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Background Allergic asthma is a T-helper type 2 (Th2) cell-mediated chronic disease that is characterized by airway hyperreactivity (AHR) and chronic eosinophilic airway inflammation. Several studies suggest co-stimulatory molecules like CD137 as potential targets for therapeutic interventions in allergic airway disease. Recently, we could show in a murine asthma model that administration of an agonistic antibody against the receptor of the co-stimulatory molecule CD137 prevented and even reversed an already-established asthma phenotype. Objective The purpose of this study was to analyse the effect of stimulation of the CD137 ligand by a monoclonal antibody (CD137L mAb). Methods To induce an asthma-like phenotype, BALB/c mice were sensitized to ovalbumin (OVA), followed by an intrapulmonary allergen challenge. Anti-CD137L or control mAb were applied 1 day before OVA immunization or after the asthma phenotype was already established. Results Stimulation of the CD137L instead of the receptor by CD137L mAb prevents the development of an asthma-like phenotype but does not reverse established disease. While the receptor-mediated effect is partly mediated by anergy of CD4+ T cells and partly by induction of IFN-γ-producing CD8+ T cells, the effect of the CD137L mAb is completely dependent on IFN-γ-producing CD8+ T cells: blockade of IFN-γ and depletion of CD8+ T cells fully abrogated the observed protective effect. In vitro experiments showed that the anti-CD137L mAb ligates directly to CD8+ T cells and induces the generation of IFN-γ by this cell population. Conclusion Our results demonstrate that anti-CD137L mAb prevents disease development via IFN-γ-producing CD8+ T cells but is inferior to stimulation of the receptor that reverses established disease by a mechanism including CD4+ T cell anergy. [ABSTRACT FROM AUTHOR]

A 41-year-old man presented in general practice with neck and back pain. Assessment showed somatic dysfunction in the cervical spine and thoracic outlet, and concurrent issues arising from orchidectomy including psychosocial problems which might determine a poor prognosis. Management included manual therapy to the symptomatic area, co-ordination of specialist services and counselling against his catastrophisation and helplessness. The interim outcome was of pain relief and a more positive attitude to planning his life-style and potential for work. [ABSTRACT FROM AUTHOR]

Transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are severe monogenic diseases with severe and potentially life-threatening manifestations. BCL11A is a transcription factor that represses γ-globin expression and fetal hemoglobin in erythroid cells. We performed electroporation of CD34+ hematopoietic stem and progenitor cells obtained from healthy donors, with CRISPR-Cas9 targeting the BCL11A erythroid-specific enhancer. Approximately 80% of the alleles at this locus were modified, with no evidence of off-target editing. After undergoing myeloablation, two patients - one with TDT and the other with SCD - received autologous CD34+ cells edited with CRISPR-Cas9 targeting the same BCL11A enhancer. More than a year later, both patients had high levels of allelic editing in bone marrow and blood, increases in fetal hemoglobin that were distributed pancellularly, transfusion independence, and (in the patient with SCD) elimination of vaso-occlusive episodes. (Funded by CRISPR Therapeutics and Vertex Pharmaceuticals; ClinicalTrials.gov numbers, NCT03655678 for CLIMB THAL-111 and NCT03745287 for CLIMB SCD-121.). [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma is the most common extracranial solid tumour in children. Relapsed or refractory neuroblastoma is associated with a poor outcome. We assessed the combination of irinotecan-temozolomide and dasatinib-rapamycin (RIST) in patients with relapsed or refractory neuroblastoma., Methods: The multicentre, open-label, randomised, controlled, phase 2, RIST-rNB-2011 trial recruited from 40 paediatric oncology centres in Germany and Austria. Patients aged 1-25 years with high-risk relapsed (defined as recurrence of all stage IV and MYCN amplification stages, after response to treatment) or refractory (progressive disease during primary treatment) neuroblastoma, with Lansky and Karnofsky performance status at least 50%, were assigned (1:1) to RIST (RIST group) or irinotecan-temozolomide (control group) by block randomisation, stratified by MYCN status. We compared RIST (oral rapamycin [loading 3 mg/m 2 on day 1, maintenance 1 mg/m 2 on days 2-4] and oral dasatinib [2 mg/kg per day] for 4 days with 3 days off, followed by intravenous irinotecan [50 mg/m 2 per day] and oral temozolomide [150 mg/m 2 per day] for 5 days with 2 days off; one course each of rapamycin-dasatinib and irinotecan-temozolomide for four cycles over 8 weeks, then two courses of rapamycin-dasatinib followed by one course of irinotecan-temozolomide for 12 weeks) with irinotecan-temozolomide alone (with identical dosing as experimental group). The primary endpoint of progression-free survival was analysed in all eligible patients who received at least one course of therapy. The safety population consisted of all patients who received at least one course of therapy and had at least one post-baseline safety assessment. This trial is registered at ClinicalTrials.gov, NCT01467986, and is closed to accrual., Findings: Between Aug 26, 2013, and Sept 21, 2020, 129 patients were randomly assigned to the RIST group (n=63) or control group (n=66). Median age was 5·4 years (IQR 3·7-8·1). 