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Distinct neuronal pathways to alcohol use disorder with and without comorbid social anxiety disorder

This study reveals that alcohol use disorder severity arises through distinct neurocognitive pathways depending on the presence of comorbid social anxiety disorder, with AUD alone linked to reduced ventral attention network activation and AUD with comorbid SAD linked to reduced default mode network activation mediated by coping drinking motives.

Original authors: Verena Wüllhorst, Malin K. Hildebrandt, Kristina Schwarz, Tanja Endrass

Published 2026-06-29

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CC BY 4.0

Original authors: Verena Wüllhorst, Malin K. Hildebrandt, Kristina Schwarz, Tanja Endrass

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ⚕️ This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer

The Big Picture: Two Different Roads to the Same Destination

Imagine Alcohol Use Disorder (AUD) as a destination called "The Heavy Drinking Zone." For a long time, scientists thought everyone took the exact same road to get there: a road where the brain's "brakes" (inhibitory control) were broken.

However, this study suggests that the road isn't the same for everyone. Specifically, the path changes depending on whether the person also suffers from Social Anxiety Disorder (SAD).

The researchers looked at 175 people and split them into four groups:

People with just Alcohol Use Disorder.
People with just Social Anxiety.
People with both Alcohol Use Disorder and Social Anxiety.
People with neither (the control group).

They asked everyone to play a mental game called the "Stop-Signal Task." Think of this like a video game where you have to run forward, but sometimes a red light flashes, and you have to hit the brakes instantly. While they played, the researchers used an MRI machine to watch which parts of their brains were lighting up.

The Two Main Brain Networks

To understand the results, you need to know about two specific "teams" inside the brain:

The "Stop Team" (Ventral Attention Network - VAN): This is the brain's emergency brake. When you need to stop an action, this team kicks in to say, "Freeze!"
The "Daydream Team" (Default Mode Network - DMN): This team is active when you are thinking about yourself, your worries, or your past. Usually, when you are focused on a task (like hitting the brakes), this team is supposed to take a nap so it doesn't distract you.

What They Found: Two Different Paths

The study discovered that the brain works differently depending on who you are:

Path A: The "Broken Brake" (Alcohol Disorder without Anxiety)

For people who drink heavily but do not have social anxiety, the study found a classic problem.

The Analogy: Imagine trying to stop a car, but the brake pedal feels mushy and weak.
The Science: When these people tried to stop themselves in the game, their "Stop Team" (VAN) didn't work very hard. The more severe their drinking problem was, the weaker their "brakes" were in a specific area called the pre-supplementary motor area.
The Takeaway: For this group, the issue is a lack of self-control. They struggle to hit the brakes when they need to.

Path B: The "Distracted Driver" (Alcohol Disorder with Anxiety)

For people who have both heavy drinking and social anxiety, the problem looked completely different.

The Analogy: Imagine a driver who has perfectly good brakes, but their mind is so busy worrying about what other drivers think of them (self-referential thoughts) that they aren't paying attention to the road. They are "daydreaming" while trying to drive.
The Science: In this group, the "Stop Team" (VAN) was working just fine. Instead, the problem was with the "Daydream Team" (DMN). Usually, this team should go quiet during a task. But in these individuals, the more severe their drinking was, the less their Daydream Team turned off.
The Connection: The study found that these people often drink to "cope" with their negative feelings. Because their brains were still stuck in "self-worry mode" (DMN) while trying to do a task, they seemed to use alcohol as a way to quiet that internal noise.

What About People with Just Anxiety?

Interestingly, people who had only Social Anxiety (and no drinking problems) didn't show these specific brain patterns. This suggests that the "Daydream Team" issue isn't just about being anxious; it's a specific mix of anxiety plus the drinking problem.

The Conclusion: One Size Does Not Fit All

The main message of this paper is that Alcohol Use Disorder isn't just one thing.

If you have AUD alone, your brain struggles to stop impulses (the brakes are weak).
If you have AUD + Social Anxiety, your brain struggles to focus because it's stuck in self-worry mode (the driver is distracted), and they drink to cope with that distraction.

The researchers suggest that because these two groups have different "engine problems," we might need different strategies to help them. Treating them exactly the same way might not work because their brains are taking different roads to get to the same destination.

Note: This study looked at a snapshot in time, so it cannot prove that one thing causes the other, but it clearly shows that the brain patterns are different depending on whether anxiety is present.

