With 41,000 deaths per year, alcohol consumption is the second leading cause of preventable mortality in France. Nearly 3.4% of adults engage in excessive and chronic alcohol use, meeting criteria for Severe Alcohol Use Disorder (SAUD).

SAUD is associated with cerebral and cognitive alterations, including deficits in social cognition. These deficits manifest as difficulties in perceiving and interpreting social cues during interactions and encompass, in particular, the recognition of emotional facial expressions and the accurate attribution of others' beliefs, emotions, and intentions (i.e., theory of mind). Such alterations contribute to interpersonal difficulties and psychological distress and are recognized as risk factors for the development and maintenance of SAUD.

To date, social cognition has primarily been explored through behavioral tests, providing a description of deficits without examining their neuro-structural correlates. Moreover, no neuroscientific study has investigated the impact of sex and concomitant tobacco use on social cognition and associated brain structures in SAUD, although these factors are known to influence both social cognitive abilities and cerebral organization in this disorder. Finally, the everyday consequences of these alterations on social functioning and the trajectory of alcohol consumption remain poorly explored.

In this context, the present project aims, first, to explore the neuro-structural correlates of social cognition deficits in SAUD using psychometric assessments (i.e., emotion recognition, theory of mind) combined with magnetic resonance imaging (MRI). The impact of sex and tobacco use will be accounted for by including these variables as covariates in statistical analyses. Second, the project seeks to assess the daily-life impact of social cognition deficits on the social functioning of individuals with SAUD (i.e., quantity and quality of social interactions) and on the evolution of alcohol use behaviors six months after hospitalization (i.e., risk of relapse).

The study will include two participant groups: individuals with SAUD and age-, sex-, and education-matched control participants.

The expected results will refine our understanding of social cognition alterations in SAUD, thereby contributing to the improvement of current neuroscientific models. These advances will pave the way for the identification of potential targets for prevention programs and therapeutic interventions.

Nearly 3.4% of adults engage in excessive and chronic alcohol use, meeting criteria for Severe Alcohol Use Disorder (SAUD). SAUD is associated with cerebral and cognitive alterations, including deficits in social cognition. These deficits manifest as difficulties in perceiving and interpreting social cues during interactions and encompass, in particular, the recognition of emotional facial expressions and the accurate attribution of others' beliefs, emotions, and intentions (i.e., theory of mind). Such alterations contribute to interpersonal difficulties and psychological distress and are recognized as risk factors for the development and maintenance of SAUD.

To date, social cognition has primarily been explored through behavioral tests, providing a description of deficits without examining their neuro-structural correlates. Moreover, no neuroscientific study has investigated the impact of sex and concomitant tobacco use on social cognition and associated brain structures in SAUD, although these factors are known to influence both social cognitive abilities and brain organization in this disorder. Finally, the everyday consequences of these alterations on social functioning and the trajectory of alcohol consumption remain poorly explored.

In this context, the present project aims, first, to explore the neuro-structural correlates of social cognition deficits in SAUD using psychometric assessments (i.e., emotion recognition, theory of mind) combined with magnetic resonance imaging (MRI). The impact of sex and tobacco use will be accounted for by including these variables as covariates in statistical analyses. Second, the project seeks to assess the daily-life impact of social cognition deficits on the social functioning of individuals with SAUD (i.e., quantity and quality of social interactions) and on the evolution of alcohol use behaviors six months after hospitalization (i.e., risk of relapse).

The study will include two participant groups: individuals with SAUD and age-, sex-, and education-matched control participants. The expected results will refine our understanding of social cognition alterations in SAUD, thereby contributing to the improvement of current neuroscientific models. These advances will pave the way for the identification of potential targets for prevention programs and therapeutic interventions.

Detailed Description

1. State of the Art Severe Alcohol Use Disorder (SAUD) is associated with structural and functional brain alterations as well as cognitive impairments affecting memory and executive functions. Recent research also highlights deficits in social cognition, including emotion recognition and theory of mind.

   However, the neural correlates of these deficits remain poorly understood. Most neuroimaging studies in SAUD have focused on functional MRI tasks involving implicit emotional processing, whereas clinical neuropsychology typically relies on explicit behavioral assessments. Consequently, the structural brain correlates (gray and white matter) of social cognition deficits in SAUD remain largely unexplored.

   Social cognition impairments may contribute to difficulties in daily social functioning and could increase relapse risk. Ecological Momentary Assessment (EMA), combined with passive smartphone data, enables real-time assessment of social interactions in naturalistic settings and may provide a more accurate measure of daily social functioning than retrospective reports.

2. Aims of this protocol

   Primary Objective:

   - To investigate structural brain correlates (gray matter and white matter) of social cognition deficits (emotion recognition and theory of mind) in patients with SAUD.

