Major Depressive Disorder

Definition

DSM-5 requires five or more symptoms in the same two-week period, at least one being depressed mood or loss of interest or pleasure, representing a change from previous functioning.

The others are appetite or weight change, sleep disturbance, psychomotor change, fatigue, worthlessness or guilt, impaired concentration, and recurrent thoughts of death.

The threshold is a convention. Nothing distinguishes four symptoms from five other than where the line was drawn.

History

Melancholia is described in classical medicine and continuously since. The modern category dates from DSM-III in 1980, which merged several previously separate conditions — notably endogenous and reactive depression — into one.

That merge is still argued about. Some of the heterogeneity that makes the category difficult to study was created by it.

Theory

No single account is adequate, and the honest position is that the mechanisms differ between people.

• Cognitive: negative schemas, biased attention and memory, and rumination maintain low mood.
• Behavioural: reduced contact with reinforcement, and withdrawal that reduces it further.
• Interpersonal: role transitions, disputes, grief and deficits.
• Biological: heritability around 35 percent, with HPA axis and inflammation findings that are real at group level and not diagnostic at individual level.

The serotonin hypothesis in its simple form — that depression is caused by low serotonin — is not supported and has not been the mainstream view among researchers for a long time, though it persists in public explanation and in some clinical conversation.

Research

Lifetime prevalence is commonly estimated around 15 to 20 percent, with roughly twice the rate in women, a difference that emerges in adolescence and is not fully explained.

Psychotherapy and antidepressants have broadly comparable average effects for moderate depression, with combination treatment doing better than either alone for severe presentations. Antidepressant effects are larger at greater baseline severity.

Effect sizes across this literature have shrunk as trial quality has improved, and publication bias in the antidepressant literature has been demonstrated directly by comparing published papers with regulatory submissions.

Applications

Assessment usually combines interview with a severity measure such as the PHQ-9 or BDI-II. Treatment is stepped: guided self-help or brief therapy for mild presentations, psychotherapy or medication for moderate, combination for severe.

Relapse is common. Around half of people who have one episode have another, and continuation treatment after remission reduces that.

Criticism

• The category is enormously heterogeneous. A person who cannot sleep, cannot eat and is agitated and a person who sleeps constantly, overeats and is slowed both meet criteria.
• The two-week, five-symptom threshold is arbitrary and creates a cliff where there is a continuum.
• The chemical imbalance explanation is still given to patients despite not being supported, and there is evidence that believing it worsens prognostic expectations.
• Bereavement. Removing the bereavement exclusion in DSM-5 was contested and remains so.
• Measurement. Common scales weight somatic symptoms heavily, which inflates scores in people with physical illness.

References

• Turner, E. H., et al. (2008). Selective publication of antidepressant trials and its influence on apparent efficacy. New England Journal of Medicine, 358(3), 252-260.
• Cuijpers, P., et al. (2020). Psychotherapy for depression across different age groups: A systematic review and meta-analysis. JAMA Psychiatry, 77(7), 694.
• Moncrieff, J., et al. (2023). The serotonin theory of depression: A systematic umbrella review. Molecular Psychiatry, 28, 3243-3256.
• Fried, E. I., & Nesse, R. M. (2015). Depression is not a consistent syndrome. Journal of Affective Disorders, 172, 96-102.