New study sheds light on the neurobiological mechanisms underlying non-suicidal self-injury

New research highlights the complexity of neurobiological abnormalities associated with non-suicidal self-injury — behaviors like cutting oneself without intending to die. The findings, published in Development and Psychopathology, indicate that severe self-injury behavior among adolescent girls is related to alterations in brain activity and physiological stress responses.

Self-injury is a strong predictor of suicide among adolescents, and has also been linked to depression and borderline personality disorder. The prevalence of non-suicidal self-injury is approximately 17% among adolescents, but the biological and cognitive mechanisms underlying this behavior remain unclear.

“I believe trying to understand how and when the developing brain becomes dysfunctional is crucial to restore mental health and even to prevent the onset of clinical problems such as major depressive disorder (MDD), suicidal thoughts and behaviors (STB), and non-suicidal self-injury (NSSI). In this study we specifically focused on NSSI in adolescents, because there are not enough evidence-based interventions available to address this highly prevalent and maladaptive behavior,” said study author Zeynep Başgöze, a postdoctoral associate at the Research in Adolescent Depression Lab at the University of Minnesota Medical School.

“Moreover, in this study we used the National Institute of Mental Health’s Research Domain Criteria (RDoC) approach, which integrates many levels of information such as biology, behavior, brain functions and connections to better comprehend mental issues,” Başgöze said. “Since NSSI is highly associated with early life stress, such as childhood abuse, in this study we specifically examined Sustained Threat, which is an aversive emotional state caused by prolonged exposure to stimuli that signal danger.”

“If we know more about how and when these mental problems occur, then we can come up with better and more individual-based treatment options, and we can learn when is the best time to intervene and even how to prevent these issues from arising.”

Başgöze and her colleagues recruited more than 100 girls between the ages of 12–17 years and had them complete an experimentally-verified procedure known as the Trier Social Stress Test. The participants delivered a short speech and performed verbal arithmetic calculations in the presence of two examiners, who were outfitted in white lab coats and trained to remain neutral. During various times throughout the test, the researchers collected saliva samples to measure the stress hormone cortisol.

The researchers found that girls with a history of severe NSSI reported higher stress during the test compared to those with moderate, mild, or no history of NSSI. However, participants with severe NSSI exhibited reduced cortisol reactivity on average compared to the other groups. (NSSI was categorized as severe if there were four or more past NSSI episodes with a frequency greater than once per month and with significant tissue damage.)

“We found that adolescents with severe NSSI, but not moderate or mild NSSI, show a blunted pattern of physiological response,” Başgöze told PsyPost. “This means that adolescents who show the most frequent and severe self-injuring behavior could be overusing and wearing out their bodies’ physiological systems, which eventually cause their threat system to dysfunction and thus become less adaptive and less protective.”

The participants also underwent functional magnetic resonance imaging (fMRI) scans, which were used to assess amygdala volume and resting-state functional connectivity between the amygdala and the medial prefrontal cortex. While receiving the brain scan, the participants also completed a threat task in which they were exposed to human faces depicting anger and fear.

“A similar divergent pattern across different NSSI severities is also observed in brain functions: Amygdala is a brain region crucial to detect and monitor threatening situations, so it can warn the sympathetic nervous system, which then makes us either fight or fly, or maybe do nothing according to the circumstances, and those circumstances are evaluated with the help of amygdala’s connection to frontal cortices,” Başgöze explained. “This connection basically helps us not to be afraid of a bear we see in a zoo, but to be afraid of a bear we encounter in a forest.”

“In this study, we showed that the abnormalities usually found in the functional connectivity between amygdala and frontal cortex are most evident in adolescents with severe NSSI compared to moderate and mild NSSI. Whereas adolescents with moderate NSSI show increased amygdala activation towards stressful stimuli (the fearful or angry faces), adolescents with severe NSSI fail to show this elevated amygdala activation. It is as if adolescents with moderate NSSI get very scared of the bear even if the bear is in the zoo, and adolescents with severe NSSI don’t get scared enough even if they see the bear in the forest; both dysfunctional, but in a different way.”

“These could mean that the amygdala response and the body’s cortisol response to threat/stress get attenuated over time,” Başgöze told PsyPost. “However, in order to prove that the threat system is actually ‘worn and torn’ in time, we need to conduct a longitudinal study.”

The researchers are doing just that. The current study is part of a larger research project called Brain Imaging Development of Girls’ Emotion and Self (BRIDGES), which is collecting longitudinal data from the participants.

“We need to analyze the data in a longitudinal way by looking at the changes in the same population over time in order to respond questions like: ‘When did these aberrant patterns of Sustained Threat emerge? Did they result from early adverse experiences? Are these biological traits present early in development which predispose a young person both to developing NSSI and suicide risk? Or do they emerge after the onset of NSSI and set the stage for a future suicide attempt?” Başgöze explained.

“Although in this paper we focused on the sustained threat system, it is not the only RDoC construct we have been examining,” she added. “We are now in the process of writing two other research papers where we investigate how different units of analysis of self-knowledge and cognitive control relate to NSSI severity.”

The study, “Multimodal assessment of sustained threat in adolescents with nonsuicidal self-injury“, was authored by Zeynep Başgöze, Salahudeen A. Mirza, Thanharat Silamongkol, Dawson Hill, Conner Falke, Michelle Thai, Melinda Westlund Schreiner, Anna M. Parenteau, Donovan J. Roediger, Timothy J. Hendrickson, Bryon A. Mueller, Mark B. Fiecas, Bonnie Klimes-Dougan and Kathryn R. Cullen.