Recent Submissions

  • The IGF-II–Insulin Receptor Isoform-A Autocrine Signal in Cancer: Actionable Perspectives

    Center for Biotechnology, Sbarro Institute for Cancer Research and Molecular Medicine (Temple University) (2020-02-05)
    Insulin receptor overexpression is a common event in human cancer. Its overexpression is associated with a relative increase in the expression of its isoform A (IRA), a shorter variant lacking 11 aa in the extracellular domain, conferring high affinity for the binding of IGF-II along with added intracellular signaling specificity for this ligand. Since IGF-II is secreted by the vast majority of malignant solid cancers, where it establishes autocrine stimuli, the co-expression of IGF-II and IRA in cancer provides specific advantages such as apoptosis escape, growth, and proliferation to those cancers bearing such a co-expression pattern. However, little is known about the exact role of this autocrine ligand–receptor system in sustaining cancer malignant features such as angiogenesis, invasion, and metastasis. The recent finding that the overexpression of angiogenic receptor kinase EphB4 along with VEGF-A is tightly dependent on the IGF-II/IRA autocrine system independently of IGFIR provided new perspectives for all malignant IGF2omas (those aggressive solid cancers secreting IGF-II). The present review provides an updated view of the IGF system in cancer, focusing on the biology of the autocrine IGF-II/IRA ligand–receptor axis and supporting its underscored role as a malignant-switch checkpoint target.
  • Pulmonary Artery Intimal Sarcoma: A Diagnostic Challenge Using a Multimodal Approach

    Nakrani, Rima; Yeung, Ho-Man; Kim, Jin Sun; Kamat, Bhishak; Kumaran, Maruti; 0000-0002-7188-9738 (2020-10-05)
    Pulmonary artery intimal sarcoma (PAIS) is a rare tumor without clear syndromic presentation other than nonspecific symptoms of cough, dyspnea, and weight loss. This diagnosis is difficult due to challenging radiographic interpretations of multiple imaging modalities. We present a case of a 60-year-old male, who presented to his pulmonologist and underwent a CT chest with IV contrast that initially suggested primary lung carcinoma. CT angiogram showed significant vascular filling defects suspicious of an intravascular mass, rather than vascular invasion by lung lesions. The PET/CT scans further suggested a malignant process, but indistinguishable between an extravascular or intravascular etiology. Taking these results together, they suggested an intravascular malignancy, prompting a tissue biopsy, which ultimately led to a diagnosis of PAIS with metastases. Establishing a definitive diagnosis is essential as treatment and prognosis are different for sarcoma compared to carcinoma. There is no standard treatment to date, and management often includes a multidisciplinary approach involving surgery, radiation, chemotherapy, and targeted therapy. PAIS is a rare entity that cannot be diagnosed clinically and needs a multimodality approach for its diagnosis.
  • Case series: Failure of imaging & biochemical markers to capture disease progression in COVID-19

    Dorey-Stein, Zachariah L.; Myers, Catherine; Kumaran, Maruti; Mamary, Albert; Criner, Gerard J.; 0000-0002-3761-153X; 0000-0002-0909-5048 (2020-09-19)
    We report four individuals admitted for acute respiratory failure due to COVID-19 who demonstrated significant clinical improvement prior to discharge and subsequently were readmitted with worsening respiratory failure, elevated inflammatory markers and worsening chest imaging. We propose a multi-disciplinary discharge criterion to establish a safer discharge process including trending inflammatory markers, daily imaging and pursuing follow up CT chest, particularly in individuals with significant morbidities and health disparities.
  • Obesity is associated with reduced orbitofrontal cortex volume: A coordinate-based meta-analysis

