Identifying biomarkers of stress-induced neurophysiological changes and emotion regulation deficits to predict relapse during nicotine abstinence

Project Information

BioNic

Grant agreement ID: 101031962

DOI

10.3030/101031962

Project closed

EC signature date 15 April 2021

Start date 1 January 2022

End date 1 May 2025

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 145 941,12

EU contribution

€ 145 941,12

Coordinated by

UNIVERSITY OF CYPRUS
Cyprus

Periodic Reporting for period 1 - BioNic (Identifying biomarkers of stress-induced neurophysiological changes and emotion regulation deficits to predict relapse during nicotine abstinence)

Reporting period: 2022-01-01 to 2023-12-31

Summary of the context and overall objectives of the project

Problem/issue being addressed: Tobacco smoking is the leading preventable cause of death and disability globally, with 26% prevalence in Europe. Despite available pharmacotherapies and psychological interventions, most users relapse, with only ~15% achieving long-term abstinence beyond 6-12 months. The heterogeneous pathophysiology of nicotine addiction, influenced by age, gender, genetics, and psychiatric comorbidities, complicates treatment outcomes. Currently, no established biomarkers can predict which smokers are at higher relapse risk before quit attempts.

Why is it important for the society: The ability to identify smokers who are most vulnerable to relapse before any quit attempt would enable the development of personalized treatment strategies, ultimately improving treatment outcomes and reducing nicotine-related mortality. Our research addresses a significant public health challenge that affects millions of people worldwide and places substantial burden on healthcare systems.

Overall Objectives: The BioNic project aimed to elucidate whether an interplay between stress-induced changes in psychophysiological and neurophysiological processes occurring in chronic smokers prior to cessation can predict relapse vulnerability. The primary objectives were to: (i) Determine whether emotion regulation ability, measured via heart rate variability (HRV) in response to psychosocial stress, can serve as a biomarker predicting maintenance of abstinence; (ii) Assess whether changes in neural activity (measured via qEEG spectral analysis and coherence) during stress exposure can predict relapse vulnerability; (iii) Examine whether qEEG changes induced by acute 24-hour abstinence can predict successful treatment outcomes; (iv) Evaluate the reciprocal interactions between stress reactivity, emotion regulation ability, and synchronized neural activity as predictors of nicotine relapse vulnerability.

Conclusions of the action: The BioNic project investigated whether stress-induced psychophysiological and neurophysiological changes in chronic smokers could predict relapse vulnerability. The study aimed to determine if: (i) emotion regulation ability (measured via HRV during stress) predicts abstinence maintenance; (ii) neural activity changes (qEEG spectral analysis and coherence) during stress predict relapse risk; (iii) qEEG changes after 24-hour abstinence predict treatment success; and (iv) interactions between stress reactivity, emotion regulation, and neural synchronization predict nicotine relapse vulnerability.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Phase 1: Participant recruitment and data collection. Participants (N=223) were recruited via social media advertisements, university-targeted announcements, referrals from collaborating pulmonologists, and local newspaper notices. 60 were ex-smokers and 163 were current smokers (long-term or recent). Recruitment targeted a community-based sample spanning a wide age range and varying levels of tobacco dependence:
• Day 1 (Baseline): Participants completed baseline assessments including the Fagerström Test of Nicotine Dependence, stress-induced psychophysiological measurements using the Paced Auditory Serial Addition Task (PASAT), HRV recordings during rest and stress, qEEG recordings, and saliva collection for cortisol, ACTH and cotinine readings.
• Day 2 (24-hour abstinence): Following acute abstinence, participants underwent repeat qEEG and HRV measurements, withdrawal symptom assessments, and smoking cue reactivity testing.
• Days 3-180 (Cessation intervention): Participants entered the Flexiquit computerized smoking cessation program with follow-up assessments at 3 and 6 months post-quit.

Phase 2: Data analysis and results. Comprehensive statistical analyses were conducted using repeated-measures ANOVAs, correlation analyses, linear regressions and principal components analysis with hierarchical clustering to identify relapse vulnerability patterns.

Phase 3: Dissemination and Exploitation:
• Apostolakis M., Georgiou A., Valiantis S., Panayiotou G., Zanos P. (2025, oral presentation). Stress Reactivity and Emotion Regulation Difficulties as Predictors of Nicotine Relapse Vulnerability. European Congress of Psychology, Paphos, Cyprus
• Apostolakis M., Georgiou A., Valiantis S., Panayiotou G., Zanos P. (2025, oral presentation). Stress Reactivity and Emotion Regulation Difficulties as Predictors of Nicotine Relapse Vulnerability. 19th Panhellenic conference of psychological research, Hellenic Psychological Society, Ioannina, Greece.
• Valiantis S., Apostolakis M., Panayiotou G., Robinson J.D. Paraskevopoulos E., Chatzittofis A., Georgiou A., Zanos P. Nicotine relapse vulnerability: The role of biomarkers in understanding risk. Submitted.
• Apostolakis M., Papamiltiadou M., Valiantis S., Panayiotou G. Zanos P. Resting-state EEG markers of abstinence: A systematic review. In Preparation
• Apostolakis M., Valiantis S., Georgiou A., Panayiotou G., Zanos P. Cortical-Autonomic coupling in nicotine dependence and under stress during acute abstinence. In Preparation

Knowledge Transfer and Training:
• Delivered lectures to students in Behavioral Neuroscience and Psychopharmacology classes at the University of Cyprus about our project and results.
• Established ongoing collaborations with research groups in the UK on identifying epigenetic biomarkers predicting nicotine relapse propensity.
• Gave invited talks in the Open University (Anoikto Panepistimio) as well as presented in an International Conference, with global outreach.
• Participated in The European Researchers Night to engage with the general public, with more than 1000 attendants.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Potential Impact of the BioNic project:

Scientific and clinical contributions: The BioNic project contributed to addiction neuroscience by demonstrating that stress-induced neurophysiological responses predict smoking cessation outcomes. The findings suggest that combining psychophysiological measures with neuroimaging data may improve understanding of individual treatment responses. This research supports personalized addiction treatment approaches and provides a foundation for future studies of neurobiological predictors in substance use disorders. The methodological framework offers new tools for studying the intersection of stress, emotion regulation, and addictive behaviors.

Broader implications and future directions: While these biomarkers require further validation for clinical use, the BioNic findings advance precision medicine in addiction treatment. The research provides preliminary evidence that neurophysiological assessments could complement existing clinical evaluations and has generated clinical interest. The project fostered international collaborations and built research capacity in addiction neuroscience. These findings may inform targeted interventions and influence future smoking cessation trial design, potentially improving treatment outcomes for individuals attempting to quit smoking.

Long-term societal vision: The BioNic project provides a foundation for shifting addiction treatment from trial-and-error approaches to neurobiologically-informed interventions. This shift could reduce tobacco addiction's global burden and serve as a model for precision medicine in mental health and addiction treatment. The project's interdisciplinary approach, combining neuroscience, psychology, and clinical medicine, exemplifies integrated research needed to address complex societal challenges.

Project summary