Depression or Major Depressive Disorder
December 4, 2025According to the National Institute for Health and Care Excellence (NICE, 2022), major depressive disorder is characterized by persistent low mood, loss of pleasure or interest in activities, and associated cognitive, behavioral, and physical symptoms that significantly impair functioning. Depression exists on a spectrum from mild to severe, with varying impacts on daily life (NICE, 2022). The condition affects individuals across all demographics and represents a leading cause of disability. MDD typically follows a recurrent course, with many individuals experiencing multiple episodes throughout their lifetime. Early recognition and appropriate intervention are essential for optimal outcomes and relapse prevention (NICE, 2022).
Epidemiology
Major depressive disorder (MDD) presents a substantial and growing global public health challenge, with significant variations across regions and nations. According to Zhao et al. (2025), depressive disorders in adolescents and young adults have shown concerning trends from 1990 to 2021, reflecting an escalating burden worldwide.
Globally, MDD affects millions of individuals, with prevalence rates varying considerably by geographic region (Zhao et al., 2025). High-income regions typically report higher diagnosed prevalence, though this may partially reflect better detection and reporting systems rather than true epidemiological differences. The Global Burden of Disease Study 2021 data reveals that depressive disorders contribute substantially to years lived with disability (YLDs), particularly among younger populations (Zhao et al., 2025).
Regional analyses demonstrate heterogeneity in MDD burden, with certain areas experiencing disproportionately high rates. Nationally, prevalence estimates range significantly, influenced by socioeconomic factors, healthcare access, and cultural attitudes toward mental health (Zhao et al., 2025). The disability-adjusted life years (DALYs) attributable to depressive disorders have increased over the three-decade period, highlighting the expanding impact on population health. These epidemiological patterns underscore the urgent need for targeted, culturally appropriate interventions addressing the global MDD crisis.
Etiology and Risk Factors
Major depressive disorder (MDD) arises from a complex interplay of biological, psychological, and environmental factors rather than a single causative agent. According to Mehra et al. (2025), genetic predisposition plays a significant role, with heritability estimates ranging from 37-40%, indicating substantial familial risk for developing the disorder.
Neurobiological factors contribute significantly to MDD's etiology. Dysregulation of neurotransmitter systems, particularly serotonin, norepinephrine, and dopamine, forms a foundational component (Mehra et al., 2025). Additionally, structural and functional brain abnormalities in regions governing mood regulation, including the prefrontal cortex, hippocampus, and amygdala, have been implicated in the disorder's development.
Environmental stressors serve as crucial triggers, with chronic stress, childhood trauma, and adverse life events significantly increasing MDD risk (Mehra et al., 2025). These experiences can induce lasting neurobiological changes through epigenetic modifications, altering gene expression without changing DNA sequences.
Psychosocial factors including social isolation, lack of support systems, and maladaptive cognitive patterns further contribute to vulnerability (Mehra et al., 2025). Medical comorbidities, particularly chronic illnesses and inflammatory conditions, also increase susceptibility to developing MDD. This multifactorial etiology underscores the need for comprehensive, individualized approaches to understanding and treating depression.
Pathophysiology
Diagnostic Criteria
Assessment/Evaluation
Assessment/Evaluation
Assessment/Evaluation
In the APA Clinical Practice Guideline for the Treatment of Depression (2019), effective the clinical features of Major Depressive Disorder (MDD) are based on the criteria established in the DSM-5. The guideline emphasizes that for a diagnosis of MDD, a patient must experience at least five of the following symptoms during the same two-week period, and at least one of the symptoms must be either (1) depressed mood or (2) loss of interest or pleasure.
Core Clinical Features (Must have at least one)
-
Depressed Mood:
Feeling sad, empty, hopeless, or appearing tearful most of the day, nearly every day. (In children and adolescents, this can manifest as an irritable mood). -
Anhedonia:
Significantly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day.
Physical and Cognitive Features
1. Weight or Appetite Changes:
Significant weight loss when not dieting, weight gain, or a decrease/increase in appetite nearly every day.
2. Sleep Disturbance:
Insomnia (difficulty sleeping) or hypersomnia (excessive sleeping) nearly every day.
3. Psychomotor Agitation or Retardation:
Observable restlessness (e.g., pacing, inability to sit still) or being "slowed down" (e.g., slowed speech or movement), as noticed by others.
4. Fatigue:
Loss of energy or daily fatigue, even without physical exertion.
5. Feelings of Worthlessness or Guilt:
Excessive or inappropriate guilt (which may be delusional) or feeling worthless nearly every day.
6. Diminished Ability to Think:
Diminished ability to concentrate, think clearly, or make decisions (often described as "brain fog").
Suicidality:
Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt/specific plan for committing suicide.
The APA guideline highlights several nuances regarding how these features present across different populations:
1. Functional Impairment:
The symptoms must cause "clinically significant distress or impairment" in social, occupational, or other important areas of functioning.
2. The Three Age Cohorts:
The guideline specifically analyzes these features across three groups—children/adolescents, adults, and older adults.
1. Children/Adolescents:
Often present with irritability rather than sadness and may fail to make expected weight gains.
2. Adults?
3. Older Adults:
May present more frequently with somatic (physical) complaints and cognitive symptoms (pseudodementia) rather than overt sadness.
3. Exclusion Criteria:
The features must not be attributable to the physiological effects of a substance (e.g., drug abuse, medication) or another medical condition.
Etiology and Risk Factors
Etiology and Risk Factors
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