One of the world's leading causes of disability: symptoms, what's happening in the brain (beyond 'low serotonin'), stress and inflammation, and treatments from talking therapy and medication to ketamine and brain stimulation.
Mental Health & Neurodevelopment
Beginner
Depression
The Editors
April 14, 2026
3 min read
In plain English
Depression is more than feeling sad. It's a persistent low mood or loss of interest lasting weeks or longer, often with sleep, appetite, energy and concentration problems. It involves changes in brain circuits for mood, reward and stress — not simply 'low serotonin'. Therapy, medication, exercise and other treatments help most people.
Beginner level: No background needed. Everyday language, everyday examples — the place to start.
Concepts to know first
Go deeper next
What depression is
Major depressive disorder involves at least two weeks of persistently low mood and/or loss of interest or pleasure (anhedonia), with symptoms such as changes in sleep and appetite, fatigue, difficulty concentrating, feelings of worthlessness or guilt, slowed movement or agitation, and sometimes thoughts of death or suicide. The WHO estimates depression affects roughly 280 million people worldwide, and it is a leading cause of disability. It is about 1.5 to 2 times more common in women.
Beyond the chemical imbalance
The idea that depression is caused by low serotonin — the "chemical imbalance" — came from the observation in the 1950s that drugs boosting monoamines improved mood. A 2022 umbrella review by Joanna Moncrieff and colleagues found no consistent evidence that depression is caused by low serotonin, prompting wide debate. Most researchers now see depression as involving many factors.
What's happening in the brain
Research implicates several systems. Stress: chronic stress and HPA-axis disruption; elevated cortisol in some people. Circuits: altered activity and connectivity between the prefrontal cortex, the anterior cingulate (especially the subgenual region), the amygdala and the reward system, contributing to negative bias and anhedonia. Plasticity: reduced synaptic connections in prefrontal and hippocampal regions, with treatments possibly working by restoring plasticity (BDNF is involved). Inflammation: a subset of people show raised inflammatory markers. Genetics contributes moderately, alongside life events such as loss, isolation and childhood adversity.
Treatment
Psychotherapies — cognitive behavioural therapy, behavioural activation, interpersonal therapy — are effective, and for mild to moderate depression often as effective as medication. Antidepressants (SSRIs, SNRIs and others) help many people, especially in more severe depression, usually over several weeks. Exercise has substantial evidence. For treatment-resistant depression: esketamine nasal spray (US approval 2019) and ketamine can act within hours; electroconvulsive therapy (ECT), given under anaesthesia, remains the most effective treatment for severe depression; transcranial magnetic stimulation is another option. Combining treatments often works best.
If you are struggling
If you or someone you know is having thoughts of suicide, contact local emergency services or a crisis line (such as 988 in the US, or Samaritans on 116 123 in the UK and Ireland). Depression is treatable, and reaching out is a strength.
Everyday examples & things to try
Analogy
A stuck thermostat
Normal sadness is like the weather — it passes. Depression can be more like a thermostat that's stuck on low: it doesn't respond properly to good things happening. Treatments aim to unstick the thermostat so the system can respond again.
Try it
Behavioural activation
A core technique of behavioural activation therapy: schedule small, achievable activities that used to give pleasure or a sense of accomplishment — a short walk, calling a friend — even when motivation is low. Action often comes before motivation, not after.
Key takeaways
- Depression involves persistent low mood or anhedonia with other symptoms for at least two weeks.
- It involves stress, circuit, plasticity and sometimes inflammatory changes — not just low serotonin.
- Therapy, antidepressants, exercise, ketamine/esketamine, ECT and TMS are effective options.
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