124 patients (78 [63%] male and 46 [37%] female) were included in the efficacy analysis. At a median follow-up of 72 months (IQR 31-88), the median progression-free survival was 11 months (95% CI 7-17) in the RIST group and 5 months (2-8) in the control group (hazard ratio 0·62, one-sided 90% CI 0·81; p=0·019). Median progression-free survival in patients with amplified MYCN (n=48) was 6 months (95% CI 4-24) in the RIST group versus 2 months (2-5) in the control group (HR 0·45 [95% CI 0·24-0·84], p=0·012); median progression-free survival in patients without amplified MYCN (n=76) was 14 months (95% CI 9-7) in the RIST group versus 8 months (4-15) in the control group (HR 0·84 [95% CI 0·51-1·38], p=0·49). The most common grade 3 or worse adverse events were neutropenia (54 [81%] of 67 patients given RIST vs 49 [82%] of 60 patients given control), thrombocytopenia (45 [67%] vs 41 [68%]), and anaemia (39 [58%] vs 38 [63%]). Nine serious treatment-related adverse events were reported (five patients given control and four patients given RIST). There were no treatment-related deaths in the control group and one in the RIST group (multiorgan failure)., Interpretation: RIST-rNB-2011 demonstrated that targeting of MYCN-amplified relapsed or refractory neuroblastoma with a pathway-directed metronomic combination of a multkinase inhibitor and an mTOR inhibitor can improve progression-free survival and overall survival. This exclusive efficacy in MYCN-amplified, relapsed neuroblastoma warrants further investigation in the first-line setting., Funding: Deutsche Krebshilfe., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Objectives: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCD and bone marrow from an HLA-matched sibling is currently the standard of care. Haploidentical HSCT from a family donor with a TCR αβ/CD19 depleted graft (T-haplo) is an increasingly successful alternative, which requires the generation of G-CSF stimulated peripheral stem cell (PBSC) from haploidentical relatives. These sickle cell trait (SCT) donors reported to develop SCD-related complications in conditions of severe stress., Methods: In this retrospective analysis, we compared the safety and efficacy of PBSC mobilization with a G-CSF intensified mobilization regimen in SCT donors with a conventional G-CSF mobilization regimen in healthy donors., Results: The reported adverse events were similar during intensified G-CSF mobilization, apheresis, and shortly after stem cell apheresis in SCT and control donors. In SCT and control donors, we were able to mobilize high yields of CD34 + stem cells and the harvested CD34 + cell count was comparable with control donors., Conclusions: Peripheral stem cell mobilization using an intensified G-CSF regimen is safe, and well tolerated among SCT donors. SCT donors are a valid alternative for collection of peripheral CD34 + stem cells for T-cell-depleted haploidentical stem cell transplantation., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Therapy-resistant viral reactivations contribute significantly to mortality after hematopoietic stem cell transplantation. Adoptive cellular therapy with virus-specific T cells (VST) has shown efficacy in various single-center trials. However, the scalability of this therapy is hampered by laborious production methods. In this study we describe the in-house production of VST in a closed system (CliniMACS Prodigy® system, Miltenyi Biotec). In addition, we report the efficacy in 26 patients with viral disease following hematopoietic stem cell transplantation in a retrospective analysis (adenovirus, n=7; cytomegalovirus, n=8; Epstein-Barr virus, n=4; multi-viral, n=7). The production of VST was successful in 100% of cases. The safety profile of VST therapy was favorable (n=2 grade 3 and n=1 grade 4 adverse events; all three were reversible). A response was seen in 20 of 26 patients (77%). Responding patients had a significantly better overall survival than patients who did not respond (P<0.001). Virus-specific symptoms were reduced or resolved in 47% of patients. The overall survival of the whole cohort was 28% after 6 months. This study shows the feasibility of automated VST production and safety of application. The scalability of the CliniMACS Prodigy® device increases the accessibility of VST treatment.

