Trauma-related mental illness is linked to altered thalamus size

Following a traumatic event, some individuals develop mental health conditions like posttraumatic stress disorder or clinical depression, and these conditions may be connected to the size of a brain region called the thalamus. A recent study found that specific parts of the thalamus vary in volume depending on a person’s exact psychiatric diagnosis, the severity of their symptoms, and the type of childhood adversity they experienced. The research was published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.

Up to 85 percent of the general population will experience a traumatic event at some point in their lives. While many people recover naturally over time, a large number of individuals develop chronic mental health conditions in the aftermath. Two of the most common conditions following trauma exposure are posttraumatic stress disorder and major depressive disorder.

Medical researchers have spent decades studying how traumatic events alter the physical structure of the human brain. Much of this past work focused on regions known to manage fear and memory, such as the amygdala and the hippocampus. The thalamus has historically received much less attention in the context of psychiatric conditions. This is changing as scientists learn more about its wide-ranging functions.

The thalamus sits deep in the center of the brain. It is often described as the central relay station for the human nervous system. Almost all sensory information travels through the thalamus before reaching the outer layers of the brain for full processing. It acts as a traffic director for sights, sounds, and physical sensations.

The thalamus is not a single uniform lump of tissue. It is actually composed of many smaller subdivisions called nuclei. Each of these tiny nuclei has a specialized job within the brain. Some nuclei wire directly into the sensory and motor systems, while others connect deeply to the brain’s emotion and memory centers.

Previous studies assessing thalamus size in trauma survivors produced a confusing mix of results. Some older studies suggested that trauma relates to a smaller thalamus, while others found a larger thalamus among affected patients. Most of these earlier projects relied on relatively small groups of participants. Small sample sizes often lead to statistical variations and results that are hard to reproduce.

Lead author Nick Steele, a researcher at Duke University and the Department of Veterans Affairs, wanted to clarify these conflicting records. Steele worked alongside an international team of scientists connected to the ENIGMA posttraumatic stress disorder working group. This collaboration allowed the team to pool brain scans and patient evaluations from 20 different research facilities around the globe.

The team analyzed structural magnetic resonance imaging brain scans from 2,058 participants. This imaging technology uses strong magnetic fields to map the exact physical dimensions of brain tissue. The participant pool included 1,018 individuals who had experienced trauma but did not develop psychiatric conditions. The remaining 1,040 participants had developed posttraumatic stress disorder, major depressive disorder, or a combination of both illnesses.

Around half of all patients diagnosed with posttraumatic stress disorder suffer from clinical depression at the same time. This combination typically leads to more severe behavioral symptoms and a much harder time finding effective medical treatments. Taking this combined group into account allowed the researchers to evaluate the worst cases of post-trauma mental illness.

The scientists used specific imaging software to measure the overall volume of the left and right thalamus in each scan. They also isolated and measured the volume of 25 distinct smaller nuclei within each side of the structure. The researchers compared these sizes across the different participant groups while adjusting for demographic variables. They accounted for the participants’ age, biological sex, and total skull size in their mathematical formulas.

Participants diagnosed solely with posttraumatic stress disorder tended to have smaller volumes in several thalamic nuclei compared to the control group. The affected regions in these patients are primarily involved in processing sensory and motor information. This structural difference might explain why people with trauma histories often display heightened or reduced physical reactivity to incoming sensory sights and sounds.

In contrast, individuals diagnosed with major depressive disorder displayed smaller volumes in the mediodorsal nuclei. These specific subregions connect heavily to the hippocampus and are heavily involved in learning, memory, and emotional regulation. Participants burdened with combined posttraumatic stress disorder and depression also displayed smaller sizes in these same emotion-focused subregions.

The researchers noticed an unusual pattern when looking at overall symptom severity. Mild to moderate symptoms of both conditions correlated with a smaller overall thalamus size. People experiencing highly severe symptoms of both posttraumatic stress disorder and depression at the same time actually exhibited larger thalamic volumes.

