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WashU weekly Neuroscience publications

“Sleep disturbances in Wolfram syndrome” (2019) Orphanet Journal of Rare Diseases

Sleep disturbances in Wolfram syndrome
(2019) Orphanet Journal of Rare Diseases, 14 (1), art. no. 188, . 

Licis, A.a , Davis, G.d e , Eisenstein, S.A.b c , Lugar, H.M.b , Hershey, T.a b c

a Department of Neurology, Washington University, School of Medicine, Campus Box 8111, 660 South Euclid Ave, St Louis, MO 63110, United States
b Department of Psychiatry, Washington University, School of Medicine, Campus Box 8134, 4525 Scott Avenue, St Louis, MO 63110, United States
c Department of Radiology, Washington University, School of Medicine, Campus Box 8134, 4525 Scott Avenue, St Louis, MO 63110, United States
d Department of Psychiatry, Washington University in St. Louis, Campus-Box 8134, 4525 Scott Avenue, St Louis, MO 63110, United States
e College of Medicine, SUNY, Downstate College of Medicine, 450 Clarkson Ave, Brooklyn, NY 11203, United States

Abstract
Background: Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients. Methods: Genetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and/or the Pediatric Sleep Questionnaire (PSQ). PSQI and PSQ questionnaire data were compared to a previously collected group of controls. Patients were characterized clinically with the Wolfram Unified Rating Scale (WURS) and a subset underwent magnetic resonance imaging (MRI) for brain volume measurements. Results: Twenty-one patients were evaluated ranging from age 8.9-29.7 years. Five of 17 (29%) adult patients fit the criteria for obstructive sleep apnea (OSA; apnea-hypopnea index [AHI] ≥ 5) and all 4 of 4 (100%) children aged 12 years or younger fit the criteria for obstructive sleep apnea (AHI’s ≥ 1). Higher AHI was related to greater disease severity (higher WURS Physical scores). Higher mixed apnea scores were related to lower brainstem and cerebellar volumes. Patients’ scores on the PSQ were higher than those of controls, indicating greater severity of childhood obstructive sleep-related breathing disorders. Conclusions: Wolfram syndrome patients had a high rate of OSA. Further study would be needed to assess how these symptoms change over time. Addressing sleep disorders in Wolfram syndrome patients would likely improve their overall health and quality of life. © 2019 The Author(s).

Author Keywords
Actigraphy;  Sleep disorders;  Sleep studies;  Wolfram syndrome

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study” (2019) Pain

Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: a randomized, placebo-controlled, crossover study
(2019) Pain, 160 (8), pp. 1835-1846. 

Hincker, A.a b , Frey, K.a , Rao, L.a b , Wagner-Johnston, N.c , Ben Abdallah, A.a , Tan, B.d , Amin, M.d , Wildes, T.a d , Shah, R.a b , Karlsson, P.e f , Bakos, K.g , Kosicka, K.h , Kagan, L.i , Haroutounian, S.a b

a Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, United States
b Washington University Pain Center, Washington University School of Medicine, St Louis, MO, United States
c Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, United States
d Department of Medicine, Washington University School of Medicine, St Louis, MO, United States
e Department of Clinical Medicine, Danish Pain Research Center, Aarhus University, Aarhus, Denmark
f Section for Stereology and Microscopy, Core Centre for Molecular Morphology, Aarhus University, Aarhus, Denmark
g Investigation Drug Service, Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, MO, United States
h Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznan, Poland
i Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, State University of New Jersey, Piscataway, NJ, United States

Abstract
Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of α2δ subunits of voltage-gated Ca channels, such as pregabalin, have shown efficacy in reducing mechanical sensitivity in animal models of neuropathic pain. In addition, some data suggest that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased sensitivity to pinprick. We hypothesized that greater mechanical sensitivity, as quantified by decreased mechanical pain threshold at the feet, would be predictive of a greater reduction in average daily pain in response to pregabalin vs placebo. In a prospective, randomized, double-blinded study, 26 patients with painful CIPN from oxaliplatin, docetaxel, or paclitaxel received 28-day treatment with pregabalin (titrated to maximum dose 600 mg per day) and placebo in crossover design. Twenty-three participants were eligible for efficacy analysis. Mechanical pain threshold was not significantly correlated with reduction in average pain (P = 0.97) or worst pain (P = 0.60) in response to pregabalin. There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, P = 0.23) or worst pain (29.2% vs 16.0%, P = 0.13) from baseline. Post hoc analysis of patients with CIPN caused by oxaliplatin (n = 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, P = 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Wireless optofluidic brain probes for chronic neuropharmacology and photostimulation” (2019) Nature Biomedical Engineering

Wireless optofluidic brain probes for chronic neuropharmacology and photostimulation
(2019) Nature Biomedical Engineering, 3 (8), pp. 655-669. Cited 1 time.

Qazi, R.a b , Gomez, A.M.c , Castro, D.C.c d , Zou, Z.e , Sim, J.Y.f , Xiong, Y.b , Abdo, J.b , Kim, C.Y.a , Anderson, A.b , Lohner, F.b , Byun, S.-H.a , Chul Lee, B.g , Jang, K.-I.h , Xiao, J.e , Bruchas, M.R.c d i j k l m n , Jeong, J.-W.a b

a School of Electrical Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea
b Department of Electrical, Computer, and Energy Engineering, University of Colorado, Boulder, CO, United States
c Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, MO, United States
d Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, United States
e Department of Mechanical Engineering, University of Colorado, Boulder, CO, United States
f Welfare & Medical ICT Research Department, Electronics and Telecommunications Research Institute, Daejeon, South Korea
g Center for BioMicrosystems, Korea Institute of Science and Technology, Seoul, South Korea
h Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology, Daegu, South Korea
i Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, United States
j Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO, United States
k Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
l Center for Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, United States
m Department of Pharmacology, University of Washington, Seattle, WA, United States
n Department of Bioengineering, University of Washington, Seattle, WA, United States

Abstract
Both in vivo neuropharmacology and optogenetic stimulation can be used to decode neural circuitry, and can provide therapeutic strategies for brain disorders. However, current neuronal interfaces hinder long-term studies in awake and freely behaving animals, as they are limited in their ability to provide simultaneous and prolonged delivery of multiple drugs, are often bulky and lack multifunctionality, and employ custom control systems with insufficiently versatile selectivity for output mode, animal selection and target brain circuits. Here, we describe smartphone-controlled, minimally invasive, soft optofluidic probes with replaceable plug-like drug cartridges for chronic in vivo pharmacology and optogenetics with selective manipulation of brain circuits. We demonstrate the use of the probes for the control of the locomotor activity of mice for over four weeks via programmable wireless drug delivery and photostimulation. Owing to their ability to deliver both drugs and photopharmacology into the brain repeatedly over long time periods, the probes may contribute to uncovering the basis of neuropsychiatric diseases. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.

Document Type: Article
Publication Stage: Final
Source: Scopus

“A Genetic Locus on Chromosome 2q24 Predicting Peripheral Neuropathy Risk in Type 2 Diabetes: Results From the ACCORD and BARI 2D Studies” (2019) Diabetes

A Genetic Locus on Chromosome 2q24 Predicting Peripheral Neuropathy Risk in Type 2 Diabetes: Results From the ACCORD and BARI 2D Studies
(2019) Diabetes, 68 (8), pp. 1649-1662. 

