About

Irina Esterlis is an Associate Professor in the Department of Psychology at Yale University. She earned her PhD in 2005 from the University of Connecticut. Her research focuses on psychological and neuroscientific aspects within the field of psychology, contributing to the understanding of mental health and related areas. She is involved in teaching and mentoring within the department, and her contact information includes a phone number at Yale and a professional email address. Further details about her specific research interests and contributions are not provided on the page.

Research topics

• Psychology
• Medicine
• Neuroscience
• Internal medicine
• Psychiatry

Selected publications

• 337. Altered Brain Network Connectivity Mediates Links Between Poor Sleep, Depression Severity, and Suicidal Ideation in Mid-to-Late Life

  Biological Psychiatry · 2026-04-25

  articleSenior author
  PublisherDOI

• Lower synaptic density in mood circuitry underlies depression in Parkinson’s disease

  Brain Communications · 2026-01-01

  articleOpen access

  Abstract Depression in Parkinson’s disease is often reported as being more debilitating than the motor symptoms and has been shown to accelerate disease progression. Identifying its underlying neurobiology is crucial in the discovery of mechanism-informed treatments. We hypothesize that lower synaptic density in mood circuitry drives symptoms of depression in Parkinson’s disease. To test this hypothesis, we used PET imaging and [11C]UCB-J—a radiotracer that binds to synaptic vesicle protein 2A (SV2A) to image synaptic density across patients with Parkinson’s disease and depressive symptoms (PDd; n = 10), Parkinson’s disease patients without depressive symptoms (PDnd; n = 20) and healthy controls (HCs; n = 18). The primary outcome was binding potential (BPND) in mood circuitry. Participants with PDd exhibited significantly lower synaptic density compared to HC and PDnd in the dorsolateral prefrontal cortex (dlPFC) (−22.0%, P < 0.001; −19.9%, P = 0.002), anterior cingulate cortex (ACC) (−27.9%, P < 0.001; −24.0%, P = 0.002), amygdala (−25.1%, P < 0.001; −18.9%, P = 0.006) and hippocampus (−28.1%, P < 0.001; −20.3%, P = 0.003). Synaptic density was significantly and negatively correlated with the severity of depressive symptoms across all participants with Parkinson’s disease (n = 30) in the dlPFC (r = −0.59, P = 0.002), ACC (r = −0.68, P < 0.001), amygdala (r = −0.53, P = 0.004) and hippocampus (r = −0.56, P = 0.003). These findings provide the first in vivo evidence that lower synaptic density in mood-related brain regions may contribute to depression in Parkinson’s disease. If confirmed, they would support the evaluation of interventions that target synaptic loss/induce synaptic plasticity in individuals with Parkinson’s disease and comorbid depression.

  PublisherOA PDFDOI

• Medication status is associated with metabotropic glutamate receptor 5 availability in bipolar disorder and with measures of attention, anhedonia, and cognition

  Journal of Affective Disorders · 2026-04-27

  articleOpen accessSenior authorCorresponding

  Bipolar disorder (BD) is a neuropsychiatric condition associated with affective and cognitive symptoms, impulsivity, and suicidality. The metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in BD, but the relationship between psychiatric medication use and mGlu5 availability remains unclear. Using [ 18 F]FPEB positron emission tomography (PET), we measured mGlu5 in ventromedial prefrontal (vmPFC), orbitofrontal (OFC), and dorsolateral prefrontal (dlPFC) cortices, amygdala, and hippocampus in 48 individuals with BD (21 medicated) and 48 age and sex-matched healthy controls (HC). Group differences in mGlu5 availability were tested with analysis of covariance, controlling for cannabis and nicotine use. Clinical assessments of depression (MADRS), anhedonia (SHAPS), attention (Barratt Impulsiveness Scale), and cognition (Groton Maze Learning Test) were examined in relation to regional mGlu5 availability using linear regression. Significant group effects were observed across ROIs, showing lower mGlu5 in unmedicated BD relative to medicated BD and HC, with effects in the vmPFC ( p = 0.003), OFC ( p = 0.006), dlPFC ( p = 0.007), amygdala ( p = 0.009), and hippocampus ( p = 0.010). Across the full sample, lower OFC mGlu5 was associated with poorer executive function (β = −0.25, p = 0.044). In unmedicated BD, lower mGlu5 correlated with greater attentional difficulties (r's = −0.52 - -0.54, all p's < 0.05). In medicated BD, worse anhedonia correlated with lower mGlu5 (r's = −0.41–0.43, all p's < 0.05). These associations remained statistically significant after adjustment for depressive symptom severity, nicotine, and cannabis use. Findings indicate that medication status is associated with differences in mGlu5 availability in BD. mGlu5 availability in medicated participants was closer to that of HC, supporting further investigation of glutamatergic mechanisms as potential therapeutic targets in BD. • Unmedicated bipolar disorder shows lower mGlu5 across frontolimbic regions. • Medication status is associated with mGlu5 availability closer to healthy controls. • Lower OFC mGlu5 is associated with poorer executive function across participants. • mGlu5 may be a potential biomarker and therapeutic target in bipolar disorder.