   Secondary Objectives:

   • To examine the influence of sex and tobacco use on cognitive and brain alterations related to social cognition
   • To assess the relationship between social cognition deficits and daily social functioning using EMA and passive smartphone data
   • To evaluate whether cognitive and brain alterations in social cognition predict relapse risk six months after detoxification.

3. Hypotheses Social Cognition and Brain Alterations H1a: SAUD patients will show reduced gray matter volume and white matter integrity in brain regions involved in socio-emotional processing.

   H1b: Structural alterations will be associated with performance on social cognition tasks.

   H1c: Sex and tobacco use may modulate these associations. Social Cognition and Daily Functioning H2: Cognitive and brain deficits will predict poorer daily social functioning, assessed through self-reported interactions and passive smartphone data.

   Social Cognition and Relapse H3: Cognitive and brain deficits will predict relapse risk (alcohol consumption, craving, anxiety, depression) six months after detoxification.

4. Recruitment of participants

   Two groups will be recruited:

   SAUD patients (n = 30): Individuals hospitalized for alcohol withdrawal, abstinent for at least two weeks, without other substance use disorders (except tobacco use disorder and occasional cannabis consumption) or severe psychiatric/neurological illness.

   Healthy controls (n = 30): Individuals without substance use disorders or severe psychiatric/neurological illness, matched for age and socioeconomic status.

5. Levels of investigation Clinical Assessment: A physician specialized in addiction medicine will collect sociodemographic and clinical data, including alcohol and drug use, psychiatric symptoms, impulsivity, and socio-emotional functioning (e.g., empathy, alexithymia, emotion regulation).

   Neuropsychological Assessment: Participants will complete tests assessing general cognitive functioning, executive functions (inhibition, mental flexibility), and social cognition (facial emotion recognition and theory of mind).

   MRI: MRI acquisition will include structural T1-weighted imaging, diffusion tensor imaging (DTI), and functional MRI during the viewing of two short movie clips.

   Ecological Momentary Assessment (EMA): For 14 days following the MRI session, participants will complete a daily smartphone questionnaire assessing social interactions. Passive smartphone data (e.g., call frequency, time on communication apps, step count) will also be collected to estimate social activity.

6. Study timeline

Assessments will occur at multiple time points:

1. Clinical evaluation
2. Neuropsychological assessment
3. MRI acquisition
4. EMA and passive smartphone data collection (14 days)
5. Six-month follow-up assessing relapse outcomes in SAUD patients 7/ Statistical analyses Group differences will be tested using mean comparisons, ANOVA, and generalized linear models. Associations between neuropsychological performance and neuroimaging measures will be examined using correlation analyses and regression models.

Structural MRI analyses will assess gray matter volume, cortical thickness, and cortical surface area across the whole brain and within social cognition-related regions of interest. White matter integrity will be evaluated using diffusion measures (fractional anisotropy, mean diffusivity) and tractography.

Regression analyses will identify predictors of social cognition deficits, daily social functioning (EMA and passive data), and relapse outcomes.

1. AUD patients

   Inclusion criteria:

   • Patients between 18 and 65 years old, men or women, right-handed, following AUD treatment as inpatients or outpatients and currently abstinent
   • Having a diagnosis of severe alcohol use disorder according to DSM-5 criteria
   • Native French speakers
   • Patients enrolled in the national healthcare insurance program
   • Patients consenting to participate in the study

   Exclusion criteria:

   • A diagnosis of schizophrenia, of any other chronic psychotic state, or of bipolar disorder according to DSM-5 criteria
   • The presence of a current depressive episode as defined by DSM-5 criteria
   • The presence of another moderate or severe substance use disorder according to DSM-5 criteria, except for tobacco and cannabis if alcohol is the primary substance consumed and the criteria for cannabis dependence are not met
   • The presence of a neurodevelopmental disorder
   • The presence of any clinically significant or unstable pathology: organic pathology affecting the central nervous system or disease likely to interfere with assessments, including the neurological complications of alcoholism
   • Having any uncorrected auditory or visual deficits
   • Contraindication to the use of MRI
   • Individuals particularly protected by the law
   • No smartphone with Apple or Android operating system

2. Healthy control participants:

Inclusion criteria:

• Participants between 18 and 65 years old, men or women, right-handed
• Native French speakers
• Participants enrolled in the national healthcare insurance program
• Participants consenting to participate in the study

Exclusion criteria:

• A diagnosis of schizophrenia, of any other chronic psychotic state, or of bipolar disorder according to DSM-5 criteria
• The presence of a current depressive episode as defined by DSM-5 criteria
• The presence of substance use disorder as defined by DSM-5 diagnostic criteria, except for tobacco dependence
• Having any first-degree relative with alcohol use disorder according to DSM-5 diagnostic criteria
• The presence of a neurodevelopmental disorder
• The presence of any clinically significant or unstable pathology: organic pathology affecting the central nervous system
• Having any uncorrected auditory or visual deficits
• Contraindication to the use of MRI
• Individuals particularly protected by the law
• No smartphone with Apple or Android operating system