Tang, Y.a b , Lenzini, P.A.c , Pop-Busui, R.d , Ray, P.R.e , Campbell, H.c f , Perkins, B.A.g , Callaghan, B.h , Wagner, M.J.i , Motsinger-Reif, A.A.j , Buse, J.B.k , Price, T.J.e , Mychaleckyj, J.C.l , Cresci, S.c f , Shah, H.b m , Doria, A.b n

a Research Division, Joslin Diabetes Center, Boston, MA, United States
b Department of Medicine, Harvard Medical School, Boston, MA, United States
c Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
d Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
e School of Behavioral and Brain Sciences and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX, United States
f Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
g Leadership Sinai Centre for Diabetes, Sinai Health System, Division of Endocrinology and Metabolism, University of Toronto, Toronto, ON, Canada
h Department of Neurology, University of Michigan, Ann Arbor, MI, United States
i Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
j Bioinformatics Research Center, Department of Statistics, North Carolina State University, Raleigh, NC, United States
k Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States
l Center for Public Health Genomics, University of Virginia, Charlottesville, VA, United States
m Research Division, Joslin Diabetes Center, Boston, MA, United States
n Research Division, Joslin Diabetes Center, Boston, MA, United States

Abstract
Genetic factors have been postulated to be involved in the etiology of diabetic peripheral neuropathy (DPN), but their identity remains mostly unknown. The aim of this study was to conduct a systematic search for genetic variants influencing DPN risk using two well-characterized cohorts. A genome-wide association study (GWAS) testing 6.8 million single nucleotide polymorphisms was conducted among participants of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial. Included were 4,384 white case patients with type 2 diabetes (T2D) and prevalent or incident DPN (defined as a Michigan Neuropathy Screening Instrument clinical examination score >2.0) and 784 white control subjects with T2D and no evidence of DPN at baseline or during follow-up. Replication of significant loci was sought among white subjects with T2D (791 DPN-positive case subjects and 158 DPN-negative control subjects) from the Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes (BARI 2D) trial. Association between significant variants and gene expression in peripheral nerves was evaluated in the Genotype-Tissue Expression (GTEx) database. A cluster of 28 SNPs on chromosome 2q24 reached GWAS significance (P < 5 × 10-8) in ACCORD. The minor allele of the lead SNP (rs13417783, minor allele frequency = 0.14) decreased DPN odds by 36% (odds ratio [OR] 0.64, 95% CI 0.55-0.74, P = 1.9 × 10-9). This effect was not influenced by ACCORD treatment assignments (P for interaction = 0.6) or mediated by an association with known DPN risk factors. This locus was successfully validated in BARI 2D (OR 0.57, 95% CI 0.42-0.80, P = 9 × 10-4; summary P = 7.9 × 10-12). In GTEx, the minor, protective allele at this locus was associated with higher tibial nerve expression of an adjacent gene (SCN2A) coding for human voltage-gated sodium channel NaV1.2 (P = 9 × 10-4). To conclude, we have identified and successfully validated a previously unknown locus with a powerful protective effect on the development of DPN in T2D. These results may provide novel insights into DPN pathogenesis and point to a potential target for novel interventions. © 2019 by the American Diabetes Association.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Superior Memory Reduces 8-year Risk of Mild Cognitive Impairment and Dementia but Not Amyloid β-Associated Cognitive Decline in Older Adults” (2019) Archives of Clinical Neuropsychology

Superior Memory Reduces 8-year Risk of Mild Cognitive Impairment and Dementia but Not Amyloid β-Associated Cognitive Decline in Older Adults
(2019) Archives of Clinical Neuropsychology, 34 (5), art. no. acy078, pp. 585-598. Cited 3 times.

Dang, C.a b , Harrington, K.D.b c , Lim, Y.Y.b , Ames, D.e f , Hassenstab, J.g h i , Laws, S.M.c j k , Yassi, N.b l , Hickey, M.a , Rainey-Smith, S.R.m n , Robertson, J.b , Rowe, C.C.o p , Sohrabi, H.R.m q , Salvado, O.r , Weinborn, M.m n s , Villemagne, V.L.b o p , Masters, C.L.b , Maruff, P.b d , for the AIBL Research Groupt

a Department of Obstetrics and Gynaecology, Melbourne Medical School, University of Melbourne, Parkville, VIC, Australia
b Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC 3052, Australia
c Cooperative Research Centre for Mental Health, Parkville, VIC, Australia
d CogState Ltd., Melbourne, VIC, Australia
e Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia
f National Ageing Research Institute, Parkville, VIC, Australia
g Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
h Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
i Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States
j Collaborative Genomics Group, Centre of Excellence for Alzheimer’s Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, WA, Australia
k School of Biomedical Sciences, Faculty of Health Sciences, Curtin Health Innovation Research Institute, Curtin UniversityWA, Australia
l Department of Medicine and Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia
m Centre of Excellence for Alzheimer’s Disease Research and Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
n Australian Alzheimer’s Research Foundation, Ralph and Patricia Sarich Neuroscience Research Institute, Nedlands, WA, Australia
o Department of Molecular Imaging and Therapy, Austin Health, Melbourne, VIC, Australia
p Department of Medicine, Austin Health, University of Melbourne, Melbourne, VIC, Australia
q Department of Biomedical Sciences, Macquarie University, Sydney, Australia
r CSIRO Health and Biosecurity, Australian EHealth Research Centre, Brisbane, QLD, Australia
s School of Psychological Science, University of Western Australia, Crawley, WA, Australia

Abstract
Objective: To prospectively examine 8-year risk of clinical disease progression to mild cognitive impairment (MCI)/dementia in older adults ≥60 with superior episodic memory (SuperAgers) compared to those cognitively normal for their age (CNFA). Additionally, to determine the extent to which SuperAgers were resilient to the negative effects of elevated amyloid-beta (Aβ+) on cognition. Method: Participants were classified as SuperAgers based on episodic memory performance consistent with younger adults aged 30-44 and no impairment on non-memory tests (n = 179), and were matched with CNFA on age, sex, education, and follow-up time (n = 179). Subdistribution hazard models examined risk of clinical progression to MCI/dementia. Linear mixed models assessed the effect of Aβ on cognition over time. Results: Prevalence of Aβ+ and APOE ϵ4 was equivalent between SuperAgers and CNFA. SuperAgers had 69%-73% reduced risk of clinical progression to MCI/dementia compared to CNFA (HR: 0.27-0.31, 95% CI: 0.11-0.73, p <. 001). Aβ+ was associated with cognitive decline in verbal memory and executive function, regardless of SuperAger/CNFA classification. In the absence of Aβ+, equivalent age-related changes in cognition were observed between SuperAgers and CNFA. Conclusions: SuperAgers displayed resilience against clinical progression to MCI/dementia compared to CNFA despite equivalent risk for Alzheimer’s disease (AD); however, SuperAgers had no greater protection from Aβ+ than CNFA. The deleterious effects of Aβ on cognition persist regardless of baseline cognitive ability. Thus, superior cognitive performance does not reflect resistance against the neuropathological processes associated with AD, and the observed resilience for SuperAgers may instead reflect neuropsychological criteria for cognitive impairment. © 2018 The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Author Keywords
Alzheimer’s disease;  Dementia;  Elderly/geriatrics/aging;  Mild cognitive impairment

Document Type: Article
Publication Stage: Final
Source: Scopus

“The Social and Functional Implications of High- Versus Low-Dose Opioids on Chronic Non-Cancer Pain” (2019) Pain Physician

The Social and Functional Implications of High- Versus Low-Dose Opioids on Chronic Non-Cancer Pain
(2019) Pain Physician, 22 (4), pp. 401-411. 

