A new study published in the journal Depression and Anxiety compared the MRI scans of people with clinical anxiety to the scans of healthy controls. The researchers uncovered differences in cortical thinning across development, specifically in the ventromedial prefrontal cortex — an area implicated in emotion regulation.
“I was interested in this topic because I noticed that there were mixed findings regarding whether brain regions involved in emotion regulation were thicker or thinner in individuals with a diagnosis of anxiety, compared to healthy controls,” said study author Cope Feurer, a postdoctoral fellow at the University of Illinois at Chicago.
“Specifically, although some studies found that individuals with anxiety showed greater thickness of these brain regions, other studies found that individuals with anxiety showed diminished thickness of these brain regions. Importantly, from childhood through adulthood, a normative process called ‘cortical thinning’ occurs where the cortex (i.e., the outmost layer of the brain) becomes thinner over time.”
“Because a few studies have shown that youth with greater anxiety symptoms show slower rates of cortical thinning than non-anxious youth, I wondered whether the mixed findings may be explained by different developmental trajectories in cortical thinning between healthy controls and anxious patients,” Feurer said.
The study involved two separate samples for a total of 233 children and adults between the ages of 7 and 35. Of these individuals, 149 were diagnosed with anxiety, while 84 had no history of mental illness. Throughout the study, participants underwent structural MRI scans. Cortical thickness measurements were calculated in three areas of interest: the insula, the ventromedial prefrontal cortex (vmPFC), and the rostral anterior cingulate cortex (rACC) —three areas involved in emotion regulation.
Using linear regression, the researchers then examined whether participants with an anxiety diagnosis showed different age-related patterns of cortical thickness than subjects without anxiety.
Across the sample, all the regions of interest showed cortical thinning with age except for the right insula and the left rACC. When comparing participants with and without anxiety, differences emerged when it came to the vmPFC.
Subjects with anxiety showed slower rates of thinning in the right vmPFC, compared to their counterparts. At around ages 10 and below, participants with anxiety showed thinner right vmPFC, while at ages 24 and up, they showed thicker right vmPFC. The researchers did not find any significant differences in left vmPFC, bilateral rACC, or insular thicknesses among the different groups.
“We found that patients with anxiety showed less cortical thinning of the vmPFC, a brain region involved in emotion regulation, across age than healthy controls. In other words, the rate at which the vmPFC became thinner over time was slower for anxious patients than healthy controls,” Feurer told PsyPost.
“This means that although anxious patients have a thinner vmPFC than healthy controls in childhood, since the vmPFC thins at a slower rate in anxious patients, eventually this relation ‘flips’ and anxious patients show thicker vmPFC compared to healthy controls in adulthood.”
As Feurer and her colleagues say, the vmPFC appears to be involved in fear extinction and emotion regulation, two processes that are also implicated in the maintenance of anxiety disorders. “Results highlight trajectories of vmPFC thinning as a promising marker of anxiety, and suggest that either thinner or thicker vmPFC may be a biomarker of clinical anxiety, depending on the developmental stage.” The authors further note that cortical thickness is especially susceptible to changes in cortical structure that appear with age. As the risk of anxiety escalates in middle childhood, cortical thickness may offer an early marker of abnormal development.
The authors stress that their study was not longitudinal, and conclusions cannot be drawn concerning whether anxiety precludes differences in cortical thinning or vice versa.
“The major caveat of the current study is that we only looked at cortical thickness and anxiety at one time point,” Feurer explained. “Therefore, we were unable to look at change in cortical thickness over time and could only examine age-related patterns of cortical thickness. Additionally, we were unable to examine whether abnormal patterns of age-related vmPFC thinning can be seen before anxiety onset. Future studies need to look at changes in cortical thinning and anxiety over time to see if slower rates of vmPFC thinning predict future anxiety diagnosis.”
The researchers remark that previous evidence suggests that cortical thickness is heritable and therefore may represent an early indication of anxiety, detectable even before a clinical diagnosis.
“The current study highlights the importance of considering developmental differences in markers of anxiety risk – particularly for risk factors that demonstrate change across age,” Feurer added.
The study, “Differences in cortical thinning across development among individuals with and without anxiety disorders”, was authored by Cope Feurer, Jennifer H. Suor, Jagan Jimmy, Heide Klumpp, Christopher S. Monk, K. Luan Phan, and Katie L. Burkhouse.