Antisocial behavior has been linked to an increased tolerance of painful stimuli; however, there is evidence that pain behavior is multidetermined. The current study used pain measures from 3 different modalities (pain tolerance, pain ratings, electrocortical reactivity) and assessed triarchic traits of boldness and meanness to clarify the dispositional basis of associations between pain processing and antisocial behavior. High boldness was significantly associated with blunted early neural response to painful and nonpainful stimuli as well as increased pain tolerance. High meanness was associated with blunted elaborative processing of painful images, lower ratings of perceived pain for self and others, and increased pain tolerance. Meanness also accounted for variance shared between pain processing and antisocial behavior. Findings demonstrate that boldness and meanness contribute to pain processing in different ways and suggest that meanness may uniquely account for the association between blunted pain processing and antisocial behavior. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

This study explored the generality versus specificity of two trait-liability factors for externalizing problems-disinhibition and callousness-in the concurrent and prospective prediction of symptoms of conduct disorder, attention-deficit/hyperactivity disorder (ADHD), and substance use (i.e., alcohol use disorder and history of illicit substance use). Disinhibition involves an impulsive, unrestrained cognitive-behavioral style; callousness entails a dispositional lack of social-emotional sensitivity. Participants were European adolescents from the multisite IMAGEN project who completed questionnaires and clinical interviews at ages 14 (N = 1,504, Mage = 14.41, 51.13% female) and 16 (N = 1,407, Mage = 16.46, 51.88% female). Disinhibition was related concurrently and prospectively to greater symptoms of conduct disorder, ADHD, and alcohol use disorder; higher scores on a general externalizing factor; and greater likelihood of having tried an illicit substance. Callousness was selectively related to greater conduct disorder symptoms. These findings indicate disinhibition confers broad liability for externalizing spectrum disorders, perhaps due to its affiliated deficits in executive function. In contrast, callousness appears to represent more specific liability for antagonistic (aggressive/exploitative) forms of externalizing, as exemplified by antisocial behavior. Results support the utility of developmental-ontogenetic and hierarchical-dimensional models of psychopathology and have important implications for early assessment of risk for externalizing problems. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Understanding factors that influence behavioral performance in high-pressure contexts is relevant to critical occupations such as first responders, military personnel, and frontline medical workers. A recent study by Yancey et al. (2019) demonstrated an association between boldness, a biobehavioral trait reflecting social dominance and fearlessness, and enhanced task-switching performance during threat of shock relative to a no-shock (safe) condition. This study used a sustained threat manipulation in which cues signaling possible shock were present throughout blocks of multiple task trials. Here, we extended this work by evaluating the relationship between boldness and task-switching performance under acute threat of shock conditions, in which cues signaling possible shock occurred during individual task trials, intermingled with safe trials. Participants ( N = 79) completed a task-switching procedure involving acute threat of shock in which unwarned noise probes were presented to elicit blink-startle responses. Boldness was associated with better switching performance under threat versus safe conditions, with high-bold participants who exhibited low startle potentiation during threat showing the best performance. These findings provide additional evidence that dispositional boldness is a meaningful