    Chen, Eunice; Eickhoff, Simon B.; Giovannetti, Tania; Smith, David; 0000-0002-9288-7133; 0000-0001-5661-152X; 0000-0001-5754-9633 (2020-09-09)
    Neural models of obesity vary in their focus upon prefrontal and striatal differences. Animal and human studies suggest that differential functioning of the orbitofrontal cortex is associated with obesity. However, meta-analyses of functional neuroimaging studies have not found a clear relationship between the orbitofrontal cortex and obesity. Meta-analyses of structural imaging studies of obesity have shown mixed findings with regards to an association with reduced orbitofrontal cortex gray matter volume. To clarify these findings, we conducted a meta-analysis of 25 voxel-based morphometry studies, and found that greater body mass index is associated with decreased gray matter volume in the right orbitofrontal cortex (Brodmanns’ areas 10 and 11), where family-wise corrected p < .05, N = 7,612. Use of the right orbitofrontal cortex as a seed in a Neurosynth Network Coactivation analysis showed that this region is associated with activity in the left frontal medial cortex, left temporal lobe, right precuneus cortex, posterior division of the left middle temporal gyrus, and right frontal pole. When Neurosynth Network Coactivation results were submitted as regions of interest in the Human Connectome Project data, we found that greater body mass index was associated with greater activity in left frontal medial cortex response to the Gambling Task, where p < .05, although this did not survive Bonferroni-correction. Our findings highlight the importance of the orbitofrontal cortex structure and functioning in neural models of obesity. Exploratory analyses suggest more studies are needed that examine the functional significance of reduced orbitofrontal cortex gray matter volume in obesity, and the effect of age and weight changes on this relationship using longitudinal designs.
  • Retrospective analysis of high flow nasal therapy in COVID-19-related moderate-to-severe hypoxaemic respiratory failure

    Patel, Maulin; Gangemi, Andrew; Marron, Robert; Chowdhury, Junad; Yousef, Ibraheem; Zheng, Matthew; Mills, Nicole; Tragesser, Lauren; Giurintano, Julie; Gupta, Rohit; Gordon, Matthew; Rali, Parth; D'Alonso, Gilbert; Fleece, David; Zhao, Huaqing; Patlakh, Nicole; Criner, Gerard; 0000-0001-6558-1924; 0000-0002-8764-6538; 0000-0003-2775-2918; 0000-0002-0953-4768| (2020-08-26)
    Invasive mechanical has been associated with high mortality in COVID-19. Alternative therapy of high flow nasal therapy (HFNT) has been greatly debated around the world for use in COVID-19 pandemic due to concern for increased healthcare worker transmission.This was a retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from 10 March 2020 to 24 April 2020 with moderate-to-severe respiratory failure treated with HFNT. Primary outcome was prevention of intubation. Of the 445 patients with COVID-19, 104 met our inclusion criteria. The average age was 60.66 (+13.50) years, 49 (47.12 %) were female, 53 (50.96%) were African-American, 23 (22.12%) Hispanic. Forty-three patients (43.43%) were smokers. Saturation to fraction ratio and chest X-ray scores had a statistically significant improvement from day 1 to day 7. 67 of 104 (64.42%) were able to avoid invasive mechanical ventilation in our cohort. Incidence of hospital-associated/ventilator-associated pneumonia was 2.9%. Overall, mortality was 14.44% (n=15) in our cohort with 13 (34.4%) in the progressed to intubation group and 2 (2.9%) in the non-intubation group. Mortality and incidence of pneumonia was statistically higher in the progressed to intubation group.
  • Case Report: Watching and Waiting? A Case of Incomplete Glenosphere Seating With Spontaneous Reversal in Reverse Shoulder Arthroplasty

    MacAskill, Micah L.; Thomas, Rachel; Barnes, Leslie A.; 0000-0001-9274-1751 (2020-08-27)
    Introduction: Reverse shoulder arthroplasty is a useful procedure with broadening applications, but it has the best outcomes when used for rotator cuff tear arthropathy. However, this procedure is not without complications. While scapular notching and aseptic loosening are more common complications that have been extensively studied in the literature, dissociation of the glenoid component and incomplete glenosphere seating has not received much attention. Specifically, little research has explored appropriate management of incomplete seating of the glenosphere component, and no gold standard for treatment of this complication has emerged. Methods: In the case described here, an elderly patient with an incompletely seated glenosphere component post-operatively opted to pursue conservative management in order to avoid revision surgery if possible. Results: The partially engaged, superiorly directed components in this case exhibited spontaneous complete and symmetric seating of the glenosphere between six and twelve months post-operatively, indicating that conservative management of this complication in low-demand patients may be a viable option to avoid the risks associated with revision surgery. Conclusion: Further research should be pursued to explore what patient and prosthesis design factors may be suited to observation with serial radiographs when incomplete seating of the glenosphere component occurs.
  • Meta-analysis of reward processing in major depressive disorder reveals distinct abnormalities within the reward circuit

