDD treatment. Selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs) are commonly used.

The effects of treatment are typically observed within 2–4 weeks, although a full clinical response may take longer. Side effects vary among individuals. Medication type, dosage and duration must be determined through regular psychiatric follow-up.

2. Psychotherapy

Cognitive Behavioral Therapy (CBT) is one of the most studied and effective psychotherapy methods for MDD. It focuses on identifying and restructuring negative automatic thoughts and enhancing functional behaviors.

Other effective approaches include interpersonal therapy (IPT), psychodynamic therapy and problem-solving therapy. Psychotherapy may be effective as a standalone treatment for mild to moderate depression.

3. Supportive Interventions and Lifestyle Adjustments

Regular physical activity, healthy nutrition, adequate sleep and social support may alleviate depressive symptoms. Mindfulness-based approaches and relaxation exercises may reduce stress levels.

Family education and support groups may help decrease feelings of isolation and improve treatment adherence. In severe depression, biological treatments such as electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) may be considered.

Impact on Daily Life

Major depressive disorder may cause functional impairment across many areas of life. Common consequences include declines in academic achievement, loss of occupational performance, strain in family relationships and social withdrawal.

Lack of energy and motivation may lead to neglect of personal care. Depression frequently co-occurs with anxiety disorders, substance use disorders and physical illnesses.

Additionally, major depressive disorder must be closely monitored due to suicide risk. Research shows that a substantial proportion of individuals who die by suicide have a history of depressive disorder. Therefore, early diagnosis and effective intervention may be lifesaving.