individual difference characteristic related to effective performance in high-pressure situations and have implications for personnel selection and assignment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The experience of phantom limb pain (PLP) is a common consequence of limb amputation, resulting in severe impairments of the affected person. Previous studies have shown that several factors such as age at or site of amputation are associated with the emergence and maintenance of PLP. In this cross-sectional study we assessed the presence of several phantom phenomena including PLP and other amputation-related information in a sample of 3,374 unilateral upper and lower limb amputees. Clinical and demographic variables (age at amputation, level of amputation) explained 10.6% of the variance in PLP and perceptual variables (intensity of phantom limb sensation [PLS], referred sensations, intensity of telescoping, residual limb pain [RLP] intensity) explained 16.9% of the variance. These variables were specific for PLP and not for RLP. These results suggest that distinct variables are associated with PLP (age at amputation, level of amputation, PLS intensity, referred sensations, intensity of telescoping, RLP intensity) and RLP (PLP intensity) and point at partly different mechanisms for the emergence and maintenance of PLP and RLP. PERSPECTIVE: Clinical/demographic variables as well as perceptual variables are 2 major components related to PLP and explain ∼11% and ∼17% of the variance. These results could potentially help clinicians to understand which factors may contribute to chronic phantom limb pain., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Granulocyte transfusions (GT) are used to treat progressive systemic or local infections in prolonged neutropenic patients with antibiotic or antifungal resistance. Granulocytes are most commonly collected from whole blood by apheresis using hydroxyethyl starch (HES) as the red blood cell (RBC) sedimentation agent. This is the first study on the safety and efficacy of transfusing granulocytes collected with modified fluid gelatin (MFG) instead of HES to pediatric patients., Methods: Clinical data from 46 pediatric and adolescent patients receiving at least one MFG-based granulocyte transfusion and in total 295 granulocyte concentrates from July 2013 to August 2019 at our local university medical center were evaluated retrospectively., Results: Forty-one patients (89%) survived at least 21 days after their last granulocyte transfusion. These survivors had lower CRP values and higher leukocyte counts after GT than non-survivors (mean delta of -5.34 mg/dl vs. -11.99 mg/dl and + 0.62 × 10 3 /μl vs. +0.18 × 10 3 /μl of all GT, respectively). The neutrophil corrected count increment (CCI) was 68.72 mm 2 /ml in survivors versus 28.00 mm 2 /ml in non-survivors. There were no major or severe adverse events., Conclusion: This study suggests that modified fluid gelatin is a safe and effective alternative to hydroxyethyl starch for the collection of granulocytes for transfusion to prolonged neutropenic patients with progressive systemic or local infections refractory to antibiotic or antifungal therapy., (© 2021 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: The mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes., Methods: In this study, we applied QST in 37 unilateral upper-limb amputees (23 with and 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain, warmth detection and two-point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth., Results: We did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = -0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP., Conclusion: We conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms., Significance: Phantom limb pain (PLP) is still poorly understood. We show that PLP intensity is associated with lower heat pain thresholds, especially in the face. This finding could be related to central nervous changes in PLP., (© 2021 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.)