    Ng, Tommy Ho-Yee; Alloy, Lauren B.; Smith, David; 0000-0003-4402-0081; 0000-0001-5754-9633 (2019-11-11)
    Many neuroimaging studies have investigated reward processing dysfunction in major depressive disorder. These studies have led to the common idea that major depressive disorder is associated with blunted responses within the reward circuit, particularly in the ventral striatum. Yet, the link between major depressive disorder and reward-related responses in other regions remains inconclusive, thus limiting our understanding of the pathophysiology of major depressive disorder. To address this issue, we performed a coordinate-based meta-analysis of 41 whole-brain neuroimaging studies encompassing reward-related responses from a total of 794 patients with major depressive disorder and 803 healthy controls. Our findings argue against the common idea that major depressive disorder is primarily linked to deficits within the reward system. Instead, our results demonstrate that major depressive disorder is associated with opposing abnormalities in the reward circuit: hypo-responses in the ventral striatum and hyper-responses in the orbitofrontal cortex. The current findings suggest that dysregulated corticostriatal connectivity may underlie reward-processing abnormalities in major depressive disorder, providing an empirical foundation for a more refined understanding of abnormalities in the reward circuitry in major depressive disorder.
  • From leads to leadless: A convoluted journey

    Dulam, Vipin; Cooper, Joshua M.; Gangireddy, Chethan; Kashem, Mohammed A.; Toyoda, Yoshiya; Keshavamurthy, Suresh; 0000-0002-5578-1911 (2020-07-21)
  • Effects of Revegetation on Soil Physical and Chemical Properties in Solar Photovoltaic Infrastructure

    Choi, Chong Seok; Cagle, Alexander E.; Macknick, Jordan; Bloom, Dellena E.; Caplan, Joshua; Ravi, Sujith; 0000-0002-6860-2038; 0000-0003-4624-2956; 0000-0002-0425-9373 (2020-08-11)
    Solar photovoltaic (PV) technology is being deployed at an unprecedented rate. However, utility-scale solar energy development is land intensive and its large-scale installation can have negative impacts on the environment. In particular, solar energy infrastructure can require extensive landscape modification that transforms soil ecological functions, thereby impacting hydrologic, vegetative, and carbon dynamics. However, reintroducing native vegetation to solar PV sites may be a means of restoring their soils. To this end, we investigated critical soil physical and chemical parameters at a revegetated photovoltaic array and an adjacent reference grassland in Colorado, United States. Seven years after revegetation, we found that carbon and nitrogen remained lower in the PV soil than in the reference soil and contained a greater fraction of coarse particles. We also found that the PV modules introduced heterogeneity in the soil moisture distribution, with precipitation accumulating along the lower edges of panels. The redistribution of soil moisture by panel arrays could potentially be used in concert with planting strategies to maximize plant growth or minimize soil erosion, and should be considered when evaluating the potential to co-locate vegetation with solar infrastructure.
  • Ultrasound-guided Hydro-dissection Facilitates Tissue Expander Placement and Components Separation in Complex Ventral Hernia Repair

    Maroney, Jenna; Taylor, George; Lo, Alexis; Golpanian, Samuel; Prus, Nelson W.; Livelsberger, Jon; Gassman, Andrew A.; 0000-0001-7382-1932 (2020-09-23)
    Summary: Tissue expanders are known adjuncts in ventral hernia repair, used in a staged approach where tissue closure or coverage of the defect is preferred but inadequate. Placement of tissue expanders in the correct tissue plane can be difficult, especially in thin patients or with loss of domain. This case series describes a technique in which tissue expander placement is facilitated by ultrasound-guided hydro-dissection, following the placement of a transversus abdominis plane (TAP) block. In short, after induction of anesthesia, the same needle used for the ultrasound-guided TAP block can be repositioned by the anesthesiologist to instill tumescent solution into the fascial plane between the internal and external oblique muscles. This allows for identification of the fascial planes in the ensuing operation. Our technique may prove to be an alternative tool in the placement of tissue expanders for ventral hernia repair, or in other procedures requiring device placement.
  • Synthesis and catalytic performance of polydopamine supported metal nanoparticles

