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Alcohol use disorder (AUD) is one of the most prevalent psychiatric disorders in the Netherlands and characterized by disconcertingly high relapse rates: 50-60% of patients relapse within one year after detoxification. While the prevalence of AUD is 2-3 times higher in men (6.6%) than in women (2.3%), this gap is quickly closing. As such, the identification of sex and gender-specific mechanisms that underlie successful AUD treatment should be top priority in addiction research. The primary aim of this project, therefore, is to identify sex- and gender difference in the psychopathology and treatment of AUD.

 

Differences between men and women with an AUD are often attributed to biological sex difference, but may be related to socio-cultural gender differences as well (i.e. gender roles, gender identity, gender relations and institutionalized gender). To date, few attempts have been made to disentangle sex- from gender-related differences in the psychopathology or treatment of AUD. As such, the first objective of this project is to compute a Composite Gender Index that includes all facets of gender and use this to investigate sex and gender differences in the clinical characteristics of AUD.

 

A central theory in addiction research is that compulsive alcohol use results from a shift in reward driven alcohol use to stress driven alcohol use. Recent studies suggest that women are particularly prone to stress-related relapse, but empirical evidence of this hypothesis is scarce. The second objective of this project is to investigate sex and gender differences in the prospective relationship between perceived stress, craving and alcohol intake during treatment and early recovery of AUD.

 

Heart-rate variability (HRV), which is regulated by the autonomic nervous system, is considered a reliable biomarker of the ability to regulate emotional responses to stress. Research consistently demonstrated that resting HRV is lower in AUD patients compared to non-dependent controls, which is suggested to reflect poorer stress regulation capacities. While resting HRV could serve as a clinically relevant predictor of AUD treatment outcome, the prospective association between resting HRV and relapse in AUD patients is unknown. As such, the third objective of this project is to investigate the association between resting HRV, craving and prospective alcohol intake during treatment and early recovery of AUD as well as sex and gender differences herein.

 

300 AUD patients (50% women) will be included in this study, who receive treatment as usual at the Dutch Jellinek addiction treatment center. During treatment and early recovery, perceived stress, craving and alcohol use will be measured daily via personal smartphones using Ecological Momentary Assessments. Resting HRV will additionally be measured over 12h periods at three time-points during treatment and early recovery, using wearable electrocardiogram recorders. Sex (assigned sex at birth) and gender (Composite Gender Index) differences in the prospective associations between perceived stress, resting HRV, craving and alcohol intake, will be evaluated using dynamic structural equational models and random-intercept cross-lagged panel models. The hypotheses in this project are that higher perceived stress and lowing resting HRV are predictive of craving and subsequent alcohol intake during treatment and early recovery of AUD and that this effect is stronger in women compared to men. It is furthermore hypothesized that gender, over and above sex, explains unique variance in this relationship.

 

Raising awareness for the relevance of sex- and gender in (mental) health care has been identified as one of the top priorities for gender sensitive care and is suggested to contribute to more equity, equality and better health for men and women. Raising awareness on the relevance of sex- and gender differences in (the treatment of) AUD will therefore be a secondary aim of the proposed project. To achieve this, an online serious game will be developed in order to provide clinicians with up-to-date information on sex and gender differences in the psychopathology and treatment of AUD.

 

Sex and gender differences in stress-related predictors of treatment outcome have not been investigate yet in a prospective manner, using daily assessments of stress, craving and alcohol intake. Through differentiating between sex- and gender-related predictors of relapse, as well as through focusing on both objective and subjective measures of stress, the proposed project is expected to provide a more accurate, rigorous and clinically relevant insight into the complex relationship between stress and relapse to AUD, as well as sex- and gender differences herein. Doing so, this project will provide novel and crucial information that could pave the way for the development of more efficient sex- and gender tailored AUD intervention and prevention strategies.

 

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