Summary: Higher activity in the brain’s endocannabinoid system and distinct patterns of neural processing of emotional social signals were found in people who remained resilient to substance use disorder after documented childhood maltreatment.
Source: Linköping University
New research from Linköping University shows that stronger activity in the body’s own cannabinoid system and altered brain responses to emotional social cues are associated with resilience against developing addiction after childhood maltreatment.
Childhood maltreatment is a well-established risk factor for later substance use disorders (SUD). Previous research from Linköping University found that exposure to maltreatment in childhood increases the risk of later addiction roughly threefold, even after accounting for genetic and family-related influences. This new study focuses on mechanisms that might explain why some exposed individuals develop SUD while others remain resilient.
“While addiction is often framed around the pursuit of pleasurable effects, for many people drug and alcohol use is driven by a need to relieve negative feelings—stress sensitivity, anxiety and low mood,” says Markus Heilig, professor and director of the Center for Social and Affective Neuroscience (CSAN) at Linköping University and consultant at the Psychiatric Clinic of Linköping University Hospital.
Endocannabinoids—naturally occurring, cannabis-like molecules in the body—are key regulators of stress and discomfort and have been proposed to act as a biological buffer against stress. The research team tested whether individual differences in endocannabinoid function and emotion regulation-related brain activity could explain susceptibility or resilience to SUD after childhood maltreatment.
To reduce recall bias common in studies that rely on retrospective self-report, the researchers selected participants using psychiatric care registers identifying children and adolescents who had received treatment for traumatic experiences. This approach provided objectively documented, prospective evidence of childhood maltreatment exposure.
The study enrolled about 100 young adults divided into four equally sized groups defined by the presence or absence of documented childhood maltreatment and by lifetime substance use disorder: (1) maltreatment-exposed with SUD, (2) maltreatment-exposed without SUD (resilient), (3) non-exposed with SUD, and (4) non-exposed without SUD (controls).
Researchers measured blood levels of endocannabinoids and cortisol, assessed behavioral and physiological stress responses in controlled tasks, and used magnetic resonance imaging (MRI) to examine brain activity during emotion-related social stimuli and at rest.
The resilient group—those with documented childhood maltreatment who did not develop SUD—stood out. Compared with the other three groups, they showed higher peripheral levels of the endocannabinoid anandamide both at baseline and during stress exposure, indicating increased endocannabinoid system function.
MRI tests revealed that the resilient group also displayed greater task-related activity in three brain regions when processing emotional social information. Two of these regions belong to a network that directs attention and cognition toward behaviorally relevant stimuli and helps adjust behavior according to situational demands. The third region, located in the frontal lobe, is closely involved in emotion regulation and interacts extensively with other emotion-processing areas.
At rest, the resilient participants showed stronger connectivity between frontal regions and other parts of the brain implicated in emotion processing. Specifically, they demonstrated greater negative connectivity between the ventromedial prefrontal cortex and anterior insula compared with controls and with maltreatment-exposed individuals who developed SUD. These patterns are consistent with more effective emotion regulation and flexible responses to emotional social cues.
The findings raise an important question: were resilient individuals born with higher basal endocannabinoid function, or are they better at upregulating this system in response to stress, thereby preventing long-term effects of early trauma? Because this study is cross-sectional, it cannot determine causality or developmental timing.
Funding: The study received funding from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Region Östergötland, Linköping University, Systembolaget’s Alcohol Research Council, and the Brain & Behaviour Research Foundation (NARSAD Young Investigator Grant). The work was conducted by Markus Heilig’s research group at CSAN. Irene Perini is the lead author, with coauthor Leah Mayo (formerly at CSAN, now at the University of Calgary).
About this neuroscience research news
Author: Karin Söderlund Leifler
Source: Linköping University
Contact: Karin Söderlund Leifler, Linköping University
Image: The image is in the public domain
Original Research: Open access. “Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation” by Markus Heilig et al., published in Molecular Psychiatry.
Abstract
Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation
Childhood maltreatment (CM) increases the risk of developing substance use disorders (SUD) in adulthood. This case-control study examined how prospectively documented CM relates to peripheral markers of endocannabinoid function and neural measures of emotion regulation in people who did or did not develop SUD. Four groups were formed across the dimensions of CM and lifetime SUD (total N = 101).
Participants completed two experimental sessions. The first assessed biochemical (cortisol, endocannabinoids), behavioral, and psychophysiological responses to stress and affective stimuli. The second used magnetic resonance imaging to study neural mechanisms underlying emotion regulation and negative affect.
Adults exposed to CM who did not develop SUD—operationally defined as resilient—had higher peripheral levels of the endocannabinoid anandamide at baseline and during stress compared to controls. They also showed increased activity in brain regions involved in salience detection and emotion regulation during task-based measures, relative to controls and CM-exposed adults with lifetime SUD. At rest, the resilient group exhibited greater negative connectivity between ventromedial prefrontal cortex and anterior insula compared to the other groups. Together, these peripheral and central findings highlight potential mechanisms of resilience to SUD after documented childhood maltreatment.