About

Daniel H. Wolf, M.D., Ph.D., is an Associate Professor of Psychiatry at the University of Pennsylvania's Perelman School of Medicine. He is an attending psychiatrist at the Hospital of the University of Pennsylvania and holds faculty positions at the Institute for Translational Medicine and Therapeutics, the Center for Functional Neuroimaging (CfN), and the Center for Biomedical Image Computing and Analytics (CBICA). Dr. Wolf's clinical expertise is in the treatment of adults with psychotic disorders, and he is a board-certified psychiatrist. His research focuses on developing a translational program to study the neural mechanisms underlying reward and motivation deficits in psychiatric conditions such as psychosis, depression, and addiction, as well as in individuals at risk for these disorders. Utilizing pharmacological challenges during functional neuroimaging combined with detailed clinical and behavioral assessments, he aims to relate these deficits to dysfunctions in specific neural circuits and to improve methods for assessing novel therapeutic interventions. Dr. Wolf actively collaborates with geneticists, animal researchers, and pharmaceutical industry scientists to facilitate the clinical translation of basic neuroscientific discoveries.

Research topics

• Psychology
• Neuroscience
• Medicine
• Natural Language Processing
• Computer Science
• Artificial Intelligence
• Gerontology
• Audiology
• Cognitive psychology
• Developmental psychology
• Psychiatry
• Speech recognition
• Cognitive science
• Internal medicine
• Cardiology
• Linguistics

Selected publications

• Body fluid biomarkers and psychosis risk in The Accelerating Medicines Partnership® Schizophrenia Program: design considerations

  Schizophrenia · 2025-05-21 · 7 citations

  articleOpen access

  Advances in proteomic assay methodologies and genomics have significantly improved our understanding of the blood proteome. Schizophrenia and psychosis risk are linked to polygenic scores for schizophrenia and other mental disorders, as well as to altered blood and saliva levels of biomarkers involved in hormonal signaling, redox balance, and chronic systemic inflammation. The Accelerating Medicines Partnership® Schizophrenia (AMP®SCZ) aims to ascertain biomarkers that both predict clinical outcomes and provide insights into the biological processes driving clinical outcomes in persons meeting CHR criteria. AMP®SCZ will follow almost 2000 CHR and 640 community study participants for two years, assessing biomarkers at baseline and two-month follow-up including the collection of blood and saliva samples. The following provides the rationale and methods for plans to utilize polygenic risk scores for schizophrenia and other disorders, salivary cortisol levels, and a discovery-based proteomic platform for plasma analyses. We also provide details about the standardized methods used to collect and store these biological samples, as well as the study participant metadata and quality control measures related to preanalytical factors that could influence the values of the biomarkers. Finally, we discuss our plans for analyzing the results of blood- and saliva-based biomarkers. Watch Dr. Perkins discuss their work and this article: https://vimeo.com/1062879582?share=copy#t=0 .

  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

• Cognitive assessment in the Accelerating Medicines Partnership® Schizophrenia Program: harmonization priorities and strategies in a diverse international sample

  UNC Libraries · 2025-12-05

  articleOpen access
  PublisherDOI

• Body fluid biomarkers and psychosis risk in The Accelerating Medicines Partnership® Schizophrenia Program: design considerations

  UNC Libraries · 2025-12-05

  articleOpen access
  PublisherDOI

• Longitudinal Trajectories of Clinical Features in Community Youth With Recurrent Psychosis Spectrum Symptoms: Findings From the Philadelphia Neurodevelopmental Cohort

