Study identifies brain regions that are almost twice as large in people living with depression

Although there are a number of symptoms that can be used to identify depression, such as a lack of energy, or a loss of interest in life, it’s unclear what happens in the brain when someone becomes depressed. Despite the emergence of techniques such as functional magnetic resonance imaging (fMRI), which measure changes in blood flow in the brain and link them to different functions, no significant differences have been found in the structure or connections of this organ between people living with and without depression. Medical researchers operate with the logic that, if the neural characteristics of individuals living with depression could be identified, it would subsequently be possible to better understand what causes the disease and how to cure it.

This past week, the scientific journal Nature published the work of an international team of scientists led by Charles Lynch and Conor Liston, from Cornell University, in which they identify a series of brain regions that are almost twice as large in people with depression. These regions are grouped together in what is known as the frontostriatal salience network, which connects more superficial areas of the brain — such as the prefrontal cortex, which we require for reasoning — with deeper regions that are essential for regulating moods or processing information gathered by our senses. This network plays a crucial role in identifying and processing relevant (and salient) stimuli, such as the smell of a food we like, or clues about a dangerous situation. It’s also involved in regulating goal-oriented behavior, decision-making and adapting to changes in our environment.

Until now, fMRI studies made comparisons between groups of people with and without depression. Scans didn’t indicate significant differences between their brains. Lynch and Liston’s team obtained their novel result thanks to an innovative technique called precision functional mapping, which they used to observe a few patients during numerous, spaced out sessions, in order to reconstruct what happens at the neural level during the good and bad times faced by someone living with depression.

“Traditional studies look at two moments in time and don’t give you a complete perspective about what’s happening [in a person’s brain]. In this study, we looked at a few subjects and characterized their evolution over time,” explains Cesar Caballero-Gaudes, a researcher at the Basque Center on Cognition, Brain and Language, in San Sebastián, Spain. His team provided high-quality brain imaging from individuals who are not living with depression, allowing the Cornell group to compare this information with their afflicted participants.

With this follow-up, the scientists wanted to see if the size of the network was different when the person was doing well, as opposed to when they were in a low mood. They discovered that it doesn’t change and that it cannot be modified with antidepressant treatments, such as transcranial magnetic stimulation, which applies magnetic fields to the scalp to modulate brain activity. In all cases, the size of the network remained stable. On top of that, the authors write, neither the severity of the depressive crisis nor the number of episodes could be related to differences in the size of these brain regions. According to Caballero-Gaudes, this stability “could have diagnostic utility.” This is because, “in children, it was observed that those who later developed depressive symptoms already presented an expansion of the [frontostriatal] salience network before showing them.”

It has been observed that the size, shape, or location of the brain’s functional network is controlled, in part, by genetics, but also by our experiences or surroundings. “An extreme example of an environmental influence that helps illustrate this idea is that different parts of the body have a certain amount of dedicated space in the primary motor cortex,” Charles Lynch explains. “If a person has an arm amputated, the representation of the amputated limb in the motor cortex will shrink, while the size of the compensatory representation of the intact limb will increase,” he adds.

The fact that the expansion of the salience network is present from early stages of brain development — and several years before the first symptoms of depression arise — suggests a strong genetic basis, although the recent findings don’t rule out the possible contribution of stressors or experiences in early life. “This is something we hope to research now,” Lynch notes. The Cornell professor speculates that having experiences processed by the salience network too often, such as those that give us immediate pleasure, or the direction of our attention towards relevant information, be it positive or negative, could contribute to depressive symptoms, such as a lack of desire, or exaggerated attention being placed on negative aspects of life and things that scare us.

Although the size of the network didn’t vary with symptoms of depression, a deeper analysis of some patients, who were observed periodically for a year and a half, in certain cases with up to 62 MRIs, showed that there were functional changes between the nodes of the network that could be related to loss of desire or anxiety. This, according to the authors, suggests that the salience network plays a crucial role in depression, not so much through structural changes, but through how its nodes communicate during different emotional states.

“There are multiple potential long-term clinical implications, but at the same time, it’s important to make clear that we don’t expect brain scans to be used to diagnose depression,” Lynch warns. “There’s still a lot of work to be done, such as determining how specific this effect is for depression compared to other types of psychiatric illness.”

“However,” he concludes, “in the short-term, we believe it would be possible to incorporate information about how these functional brain networks are organized in individuals with depression to adjust [via personalized treatments] the way in which we apply brain stimulation therapies, such as transcranial magnetic stimulation, or deep brain stimulation.”

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