    Li, Haoqi; Xi, Jiaxin; Donaghue, Adrienne G.; Keum, Jong; Zhao, Yao; An, Ke; McKenzie, Erica; Ren, Fei; 0000-0002-9943-329X; 0000-0001-8997-9670; 0000-0003-1982-2533; 0000-0002-8868-4536 (2020-06-26)
    Polydopamine (PDA) is an emerging nature-inspired biopolymer material that possesses many interesting properties including self-assembly and universal adhesion. PDA is also able to form coordination bonds with various metal ions, which can be reduced to metal nanoparticles (NPs) as a result of thermal annealing under protective environment. In this study, PDA has been utilized as a support material to synthesize Pt NPs in an aqueous solution at room temperature. The catalytic performance of the resulting PDA-Pt nanocomposite was evaluated using an electrochemical workstation which showed comparable activity to Pt/C material for hydrogen evolution reaction (HER). Furthermore, Cu, Ni, and Cu–Ni NPs supported on PDA were also obtained using this strategy with assistance of subsequent thermal annealing. The phase evolution of the NPs was studied by in-situ X-ray diffraction while the morphology of the nanoparticles was investigated using electron microscopic techniques. Preliminary results showed the NPs supported on PDA also possessed HER activity. This work demonstrates that PDA can be utilized as a potential support for synthesis of metal NPs that can be exploited in engineering applications such as catalysts.
  • Responses to affect subtypes differentially associate with anxious and depressive symptom severity

    Mennies, Rebekah J.; Birk, Samantha L.; Case, Julia; Olino, Thomas; 0000-0002-1964-8523; 0000-0001-5139-8571 (2020-07-02)
    Responses to affect include cognitive processes (i.e., perseverative vs. non-perseverative) and valence (i.e., modulation of positive vs. negative affect). However, little research has examined how the factor structure of responses to affect is defined along one or both of these dimensions. The present study conducted an exploratory factor analysis (EFA) of items from assessments of repetitive negative thinking, rumination on positive affect (PA), and dampening. We also examined the associations between emergent factors and measures of depressive symptoms, social anxiety symptoms, and non-social state anxiety. EFA results suggested a three-factor model of repetitive negative thinking, dampening, and rumination on PA. There was a significant association between repetitive negative thinking and dampening factors, but not between other factors. Repetitive negative thinking and dampening were associated with greater internalizing symptoms, whereas rumination on PA was associated with fewer internalizing symptoms. These findings clarify the structure of these responses to affect and their differential associations with symptoms, which may be used to tailor cognitive interventions for anxiety and/or depression.
  • A Rare Case of Primary Anorectal Melanoma and a Review of the Current Landscape of Therapy

    Yeung, Ho-Man; Gupta, Brinda; Kamat, Bhishak; 0000-0002-7188-9738 (2020-08-02)
    Introduction: Anorectal mucosal melanoma (ARMM) is an uncommon and highly aggressive malignancy. Given its rarity, there is insufficient evidence on the optimal medical management which presents as a clinical challenge to its diagnosis and treatment. Treatment of ARMM typically involves a multimodal approach including surgical resection, chemotherapy, targeted therapy and/or immunotherapy. Case Presentation: Here, we present a case of a 78-year-old female who presented with a four-month history of rectal bleeding and bowel incontinence. Ultimately, colonoscopy revealed a mass at the anal verge, and biopsy of the mass showed malignant cells that stained positive for S100, Melan-A and HMB-45, consistent with the diagnosis of malignant melanoma. Molecular testing revealed no BRAF, KIT or NRAS gene mutations. PD-L1 immunohistochemistry showed tumor proportion score of 1%. She underwent abdominoperineal resection with a plan to initiate immunotherapy with an anti-PD-1 checkpoint inhibitor. This case highlights a rare aggressive malignancy and reviews its treatment option, which are mostly extrapolated from its cutaneous counterpart and some derived from a few case reports. Due to its rarity, there is no consensus guideline for the treatment of ARMM.
  • Improving thermal conduction across cathode/electrolyte interfaces in solid-state lithium-ion batteries by hierarchical hydrogen-bond network

    He, Jinlong; Zhang, Lin; Liu, Ling (2020-09)
    Effective thermal management is an important issue to ensure safety and performance of lithium-ion batteries. Fast heat removal is highly desired but has been obstructed by the high thermal resistance across cathode/electrolyte interface. In this study, self-assembled monolayers (SAMs) are used as the vibrational mediator to tune interfacial thermal conductance between an electrode, lithium cobalt oxide (LCO), and a solid state electrolyte, polyethylene oxide (PEO). Embedded at the LCO/PEO interface, SAMs are specially designed to form hierarchical hydrogen-bond (H-bond) network with PEO. Molecular dynamics simulations demonstrate that all SAM-decorated interfaces show enhanced thermal conductance and dominated by H-bonds types. The incorporation of poly(acrylic acid) (PAA) SAM drastically enhances interfacial thermal conductance by approximately 211.69%, largely due to the formation of a strong H-bond, -COOH···:O, between PAA and PEO. Even with weaker H-bonds such as -OH···:O, it still outperforms the pristine interface as well as interfaces decorated with non-H-bonded SAMs, e.g. PE. Such improvement is attributed to the unique hierarchical H-bond network at the interface, which removes discontinuities in temperature field, straighten SAM chains, make materials strongly adhere, and couple the vibrational modes of materials. The study is expected to guide surface engineering for more effective thermal management in lithium-ion batteries.
  • Integrating environmental and neighborhood factors in MaxEnt modeling to predict species distributions: A case study of Aedes albopictus in southeastern Pennsylvania