Denawa, Y.a , Kurtz, W.b , Conermann, T.c

a Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mt Sinai, New York, NY
b Department of Anesthesiology Washington University School of Medicine in St. Louis, St. Louis, MO, United States
c Department of Anesthesiology and Pain Medicine, Allegheny Health Network, Pittsburgh, PA, United States

Abstract
BACKGROUND: Chronic non-cancer pain (CNCP) is a major health concern. Opioids may be a useful treatment option, but their use still remains controversial given the significant risks and epidemic of opioid addiction and abuse. There is limited data on whether opioid therapy is an effective treatment option for chronic non-cancer pain. OBJECTIVE: To assess both physical and emotional dimensions of health for patients on opioid therapy for CNCP by reviewing the 36-Item Short Form Health Survey (SF-36) . STUDY DESIGN: This study was a retrospective cohort review. SETTING: Outpatient pain clinic. METHODS: We recruited 182 patients at the West Penn Pain Institute outpatient pain clinic: 94 patients were recruited for the low-dose opioid group (5-30 morphine milligram equivalents [MME]) while 88 patients were recruited for the high-dose opioid group (> 90 MME). Each patient filled out the SF-36 survey used to assess both the physical and emotional dimensions of their health. We also analyzed patients’ employment status, reasons for unemployment, pain diagnosis, side effects, and compliance issues through the electronic medical record (EMR). RESULTS: Mean scores on General Health Perceptions for the low-dose and high-dose opioid groups were 50.3 ± 21.6 and 44.4 ± 21.9, respectively (P = .07). Though not reaching statistical significance, high-dose patients had lower item scores, indicating a perception of poorer health. There were no significant differences between the low-dose and high-dose opioid treatment groups on any of the mean scores from the 8 domains of the SF-36. There was a statistically significant association between opioid treatment group and working status, noncompliance, and the self-reported number of side effects. Patients treated with high-dose opioids had significantly higher rates of unemployment (85%) than did low-dose opioid patients (66%) (x-squared[1] = 8.48, P =.004; odds ratio [OR] = 2.89 [95% confidence interval (CI), 1.39-6.01]). Unemployed patients in the high-dose treatment group were more likely to list disability as unemployment while retirement was the most common response in the low-dose treatment group. Patients treated with high-dose opioids had significantly higher rates of self-reported side effects (46%) than did low-dose opioid patients (21%) (x-squared[1] = 12.02, P =.001; OR = 3.08 [95% CI, 1.61-5.89]). Patients treated with high-dose opioids had significantly higher rates of noncompliance (49%) than did low-dose opioid patients (33%) (x-squared[1] = 4.75, P =.029; OR = 1.94 [95% CI, 1.07-3.54]). Thus, the odds of a high-dose opioid patient being unemployed were 2.89 times greater than the odds for a low-dose opioid patient; the odds of a high-dose opioid patient self-reporting side-effects were 3.08 times greater than the odds for a low-dose opioid patient; and the odds of a high-dose opioid patient being noncompliant with their medications were 1.94 times greater than the odds for a low-dose opioid patient. LIMITATIONS: The observation al design prohibits drawing causal relationships, and entry criteria was restricted. CONCLUSIONS: These data suggest that patients receiving low-dose and high-dose opioid treatment do not have significantly different quality-of-life outcomes. Future studies that incorporate longitudinal data are necessary to examine the temporal relationship between quality of life and opioid therapy. KEY WORDS: Chronic pain, chronic non-cancer pain, opioids, pain, quality of life, side effects, noncompliance, unemployment.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Identification of Retinal Vascular Lesions Using Ultra-Widefield Angiography in Hereditary Hemorrhagic Telangiectasia Patients” (2019) Ophthalmology Retina

Identification of Retinal Vascular Lesions Using Ultra-Widefield Angiography in Hereditary Hemorrhagic Telangiectasia Patients
(2019) Ophthalmology Retina, 3 (6), pp. 510-515. 

Sindhar, S.a , O’Bryhim, B.E.b , Licata, J.a , Piccirillo, J.F.a , Apte, R.S.b c d

a Department of Otolaryngology-Head and Neck Surgery, Washington University in St. Louis, St. Louis, MO, United States
b Department of Ophthalmology and Vision Science, Washington University in St. Louis, St. Louis, MO, United States
c Department of Medicine, Washington University in St. Louis, St. Louis, MO, United States
d Department of Developmental Biology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Purpose: To determine the presence and to characterize location of retinal vascular lesions in patients with hereditary hemorrhagic telangiectasia (HHT). Design: Prospective cross-sectional pilot descriptive study. Participants: Eighteen patients (age range, 22–65 years) with a clinical diagnosis of HHT. Methods: Patients completed the 25-item National Eye Institute Visual Function Questionnaire and underwent a single study visit with dilated ophthalmic examination, OCT angiography (OCTA), and fluorescein angiography (FA) with widefield imaging. Main Outcome Measures: Presence of retinal vascular abnormalities in 1 or more quadrants identified on widefield FA, Visual Function Questionnaire scores, retinal vessel architecture on FA and OCTA, and dilated ophthalmic examination findings. Results: Of the 18 patients recruited, fine telangiectatic vessels with capillary dilation and tortuosity were identified in 78% by FA imaging. Conclusions: In the first FA and OCTA analysis of the retina of unrelated HHT patients, we found a high rate of temporal and nasal telangiectasias. These telangiectasias were more apparent in older patients, suggesting that they may appear in later stages of HHT development. No abnormalities of the macular vasculature and architecture were identified, explaining the generally well-preserved visual acuity. Temporal and nasal telangiectasias may have clinical significance in a patient’s risk for retinal hemorrhage and likely warrant periodic surveillance by annual FA imaging. © 2019 American Academy of Ophthalmology

Document Type: Article
Publication Stage: Final
Source: Scopus

“Individualized Connectome-Targeted Transcranial Magnetic Stimulation for Neuropsychiatric Sequelae of Repetitive Traumatic Brain Injury in a Retired NFL Player” (2019) The Journal of Neuropsychiatry and Clinical Neurosciences

Individualized Connectome-Targeted Transcranial Magnetic Stimulation for Neuropsychiatric Sequelae of Repetitive Traumatic Brain Injury in a Retired NFL Player
(2019) The Journal of Neuropsychiatry and Clinical Neurosciences, 31 (3), pp. 254-263. 

Siddiqi, S.H., Trapp, N.T., Shahim, P., Hacker, C.D., Laumann, T.O., Kandala, S., Carter, A.R., Brody, D.L.

The Departments of Psychiatry, Neurology, and Neurosurgery, Washington University School of Medicine, St. Louis (Siddiqi, Trapp, Laumann, Kandala, Shahim, Carter, Brody, Hacker); and Department of Neurology, Harvard Medical School, McLean Hospital, Boston (Siddiqi); and the Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md. (Siddiqi, Shahim); and Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa (Trapp)

Abstract
OBJECTIVE: The recent advent of individualized resting-state network mapping (RSNM) has revealed substantial interindividual variability in anatomical localization of brain networks identified by using resting-state functional MRI (rsfMRI). RSNM enables personalized targeting of focal neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS). rTMS is believed to exert antidepressant efficacy by modulating connectivity between the stimulation site, the default mode network (DMN), and the subgenual anterior cingulate cortex (sgACC). Personalized rTMS may be particularly useful after repetitive traumatic brain injury (TBI), which is associated with neurodegenerative tauopathy in medial temporal limbic structures. These degenerative changes are believed to be related to treatment-resistant neurobehavioral disturbances observed in many retired athletes. METHODS: The authors describe a case in which RSNM was successfully used to target rTMS to treat these neuropsychiatric disturbances in a retired NFL defensive lineman whose symptoms were not responsive to conventional treatments. RSNM was used to identify left-right dorsolateral prefrontal rTMS targets with maximal difference between dorsal attention network and DMN correlations. These targets were spatially distinct from those identified by prior methods. Twenty sessions of left-sided excitatory and right-sided inhibitory rTMS were administered at these targets. RESULTS: Treatment led to improvement in Montgomery-Åsberg Depression Rating Scale (72%), cognitive testing, and headache scales scores. Compared with healthy individuals and subjects with TBI-associated depression, baseline rsfMRI revealed substantially elevated DMN connectivity with the medial temporal lobe (MTL). Serial rsfMRI scans revealed gradual improvement in MTL-DMN connectivity and stimulation site connectivity with sgACC. CONCLUSIONS: These results highlight the possibility of individualized neuromodulation and biomarker-based monitoring for neuropsychiatric sequelae of repetitive TBI.

Author Keywords
CTE;  fMRI;  Imaging Techniques;  Mood Disorders (Neuropsychiatric Aspects);  Neuroanatomy;  Organic Mental Disorders;  rTMS;  TBI;  Traumatic Brain Injury

Document Type: Article
Publication Stage: Final
Source: Scopus

“Sex modulates the ApoE ε4 effect on brain tau deposition measured by 18F-AV-1451 PET in individuals with mild cognitive impairment” (2019) Theranostics

Sex modulates the ApoE ε4 effect on brain tau deposition measured by 18F-AV-1451 PET in individuals with mild cognitive impairment
(2019) Theranostics, 9 (17), pp. 4959-4970. 