This specific observation about severe symptoms helps explain the conflicting results of older studies. Mild psychiatric distress shrinks the expected volume measurements, but extreme distress combined with multiple diagnoses inflates the measurements. The researchers suggest that differing biological mechanisms might shape the brain as mental illness worsens.

Peeling apart the distinct symptoms of posttraumatic stress disorder revealed mixed relationships as well. Symptoms categorized as re-experiencing the trauma or having persistent negative moods tracked alongside smaller thalamic volumes. Conversely, symptoms involving physical hyperarousal and the avoidance of trauma reminders tracked alongside larger thalamic volumes.

The team also evaluated the participants’ histories of childhood trauma. Childhood adversity is a known risk factor for developing psychiatric conditions during adulthood. The developing brain is highly sensitive to environmental stress and early life threats.

When they isolated different types of childhood trauma, the researchers found that abuse correlated with brain volume in opposite ways. A history of childhood physical abuse was associated with a larger left thalamus volume in adulthood. Meanwhile, a history of childhood emotional abuse was associated with a smaller left thalamus volume. The emotional abuse metric particularly tracked with smaller limbic nuclei, which run the brain’s emotional circuitry.

The researchers noted a few caveats regarding their observational work. The study lacked complete information regarding other underlying medical conditions across the patient pool. The team also did not have complete data on history of substance use or the use of psychiatric medications among the participants, though many of the individual research sites excluded drug users automatically.

The participant groups were also unequal in size, with heavily skewed numbers toward the healthy control group. The researchers did not possess a standardized measure to calculate the total lifetime trauma each person experienced. It remains possible that differences in the sheer quantity of traumatic events influenced the results rather than the psychiatric conditions alone.

Because the study looked at a single point in time, it remains unknown whether thalamus size acts as a pre-existing risk factor for mental illness or comes about as a result of the psychiatric symptoms themselves. Future investigations will need to track individuals over time to see how the brain changes in real time. Following patients as they receive treatment could clarify how the thalamus adapts to recovery.

The study, “Volumetric Differences of Thalamic Nuclei are Associated with Post-Trauma Psychopathology,” was authored by Nick Steele, Ahmed Hussain, C. Lexi Baird, Courtney C. Haswell, Delin Sun, Leonel Rangel-Jimenez, Chadi G. Abdallah, Michael Angstadt, Geoffrey May, Hannah Berg, Jennifer U. Blackford, Josh M. Cisler, Judith K. Daniels, Nicholas D. Davenport, Richard J. Davidson, Maria Densmore, Seth G. Disner, Wissam El-Hage, Amit Etkin, Negar Fani, Jessie L. Frijling, Evan M. Gordon, Daniel W. Grupe, Ryan J. Herringa, Anna R. Hudson, Neda Jahanshad, Tanja Jovanovic, Anthony King, Saskia B.J. Koch, Ruth Lanius, Amit Lazarov, Gen Li, Israel Liberzon, Shmuel Lissek, Guangming Lu, Antje Manthey, Adi Maron-Katz, Laura Nawijn, Steven M. Nelson, Yuval Neria, Richard W.J. Neufeld, Jack B. Nitschke, Bunmi O. Olatunji, Miranda Olff, Matthew Peverill, Yann Quidé, Orren Ravid, Gopalkumar Rakesh, Kerry Ressler, Marisa Ross, Kelly Sambrook, Anika Sierk, Scott R. Sponheim, Jennifer Stevens, Benjamin Suarez-Jimenez, Jean Théberge, Sanne J.H. van Rooij, Mirjam van Zuiden, Dick J. Veltman, Robert R.J.M. Vermeiren, Henrik Walter, Li Wang, Xi Zhu, Ye Zhu, Sigal Zilcha-Mano, Christine Larson, Terri A. deRoon-Cassini, Carissa W. Tomas, Jacklynn M. Fitzgerald, Andrew S. Cotton, Erin N. O’Leary, Hong Xie, Xin Wang, Emily L. Dennis, David F. Tate, David X. Cifu, William C. Walker, Elisabeth A. Wilde, Paul M. Thompson, and Rajendra A. Morey.