    Wiese, Daniel; Escalante, Ananias; Murphy, Heather; Gutiérrez-Vélez, Víctor Hugo; Henry, Kevin; 0000-0002-1603-7583; 0000-0002-1532-3430; 0000-0002-0435-8515; 0000-0002-5348-9669 (2019-10-17)
    Aedes albopictus is a viable vector for several infectious diseases such as Zika, West Nile, Dengue viruses and others. Originating from Asia, this invasive species is rapidly expanding into North American temperate areas and urbanized places causing major concerns for public health. Previous analyses show that warm temperatures and high humidity during the mosquito season are ideal conditions for A. albopictus development, while its distribution is correlated with population density. To better understand A. albopictus expansion into urban places it is important to consider the role of both environmental and neighborhood factors. The present study aims to assess the relative importance of both environmental variables and neighborhood factors in the prediction of A. albopictus’ presence in Southeast Pennsylvania using MaxEnt (version 3.4.1) machine-learning algorithm. Three models are developed that include: (1) exclusively environmental variables, (2) exclusively neighborhood factors, and (3) a combination of environmental variables and neighborhood factors. Outcomes from the three models are compared in terms of variable importance, accuracy, and the spatial distribution of predicted A. albopictus’ presence. All three models predicted the presence of A. albopictus in urban centers, however, each to a different spatial extent. The combined model resulted in the highest accuracy (74.7%) compared to the model with only environmental variables (73.5%) and to the model with only neighborhood factors (72.1%) separately. Although the combined model does not essentially increase the accuracy in the prediction, the spatial patterns of mosquito distribution are different when compared to environmental or neighborhood factors alone. Environmental variables help to explain conditions associated with mosquitoes in suburban/rural areas, while neighborhood factors summarize the local conditions that can also impact mosquito habitats in predominantly urban places. Overall, the present study shows that MaxEnt is suitable for integrating neighborhood factors associated with mosquito presence that can complement and improve species distribution modeling.
  • Reducing Wound Hemorrhage: Use of Bilayer Collagen Matrix in Chronic Myelogenous Leukemia

    Lo, Alexis L.; Tyrell, Richard O.; Golarz, Scott R.; Jones, Christine M. (2019-11-27)
    Summary: Donor site preparation is a critical step before the application of an autologous split-thickness skin graft (STSG). Comorbidities can lead to complications and graft loss, including that due to hematoma. In this case, a bilayer collagen matrix was used as a temporary wound dressing in a 25-year-old woman with active chronic myelogenous leukemia. She presented with a bleeding diathesis and spontaneous intramuscular and intracompartmental hematomas of the right leg. She experienced ongoing high-volume blood loss from her fasciotomy wounds, requiring wound care to be performed in the operating room under general anesthesia, and requiring multiple blood and platelet transfusions. Instead of immediate STSG, a bilayer collagen matrix was placed to reduce the bleeding and further prepare the wound bed over a 9-week period while she underwent medical optimization. Once stabilized from a hematologic standpoint, STSG was performed with total graft take. Both uncontrolled chronic myelogenous leukemia and its therapy, tyrosine kinase inhibitors, have a risk of hemorrhagic and thrombotic complications. Bilayer collagen matrix serves as an adjunct in the limb salvage algorithm that can reduce transfusion needs whereas a temporary bleeding diathesis is medically corrected before the application of an autologous skin graft.
  • Residential Land Use Change in the Wissahickon Creek Watershed: Profitability and Sustainability?

