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Depression: A Modern Scientific and Clinical Perspective

Updated: Sep 3


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Depression, or Major Depressive Disorder (MDD), is one of the most significant challenges to global health. Due to its high prevalence, serious impact on quality of life, and broad spectrum of symptoms, depression ranks among the leading causes of disability worldwide. According to the World Health Organization, around 280 million people worldwide were affected by depression in 2019, accounting for approximately 5% of the adult population (WHO Fact Sheet). In the United States, for example, 21 million people experienced at least one depressive episode in 2021 (NIMH).


What Is Depression? Depression is not simply “feeling down” or experiencing temporary sadness. It is a clinical syndrome that affects emotions, thinking, behavior, and overall physical health. The main diagnostic criteria include persistently low mood, loss of interest or pleasure in usual activities, and difficulties in daily functioning, often accompanied by cognitive and somatic symptoms such as insomnia, fatigue, appetite disturbances, and thoughts of death or suicide (Cui et al., 2024, Medscape 2024). To be diagnosed, symptoms must be present for at least two weeks and cause significant distress or impairment.


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Causes and Risk Factors

Multifactorial Origins Depression does not stem from a single cause, but from a complex interplay of biological, psychological, and social factors. Genetic predisposition plays a key role—people with a family history of depression are at higher risk. New genetic and epigenetic studies reveal specific genes and mechanisms that increase vulnerability (Cui et al., 2024; OpenTargets, 2023).


Biological Mechanisms

  • Imbalances in neurotransmitters such as serotonin, norepinephrine, and dopamine.

  • Impaired neuroplasticity and neuroinflammation (Pitsillou et al., 2020).

  • Dysregulation in hormonal systems, particularly the hypothalamic-pituitary-adrenal (HPA) axis, often triggered by chronic stress (Marx et al., 2023).

  • Exposure to artificial light at night (ALAN), which has been linked to an increased risk of depression (Jstage, 2024).


Psychological and Social Factors

  • Personality traits (e.g., neuroticism, low self-esteem, ruminative thinking).

  • Traumatic experiences, childhood conflicts, abuse, or loss.

  • Social isolation, lack of support, low socioeconomic status.

  • Chronic illness, disability, and poverty also raise the risk.



Key Symptoms and Diagnosis

Symptoms Depression manifests across emotional, cognitive, and physical dimensions:

  • Emotional: persistently low or "empty" mood, loss of pleasure (anhedonia).

  • Cognitive: difficulty concentrating, indecisiveness, negative thoughts, and hopelessness.

  • Physical: changes in appetite and weight, insomnia or excessive sleep, loss of energy, slowed or agitated movements, and unexplained physical pain.

For a clinical diagnosis (based on DSM-5/ICD-11), at least five of the symptoms listed above must be present, one of which must be either depressed mood or anhedonia, for a period of at least two weeks (Medscape, 2024).


Diagnostic Tools

  • Standardized scales such as PHQ-9, HAM-D, MADRS.

  • Comprehensive psychiatric evaluation, including screening for anxiety disorders, substance use, and physical illnesses.

  • Systematic screening is recommended for adults, including pregnant individuals, the elderly, and patients with chronic conditions (USPSTF, 2023).


Treatment and Recommendations

Stepwise and Personalized Strategy

  • Mild depression: Psychotherapy is the preferred approach—cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), and guided self-help.

  • Moderate to severe depression: A combination of psychotherapy and medication. Selective serotonin reuptake inhibitors (SSRIs) are most commonly used, but serotonin-norepinephrine reuptake inhibitors (SNRIs) and newer agents are also prescribed.

  • Treatment-resistant depression: Augmentation with atypical antipsychotics, mood stabilizers, or novel therapies like ketamine/esketamine—these show rapid effects but require careful monitoring due to potential side effects and risk of misuse (McIntyre et al., 2021).


Other Approaches:

  • Digital and internet-based therapies (online CBT) have proven effective, especially for individuals with limited access to specialists (Moshe et al., 2021).

  • Brain activity modulation: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) have shown good results as adjunct treatments.

  • Lifestyle changes: Physical activity, balanced nutrition (e.g., Mediterranean diet), sleep hygiene, reducing nighttime artificial light exposure, and social engagement are recommended as essential parts of a comprehensive treatment plan (Marx et al., 2023).


Prevention and Early Intervention According to the WHO, prevention programs targeting children and adolescents, the workplace, and families have been shown to reduce the risk of developing depression. Early diagnosis and treatment are key to preventing chronicity and complications.


Latest Scientific Advances

  • Expanding understanding of the neurobiology of depression through multi-omic approaches, neuroimaging, and biomarker discovery to support personalized therapies.

  • Development of new medications—ketamine and its derivatives—as fast-acting antidepressants, especially in treatment-resistant cases, though their long-term effects are still under investigation (Wilkinson, 2025).

  • Discovery of links between depression and other conditions, such as long COVID—depression, anxiety, and fatigue are among the most common consequences.


Expert Consensus Current scientific and clinical consensus holds that depression is a complex and heterogeneous disorder requiring an individualized, multi-layered therapeutic approach. Success in treatment depends on early diagnosis, use of standardized criteria and tools, a combination of psychotherapy and medication, inclusion of lifestyle interventions, digital solutions, and new therapies, as well as ongoing monitoring of suicide risk and treatment effectiveness.


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