  Schizophrenia Bulletin · 2025-06-09 · 1 citations

  article

  BACKGROUND AND HYPOTHESIS: In the general population, more severe, recurrent subthreshold psychosis spectrum (PS) symptoms are associated with a heightened risk of poor outcomes. Here, we expanded and temporally extended our prior 2-year follow-up of community youth with recurrent PS symptoms in the Philadelphia Neurodevelopmental Cohort (PNC) by characterizing longer-term trajectories of symptom domains and global functioning compared to youth with other recurrent psychopathology. STUDY DESIGN: The PNC Time 1 included 9498 community youth (age 8-21) recruited from a pediatric healthcare network. A subsample (n = 752) participated in prospective evaluations (mean visits = 2.75; interval range years first:last visit = 0.2:9.3; mean = 4.52 years; age range years first:last visit = 8.1-21.9:9.5-29.9). Youth were classified based on psychopathology at first and last visits. Longitudinal trajectories of symptom domains (positive, negative, disorganized, general) and global functioning were modeled using generalized additive mixed models. STUDY RESULTS: Youth with recurrent PS displayed a nonlinear developmental trajectory of positive psychosis symptoms such that severity increased slowly until the early 20s, and then briefly plateaued before increasing significantly in the late 20s. They also exhibited increases over time in disorganized and negative symptoms, and in general symptoms, which were lower in severity and relatively stable in other groups. Global functioning in recurrent PS declined from moderate to serious impairment over time, compared to youth with recurrent other psychopathology, where higher and more stable functioning was observed. CONCLUSIONS: Results underscore that PS symptoms in community adolescents reflect dynamic developmental processes into early adulthood, and support evaluating trajectories of multiple symptom and functional domains.

  PublisherDOI

• Data analysis strategies for the Accelerating Medicines Partnership® Schizophrenia Program

  UNC Libraries · 2025-12-05

  articleOpen access
  PublisherDOI

• The MR neuroimaging protocol for the Accelerating Medicines Partnership® Schizophrenia Program

  UNC Libraries · 2025-12-04

  articleOpen access
  PublisherDOI

• Longitudinal Development of Neurocognitive Functioning and Gray Matter Volume in Youths With Recurrent Psychosis Spectrum Symptoms

  Schizophrenia Bulletin · 2025-05-18 · 2 citations

  articleOpen access

  BACKGROUND AND HYPOTHESIS: Neurodevelopmental risk-factor models of psychosis highlight the importance of early developmental deviations in the emergence of psychosis. However, few longitudinal studies map neurodevelopment and neurocognitive trajectories across age in preclinical psychosis. We investigated longitudinal trajectories in neurocognition and brain volume in a community cohort of adolescents with recurrent psychosis spectrum (PS) symptoms, tracking their development into young adulthood compared to their typically developing (TD) peers. STUDY DESIGN: Utilizing the Philadelphia Neurodevelopmental Cohort, we analyzed data of 231 youths aged 8-30 with at least one follow-up assessment, including 88 with PS. STUDY RESULTS: Individuals with PS showed similar developmental trajectories but demonstrated significant impairments in executive functioning (t = -2.81, q = 0.010), memory (t = -2.34, q = 0.019), complex cognition (t = -3.72, q = 0.001), social cognition (t = -2.73, q = 0.010), motor (t = -2.50, q = 0.015), and general cognition (t = -3.20, q = 0.004). Lower cortical (t = -2.46, P = .014) and subcortical (t = -2.41, P = .016) gray matter volume in the recurrent PS group compared to the TD group were documented with age-related group differences becoming less pronounced by young adulthood. Further analyses revealed age-by-group interactions (qs < 0.05) observed in a few temporal and frontal regions, with differences between groups at earlier ages. CONCLUSIONS: These findings suggest that recurrent PS symptoms are linked to early neurocognitive and brain structure deficits, highlighting the need for interventions to reduce psychosis risk and support healthy neurodevelopment.

  PublisherOA PDFDOI

• Characterizing Spatial Associations Between <scp>GluCEST MRI</scp> and Neurotransmitter Receptor Density in the Human Cortex