  PublisherDOI

• Multiple sources of β2*-nicotinic acetylcholine receptor binding are differentially affected during tobacco smoking abstinence as revealed by Independent Component Analysis of [18F]Flubatine PET images

  Neuropsychopharmacology · 2026-01-20

  articleOpen access

  Abstract Tobacco smoking, a major cause of preventable mortality, upregulates β2 subunit-containing nicotinic acetylcholine receptors (β2*-nAChR) in most brain regions. Although the α4 subunit most frequently co-assembles with β2, other subunits likely assemble with β2 and contribute to distinct aspects of nicotine-mediated behaviors, but these factors are poorly understood in people. This work performed independent component analysis (ICA) of [ 18 F]Flubatine positron emission tomography (PET) image data to identify maximally independent sources of specific binding to β2*-nAChRs. We then compared their magnitudes (loading coefficients) in people who recently stopped smoking cigarettes (abstinent smokers; n = 26) and people who never smoked cigarettes (non-smokers; n = 20). ICA identified 3 reproducible components: IC1 (36% of variance) in medial thalamus, lateral thalamus, and red nucleus; IC2 (18% of variance) in ventral thalamus, lateral geniculate, and midbrain; IC3 (19% of variance) in cerebellum and optic circuitry in midbrain. Nicotine challenge in an independent sample ( n = 9) reduced loading coefficients of all components, confirming specific binding to nAChRs. Post-mortem autoradiography of cerebellum showed greatest [ 18 F]Flubatine displacement by α3/α6β2*-nAChR blocker (α-Conotoxin MII) but low displacement by α6β2*-nAChR blocker (α-Conotoxin PIA), suggesting that IC3 measures α3β2*-nAChRs specific binding – a novel finding in living people. Loading coefficients of IC1 and IC2 were significantly lower in abstinent smokers compared to non-smokers. IC3 loading coefficients were significantly higher during extended smoking abstinence, and exploratory analyses suggested initial evidence for daily smoking amount correlating with nicotine dependence severity. These results could inform novel treatment development to help people quit smoking.

  PublisherOA PDFDOI

• Optimized reference region and the effect on test-retest reliability and sensitivity to differences between Parkinson’s disease and control groups with [ ¹¹ C]UCB-J

  Journal of Cerebral Blood Flow & Metabolism · 2026-04-10

  articleOpen access

  [ 11 C]UCB-J is a radioligand targeting synaptic vesicle glycoprotein 2A, used to image synaptic density. For quantification, a small-volume centrum semiovale area was previously optimized as a [ 11 C]UCB-J reference region (CS2mL); however, due to its small volume, its high variability resulted in reduced reliability. Herein, we evaluated an alternative reference region method to assess longitudinal test-retest reliability and detection of Parkinson’s disease (PD). For estimating distribution volume ratio (DVR), CS2mL and eleven white matter (WM) reference regions (range: 0.5–200 mL) were generated. Same-day and longitudinal test-retest variability (TRV) were assessed (24 healthy subjects (HS); n = 10 same-day and n = 20 longitudinal scans, range: 7–1028 days). Each reference region was used to evaluate the substantia nigra (SN) and caudate DVRs in HS ( n = 25) and PD ( n = 20); 10 mL was the optimal reference region volume, yielding [ 11 C]UCB-J DVR measurements with reduced variability in TRV (same-day: 10 mL: 1.2 ± 5.7%, same-day: CS2mL: −0.9 ± 9.2% longitudinal: 10 mL: 1.5 ± 7.0%, CS2mL: 1.6 ± 11.9%), while maintaining &lt;10% volume of distribution difference, compared to CS2mL. Further, a significant difference between PD and HS groups in SN and caudate DVRs was found using 10 mL, with greater effect size (Cohen’s d 0.61 for SN and 0.66 for caudate) compared to CS2mL (0.38 for SN and 0.43 for caudate).

