Can Childhood Trauma Prime Brain Dynamics for Nicotine Dependence?

Childhood trauma-related emotion dysregulation may partly explain why some long-term smokers are unable to give up nicotine, a cross-sectional study suggested.

Using 16-minute resting-state functional MRI to show the dynamic patterns of functional coordination among brain systems, researchers found that nicotine smokers spent approximately 25.63 more seconds in the frontoinsular default mode network (FI-DMN) state than nonsmoker controls (P=0.004). The large-scale brain network has previously been implicated in substance use disorders.

Notably, nicotine smokers with greater alexithymia tended to show reduced time in the FI-DMN brain dynamic state. Supporting a relationship between childhood trauma and temporal dynamics, however, alexithymia was found to significantly mediate the association between childhood trauma and time spent in the FI-DMN state in nicotine smokers, reported Amy Janes, PhD, of the National Institute on Drug Abuse (NIDA) at the NIH in Baltimore, and coauthors in JAMA Network Open.

“This is consistent with previous literature indicating that there are neurobiological differences within psychiatric diagnoses depending on whether individuals have been maltreated or not and suggests that specific neurobiological risk profiles are associated with trauma-related factors,” Janes and colleagues noted.

“Together with the current findings, we suggest that too much or too little FI-DMN function may correspond with different aspects of emotional dysregulation (i.e., rumination and alexithymia, respectively), both of which contribute to nicotine craving and use,” they continued.

Alexithymia, a form of emotional dysregulation where it can be difficult to identify or explain emotions, can put patients experiencing the condition at a greater risk for other substance use and psychiatric issues. The condition is also more present among smokers, and has had various associations with childhood trauma in prior work.

The investigators cautioned that they were not able to determine causality in their study, namely whether greater time spent in the FI-DMN state was the result of long-term nicotine smoking or was a pre-existing risk factor for nicotine use, and whether the missing link between FI-DMN engagement and alexithymia was the consequence of the patient learning maladaptive coping behaviors or because of trauma-induced changes in their neurobiological functioning.

Frank Leone, MD, MS, of Penn Medicine in Philadelphia, who was not involved with the study, explained more about how smoking has been shown to impact the brain.

“Generally speaking, it’s like the brain has a set of structures that are preferentially activated when the brain is in neutral and a set of structures that are preferentially active when the brain is in drive,” he told MedPage Today. “And the way nicotine works, in part — particularly around the notion of how smoking helps people manage stress — is that it facilitates the switch from the drive state, executive mode, back down to the default mode. It makes that much more likely, makes it much easier, much less energy intensive.”

Leone expressed hope for further research and encouraged both providers and patients to utilize this kind of data to provide a more nuanced understanding of quitting smoking.

“For the physician perspective, it’s very important not to think about smoking as a monolithic problem, it’s not one thing. There are many influences on the patient that will influence the smoking behavior. Smoking should be seen as the sign of a complex disorder or [an] imbalance in brain physiology,” said Leone.

“From the patient’s point of view … this is not about willpower,” he continued. “There are influences on the brain that drive behaviors that are invisible to the outside world. And those are the influences that seeking advice or insight from a professional can help to rectify, help to minimize, and help a person achieve their tobacco-related goals.”

For their study, Janes and colleagues enrolled participants in an ongoing NIDA study. Individuals who smoked nicotine long-term were matched to controls who had not used nicotine products within the previous year and had not used the products 10 or more times throughout their life. Patients experiencing other neurological disorders, major mood disorders, substance or alcohol use disorders, anxiety, or psychotic disorders were excluded from the study.

The final study cohort comprised 102 pairs of smoker-control pairs for comparison. The average patient age was 37.5 years and the sample population was 46% female. By race, 51% were white and approximately 38% were Black. On average, the nicotine group smoked 9.34 cigarettes per day.

Childhood trauma was assessed using the Childhood Trauma Questionnaire. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale.

Researchers noted that the study only accounted for brain dynamics after “ad lib” smoking, limiting their ability to comment on nicotine’s direct pharmacological influence.