About

Mariella De Biasi, Ph.D., is a Professor of Psychiatry at the Perelman School of Medicine at the University of Pennsylvania. She serves as the Director of the Program on Cholinergic Mechanisms in Addiction and Mental Illness within the Department of Psychiatry. Her research expertise includes neuropharmacology, drug addiction, electrophysiology, behavioral testing, and preclinical genetic models. Dr. De Biasi has made significant contributions to understanding the cholinergic system's role in addiction and mental health, and her work involves investigating neural mechanisms underlying substance use and related behaviors.

Research topics

• Neuroscience
• Chemistry
• Internal medicine
• Biology
• Endocrinology

Selected publications

• Role of the Alpha 5 Nicotinic Receptor Subunit in Alcohol Consumption

  Scholarly Commons (University of Pennsylvania) · 2025-01-01

  otherOpen accessSenior author

  Genome-wide association studies (GWAS) have identified a strong association between alcohol consumption and a single nucleotide polymorphism (SNP) in the CHRNA5 gene (rs16969968), which encodes the α5 subunit of neuronal nicotinic acetylcholine receptors (nAChRs). While extensively studied in nicotine dependence, the role of this subunit in alcohol-related behaviors remains unclear. To address this, we examined ethanol consumption and withdrawal-related behaviors in α5 mutant and wild-type (WT) mice using the intermittent two-bottle choice (I2BC) paradigm. Male and female α5 mutant and WT mice were given intermittent access to 20% ethanol, followed by behavioral testing in the Open Field Arena (OFA) and Elevated Plus Maze (EPM). Analyses revealed no significant differences between genotypes in ethanol intake, preference, or dosage across the I2BC paradigm. Similarly, locomotor activity and anxiety-like behavior in the OFA and EPM did not differ between groups. These findings suggest that the α5 subunit does not significantly influence voluntary ethanol consumption or withdrawal-related behaviors under these conditions, highlighting the complexity of genetic contributions to alcohol use phenotypes.

  Publisher

• Cannabis Use and Glutamate across the Psychosis Spectrum: In Vivo Evidence from 7T Proton Magnetic Resonance Spectroscopy

  Research Square · 2025-11-23

  preprintOpen access
  PublisherOA PDFDOI

• Cannabis Use and Glutamate across the Psychosis Spectrum: In Vivo Evidence from 7T Proton Magnetic Resonance Spectroscopy

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-09

  preprintOpen access

  Abstract Cannabis use is linked to elevated psychosis risk, yet the neurobiological mechanisms that couple use to symptom expression remain unclear. Because glutamatergic dysregulation has been implicated in both cannabis effects and psychosis vulnerability, we examined whether brain glutamate relates to dimensional symptoms as a function of cannabis use across the psychosis spectrum. Seventy-nine participants—typically developing controls, clinical high-risk individuals, and patients with psychosis—completed dimensional clinical assessments, detailed cannabis surveys, urine toxicology, and ultra-high-field 7T 1 HMRS quantification of anterior cingulate cortex (ACC) glutamate levels. Linear models assessed the main and interactive effects of ACC glutamate and cannabis use on positive and negative symptoms. Self-reported cannabis use showed strong concordance with urine toxicology. Cannabis use was associated with higher positive and negative symptoms. Independently, higher ACC glutamate predicted greater positive and negative symptoms. Notably, lower glutamate levels were associated with higher positive symptoms in cannabis users. Exploratory analyses suggested interactions for depressive and manic symptoms, indicating that glutamatergic abnormalities may amplify the overall severity of cannabis-related symptoms. Sensitivity analyses revealed lower ACC glutamate in psychosis patients—especially cannabis users—highlighting diagnostic group differences and reinforcing the link between cannabis exposure and glutamatergic dysfunction. These findings implicate ACC glutamatergic dysfunction as a transdiagnostic correlate of symptom burden, particularly in those with psychosis who are cannabis users. Glutamate-targeted interventions and longitudinal designs will be needed to examine causal pathways linking cannabis exposure to psychosis-relevant outcomes.

  PublisherOA PDFDOI

• Editorial overview: Addiction

  Current Opinion in Neurobiology · 2024-11-28

  editorial1st authorCorresponding
  PublisherDOI

• Smoking-related increases in alcohol outcomes and preliminary evidence for the protective effect of a functional nicotine receptor gene (<i>CHRNA5)</i> variant on alcohol consumption in individuals without alcohol use disorder

  The International Journal of Neuropsychopharmacology · 2024-08-29 · 1 citations

  articleOpen access

  BACKGROUND: Alcohol and nicotine interact with the nicotinic acetylcholine receptor system to alter reward-related responses, thereby contributing to the co-use and misuse of these drugs. A missense polymorphism rs16969968 (G>A) in the CHRNA5 gene has shown a strong association with nicotine-related phenotypes. However, less is known about the impact of this variant on alcohol-related phenotypes. METHODS: We assessed the main and interactive effect of smoking and rs16969968 polymorphism on alcohol consumption using the Alcohol Use Disorders Identification Test (AUDIT), Timeline Follow Back (TLFB), and Lifetime Drinking History (LDH) in 980 healthy adults without alcohol use disorder. We further examined the effect of the rs16969968 polymorphism on acute alcohol consumption using a free-access i.v. alcohol self-administration (IV-ASA) human laboratory paradigm in a subset of 153 nonsmoking participants. Subjective alcohol responses, alcohol sensitivity, and expectancy measures were compared between genotype groups (GG; AA/AG). RESULTS: We observed a significant association of smoking with AUDIT, TLFB, and LDH measures across genotype groups, with smokers showing higher scores compared with nonsmokers. Additionally, we found an association between genotype and TLFB-total drinks in the IV-ASA subset, with the GG group showing higher scores than AA/AG group. Relatedly, the alcohol negative expectancy score was significantly lower in the GG group than the AA/AG group. CONCLUSIONS: Our findings underscore the association of smoking with alcohol measures. We found preliminary evidence for the protective effect of the functional CHRNA5 polymorphism on alcohol consumption and its association with increased negative alcohol expectancies, which highlights the substantial heterogeneity in alcohol responses.

