Psychology › Mental health & disorders › Depression and mood disorders
The 'chemical imbalance' theory of depression
1965; reviewed 2022· Theory or model
Historical, now abandonedImportant in its time, no longer accepted.
The once-popular idea that depression is caused by a shortage of brain chemicals, especially serotonin.
See it on the Psychology map →What it says
In 1965 Joseph Schildkraut proposed that depression reflects low norepinephrine; British researcher Alec Coppen pointed to serotonin in 1967. The theory fit early antidepressants, which raise these chemicals, and drug advertising after Prozac (1987) made 'chemical imbalance' a household phrase. A 2022 review led by Joanna Moncrieff found no consistent evidence that depressed people have low serotonin. Many psychiatrists say they long saw it as a simplification. Antidepressants still help many people; how is unclear.
Why it matters
It shaped how millions understood their illness and eased stigma, but it oversold biology. Whether antidepressants work is a separate question from why.
The evidence
Studies of serotonin byproducts, receptors and genes, plus experiments lowering serotonin in volunteers, mostly failed to show a deficit, as the 2022 umbrella review in Molecular Psychiatry summarized.
Open questions
How antidepressants help is open: leading ideas include rewiring brain connections, shifting emotional biases and reducing inflammation. Some researchers dispute parts of the 2022 review.
Connections (2)
▸The 'chemical imbalance' theory of depression blamed low levels of SerotoninWeak or failed to replicate
The connection
Early antidepressants raised serotonin and norepinephrine, so researchers reasoned backward that depression must involve too little of them. SSRIs, which block serotonin's recycling, then made serotonin the star of the theory and of drug advertising in the 1990s.
Who showed it and when
Alec Coppen in Britain (1967) and others in the 1960s–70s; it reached the public with Prozac's US launch in 1988 and TV drug ads after 1997.
How solid is it?
The link was the theory's own claim; tests of it, summarized in the 2022 Moncrieff review, found no consistent evidence of low serotonin in depression.
Open questions
Serotonin may still play some role in mood and in how drugs work; the debate is whether a deficit causes depression.
▸The 'chemical imbalance' theory of depression oversimplified the causes of Depression and mood disordersWeak or failed to replicate
The connection
The theory reduced depression to a chemical shortfall fixable by a pill, sidelining stress, loss, sleep, inflammation and life circumstances. It helped reduce stigma, but research shows depression arises from many interacting causes, and some studies suggest the message makes people more pessimistic about recovering.
Who showed it and when
Popular from the 1990s through drug ads and doctors' explanations; challenged by researchers such as Joanna Moncrieff and Irving Kirsch, and by the 2022 umbrella review.
How solid is it?
Studies find no consistent serotonin deficit in depression; experiments show telling people their depression is chemical can lower confidence in their own ability to recover.
Open questions
Biology clearly matters in depression; the open questions are which processes, and whether they differ between subtypes of patients.