Liu, M.a b , Paranjpe, M.D.c , Zhou, X.d , Duy, P.Q.e , Goyal, M.S.f , Benzinger, T.L.S.f , Lu, J.g , Wang, R.a , Zhou, Y.a b f , Alzheimer’s Disease Neuroimaging Initiativeh

a Department of Nuclear Medicine, Peking University First Hospital, Beijing, China
b Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States
c Harvard-MIT Program in Health Sciences and Technology, Harvard Medical School, Boston, MA, United States
d Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
e Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT, United States
f Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
g Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China

Abstract
The strongest genetic risk factor for Alzheimer’s disease (AD) is the Apolipoprotein E type 4 allele (ApoE ε4). The interaction between sex and ApoE ε4 carrier status on AD risk remains an area of intense investigation. We hypothesized that sex modulates the relationship between ApoE ε4 carrier status and brain tau deposition (a quantitative endophenotype in AD) in individuals with mild cognitive impairment (MCI). Methods: Preprocessed 18F-AV-1451 tau and 18F-AV-45 amyloid PET images, T1-weighted structural magnetic resonance imaging (MRI) scans, demographic information, and cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 108 MCI subjects in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were included. After downloading pre-processed images from ADNI, an iterative reblurred Van Cittertiteration partial volume correction (PVC) method was applied to all PET images. MRIs were used for PET spatial normalization. Regions of interest (ROIs) were defined in standard space, and standardized uptake value ratio (SUVR) images relative to cerebellum were computed. ApoE ε4 by sex interaction analyses on 18F-AV-1451 and CSF tau (t-tau, p-tau) were assessed using generalized linear models. The association between 18F-AV-1451 SUVR and CSF tau (t-tau, p-tau) was assessed. Results: After applying PVC and controlling for age, education level and global cortical 18F-AV-45 SUVR, we found that the entorhinal cortex, amygdala, parahippocampal gyrus, posterior cingulate, and occipital ROIs exhibited a significant ApoE ε4 by sex interaction effect (false discovery rate P &lt; 0.1) among MCI individuals. We also found a significant ApoE ε4 by sex interaction effect on CSF t-tau and p-tau. 18F-AV-1451 SUVR in the 5 ROIs with ApoE ε4 by sex interaction was significantly correlated with CSF p-tau and t-tau. Conclusions: Our findings suggest that women are more susceptible to ApoE ε4-associated accumulation of neurofibrillary tangles in MCI compared to males. Both CSF tau (p-tau, t-tau) and brain tau PET are robust quantitative biomarkers for studying ApoE ε4 by sex effects on brain tau deposition in MCI participants. © The author(s).

Author Keywords
18F-AV-1451;  ApoE ε4;  Mild cognitive impairment;  Partial volume correction;  Tau deposition

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Targeting Sporadic and Neurofibromatosis Type 1 (NF1) Related Refractory Malignant Peripheral Nerve Sheath Tumors (MPNST) in a Phase II Study of Everolimus in Combination with Bevacizumab (SARC016)” (2019) Sarcoma

Targeting Sporadic and Neurofibromatosis Type 1 (NF1) Related Refractory Malignant Peripheral Nerve Sheath Tumors (MPNST) in a Phase II Study of Everolimus in Combination with Bevacizumab (SARC016)
(2019) Sarcoma, 2019, art. no. 7656747, . 

Widemann, B.C.a , Lu, Y.b , Reinke, D.c , Okuno, S.H.d , Meyer, C.F.e , Cote, G.M.f , Chugh, R.g , Milhem, M.M.h , Hirbe, A.C.i , Kim, A.j , Turpin, B.k , Pressey, J.G.l , Dombi, E.a , Jayaprakash, N.a , Helman, L.J.a , Onwudiwe, N.c , Cichowski, K.m , Perentesis, J.P.k

a National Cancer Institute, Center for Cancer Research, Pediatric Oncology Branch, Building 10, 10 Center Drive, Bethesda, MD 20892, United States
b SARC Statistics, Weill Cornell Medicine Healthcare and Policy Research, 402 East 67th Street, New York, NY 10065, United States
c SARC, 24 Frank Lloyd Wright Drive, Ann Arbor, MI 48105, United States
d Mayo Clinic, 200 First St, SW, Rochester, MN 55905, United States
e Johns Hopkins Hospital, 1650 Orleans St., Baltimore, MD 21231, United States
f Massachusetts General Hospital Cancer Center, Harvard Medical School, 10 North Grove Street, Boston, MA 02114, United States
g University of Michigan, 1500 E. Medical Center Dr, Ann Arbor, MI 48109, United States
h University of Iowa, 200 Hawkins Drive, Iowa, IA 52242, United States
i Washington University of St. Louis, 660 S, Euclid Ave, St. Louis, MO 63110, United States
j Children’s National Medical Center, 111 Michigan Ave, NW, Washington, DC 20010, United States
k Cincinnati Children’s Hospital, 3333 Burnet Ave, Cincinnati, OH 45229, United States
l Cincinnati Children’s Hospital Medical Center, University of Alabama, 1600 7th Avenue South, Birmingham, AL 35233, United States
m Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, United States

Abstract
Purpose. There are no known effective medical treatments for refractory MPNST. Inactivation of the NF1 tumor suppressor in MPNST results in upregulation of mTOR (mammalian target of rapamycin) signaling and angiogenesis, which contributes to disease progression. We conducted a phase II study for patients (pts) with refractory MPNST combining everolimus (10 mg PO once daily) with bevacizumab (10 mg/kg IV every 2 weeks) to determine the clinical benefit rate (CBR) (complete response, partial response (PR), or stable disease (SD) ≥ 4 months). Patients and Methods. Patients ≥18 years old with chemotherapy refractory sporadic or NF1 MPNST were eligible. Tumor response was assessed after every 2 cycles (the WHO criteria). A two-stage design targeting a 25% CBR was used: if ≥ 1/15 pts in stage 1 responded, enrollment would be expanded by 10 pts, and if ≥ 4/25 patients had clinical benefit, the combination would be considered active. Results. Twenty-five pts, 17 with NF1 and 8 with sporadic MPNST, enrolled. One of 15 pts in stage 1 had clinical benefit. Of 10 additional pts enrolled, 2 had clinical benefit. The median number of completed cycles was 3 (range 1-16). Adverse events were similar to those known for this combination. Conclusion. With a CBR of 12% (3/25), the combination of everolimus and bevacizumab did not reach the study’s target response rate and is not considered active in refractory MPNST. © 2019 Brigitte C. Widemann et al.

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“An Atypical and Multifactorial Acute Immune Polyradiculopathy: A Case Report” (2019) Neurohospitalist

An Atypical and Multifactorial Acute Immune Polyradiculopathy: A Case Report
(2019) Neurohospitalist, . 

Brier, M.R., Everett, E.A., Bucelli, R.C.

Department of Neurology, School of Medicine, Washington University in St Louis, St Louis, MO, United States

Abstract
Clinical diagnosis often focuses on identifying the single cause of a patient’s symptoms but it is becoming increasingly recognized that a subset of patients exist where 2 pathological entities coexist. These patients present a particular diagnostic challenge because the first “positive” diagnostic test is not the definitive stopping point in their evaluation. Here, we present the case of a 47-year-old woman with multiple cranial neuropathies and a polyradiculopathy. A significant pleocytosis in the cerebrospinal fluid sparked a broad evaluation which revealed pathologic evidence of sarcoidosis and molecular evidence of neurofascin (NF)-155 and NF-140 antibodies. The pathogenic contribution of these 2 pathologic entities, or interaction, to this patient’s case is not clear. Nevertheless, the patient responded robustly to steroids and symptoms significantly improved. This case is a demonstration of the balance between Occam’s razor and Hickam’s dictum in clinical practice. © The Author(s) 2019.