  Human Brain Mapping · 2025-12-15 · 1 citations

  articleOpen access

  ABSTRACT Glutamate‐weighted Chemical Exchange Saturation Transfer (GluCEST) captures in vivo glutamate (Glu) levels with high spatial resolution and has been used to assess glutamatergic function in healthy and clinical populations. While GluCEST is well‐validated against proton magnetic resonance spectroscopy ( 1 H‐MRS), its correspondence with local expression of glutamatergic neurotransmitter receptors remains unclear. Recent initiatives, such as Neuromaps, have collated positron emission tomography (PET) data into curated, publicly available databases, providing a novel opportunity to establish convergence in the regional distribution of GluCEST and normative receptor density maps. Here, we examine the spatial correspondence between GluCEST signal and PET‐based cortical receptor density levels of N‐methyl‐D‐aspartate (NMDA), metabotropic glutamate receptor 5 (mGluR5), and gamma‐aminobutyric acid A (GABA A ). A cohort of 86 participants (age: 22.7 years [3.7 years], 45% female) included 34 individuals with no psychiatric history, 31 participants with significant sub‐threshold psychosis symptoms, and 21 participants with first‐episode psychosis. All participants underwent 7T GluCEST imaging. Data were processed using in‐house and field‐standard pipelines. Mean receptor density levels were computed using the Neuromaps PET receptor density data. GluCEST and Neuromaps data were parcellated using the Cammoun 500 atlas. Pearson correlations assessed the correspondence between GluCEST signal and PET‐based receptor density, and spin tests were used for empirical significance testing of the spatial correlations across all parcels. Sensitivity analyses examined the effect of age, sex, and diagnosis and other covariates. Exploratory analyses assessed regional variability across cytoarchitecturally defined von Economo regions and overall trends with gene expression. Analyses were performed in Python and R. GluCEST signal converged with the regional distribution of both NMDA ( r = 0.23, p spin = 0.039) and GABA A ( r = 0.35, p spin = 0.004). There was no significant effect for mGluR5 ( r = 0.09, p spin &gt; 0.05). Exploratory analyses indicated that cytoarchitecturally defined von Economo regions showed variable GluCEST‐receptor association patterns across the cortex and that gene expression patterns generally correspond with receptor density findings. Our findings reveal a positive spatial association between GluCEST signal in a transdiagnostic cohort and atlas‐based PET‐derived cortical receptor density of NMDA and GABA A , and a nominal positive association with mGluR5. The association between GluCEST and NMDA suggests that regions with dense ionotropic Glu receptors exhibit higher Glu levels, while the coupling between GluCEST and GABA A may reflect tight regulation of excitation‐inhibition balance. Regional differences in these associations point to the potential influence of local cytoarchitectural specialization on Glu‐receptor dynamics. These results advance our understanding of the neurobiological basis of GluCEST and highlight its potential utility as a non‐invasive tool for probing receptor‐mediated glutamatergic neurotransmission.

  PublisherOA PDFDOI

• Baseline Clinical Characterization of Participants in the Accelerating Medicines Partnership Schizophrenia Program

  UNC Libraries · 2025-12-04

  articleOpen access

  This paper focuses on the baseline clinical characterization of the participants in the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program. The AMP SCZ program is designed to investigate a wide array of clinical variables and biomarkers in a total of 2040 clinical high-risk (CHR) participants and 652 community control (CC) participants. The dataset analyzed includes 1642 individuals at clinical high risk for psychosis and 519 CCs. Key measures include the Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the Structured Interview for Psychosis-Risk Syndromes, which determined CHR criteria and the severity of attenuated psychotic symptoms (APS). Other measures included the Structured Clinical Interview for DSM-5, scales to assess negative symptoms, depression, suicidal ideation, substance use, social and role functioning, and a selection of patient-reported outcomes. CHR participants presented with more severe ratings on all clinical measures and poorer functioning relative to the CC. There were a few significant small associations between measures of APS and other clinical measures. The results from this study support previous research indicating that CHR individuals face serious clinical challenges beyond the risk of developing psychosis. Findings indicate significant associations among various clinical measures, underscoring the complex nature of the CHR population. Limitations are acknowledged, including the preliminary nature of the data and the need for more in-depth analyses from AMP SCZ papers already in progress. Future work will focus on longitudinal data and further exploration of clinical variables and their relationship with biomarkers.

  PublisherDOI

Recent grants

• Adolescent Neurodevelopment and Impaired Intrinsic Motivation in Psychosis Risk

  NIH · $2.9M · 2018–2023

• NIH Grant K23MH085096

  NIH · $897k · 2013

• NIH Grant R01MH101111

  NIH · $1.6M · 2018

Frequent coauthors

• Ruben C. Gur

  Children's Hospital of Philadelphia

  383 shared

• Theodore D. Satterthwaite

  Children's Hospital of Philadelphia

  368 shared

• Raquel E. Gur

  Children's Hospital of Philadelphia

  364 shared

• Monica E. Calkins

  University of Pennsylvania

  263 shared

• Tyler M. Moore

  California University of Pennsylvania

  239 shared

• David R. Roalf

  191 shared

• Kosha Ruparel

  139 shared

• Russell T. Shinohara

  127 shared

Labs

• Daniel H. Wolf LabPI