Background: Recent efforts to classify subtypes of major depressive disorder marked by different psychophysiological indicators have identified blunted reward-related brain activation in gambling tasks as a characteristic linked specifically to depressed participants with impaired mood reactivity., Methods: The current study compared individuals diagnosed with current depressive disorder (n = 26) with healthy controls (n = 24) regarding brain responses to gain and loss trials in an fMRI version of the "Doors" choice-feedback task. Study aims were to examine reward-related brain activation in relation to depression, depressive subtypes, and course of depression., Results: Across the sample, participants showed a significant response to gain versus loss in left and right ventral striatum as well as medial and left lateral prefrontal cortex. Relative to controls, participants with current depression were characterized by blunted reactivity in left ventral striatum. Furthermore, activation in the left ventral striatum differentiated subgroups of depression with and without impaired mood reactivity. Finally, left striatal hypoactivation to reward predicted remission when controlling for current depressive symptomatology, albeit at a trend level., Conclusions: Blunted reward-related activation in the left ventral striatum might be useful as a marker for depression subtype and may have the potential to predict future course of depression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The DSM-5 alternative model for personality disorders (AMPD) groups traits into domains based on factor analyses of self-report data. AMPD traits may need to be configured differently to interface with neurobiology. Focusing on biobehavioral risk for externalizing problems in 334 adults, the authors used structural modeling to evaluate how well alternative configurations of AMPD traits, operationalized using the Personality Inventory for DSM-5 (PID-5), interface with neural indicators of externalizing liability. A model specifying two correlated factors defined by traits within the PID-5 Disinhibition domain and brain-response indicators of externalizing proneness exhibited inadequate fit. However, a model using PID-5 traits with better coverage of biobehavioral externalizing liability evidenced good fit. Scores on this PID-5 trait factor, termed "PID-5 Externalizing Proneness," converged well with criterion measures of externalizing proneness and diverged from measures of threat sensitivity. Findings illustrate how AMPD traits can be configured for use in investigations of biobehavioral risk for psychopathology.

Sickle cell disease (SCD) is an inherited disorder; despite significant improvements in supportive care, SCD continues to cause substantial morbidity, mortality, and reduced life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only widely available curative therapy for SCD, which is offered as a standard of care for patients with a matched sibling donor (MSD). Donor availability is limited to a minority of patients. Thus, αβ/CD3-depleted haploidentical HSCT, as an efficient means for depletion of graft-versus-host disease (GvHD)-mediating T cells, can be offered as an alternative curative therapy, particularly for nonmalignant diseases such as SCD. Out of 38 patients with advanced stage SCD, 25 were transplanted with CD3/CD19- or T-cell receptor αβ/CD19 T-cell-depleted peripheral stem cell grafts (T-haplo-HSCT group), whereas 13 transplanted from MSD (MSD group); both groups received an almost identical conditioning regimen. Engraftment was achieved in all. However, in the T-haplo-HSCT group, three patients succumbed to an uncontrolled cytomegalovirus pneumonitis, a macrophage activation syndrome, and a major blood group incompatibility with a late graft failure and multiorgan failure. The overall survival was 88% and 100% in T-haplo-HSCT and MSD groups, respectively. None of our patients developed a Glucksberg Grade III-IV acute GvHD. Four patients (16%) in the T-haplo-HSCT group and two patients (15%) in the MSD group developed a steroid-sensitive, mild-to-moderate chronic GvHD that resolved within 18 months posttransplant. These results are encouraging and demonstrate the feasibility, safety, and efficacy of T-haplo-HSCT in advanced stage SCD in children and adults, thus offering a curative alternative to majority of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Despite significant improvements in the supportive care, sickle cell disease (SCD) leads to significant morbidity and mortality. Allogeneic hematopoietic stem cell transplantation (HSCT), the only curative option, is limited due to matched donor availability. This could be met with T-cell-depleted haploidentical HSCT. Twenty advanced-stage SCD patients, median age 15 years, and 9 patients, median age 14 years, were transplanted with CD3/CD19- or TCRαβ/CD19-depleted grafts and from matched sibling donors (MSDs). The conditioning consisted of ATG, thiotepa, fludarabine, and treosulfan. The median follow-up in the T-haplo-HSCT and the MSD patients was 21 (9-62) and 25 (7-60) months, respectively. The OS in the T-haplo-HSCT and MSD was 90% and 100%, respectively. In the T-haplo-HSCT group, two patient succumbed to a CMV pneumonitis and a macrophage activation syndrome (MAS). One patient in the T-haplo-HSCT group requires renal replacement therapy because of BK virus nephritis. None developed grade III-IV acute GvHD. In the T-haplo-HSCT and in the MSD, 20% and 22%, respectively, developed a mild or moderate chronic GvHD. These results demonstrate the feasibility, safety, and efficacy of T-haplo-HSCT also for adult advanced stage SCD patients.