  PublisherDOI

• Network-based Molecular Constraints on in vivo Synaptic Density Alterations in Schizophrenia

  medRxiv · 2025-03-23 · 2 citations

  preprintOpen access

  Converging neuroimaging, genetic, and post-mortem evidence highlights the fundamental role of synaptic density reductions in schizophrenia pathogenesis. However, the brain-wide spatial pattern of these alterations and the mechanisms underlying this patterning remain to be established. Here, using [11C]UCB-J radiotracer positron emission tomography (PET) imaging in individuals with schizophrenia (n=29) and healthy controls (n=93), we find a prominent and widespread pattern of lower synaptic density (0.58 &lt; Cohens D &lt; 1.47; pFWE&lt;0.05) in patients. The left hemisphere is substantially more impacted than the right (Cohens D = 1.14; p &lt; .001), with frontal, temporal, cingulate, thalamic, striatal and hippocampal areas particularly affected. Synaptic density alterations were not spatially aligned with gray matter alterations indexed using anatomical Magnetic Resonance Imaging. Lower synaptic density in the left hemisphere is associated with higher normative concentrations of GABAA/BZ, 5HT2A, mGluR5 and 5HT1B (r_cca=.68; p=.022). Simulation-based network diffusion models identified regions that may represent the initial sources of pathology, nominating left inferior frontal areas (p_FWE &lt;.05) as potential foci from which synaptic pathology initiates and then propagates to structurally connected and molecularly similar areas. Overall, our findings provide in vivo evidence for widespread synaptic density deficits in schizophrenia that are left-lateralized, independent of gray matter alterations, aligned to specific neurochemical systems, and suggest that such synaptic pathology may propagate in a pattern consistent with axonal networks.

  PublisherOA PDFDOI

• Generating synthetic brain PET images of synaptic density based on MR T1 images using deep learning

  EJNMMI Physics · 2025-03-31 · 4 citations

  articleOpen access

  Abstract Purpose Synaptic vesicle glycoprotein 2 A (SV2A) in human brains is an important biomarker of synaptic loss associated with several neurological disorders. However, SV2A tracers, such as [ 11 C]UCB-J, are less available in practice due to constrains such as cost, radiation exposure and onsite cyclotron. We therefore aim to generate synthetic [ 11 C]UCB-J PET images based on MRI in this study. Methods We implemented a convolution-based 3D encoder-decoder to predict [ 11 C]UCB-J SV2A PET images. A total of 160 participants who underwent both MRI and [ 11 C]UCB-J PET imaging, including individuals with schizophrenia, cannabis use disorder, Alzheimer’s disease, were used in this study. The model was trained on pairs of T1-weighted MRI and [ 11 C]UCB-J distribution volume ratio images, and tested through a 10-fold cross-validation process. The image translation accuracy was evaluated based on the mean squared error, structural similarity index, percentage bias and Pearson’s correlation coefficient between the ground truth and the predicted images. Additionally, we assessed the prediction accuracy of selected regions of interest (ROIs) crucial for brain disorders to evaluate our results. Results The generated SV2A PET images are visually similar to the ground truth in terms of contrast and tracer distribution, quantitatively with low bias (&lt; 2%) and high similarity (&gt; 0.9). Across all diagnostic categories and ROIs, including the hippocampus, frontal, occipital, parietal, and temporal regions, the synthetic SV2A PET images exhibit an average bias of less than 5% compared to the ground truth. The model also demonstrates a capacity for noise reduction, producing images of higher quality compared to the low-dose scans. Conclusion We conclude that it is feasible to generate robust SV2A PET images with promising accuracy from MRI via a data-driven approach.