Technical Summary: Distinct Neuronal Pathways to Alcohol Use Disorder with and without Comorbid Social Anxiety Disorder

Problem Statement
Alcohol use disorder (AUD) is a prevalent condition characterized by impaired control and continued use despite negative consequences. While inhibitory control deficits are widely considered a core phenotype of substance use disorders (SUDs), empirical findings regarding the neural mechanisms underlying AUD severity remain inconsistent. Previous studies have reported hyperactivation, ambiguous results, or a lack of categorical differences between AUD and control groups, often finding stronger dimensional associations with AUD severity rather than group membership. A potential source of this inconsistency is the frequent neglect of psychiatric comorbidity. Social anxiety disorder (SAD) is a highly prevalent comorbidity in AUD (affecting 11–17% of individuals) and is linked to worse clinical outcomes. However, it remains unknown whether the neural correlates of AUD severity, specifically regarding inhibitory control and the ventral attention network (VAN), depend on the presence of comorbid SAD. Furthermore, given that individuals with comorbid AUD and SAD often utilize alcohol as a coping mechanism for self-referential negative affect, it is hypothesized that the default mode network (DMN)—typically suppressed during goal-directed tasks—may play a distinct role in this subgroup.

Methodology
This study employed a well-powered, preregistered functional magnetic resonance imaging (fMRI) design to investigate neural mechanisms in four distinct groups:

AUD: Individuals with Alcohol Use Disorder without anxiety disorders ( $n=43$ ).
COM: Individuals with comorbid AUD and Social Anxiety Disorder ( $n=41$ ).
SAD: Individuals with Social Anxiety Disorder without externalizing disorders ( $n=49$ ).
CP: Control participants with no current or lifetime DSM-5 diagnosis ( $n=42$ ).

The total final sample consisted of 175 participants (mean age = 26.0 years). Diagnoses were established using the Structured Clinical Interview for DSM-5 (SCID-5-CV). AUD severity was quantified via a severity rating of DSM-5 A-criterion symptoms. Participants completed a Stop-Signal Task (SST) during fMRI scanning to assess inhibitory control.

Neuroimaging and Analysis

Paradigm: The SST consisted of two blocks with 25% stop trials. Neuronal inhibitory control was operationalized as the contrast of successful stop trials versus successful go trials ($sStop > sGo$).
Regions of Interest (ROIs): Analyses were restricted to two a-priori defined networks derived from the Multiresolution Intrinsic Segmentation Template (MIST): the Ventral Attention Network (VAN) and the midline core of the Default Mode Network (DMN).
Statistical Approach:
- Categorical Analysis: A voxelwise general linear model (GLM) tested for group differences in inhibition-related activation within the VAN and DMN.
- Dimensional Analysis: A full-factorial design tested associations between AUD severity and neural activation separately within the AUD and COM groups.
- Mediation: The study explored whether drinking motives (specifically coping motives) mediated the relationship between neural activation and AUD severity.
Controls: Analyses controlled for sex, age, and scanner version. Significance was assessed at $p < 0.05$ , family-wise error (FWE) corrected within ROIs.

Key Results

Group Differences: No significant categorical differences were found in inhibition-related VAN or DMN activation between the four groups, nor were there differences in Stop-Signal Reaction Time (SSRT).
AUD without SAD (AUD Group): Greater AUD severity was significantly associated with reduced VAN activation in the pre-supplementary motor area (preSMA) ( $t = 4.34, p_{FWE} = 0.036$ ). This association was not observed in the COM group.
Comorbid AUD and SAD (COM Group): Greater AUD severity was significantly associated with reduced DMN activation in the medial prefrontal cortex (mPFC) ( $t = 4.28, p_{FWE} = 0.021$ ). This association was not observed in the AUD group.
Mediation: In the COM group, coping motives partially mediated the association between reduced DMN activation in the mPFC and greater AUD severity (accounting for approximately 35% of the total association). Coping motives did not mediate the VAN-AUD severity link in the AUD group.
Control Analyses: Social anxiety severity alone was not associated with inhibition-related VAN or DMN activation, nor did it explain the COM-specific associations.

Significance and Claims
The authors claim that these findings suggest AUD severity arises through partially distinct neurocognitive pathways depending on the presence of comorbid SAD:

In AUD without SAD: Severity is linked to impaired engagement of top-down inhibitory control circuits (VAN/preSMA), consistent with dual-process models of SUD involving reduced self-control.
In AUD with SAD: Severity is linked to altered regulation of self-referential internal processes (DMN/mPFC), potentially reflecting a failure to suppress task-irrelevant self-referential processing (e.g., rumination or craving) during goal-directed tasks. This pathway is partially driven by coping motives to drink.

The study concludes that explicitly modeling comorbidity refines mechanistic accounts of AUD. The authors suggest that the frequent neglect of comorbidity in previous research may have contributed to inconsistent findings in case-control studies. By identifying these distinct pathways, the findings support the development of more targeted prevention and intervention strategies that address the specific neurocognitive mechanisms (inhibitory control vs. self-referential regulation) relevant to specific patient subgroups. The authors note that causal inference is limited by the cross-sectional nature of the study and that the observed brain-behavior links were modest in magnitude, consistent with biopsychosocial models of psychopathology.