Author Keywords
cranial neuropathy;  neurofascin;  polyradiculopathy;  sarcoid

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Measurement error cannot account for failed replications of historic candidate gene-by-environment hypotheses: Response to Vrshek-Schallhorn et al” (2019) American Journal of Psychiatry

Measurement error cannot account for failed replications of historic candidate gene-by-environment hypotheses: Response to Vrshek-Schallhorn et al
(2019) American Journal of Psychiatry, 176 (8), pp. 668-669. 

Border, R.a b d , Johnson, E.C.e , Evans, L.M.a c , Keller, M.C.a b

a Institute for Behavioral Genetics, Boulder, United States
b Department of Psychology and Neuroscience, Boulder, United States
c Department of Ecology and Evolutionary Biology, Boulder, United States
d University of Colorado Boulder, Boulder, United States
e Department of Psychiatry, Washington University School of Medicine, St. Louis, United States

Document Type: Letter
Publication Stage: Final
Source: Scopus

“Model-based cognitive neuroscience: Multifield mechanistic integration in practice” (2019) Theory and Psychology

Model-based cognitive neuroscience: Multifield mechanistic integration in practice
(2019) Theory and Psychology, . 

Povich, M.

Washington University in St. Louis, United States

Abstract
Autonomist accounts of cognitive science suggest that cognitive model building and theory construction (can or should) proceed independently of findings in neuroscience. Common functionalist justifications of autonomy rely on there being relatively few constraints between neural structure and cognitive function. In contrast, an integrative mechanistic perspective stresses the mutual constraining of structure and function. In this article, I show how Model-Based Cognitive Neuroscience (MBCN) epitomizes the integrative mechanistic perspective and concentrates the most revolutionary elements of the cognitive neuroscience revolution. I also show how the prominent subset account of functional realization supports the integrative mechanistic perspective I take on MBCN and use it to clarify the intralevel and interlevel components of integration. © The Author(s) 2019.

Author Keywords
cognitive models;  functionalism;  mechanistic explanation;  model-based cognitive neuroscience;  realization

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Intellectual and developmental disabilities research centers: Fifty years of scientific accomplishments” (2019) Annals of Neurology

Intellectual and developmental disabilities research centers: Fifty years of scientific accomplishments
(2019) Annals of Neurology, . 

Walkley, S.U.a , Abbeduto, L.b , Batshaw, M.L.c , Bhattacharyya, A.d , Bookheimer, S.Y.e , Christian, B.T.f , Constantino, J.N.g , de Vellis, J.e , Doherty, D.A.h , Nelson, D.L.i , Piven, J.j , Poduri, A.k , Pomeroy, S.L.k , Samaco, R.C.i , Zoghbi, H.Y.i , Guralnick, M.J.l , Abbeduto, L.m , Bookheimer, S.m , Chang, Q.m , Colombo, J.m , Constantino, J.N.m , Gallo, V.m , Guralnick, M.J.m , Mahone, E.M.m , Neul, J.m , Piven, J.m , Pomeroy, S.L.m , Robinson, M.B.m , Smith, P.G.m , Walkley, S.U.m , Zoghbi, H.Y.m , for the Intellectual and Developmental Disabilities Research Centers Directors Committeem

a Department of Neuroscience, Albert Einstein College of Medicine, Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Bronx, NY, United States
b Department of Psychiatry and Behavioral Sciences, University of California, Davis, University of California, Davis Memory Impairments and Neurological Disorders Institute, Sacramento, CA, United States
c Children’s Research Institute, Children’s National Medical Center, Washington, DC, United States
d Department of Cell and Regenerative Biology, Waisman Center, University of Wisconsin–Madison, Madison, WI, United States
e Department of Psychiatry and Biobehavioral Sciences, Intellectual and Developmental Research Center, University of California, Los Angeles School of Medicine, Los Angeles, CA, United States
f Departments of Medical Physics and Psychiatry, Waisman Center, University of Wisconsin–Madison, Madison, WI, United States
g Departments of Psychiatry and Pediatrics, Washington University School of Medicine, Washington University in St Louis Intellectual and Developmental Disabilities Research Center, St Louis, MO, United States
h Department of Pediatrics, Center on Human Development and Disability, University of Washington, Seattle, WA, United States
i Department of Molecular and Human Genetics, Baylor College of Medicine, Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Baylor College of Medicine Intellectual and Developmental Disabilities Research Center, Houston, TX, United States
j Carolina Institute for Developmental Disabilities, University of North Carolina, University of North Carolina Intellectual and Developmental Disabilities Research Center, Chapel Hill, NC, United States
k Department of Neurology, Harvard Medical School, Boston Children’s Hospital and Harvard Medical School Intellectual and Developmental Disabilities Research Center, Boston, MA, United States
l Departments of Psychology and Pediatrics, Center on Human Development and Disability, University of Washington, Seattle, WA, United States

Abstract
Progress in addressing the origins of intellectual and developmental disabilities accelerated with the establishment 50 years ago of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health and associated Intellectual and Developmental Disabilities Research Centers. Investigators at these Centers have made seminal contributions to understanding human brain and behavioral development and defining mechanisms and treatments of disorders of the developing brain. ANN NEUROL 2019. © 2019 American Neurological Association

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

“Mechanisms of Pathogen Invasion into the Central Nervous System” (2019) Neuron

Mechanisms of Pathogen Invasion into the Central Nervous System
(2019) Neuron, . 

Cain, M.D.a , Salimi, H.a , Diamond, M.S.a b c d , Klein, R.S.a b e

a Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, United States
d The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
CNS infections continue to rise in incidence in conjunction with increases in immunocompromised populations or conditions that contribute to the emergence of pathogens, such as global travel, climate change, and human encroachment on animal territories. The severity and complexity of these diseases is impacted by the diversity of etiologic agents and their routes of neuroinvasion. In this review, we present historical, clinical, and molecular concepts regarding the mechanisms of pathogen invasion of the CNS. We also discuss the structural components of CNS compartments that influence pathogen entry and recent discoveries of the pathways exploited by pathogens to facilitate CNS infections. Advances in our understanding of the CNS invasion mechanisms of different neurotropic pathogens may enable the development of strategies to control their entry and deliver drugs to mitigate established infections. Cain et al. provide a comprehensive overview of our current knowledge of the mechanisms by which neurotropic pathogens gain access into the CNS, including those that may be exploited for drug delivery. © 2019

Author Keywords
axonal transport;  blood-brain barrier;  CNS;  neuroinfectious diseases;  neuroinvasion;  pathogen

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

“Selective serotonin reuptake inhibitors and benzodiazepines in panic disorder: A meta-analysis of common side effects in acute treatment” (2019) Journal of Psychopharmacology

Selective serotonin reuptake inhibitors and benzodiazepines in panic disorder: A meta-analysis of common side effects in acute treatment
(2019) Journal of Psychopharmacology, . 

Quagliato, L.A.a , Cosci, F.b c , Shader, R.I.d , Silberman, E.K.e , Starcevic, V.f , Balon, R.g , Dubovsky, S.L.h , Salzman, C.i , Krystal, J.H.j , Weintraub, S.J.k , Freire, R.C.a , Nardi, A.E.a , International Task Force on Benzodiazepinesl

a Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
b Department of Health Sciences, University of Florence, Florence, Italy
c Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, Netherlands
d Department of Immunology, Tufts University School of Medicine, Boston, MA, United States
e Department of Psychiatry, Tufts Medical Center, Boston, MA, United States
f University of Sydney, Sydney, NSW, Australia
g Departments of Psychiatry and Behavioral Neurosciences and Anesthesiology, Wayne State University School of Medicine, Detroit, MI, United States
h Department of Psychiatry, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY, United States
i Harvard Medical School, Beth Israel Deaconess Medical Center, Massachusetts Mental Health Center, Boston, MA, United States
j Yale University, New Haven, CT, United States
k Washington University, Saint Louis, MO, United States

Abstract
Background: Benzodiazepines (BZs) and selective serotonin reuptake inhibitors (SSRIs) are effective in the pharmacologic treatment of panic disorder (PD). However, treatment guidelines favor SSRIs over BZs based on the belief that BZs are associated with more adverse effects than SSRIs. This belief, however, is currently supported only by opinion and anecdotes. Aim: The aim of this review and meta-analysis was to determine if there truly is evidence that BZs cause more adverse effects than SSRIs in acute PD treatment. Methods: We systematically searched Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and clinical trials register databases. Short randomized clinical trials of a minimum of four weeks and a maximum of 12 weeks that studied SSRIs or BZs compared to placebo in acute PD treatment were included in a meta-analysis. The primary outcome was all-cause adverse event rate in participants who received SSRIs, BZs, or placebo. Results: Overall, the meta-analysis showed that SSRIs cause more adverse events than BZs in short-term PD treatment. Specifically, SSRI treatment was a risk factor for diaphoresis, fatigue, nausea, diarrhea, and insomnia, whereas BZ treatment was a risk factor for memory problems, constipation, and dry mouth. Both classes of drugs were associated with somnolence. SSRIs were associated with abnormal ejaculation, while BZs were associated with libido reduction. BZs were protective against tachycardia, diaphoresis, fatigue, and insomnia. Conclusion: Randomized, blinded studies comparing SSRIs and BZs for the short-term treatment of PD should be performed. Clinical guidelines based on incontrovertible evidence are needed. © The Author(s) 2019.