  PublisherOA PDFDOI

• Imaging Metabotropic Glutamate Receptor 5 and Excitatory Neural Activity in Autism

  American Journal of Psychiatry · 2025-12-10 · 3 citations

  article

  OBJECTIVE: Autism spectrum disorder is a prevalent and heterogeneous condition with features ranging from social and communication differences to sensory sensitivities. Differences in excitatory neurotransmission have been identified in autism, but the molecular underpinnings are poorly understood. To investigate the mechanism underlying these observed differences, the authors assessed glutamatergic receptor density in autistic adults using positron emission tomography (PET) and related it to a functional EEG measure of excitatory activity. METHODS: were calculated using Spearman's rho. RESULTS: Across all brain regions, mGlu5 availability was significantly lower (by ~15%) in autistic relative to neurotypical control participants. Group differences were generally greatest in the cerebral cortex. Within the autistic group, mGlu5 availability in all regions was significantly correlated with the slope of the EEG (e.g., cerebral cortex, r=0.67), such that shallower slope was associated with lower mGlu5 availability. CONCLUSIONS: This brain-wide investigation of mGlu5 availability with PET revealed pervasive lower mGlu5 availability across multiple brain areas in autism. Additionally, multimethod analyses revealed associations with a noninvasive electrophysiological index of excitatory neurotransmission. These results indicate that lower brain-wide mGlu5 availability may represent a molecular mechanism underlying altered excitatory neurotransmission that has the potential to stratify the heterogeneous autism phenotype.

  PublisherDOI

• Optimized reference region and the effect on test-retest reliability and detection of Parkinson’s disease with [ ¹¹ C]UCB-J

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-15 · 1 citations

  preprintOpen access

  Abstract [ 11 C]UCB-J is a radioligand targeting synaptic vesicle glycoprotein 2A, used to image synaptic density. For quantification, a small-volume centrum semiovale area was previously optimized as a [ 11 C]UCB-J reference region (CS2mL); however, its high variability resulted in reduced reliability. Herin, we evaluated an alternative reference region method to assess longitudinal test-retest reliability and detection of Parkinson’s disease (PD). For estimating distribution volume ratio (DVR), CS2mL and eleven white matter (WM) reference regions (range: 0.5-200 mL) were generated using the Freesurfer WM map. Same-day and longitudinal test-retest variability (TRV) were assessed (24 healthy subjects (HS); n=10 same-day and n=20 longitudinal HRRT scans, range: 7-1028 days). Each reference region was used to evaluate the substantia nigra (SN) and caudate DVRs in HS (n=25) and PD (n=20). The 10mL WM reference region yielded [ 11 C]UCB-J DVR measurements with reduced variability in TRV (same-day: 10mL: 1.2±5.7%, same-day: CS2mL: -0.9±9.2% longitudinal: 10mL: 1.5±7.0%, CS2mL: 1.6±11.9%,) while maintaining &lt;10% volume of distribution difference, compared to CS2mL. Further, a significant difference between PD and HS groups in SN and caudate DVRs was found using 10mL, with greater effect size (Cohen’s d 0.61 for SN and 0.66 for caudate) compared to CS2mL (0.38 for SN and 0.43 for caudate).

  PublisherOA PDFDOI

• 452. Examining the Role of the Kappa Opioid Receptor in Trauma-Related Psychopathology and Chronic Pain Using [11C]EKAP Positron Emission Tomography

  Biological Psychiatry · 2025-04-09

  article
  PublisherDOI

Recent grants

• NIH Grant R21MH085198

  NIH · $383k · 2012

• NIH Grant R21DA024388

  NIH · $351k · 2011

• NIH Grant K01MH092681

  NIH · $850k · 2017

• In vivo imaging of a neural marker of suicidal behavior in Bipolar Disorder

  NIH · $4.0M · 2018–2024

• NIH Grant R01MH104459

  NIH · $3.6M · 2021

Frequent coauthors

• Kelly Cosgrove

  Yale University

  194 shared

• Robert H. Pietrzak

  United States Department of Veterans Affairs

  175 shared

• John H. Krystal

  Yale University

  143 shared

• Richard E. Carson

  121 shared

• Frédéric Y. Bois

  Simcyp (United Kingdom)

  117 shared

• Julie K. Staley

  Memorial Sloan Kettering Cancer Center

  96 shared

• John Seibyl

  Invicro (United States)

  87 shared

• Nabeel Nabulsi

  Yale University

  79 shared