  PublisherDOI

• Decreased voluntary alcohol intake and ventral striatal epigenetic and transcriptional remodeling in male Acss2 KO mice

  Neuropharmacology · 2024-12-09 · 3 citations

  articleOpen accessCorresponding

  Metabolic-epigenetic interactions are emerging as key pathways in regulating alcohol-related transcriptional changes in the brain. Recently, we have shown that this is mediated by the metabolic enzyme Acetyl-CoA synthetase 2 (Acss2), which is nuclear and chromatin-bound in neurons. Mice lacking ACSS2 fail to deposit alcohol-derived acetate onto histones in the brain and show no conditioned place preference for ethanol reward. Here, we further explored the role of this pathway during voluntary alcohol intake. We found that Acss2 KO mice consume significantly less alcohol in a model of binge drinking, an effect primarily driven by males. Genome-wide transcriptional profiling of 7 key brain regions implicated in alcohol and drug use revealed that, following drinking, Acss2 KO mice exhibit blunted gene expression in the ventral striatum. Similarly to the behavioral differences, transcriptional dysregulation was more pronounced in male mice. Further, we found that the gene expression changes were associated with depletion of ventral striatal histone acetylation (H3K27ac) in Acss2 KO mice compared to WT. Taken together, our data suggest that ACSS2 plays an important role in orchestrating ventral striatal epigenetic and transcriptional changes during voluntary alcohol drinking, especially in males. Consequently, targeting this pathway could be a promising new therapeutic avenue. • Acss2 KO mice consume less alcohol during drinking-in-the-dark • Loss of Acss2 affects drinking more strongly in males compared to females • Transcriptional profiling indicates the role of ventral striatal gene expression • Decreased histone acetylation in the ventral striatum of male Acss2 KO mice

  PublisherDOI

• Supplementary Movie 2 from Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction

  2023-03-31

  preprintOpen access

  &lt;p&gt;CARS imaging of ex vivo ovarian cancer samples&lt;/p&gt;

  PublisherDOI

• Corticofugal regulation of predictive coding

  The Journal of the Acoustical Society of America · 2023-10-01

  article

  Sensory systems must account for both contextual factors and prior experience to adaptively engage with the dynamic external environment. In the central auditory system, neurons modulate their responses to sounds based on statistical context. These response modulations can be understood through a hierarchical predictive coding lens: responses to repeated stimuli are progressively decreased, in a process known as repetition suppression, whereas unexpected stimuli produce a prediction error signal. A potential substrate for top-down predictive cues is the massive set of descending projections from the cortex to subcortical structures, although the role of these corticofugal neurons in predictive processing has never been directly assessed. We tested the effect of optogenetic inactivation of the auditory cortico-collicular feedback in awake mice on responses of auditory midbrain neurons to stimuli designed to test prediction error and repetition suppression. Inactivation of the cortico-collicular pathway led to a decrease in prediction error and repetition enhancement in these neurons. Overall, our results demonstrate that the auditory cortex provides cues about the statistical context of sound to subcortical brain regions via direct feedback, regulating processing of both prediction and repetition.

  PublisherDOI

• CHRNA5 gene variation affects the response of VTA dopaminergic neurons during chronic nicotine exposure and withdrawal

  Neuropharmacology · 2023-04-27 · 8 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Figures S1-S6, Table S1-S3 from Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction

  2023-03-31

  preprintOpen access

  &lt;p&gt;Fig. S1. Sustained adrenergic signaling increases nerve counts in tumors. Fig. S2. Characterization of tumoral innervation. Fig. S3. NE induces BDNF expression. Fig. S4. NE-induced BDNF expression is mediated by ADRB3/Epac/Jnk. Fig. S5. BDNF increases nerve counts. Fig. S6. Adrenergic-mediated mTrkB activation leads to increased in vivo tumor nodule counts. Table S1. Alteration in pathways associated with neuronal growth and function after NE treatment (HeyA8 and SKOV3ip1 cells). Table S2. Association of Clinicopathologic variables with BDNF protein expression. Table S3. Association of Clinicopathologic variables with Nerve Counts.&lt;/p&gt;

  PublisherDOI

Recent grants

• NIH Grant R21DA029157

  NIH · $420k · 2013

• NIH Grant R01DA017173

  NIH · $2.2M · 2013

• Flavored e-cigarette use in adolescents: Behavioral, cellular, and epigenetic mechanisms

  NIH · $2.2M · 2018–2023

• NIH Grant R21DA024385

  NIH · $307k · 2010

• Translational study on CHRNA5 variation and alcohol reward mechanisms

  NIH · $1.8M · 2018–2023

Frequent coauthors

• Barbara A. Wible

  23 shared

• Ramiro Salas

  Baylor College of Medicine

  21 shared

• Arthur Brown

  Eli Lilly (United States)

  21 shared

• John A. Dani

  University of Pennsylvania

  21 shared

• Arthur L. Beaudet

  21 shared

• Maurizio Taglialatela

  University of Naples Federico II

  20 shared

• James W. Patrick

  20 shared

• Eugenio Ragazzi

  University of Padua

  18 shared

Labs

• De Biasi LabPI

Awards & honors

• Director, Program on Cholinergic Mechanisms in Addiction and…
• Advisory Board Member, Clinical Neuroscience Training (CNST)…