Set shifting involves the capacity to effectively and efficiently direct mental resources in the service of dynamically changing goal representations. This capacity is important in everyday life and may be vital in situations where processing resources needed for adaptive action may be diverted by cues for external danger or threat (e.g., first responding, military combat, trauma surgery). Although considerable research has investigated performance in set-shifting tasks, little work exists on how the presence of external threats may affect the capacity to flexibly deploy cognitive resources. Even less is known about individual difference factors that might moderate such effects. The current study addressed these gaps in the literature through use of a novel task-switching procedure in which participants (N = 77) performed two tasks in alternation under shock-threat and no-shock ("safe") conditions. Results indicated that behavioral performance was impacted by the presence of threat. However, these effects were moderated by individual differences in threat reactivity as indexed by both self-report and physiological measures. Our findings serve to clarify the impact of explicit threat on set-shifting performance. In addition, they encourage further use of the threat/task-switching paradigm as a laboratory model for studying individual differences in performance under conditions of pressure or peril. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Trait disinhibition, a clinical-liability construct, has well-established correlates in the diagnostic, self-rating, task-behavioral, and brain potential response domains. Recently, studies have begun to test for neuroimaging correlates of this liability factor, but more work of this type using larger data sets is needed to clarify its brain bases. The current study details the development and validation of a scale measure of trait disinhibition composed of questionnaire items available in the IMAGEN project, a large-scale longitudinal study of factors contributing to substance abuse that includes clinical interview, self-report personality, task-behavioral, neuroimaging, and genomic measures. Using a construct-rating and psychometric refinement approach, a scale was developed that evidenced: (a) positive relations with interview-assessed psychopathology in the IMAGEN sample, both concurrently and prospectively and (b) positive associations with scale measures of disinhibition and reported psychopathology, and a robust negative correlation with P3 brain response, in a separate adult sample ( M age = 19.5). These findings demonstrate that a common scale measure can index this construct from adolescence through to early adulthood, and set the stage for systematic work directed at identifying neural and genetic biomarkers of this key liability construct using existing and future data from the IMAGEN project.

Background: Nearly all paediatric patients require deep sedation when undergoing bone marrow aspiration (BMA). We analyzed the data from our protocols documented in a standardised procedure for bone marrow puncture over a period of 2 years., Methods: Our standard included the documentation of personal data as well as vital parameters. In addition, we documented all medications administered, potential complications and required intervention measures, as necessary., Results: A total of 107 protocols were available for the evaluation. Our standard covered the usage of midazolam and S‑ketamine and resulted in complications in just 9 patients, which could be remedied using simple measures. For both active substances, the dosage necessary to reach sufficient deep analgosedation was significantly higher for patients under 24 months of age., Conclusions: Our standard for BMA provides a practical and feasible procedure. In addition to good examination conditions, our standard also helps ensure the safety of our patients.

Current literature on the relationship between dispositional fear (or threat sensitivity) and amygdala gray matter volume (GMV) is heterogeneous, with findings including positive, negative, and null correlations. A clearer understanding of this relationship would help to determine the potential utility of amygdala volume as a biomarker of anxious/depressive (internalizing) disorders and contribute to understanding of neural mechanisms for variations in fearfulness. The study reported here used voxel-based morphometry to quantify amygdala GMV scores from structural neuroimaging data in a sample of 44 monozygotic twins (i.e., 22 pairs). Dispositional threat sensitivity (THT) was quantified using a biobehavioral cross-domain score that combined neurophysiological indicators with a psychological scale measure. Analyses revealed expected high concordance for amygdala GMV between co-twins. With respect to the major question of the study, a negative correlation was found between biobehavioral THT scores and amygdala volume - with individuals higher in THT showing smaller amygdala GMV scores. More modest associations of amygdala GMV with symptoms of social phobia, and fear disorder symptomology more broadly, were mediated by THT. These results provide insight into prior mixed findings and support the combined use of biological and behavioral measures to quantify characteristics relevant to mental health problems., (Copyright © 2018 Elsevier Inc. All rights reserved.)