Author Keywords
Adverse events;  antidepressants;  panic attacks;  treatment

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

“A role for the CD38 rs3796863 polymorphism in alcohol and monetary reward: evidence from CD38 knockout mice and alcohol self-administration, (11C)-raclopride binding, and functional MRI in humans” (2019) American Journal of Drug and Alcohol Abuse

A role for the CD38 rs3796863 polymorphism in alcohol and monetary reward: evidence from CD38 knockout mice and alcohol self-administration, [11C]-raclopride binding, and functional MRI in humans
(2019) American Journal of Drug and Alcohol Abuse, . 

Lee, M.R.a , Shin, J.H.b , Deschaine, S.a , Daurio, A.M.a , Stangl, B.L.c , Yan, J.c , Ramchandani, V.A.c , Schwandt, M.L.d , Grodin, E.N.e f , Momenan, R.e , Corral-Frias, N.S.g h , Hariri, A.R.i , Bogdan, R.g , Alvarez, V.A.b , Leggio, L.a j

a Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, NIAAA and NIDA, NIH, Bethesda, MD, United States
b Laboratory on Neurobiology of Compulsive Behaviors, NIAAA, NIH, Rockville, MD, United States
c Section on Human Psychopharmacology, NIAAA, NIH, Bethesda, MD, United States
d Office of the Clinical Director, NIH, NIAAA, Bethesda, MD, United States
e Clinical NeuroImaging Research Core, NIAAA, NIH, Bethesda, MD, United States
f Department of Neuroscience, Brown University, Providence, RI, United States
g BRAIN Laboratory, Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
h Psychology Department, University of Sonora, Hermosillo, Sonora, Mexico
i Laboratory of NeuroGenetics, Department of Psychology and Neuroscience, Duke University, Durham, NC, United States
j Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, United States

Abstract
Background: Cluster of differentiation 38 (CD38) is a transmembrane protein expressed in dopaminergic reward pathways in the brain, including the nucleus accumbens (NAc). The GG genotype of a common single nucleotide polymorphism (SNP) within CD38, rs3796863, is associated with increased social reward. Objective: Examine whether CD38 rs3796863 and Cd38 knockout (KO) are associated with reward-related neural and behavioral phenotypes. Methods: Data from four independent human studies were used to test whether rs3796863 genotype is associated with: (1) intravenous alcohol self-administration (n = 64, 30 females), (2) alcohol-stimulated dopamine (DA) release measured using 11C-raclopride positron emission tomography (n = 22 men), (3) ventral striatum (VS) response to positive feedback measured using a card guessing functional magnetic resonance imaging (fMRI) paradigm (n = 531, 276 females), and (4) resting state functional connectivity (rsfc) of the VS (n = 51, 26 females). In a fifth study, we used a mouse model to examine whether cd38 knockout influences stimulated DA release in the NAc core and dorsal striatum using fast-scanning cyclic voltammetry. Results: Relative to T allele carriers, G homozygotes at rs3796863 within CD38 were characterized by greater alcohol self-administration, alcohol-stimulated dopamine release, VS response to positive feedback, and rsfc between the VS and anterior cingulate cortex. High-frequency stimulation reduced DA release among Cd38 KO mice had reduced dopamine release in the NAc. Conclusion: Converging evidence suggests that CD38 rs3796863 genotype may increase DA-related reward response and alcohol consumption. ©, This article not subject to U.S. copyright law.

Author Keywords
alcohol;  CD38;  dopamine;  genetics;  knockout;  nucleus accumbens;  reward;  ventral striatum

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“The Genesis of Pain Medicine as a Subspecialty in Anesthesiology” (2019) Journal of Anesthesia History

The Genesis of Pain Medicine as a Subspecialty in Anesthesiology
(2019) Journal of Anesthesia History, . 

Owens, W.D.a , Abram, S.E.b

a Professor Emeritus of Anesthesiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
b Professor Emeritus of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, United States

Abstract
Certification in pain medicine as a subspecialty in Anesthesiology was conceived in 1989 and first discussed by the American Board of Anesthesiology in 1990. Shortly thereafter, the ABA submitted an application to the American Board of Medical Specialties for recognition to certify in pain management. That was approved in 1991. The Accreditation Council of Graduate Medical Education approved an application from the Anesthesiology Residency Review Committee to accredit programs in pain management education and training in 1992. The first examination for Pain Management certification was given in 1993. The certificate was modified in 2002 to Pain Medicine rather than Pain Management. Five member boards of ABMS are now approved for certification in pain medicine and all use the ABA Pain Medicine examination. © 2019 Elsevier Inc.

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

“Predicting extended operative time and length of inpatient stay in cervical deformity corrective surgery” (2019) Journal of Clinical Neuroscience

Predicting extended operative time and length of inpatient stay in cervical deformity corrective surgery
(2019) Journal of Clinical Neuroscience, . 

Horn, S.R.a , Passias, P.G.b , Bortz, C.A.a , Pierce, K.E.a , Lafage, V.c , Lafage, R.c , Brown, A.E.a , Alas, H.a , Smith, J.S.d , Line, B.e , Deviren, V.f , Mundis, G.M.g , Kelly, M.P.h , Kim, H.J.c , Protopsaltis, T.a , Daniels, A.H.i , Klineberg, E.O.j , Burton, D.C.k , Hart, R.A.l , Schwab, F.J.c , Bess, S.e , Shaffrey, C.I.d , Ames, C.P.m , International Spine Study Groupn

a Department of Orthopedic Surgery, NYU Langone Orthopedic Hospital, New York, NY, United States
b Departments of Orthopedic and Neurologic Surgery, NYU Langone Orthopedic Hospital, New York Spine Institute, New York, NY, United States
c Department of Orthopedic Surgery, Hospital for Special Surgery, New York, NY, United States
d Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, VA, United States
e Rocky Mountain Scoliosis and Spine, Denver, CO, United States
f Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA, United States
g San Diego Center for Spinal Disorders, La JollaCA, United States
h Department of Orthopaedic Surgery, Washington University, St. Louis, MO, United States
i Department of Orthopaedic Surgery, Warren Alpert School of Medicine, Brown University, Providence, RI, United States
j Department of Orthopedic Surgery, University of California, Davis, Davis, CA, United States
k Department of Orthopedic Surgery, University of Kansas, Medical Center, Kansas City, KS, United States
l Department of Orthopedic Surgery, Swedish Neuroscience Institute, Seattle, WA, United States
m Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States

