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Depression: An Issue With Neuroplasticity?

Here's how brain wiring issues may help to explain depression.


  • Brains of people with depression show several changes that may represent issues with neuroplasticity.

  • Many conventional antidepressant medications as well as drugs like ketamine may act in part by enhancing healthy neuroplasticity.

  • Lifestyle changes including diet, physical activity, sleep, and cognitive exercises may represent a way to improve neuroplasticity.

In the last hundred years, we’ve seen incredible scientific advances in our treatment of disease. Unfortunately, mental health conditions including depression remain major causes of disability around the world. It’s now known that these conditions are significantly influenced by the state of our brains and bodies. In hopes of better understanding what's driving this process, scientists have been actively investigating a number of new biological frameworks, especially around depression. One more recent hypothesis explores how depression may stem from problems with the brain’s ability to rewire itself.

What exactly is neuroplasticity?

When researchers compare the brains of infants, children, adolescents, and adults, they see notable differences. For example, adults obviously have bigger brains than children, but not for the reason you might think. By the time we are around 5 years old, our brains are 90% the size of an adult’s. However, this isn’t due to a massive addition in brain cells. Rather, it’s because of widespread and rapid changes in the wiring of our neurons as a result of events in our early life.

The brain’s ability to rewire itself as a response to life experiences is called neuroplasticity. While it’s most prominent in our early years, neuroplasticity continues throughout our lives. There are many complicated ways in which neuroplasticity may occur in our brains. However, this process is often explained as changes in the number and strength of connections between our neurons in response to our environments. Multiple lines of research indicate that healthy neuroplasticity is key to good brain function. And in depression, there’s now evidence that certain aspects of neuroplasticity may be significantly impaired.

Neuroplasticity issues in depression

If you were to take a large set of people with depression and people without depression and put them in an MRI or a CT scanner, some of the most likely findings would be atrophy (decreased brain volume) in a part of the brain called the prefrontal cortex, which is involved in higher-order thinking and emotional regulation. You might also see atrophy in the hippocampus, which is involved in memory. If you happened to have access to a functional MRI machine, you could also see evidence of reduced connectivity in these two parts of the brain. These structural and functional changes have been proposed to reflect deficits in neuroplasticity in the brains of people with depression.

There’s also more indirect data connecting depression and problems with neuroplasticity. This relates to an important protein called brain-derived neurotrophic factor (BDNF). BDNF is a key molecule in neuroplasticity. It may in fact be one of the strongest signals for a neuron to form new or stronger connections with other neurons. Levels of BDNF have been found to be lower in the brains of people with depression, and in animal models, getting rid of BDNF production leads to depressive symptoms.

Depression therapies and neuroplasticity

In recent years, researchers have proposed that many standard antidepressant therapies may actually improve mood for reasons other than their effects on neurotransmitters. In fact, we now understand (primarily from cell and animal research) that many commonly prescribed antidepressant drugs may positively augment neuroplasticity. One shared mechanism appears to involve an increase in levels of BDNF.

Another key part of this story relates to ketamine, a drug initially used for anesthesia and more recently used for treatment-resistant depression. Unlike most antidepressants (which can take weeks to start working), the effects of ketamine often kick in within a few hours of the initial dose. Researchers believe this may be the result of the drug’s effects on neuroplasticity. While the science is relatively limited, there’s also a suggestion that other psychedelic molecules including LSD, ayahuasca, and psilocybin may have positive effects on neuroplasticity.

Lifestyle interventions to improve neuroplasticity

The role of lifestyle factors in depression has increasingly received press in academic and non-academic circles alike. Many have now started to advocate for dietary interventions to improve mood, and several randomized trials have shown a Mediterranean-style diet to have potential benefit in depression. Exercise, sleep, and even nature exposure may also hold promise in helping mood. One of the explanations for how these interventions might improve brain function and therefore our mental health? Neuroplasticity.

Moving your body and mind

Increasingly, researchers have focused on the role of lifestyle modification in the management of depression. Engaging in physical activity has long been known to correlate with decreased risk for diseases, and it’s now considered a potential intervention for depression prevention. It turns out exercise may be one of the best ways to promote healthy neuroplasticity in parts of the brain that are implicated in depression. Multiple studies have shown that exercise (especially aerobic exercise) can increase the levels of BDNF in the brain, and other research shows a correlation between more exercise and a bigger hippocampus.

Exercising the mind may also represent a way to improve the brain’s neuroplasticity mechanisms. In animal research, it’s been found that stimulating environments correlate with increases in BDNF as well as the actual creation of new neurons. What does this mean in practice? Challenging the brain by learning something new or even putting ourselves in slightly uncomfortable situations could help promote neuroplasticity. And while it may seem counterintuitive, working to still your mind through mindfulness practice may also be a way to reap these benefits.

Sleeping your way to better brain health

Sleep has been making major waves in brain research for its role in about every aspect of our brain health—including mood. In animal research, gene activation related to neuroplasticity in the cortex and the hippocampus is under the control of sleep. In fact, sleep may represent one of the most important regulators of brain-wide plasticity we have! Strategies to promote better sleep include cutting out caffeine intake in the afternoon, winding down before bed, cooling the room you sleep in, and removing electronic devices from the bedroom in addition to having a more consistent evening routine.

Eating for improved neuroplasticity

Finally, there’s reason to suspect that our diet can play a significant role in our mood, potentially by way of augmenting neuroplasticity. There are many ways the food we eat may influence neuroplasticity. These include pathways like the gut-brain axis, food-related hormones, and even ketone bodies (which we make when we put a pause on our calorie consumption). Some largely pre-clinical research suggests that certain foods (e.g., curcumin, omega-3 fats, and whole coffee fruit) may help enhance neuroplasticity. However, when it comes to the diet-depression research, it seems that adherence to a diet rich in minimally processed foods, especially whole grains, vegetables, nuts, legumes, and fatty fish may be of the biggest benefit.


When considering depression, it’s clear we still don’t have all the answers. Yet scientific advancement is increasingly providing new avenues for exploration. As we consider the potential biological states driving this condition, new understandings will enhance our approaches to management and prevention. Neuroplasticity deficits have emerged as one potential contributor to depression, and this research adds valuable insight to the bigger puzzle

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