    Sorrentino, John; Meenar, Mahbubur; Wargo, Donald; 0000-0003-1597-4564 (2019-10-25)
    The Wissahickon Creek Watershed is one of five major watersheds in the Philadelphia metro region. The main objective of the work in this paper was to determine and compare the energy and environmental impacts of placing housing in the Watershed according to profitability and environmental sustainability criteria, respectively, in the context of increasing urbanization. Future population and employment for the Watershed have been projected by the Delaware Valley Regional Planning Commission. Housing requirements for the projected populations in each municipality were computed, and their location was influenced by the local zoning ordinances. Suitability analysis using ArcGIS 10.6 generated areas for development based alternatively on profitability and local sustainability. CommunityViz 5.2 Scenario 360 software was used to place buildings within the appropriately-zoned areas. Using Argonne National Laboratory’s Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation (GREET1 2018) software and water quality monitoring information from the Philadelphia Water Department, impacts were directly estimated. The impacts were related to effects on ecosystem functioning, ecosystem goods and services, and broad value estimated for the latter. The effects were used to indicate what might be appropriate policies to reduce the negative environmental consequences of residential development in the watershed. Unexpectedly, the environmental impacts of the profitable and sustainable scenarios were not very different. This suggests that profitability and sustainability need not be mutually exclusive.
  • Examining Adolescence as a Sensitive Period for High-Fat, High-Sugar Diet Exposure: A Systematic Review of the Animal Literature

    Ozanne, Susan (2019-10-25)
    Animal studies suggest that poor nutrition (e.g., high-fat, high-sugar diets) may lead to impairments in cognitive functioning. Accumulating evidence suggests that the deleterious effects of these diets appear more pronounced in animals maintained on this diet early in life, consistent with the notion that the developing brain may be especially vulnerable to environmental insults. The current paper provides the first systematic review of studies comparing the effects of high-fat, high-sugar diet exposure during adolescence and adulthood on memory performance. The majority of studies (7/8) identified here report diet-induced memory problems when diet exposure began in adolescence but not adulthood. These findings lend support to the hypothesis that adolescence is a sensitive period during which palatable diets may contribute to negative neurocognitive effects. The current review explores putative mechanisms involved in diet-induced cognitive dysfunction and highlights promising areas for further research.
  • The Effect of Historic Paving Materials on Traffic Speed

    Nogueira, Xavier; Mennis, Jeremy; 0000-0002-3458-1646; 0000-0001-6319-8622 (2019-10-01)
    Slowing traffic speed in urban areas has been shown to reduce pedestrian injuries and fatalities due to automobile accidents. This research aims to measure how brick and granite block paving materials, which were widely used historically prior to the use of asphalt paving in many cities, may influence free flow traffic speed. Traffic speeds for 690 vehicles traversing street blocks paved with asphalt, granite block, and brick materials were measured using a radar gun on a sample of 18 matched pair (asphalt and historic paving material) street blocks in Philadelphia, Pennsylvania. Fixed effects linear regression was used to estimate the effect of paving material on vehicle speed after controlling for the street class (e.g., arterial versus local road) and the matched pair. Results indicate that brick reduced speeds by approximately 3 mph (~5 km/h) and granite block reduced speeds by approximately 7 mph (~11 km/h), as compared to asphalt paved city streets, which we attribute to drivers intentionally slowing due to road roughness. This research suggests that brick and granite block paving materials may be an effective traffic calming strategy, having implications for reducing negative health outcomes associated with pedestrian–automobile collisions.
  • Meta-analysis of Reward Processing in Major Depressive Disorder Reveals Distinct Abnormalities within the Reward Circuit

    Ng, Tommy H.; Alloy, Lauren B.; Smith, David; 0000-0001-5754-9633 (2019-08-09)
    Many neuroimaging studies have investigated reward processing dysfunction in major depressive disorder. These studies have led to the common idea that major depressive disorder is associated with blunted responses within the reward circuit, particularly in the ventral striatum. Yet, the link between major depressive disorder and reward-related responses in other regions remains inconclusive, thus limiting our understanding of the pathophysiology of major depressive disorder. To address this issue, we performed a coordinate-based meta-analysis of 41 whole-brain neuroimaging studies encompassing reward-related responses from a total of 794 patients with major depressive disorder and 803 healthy controls. Our findings argue against the common idea that major depressive disorder is primarily linked to deficits within the reward system. Instead, our results demonstrate that major depressive disorder is associated with opposing abnormalities in the reward circuit: hypo-responses in the ventral striatum and hyper-responses in the orbitofrontal cortex. The current findings suggest that dysregulated corticostriatal connectivity may underlie reward-processing abnormalities in major depressive disorder, providing an empirical foundation for a more refined understanding of abnormalities in the reward circuitry in major depressive disorder.

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