Abstract
It’s increasingly common for surgeons to operate on more challenging cases and higher risk patients, resulting in longer op-time and inpatient LOS. Factors predicting extended op-time and LOS for cervical deformity (CD) patients are understudied. This study identified predictors of extended op-time and length of stay (LOS) after CD-corrective surgery. CD patients with baseline (BL) radiographic data were included. Patients were stratified by extended LOS (ELOS; &gt;75th percentile) and normal LOS (N-LOS; &lt;75th percentile). Op-time analysis excluded staged cases, cases &gt;12 h. A Conditional Variable Importance Table used non-replacement sampling set of Conditional Inference trees to identify influential factors. Mean comparison tests compared LOS and op-time for top factors. 142 surgical CD patients (61 yrs, 62%F, 8.2 levels fused). Op-time and LOS were 358 min and 7.2 days; 30% of patients experienced E-LOS (14 ± 13 days). Overlapping predictors of E-LOS and op-time included levels fused (&gt;7 increased LOS 2.7 days; &gt;5 increased op-time 96 min, P &lt; 0.001), approach (anterior reduced LOS 3.0 days; combined increased op-time 69 min, P &lt; 0.01), BMI (&gt;38 kg/m2 increased LOS 8.1 days; &gt;39 kg/m2 increased op-time 17 min), and osteotomy (LOS 2.0 days, op-time 62 min, P &lt; 0.005). BL cervical parameters increased LOS and op-time: cSVA (&gt;42 mm increased LOS; &gt;50 mm increased op-time, P &lt; 0.030), C0 slope (&gt;@−0.9° increased LOS, &gt;0.3° increased op-time, P &lt; 0.003.) Additional op-time predictors: prior cervical surgery (p = 0.004) and comorbidities (P = 0.015). Other predictors of E-LOS: EBL (P &lt; 0.001), change in mental status (P = 0.001). Baseline cervical malalignment, levels fused, and osteotomy predicted both increased op-time and LOS. These results can be used to better optimize patient care, hospital efficiency, and resource allocation. © 2019 Elsevier Ltd

Author Keywords
CD;  Cervical deformity;  Length of stay;  LOS;  Operative time

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Efficacy and safety of gamma knife radiosurgery for posterior cranial fossa meningioma: a systematic review” (2019) Neurosurgical Review

Efficacy and safety of gamma knife radiosurgery for posterior cranial fossa meningioma: a systematic review
(2019) Neurosurgical Review, . 

Jumah, F.a , Narayan, V.a , Samara, A.b , Quinoa, T.R.a , Dossani, R.H.c , Gupta, G.a , Nanda, A.a d

a Department of Neurosurgery, Rutgers-Robert Wood Johnson Medical School & University Hospital, New Brunswick, NJ, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurosurgery, LSUHSC, Shreveport, LA, United States
d Department of Neurosurgery, Rutgers-Robert Wood Johnson Medical School, Rutgers-New Jersey Medical School, New Brunswick, NJ, United States

Abstract
The management of posterior cranial fossa meningioma [PCFM] is challenging and many neurosurgeons advise gamma knife radiosurgery [GKRS] as a modality for its upfront or adjuvant treatment. Due to the varying radiosurgical response based on lesion location, tumor biology, and radiation dosage, we performed a pioneer attempt in doing a systematic review analyzing the treatment efficacy and safety profile of GKRS for PCFM based on current literature. A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] guidelines. A thorough literature search was conducted on PubMed, Web of science, and Cochrane data base; articles were selected systematically based on PRISMA protocol, reviewed completely, and relevant data was summarized and discussed. A total of 18 publications pertaining to GKRS for PCFM were included with a pooled sample size of 2131 patients. The median pre-GKRS tumor volume ranged from 2.28 to 10.5 cm [3]. Primary GKRS was administered in 61.1% of the pooled study cohorts, adjuvant treatment in 32.9%, and salvage therapy in 6.5% patients. Majority of the meningiomas were WHO grade 1 tumors (99.7%). The pooled mean marginal dose in the studies was 13.6 Gy (range 12–15.2 Gy) while the mean of maximum doses was 28.6 Gy (range 25–35 Gy). Most studies report an excellent radiosurgical outcome including the tumor control rate and the progression-free survival [PFS] of over 90%. The tumor control, PFS, and adverse radiation effect [ARE] rates in author’s series were 92.3%, 91%, and 9.6%, respectively. The favorable radiosurgical outcome depends on multiple factors such as small tumor volume, absence of previous radiotherapy, tumor location, elderly patients, female gender, longer time from symptom onset, and decreasing maximal dose. GKRS as primary or adjuvant treatment modality needs to be considered as a promising management strategy for PCFM in selected patients in view of the growing evidence of high tumor control rate, improved neurological functions, and low incidence of ARE. The use of multiple isocenters, 3-D image planning, and limit GKRS treatment to tumors less than 3.5 cm help to avoid complications and achieve the best results. The treatment decisions in PCFM cases must be tailored and should consider the factors such as radiological profile, symptom severity, performance level, and patient preference for a good outcome. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Author Keywords
Gamma knife radiosurgery;  Meningioma;  Outcome;  Posterior cranial fossa;  Survival;  Treatment

Document Type: Review
Publication Stage: Article in Press
Source: Scopus

“Intrapartum oxytocin: time to focus on longer term consequences?” (2019) Anaesthesia

Intrapartum oxytocin: time to focus on longer term consequences?
(2019) Anaesthesia, . 

Monks, D.T., Palanisamy, A.

Department of Anesthesiology, Washington University School of Medicine, St. Louis, MI, United States

Author Keywords
labour and delivery;  oxytocic drugs;  oxytocin;  postpartum depression;  postpartum haemorrhage;  uterine atony

Document Type: Editorial
Publication Stage: Article in Press
Source: Scopus

“New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders” (2019) Nature Human Behaviour

New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders
(2019) Nature Human Behaviour, . 

Evangelou, E.a b , Gao, H.a c , Chu, C.d , Ntritsos, G.b , Blakeley, P.a e , Butts, A.R.f , Pazoki, R.a , Suzuki, H.g h , Koskeridis, F.b , Yiorkas, A.M.i j , Karaman, I.a k , Elliott, J.a , Luo, Q.l m , Aeschbacher, S.n , Bartz, T.M.o p , Baumeister, S.E.q r , Braund, P.S.s t , Brown, M.R.u , Brody, J.A.o , Clarke, T.-K.v , Dimou, N.b , Faul, J.D.w , Homuth, G.x , Jackson, A.U.y , Kentistou, K.A.z aa , Joshi, P.K.z , Lemaitre, R.N.o , Lind, P.A.ab , Lyytikäinen, L.-P.ac ad ae , Mangino, M.af ag , Milaneschi, Y.ah , Nelson, C.P.s t , Nolte, I.M.ai , Perälä, M.-M.aj ak , Polasek, O.al , Porteous, D.am an , Ratliff, S.M.ao , Smith, J.A.w ao , Stančáková, A.ap , Teumer, A.q aq , Tuominen, S.ar , Thériault, S.as at , Vangipurapu, J.ap , Whitfield, J.B.au , Wood, A.av , Yao, J.aw , Yu, B.u , Zhao, W.ao , Arking, D.E.ax , Auvinen, J.ay az , Liu, C.ba , Männikkö, M.bb , Risch, L.bc bd be , Rotter, J.I.bf , Snieder, H.ai , Veijola, J.bg bh bi , Blakemore, A.I.i j , Boehnke, M.y , Campbell, H.z , Conen, D.as , Eriksson, J.G.bj bk bl , Grabe, H.J.bm bn , Guo, X.aw , van der Harst, P.bo bp bq , Hartman, C.A.br , Hayward, C.bs , Heath, A.C.bt , Jarvelin, M.-R.bu bv bw bx by , Kähönen, M.bz ca , Kardia, S.L.R.ao , Kühne, M.n , Kuusisto, J.cb , Laakso, M.cb , Lahti, J.ar , Lehtimäki, T.ac ad , McIntosh, A.M.v an , Mohlke, K.L.cc , Morrison, A.C.u , Martin, N.G.au , Oldehinkel, A.J.br , Penninx, B.W.J.H.ah , Psaty, B.M.cd ce , Raitakari, O.T.cf cg ch , Rudan, I.z , Samani, N.J.s t , Scott, L.J.y , Spector, T.D.af , Verweij, N.bo , Weir, D.R.w , Wilson, J.F.z bs , Levy, D.ci cj , Tzoulaki, I.a c , Bell, J.D.ck , Matthews, P.M.g k , Rothenfluh, A.f cl , Desrivières, S.d , Schumann, G.d cm , Elliott, P.a c k cn co

a Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom
b Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece
c MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom
d Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
e NIHR Imperial Biomedical Research Centre, ITMAT Data Science Group, Imperial College London, London, United Kingdom
f Molecular Medicine, School of Medicine, University of Utah, Salt Lake City, UT, United States
g Centre for Restorative Neurosciences, Division of Brain Sciences, Department of Medicine, Hammersmith Campus, Imperial College London, London, United Kingdom
h Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
i Department of Life Sciences, Brunel University London, London, United Kingdom
j Section of Investigative Medicine, Imperial College London, London, United Kingdom
k UK Dementia Research Institute, Imperial College London, London, United Kingdom
l Institute of Science and Technology for Brain-Inspired Intelligence, MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China
m Department of Psychology and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom
n Cardiology Division, University Hospital Basel, Basel, Switzerland
o Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, United States
p Department of Biostatistics, University of Washington, Seattle, WA, United States
q Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
r Chair of Epidemiology, Ludwig-Maximilians-Universitat Munchen, UNIKA-T Augsburg, Augsburg, Germany
s Department of Cardiovascular Sciences, University of Leicester, Cardiovascular Research Centre, Glenfield Hospital, Leicester, United Kingdom
t NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
u Human Genetics Center, Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, United States
v Department of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom
w Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, United States
x Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
y Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States
z Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
aa Centre for Cardiovascular Sciences, Queens Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
ab Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
ac Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
ad Department of Clinical Chemistry, Finnish Cardiovascular Research Center – Tampere, Faculty of Medicine and LHealth Technology, Tampere University, Tampere, Finland
ae Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, Finland
af Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
ag NIHR Biomedical Research Centre, Guy’s and St Thomas Foundation Trust, London, United Kingdom
ah Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, Netherlands
ai Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
aj Folkhälsan Research Center, Helsinki, Finland
ak Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland
al Faculty of Medicine, University of Split, Split, Croatia
am Generation Scotland, Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
an Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom
ao Department of Epidemiology, University of Michigan, Ann Arbor, MI, United States
ap Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland
aq German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Greifswald, Germany
ar Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland
as Population Health Research Institute, McMaster University, Hamilton, ON, Canada
at Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec City, QC, Canada
au Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
av Department of Pediatrics/Nutrition, Baylor College of Medicine, Houston, TX, United States
aw The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States
ax McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
ay Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
az Oulunkaari Health Center, Ii, Finland
ba Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States
bb Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, Oulu, Finland
bc Institute of Clinical Chemistry, Inselspital Bern, University Hospital, University of Bern, Bern, Switzerland
bd Labormedizinisches Zentrum Dr. Risch, Vaduz, Liechtenstein
be Private University of the Principality of Liechtenstein, Triesen, Liechtenstein
bf The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, United States
bg Department of Psychiatry, Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland
bh Department of Psychiatry, University Hospital of Oulu, Oulu, Finland
bi Medical research Center Oulu, University and University Hospital of Oulu, Oulu, Finland
bj Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
bk National Institute for Health and Welfare, Helsinki, Finland
bl Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland
bm Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany
bn German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Greifswald, Germany
bo Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
bp Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
bq Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, Netherlands
br Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
bs MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
bt Department of Psychiatry, School of Medicine, Washington University in St Louis, St Louis, MO, United States
bu Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom
bv Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland
bw Biocenter Oulu, University of Oulu, Oulu, Finland
bx Unit of Primary Health Care, Oulu University Hospital, OYS, Oulu, Finland
by Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, United Kingdom
bz Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
ca Department of Clinical Physiology, Finnish Cardiovascular Research Center – Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
cb Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
cc Department of Genetics, University of North Carolina, Chapel Hill, NC, United States
cd Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, United States
ce Kaiser Permanente Washington Health Research Institute, Seattle, WA, United States
cf Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
cg Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
ch Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland
ci Framingham Heart Study, Framingham, MA, United States
cj Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States
ck Research Centre for Optimal Health, Department of Life Sciences, University of Westminster, London, United Kingdom
cl Departments of Psychiatry, Neurobiology & Anatomy, Human Genetics, School of Medicine, University of Utah, Salt Lake City, UT, United States
cm PONS Research Group, Dept of Psychiatry and Psychotherapy, Campus Charite Mitte, Humboldt University, Berlin, Germany and Institute for Science and Technology of Brain-inspired Intelligence (ISTBI), Fudan University, Shanghai, China
cn National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare NHS Trust and Imperial College London, London, United Kingdom
co Health Data Research UK London Substantive Site, London, United Kingdom

Abstract
Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d−1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“A video-based measure to identify autism risk in infancy” (2019) Journal of Child Psychology and Psychiatry and Allied Disciplines

A video-based measure to identify autism risk in infancy
(2019) Journal of Child Psychology and Psychiatry and Allied Disciplines, . 

Young, G.S.a , Constantino, J.N.b , Dvorak, S.c , Belding, A.a , Gangi, D.a , Hill, A.a , Hill, M.a , Miller, M.a , Parikh, C.a , Schwichtenberg, A.J.d , Solis, E.a , Ozonoff, S.a

a Department of Psychiatry & Behavioral Sciences, MIND Institute, University of California, Davis, Davis, CA, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Information and Educational Technology, University of California, Davis, Davis, CA, United States
d Department of Human Development & Family Studies, Purdue University, West Lafayette, IN, United States

Abstract
Background: Signs of autism are present in the first 2 years of life, but the average age of diagnosis lags far behind. Instruments that improve detection of autism risk in infancy are needed. This study developed and tested the psychometric properties of a novel video-based approach to detecting ASD in infancy. Methods: A prospective longitudinal study of children at elevated or lower risk for autism spectrum disorder was conducted. Participants were 76 infants with an older sibling with ASD and 37 infants with no known family history of autism. The Video-referenced Infant Rating System for Autism (VIRSA) is a web-based application that presents pairs of videos of parents and infants playing together and requires forced-choice judgments of which video is most similar to the child being rated. Parents rated participants on the VIRSA at 6, 9, 12, and 18 months of age. We examined split-half and test–retest reliability; convergent and discriminant validity; and sensitivity, specificity, and negative and positive predictive value for concurrent and 36-month ASD diagnoses. Results: The VIRSA demonstrated satisfactory reliability and convergent and discriminant validity. VIRSA ratings were significantly lower for children ultimately diagnosed with ASD than children with typical development by 12 months of age. VIRSA scores at 18 months identified all children diagnosed with ASD at that age, as well as 78% of children diagnosed at 36 months. Conclusions: This study represents an initial step in the development of a novel video-based approach to detection of ASD in infancy. The VIRSA’s psychometric properties were promising when used by parents with an older affected child, but still must be tested in community samples with no family history of ASD. If results are replicated, then the VIRSA’s low-burden, web-based format has the potential to reduce disparities in communities with limited access to screening. © 2019 Association for Child and Adolescent Mental Health

Author Keywords
Autism;  infancy;  screening;  social development

Document Type: Article
Publication Stage: Article in Press
Source: Scopus

“Inadvertent Intravitreous Ink Injection from Subconjunctival Tattooing Causing Intraocular Inflammation and Retinal Trauma” (2018) Ophthalmology Retina

Inadvertent Intravitreous Ink Injection from Subconjunctival Tattooing Causing Intraocular Inflammation and Retinal Trauma
(2018) Ophthalmology Retina, 2 (10), pp. 1080-1082. 

Dixon, M.W.a , Harocopos, G.J.a b , Li, A.S.a , Liu, J.C.a , Rajagopal, R.a

a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States

Document Type: Article
Publication Stage: Final
Source: Scopus

“No Bad Blood: A Pars Plana Approach to Controlled Drainage of Suprachoroidal Hemorrhage” (2018) Ophthalmology Retina

No Bad Blood: A Pars Plana Approach to Controlled Drainage of Suprachoroidal Hemorrhage
(2018) Ophthalmology Retina, 2 (10), pp. 1082-1083. 

Li, A.S., Apte, R.S.

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States

Document Type: Article
Publication Stage: Final
Source: Scopus