Biology subjects

Sommer, W. H.

Publications and source records attributed to Sommer, W. H..

4 recordsLinked to original sources

bioRxiv2026

Brain Functional Connectivity Signatures of Craving Across Substance Use Disorders: A Transdiagnostic Approach

Craving is a hallmark feature of substance use disorders (SUDs) and a major risk factor for relapse, yet reliable biomarkers that enable individual-level prediction remain scarce. Here, we applied connectome-based predictive modeling (CPM) to resting-state functional magnetic resonance imaging (fMRI) data in a transdiagnostic sample of individuals with cannabis, opioid, or tobacco use disorder (n = 78). Using CPM, we identified a distributed functional brain network that reliably predicted self-reported craving. Computational lesion analyses revealed key contributions from the right medial orbitofrontal cortex, right dorsal posterior cingulate cortex, and left lateral medial frontal gyrus. Importantly, the craving network generalized across two independent datasets. In alcohol-dependent patients (n = 41), the identified craving network, along with its positive and negative subnetworks, predicted distinct cognitive and motivational components of craving. In a second external dataset of smokers (n = 28), the craving network predicted both nicotine craving after abstinence as well as intra-individual changes in craving between sated and craving states. Together, these findings provide evidence for a robust, transdiagnostic craving signature in SUDs. Future work should assess the networks predictive utility for longitudinal outcomes such as relapse risk and treatment response.

neuroscience↗

bioRxiv2022

A Systematic Review and Meta-analysis on the Transcriptomic Signatures in Alcohol Use Disorder- a Translational Approach

Alcohol use disorder (AUD) is a complex mental health condition. Currently available clinical treatments exhibit limited efficacy and new druggable targets are required. One promising approach to discover new molecular treatment targets involves the transcriptomic profiling of brain regions within the addiction neurocircuitry, utilizing animal models and post-mortem brain tissue from deceased AUD patients. Unfortunately, such studies suffer from large heterogeneity and small sample sizes. To address these limitations, we conducted a cross-species meta-analysis on transcriptome-wide data obtained from brain tissue of AUD patients and animal models. We integrated 36 cross-species transcriptome-wide RNA-expression datasets with an alcohol-dependent phenotype vs. controls, following the PRISMA guidelines. In total, we meta-analyzed 1,000 samples - 502 samples for the prefrontal cortex (PFC), 318 nucleus accumbens (NAc) samples, and 180 amygdala (AMY) samples. The PFC had the highest number of differentially expressed genes (DEGs) across rodents, monkeys, and humans. Commonly dysregulated DEGs pointed towards enrichment in inflammatory responses and alterations in BBB-regulatory mechanisms in astrocytes, microglia and endothelial cells. Gene set enrichment analysis further showed that MAPK/ERK-signaling plays a critical role in AUD and especially in monkeys Dusp4 as a major inhibitor of the MAPK pathway may be a main driver of these pathway alterations. Our data also suggest that the transcriptomic profile in the NAc is less vulnerable to the maintenance of AUD. Finally, we provide a combination of DEGs that are commonly regulated across different brain tissues as potential biomarker for AUD. In summary, we provide a compendium of genes, signaling pathways, and physiological and cellular processes that are altered in AUD and that require future studies for functional validation.

neuroscience↗

bioRxiv2022

Generalized habitual tendencies in alcohol dependent rats

Habitual responses and ultimately compulsive behavior are thought to be at the core of addiction including alcohol use disorder (AUD). Little is known whether the habitization concerns exclusively the response towards alcohol or generalizes to other daily activities. Here, we address this question in a well-established animal model of AUD - the postdependent rat model - by testing habitual responses towards a sweet palatable reward in two striatal learning paradigms: spatial navigation and reward conditioning. For the spatial navigation task, alcohol-dependent and control rats were tested on a sequential decision-making test after short and prolonged T-Maze training; for the reward conditioning task, rats were trained under a random interval schedule for a short and prolonged period and tested in a satiety devaluation test at each time point. Another cohort of alcohol-naive rats was trained and tested on both paradigms under DREADD (designer receptors exclusively activated by designer drugs)-mediated inactivation of the dorsomedial striatum (DMS) which controls goal-directed behavior. Our results show that alcohol-dependent rats displayed increased habitual behavior to obtain saccharin reward on both paradigms, with overall more habitual choices after prolonged training on the spatial navigation task, and increased habitual responses already after short training on the reward conditioning task. Finally, DREADD-mediated inactivation of the DMS increased habitual behavior in non-dependent rats on both paradigms. Our results provide evidence that a history of alcohol dependence produces a bias towards habitual responding that generalizes to a natural reward in rats. Similarly, a habitual bias was induced in non-dependent rats after inactivation of the DMS, thus confirming the critical role of this region in maintaining goal-directed behavior and suggesting its diminished control in AUD.

neuroscience↗

bioRxiv2020

A common molecular mechanism for cognitive deficits and craving in alcoholism

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. The medial prefrontal cortex, a key brain region for executive control, is prone to alcohol-induced neuroadaptations. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood. Here using a bi-directional neuromodulation approach we demonstrate a causal link for reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. By neuron-specific prefrontal knockdown of mGluR2 in rats, we generated a phenotype of reduced cognitive flexibility and excessive alcohol-seeking. Conversely, restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. Also targeting mGluR2 pharmacologically reduced relapse behavior. Finally, we developed a FDG-PET biomarker to identify those individuals that respond to mGluR2-based interventions. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving, and provide a personalized mGluR2-mechanism-based intervention strategy for medication development of alcoholism.

neuroscience↗