How Depression Affects The Brain - Yale Medicine Explains

The current standard of care for the treatment of depression is based on what we call the monoamine deficiency hypothesis, essentially presuming that one of three neurotransmitters in the brain is deficient or underactive. Neurotransmitters can be thought of as the chemical messengers within the brain. They help one cell in the brain communicate with another to pass that message along.

However, the reality is there are more than a hundred neurotransmitters in the brain and billions of connections between neurons. So, we know that the monoamine deficiency hypothesis is limited. For decades, we thought that the primary pathology, the primary cause of depression, was some abnormality in these neurotransmitters, specifically serotonin or norepinephrine.

However, norepinephrine and serotonin did not seem to account for the symptoms of depression in people who had major depression. Instead, the chemical messengers between the nerve cells in the higher centers of the brain involved in regulating mood and emotion, which include glutamate and GABA, were possibilities as alternative causes for the symptoms of depression.

We know that these two, which are the most ubiquitous and abundant neurotransmitters in the brain, actually regulate how the brain is changing over time and adapting. When you are exposed to severe and chronic stress, like people experience when they have depression, you lose some of these connections between the nerve cells, and the communication in these circuits becomes inefficient and noisy. Because of the noisy communication in the circuits involved in regulating mood and emotion, we think that the loss of these synaptic connections contributes to the biology of depression.

It's critical to understand the neurobiology of depression and how the brain plays a role in it for two main reasons. First, it helps us understand how the disease develops and progresses, allowing us to start targeting treatments based on that. Second, there are clear differences between a healthy brain and a depressed brain. The exciting thing is, when you treat that depression effectively, the brain goes back to looking like a healthy brain.

We recognize that the treatment for depression is a long-term process because, for many people, depression is a long-term disorder. Therefore, we need new treatments and new ways to approach depression for people who haven't responded well to their prior treatments. We are in a new era of psychiatry. This is a paradigm shift away from a model of monoaminergic deficiency to a fuller understanding of the brain as a complex neurochemical organ. The current standard of care for the treatment of depression is based on what we call the monoamine deficiency hypothesis, essentially presuming that one of three neurotransmitters in the brain is deficient or underactive. Neurotransmitters can be thought of as the chemical messengers within the brain. They help one cell in the brain communicate with another to pass that message along.However, the reality is there are more than a hundred neurotransmitters in the brain and billions of connections between neurons. So, we know that the monoamine deficiency hypothesis is limited. For decades, we thought that the primary pathology, the primary cause of depression, was some abnormality in these neurotransmitters, specifically serotonin or norepinephrine.

Understanding the intricate neurobiology of depression is crucial in advancing effective treatments. As we move away from the limited monoamine deficiency hypothesis, we embrace a more comprehensive view of the brain's complex neurochemical interactions. This shift opens the door to innovative therapies that address the root causes of depression, offering hope for those who have not found relief with traditional treatments. By continuing to explore and understand the brain's complexities, we pave the way for a future where depression can be more effectively managed and treated.