How does a depressed brain work differently from a healthy brain? Can depression be cured?
These are complex questions and, as with all science, there is still much to be discovered and understood. But research in recent decades has come a long way in describing what’s going on in the depressed brain and what treatments help patients to recover.
Originating with research in the 1950’s and ‘60’s, a theory of “chemical imbalance” became the beginning of modern approaches to treating depression. It was thought that depression was caused by a deficit of monoamines—serotonin, norepinephrine, and dopamine in the brain, so drugs that increased monoamine transmission, especially serotonin, were used to reduce the symptoms of depression. Thus selective serotonin reuptake inhibitors (SSRIs) became the treatment of choice, and due to intense advertisement and very real successes, the idea that a deficit of serotonin causes depression took hold in the popular imagination.
But, although the science has moved on from the straightforward chemical deficit explanation, public understanding of depression remains fixed around serotonin. It’s understandable: the explanation is clear and easily understood. It rejects stigma, since the whole thing is a chemical problem that can be easily corrected, and, as noted above, it has had some real successes. However, the public’s trust in medical treatment, especially psychiatric treatment is being undermined in recent years, and letting an incomplete or outdated explanation stand for major depressive illness can have the unintended consequence of contributing to this lack of trust.
In recent decades, researchers and clinicians have focused on approaches to major depressive disorder (MDD) that take into account contributing factors such as genetic load, in utero exposures, stress and trauma, neuroinflammation, and medical conditions. This does not negate the real importance of serotonin in brain chemistry, but it places it in a constellation of other causative factors.
A general description of the brain in MDD is now emerging that sees the brain processing networks as “stuck”, or more inflexible when approaching tasks requiring cognitive and/or emotional processing. Another result of being “stuck” is negativity bias, where the brain doesn’t respond to positive stimuli or rewards, but gives excessive attention to negative input and punishment. Normal pathways of communication between different areas of the brain are impaired in their ability to regulate one another, leaving the brain with more inflexibility and negativity bias.
To increase flexibility, restore communication between core functional hubs within the brain, and to balance negativity bias with a healthy response to positive input, neuroplasticity is key. Neuroplasticity is defined as synaptic changes that alter the activity and connectivity of brain regions, improving cognitive and emotional processing, and increasing activity in those regions that have been underperforming.
SSRIs and other treatments work best when combined with positive experiences in everyday life. In general, combined psychotherapy and pharmacotherapy are more effective than either treatment alone. Neuroplasticity enhances the brain’s capacity for change, but positive experiences are still important for shaping adaptive outcomes.
The latest research continues to show that depression is a real disease with biological roots: it is not a result of personal weakness or failure. Pharmacological and psychological treatments are best combined to enable the brain to regain flexibility and plasticity and get back on the road to health.