“Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease” (2021) BMC Neurology
Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease
(2021) BMC Neurology, 21 (1), art. no. 154, .
Gregori-Pla, C.a , Mesquita, R.C.b , Favilla, C.G.c , Busch, D.R.d , Blanco, I.a , Zirak, P.a , Frisk, L.K.a , Avtzi, S.a , Maruccia, F.a e , Giacalone, G.a f , Cotta, G.a , Camps-Renom, P.g , Mullen, M.T.c , Martí-Fàbregas, J.g , Prats-Sánchez, L.g , Martínez-Domeño, A.g , Kasner, S.E.c , Greenberg, J.H.c , Zhou, C.h , Edlow, B.L.i , Putt, M.E.j , Detre, J.A.c , Yodh, A.G.k , Durduran, T.a l , Delgado-Mederos, R.g
a ICFO-Institut de Ciències Fotòniques, The Barcelona Institute of Science and Technology, Castelldefels, Barcelona 08860, Spain
b Institute of Physics, University of Campinas, Campinas, Brazil
c Department of Neurology, University of Pennsylvania, Philadelphia, United States
d Departments of Anesthesiology and Pain Management and Neurology, University of Texas Southwestern Medical Center, Dallas, United States
e Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d’Hebron University Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
f San Raffaele Scientific Institute, Milan, Italy
g Department of Neurology (Stroke Unit). Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
h McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, United States
i Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital, Boston, MA, United States
j Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, United States
k Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, United States
l Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, 08015, Spain
Abstract
Background: The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. Methods: Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. Results: After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [− 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). Conclusions: The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon. © 2021, The Author(s).
Author Keywords
Cerebral autoregulation; Cerebral blood flow; Cerebrovascular disease; Diffuse correlation spectroscopy; Diffuse optics; Mean arterial pressure
Funding details
2017SGR-1380, EU-H2020 654148
71329, OILTEBIA 317526, T32 HL007954
National Institutes of HealthNIHDP2-HD101400, K24-NS058386, P41-EB015893, R01-NS060653, R24-HD050836, U54-HD086984
Whitaker International Program
Fundació la Marató de TV3201709.30, 201709.31
Fundação de Amparo à Pesquisa do Estado de São PauloFAPESP2012/02500–8
Agència de Gestió d’Ajuts Universitaris i de RecercaAGAUR
Ministerio de Economía y CompetitividadMINECO
Instituto de Salud Carlos IIIISCIIIDTS16/00087, FIS PI09/0557, SEV-2015-0522
European Regional Development FundERDFDPI2015–64358-C2–1-R, PRE2018-085082
Document Type: Article
Publication Stage: Final
Source: Scopus
“Bidirectional sensory neuron–immune interactions: a new vision in the understanding of allergic inflammation” (2021) Current Opinion in Immunology
Bidirectional sensory neuron–immune interactions: a new vision in the understanding of allergic inflammation
(2021) Current Opinion in Immunology, 72, pp. 79-86.
Tauber, M.a b , Wang, F.c d e , Kim, B.c d f g , Gaudenzio, N.a
a Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Inserm UMR1291 CNRS UMR5051, University of Toulouse III, Toulouse, France
b Department of Dermatology, Toulouse University Hospital, France
c Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States
d Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
f Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
g Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Peripheral neurons (including sensory neurons) are ubiquitously distributed in all tissues, particularly at the interface with the environment. The primary function of sensory neurons is the transmission of sensations of temperature, pain and itch to elicit appropriate behavioral responses. More recently, sensory neurons have emerged as potent regulators of type 2 immune responses and allergic inflammation. There is increasing evidence showing that neurons can express receptors previously thought to be restricted to the immune compartment. In addition, certain subtypes of immune cells (e.g. mast cells, ILC2s or macrophages) also express specific neuroreceptors that provide them with the capacity to integrate neuron-derived signals and modulate their activation status during the development of allergic inflammation. © 2021 Elsevier Ltd
Funding details
European Research CouncilERCERC-2018-STG #802041
Institut National de la Santé et de la Recherche MédicaleInserm
Société Française de Dermatologie et de Pathologie Sexuellement TransmissibleSFD
Société Francophone du DiabèteSFD
Document Type: Review
Publication Stage: Final
Source: Scopus
“In vivo evaluation of heme and non-heme iron content and neuronal density in human basal ganglia” (2021) NeuroImage
In vivo evaluation of heme and non-heme iron content and neuronal density in human basal ganglia
(2021) NeuroImage, 235, art. no. 118012, .
Yablonskiy, D.A.a , Wen, J.b , Kothapalli, S.V.V.N.a , Sukstanskii, A.L.a
a Department of Radiology, Washington University in St. Louis, 4525 Scott Ave. Room 3216, St. Louis, MO 63110, United States
b Department of Radiology, The First Affiliated Hospital of USTC, Hefei, Anhui 230001, China
Abstract
Non-heme iron is an important element supporting the structure and functioning of biological tissues. Imbalance in non-heme iron can lead to different neurological disorders. Several MRI approaches have been developed for iron quantification relying either on the relaxation properties of MRI signal or measuring tissue magnetic susceptibility. Specific quantification of the non-heme iron can, however, be constrained by the presence of the heme iron in the deoxygenated blood and contribution of cellular composition. The goal of this paper is to introduce theoretical background and experimental MRI method allowing disentangling contributions of heme and non-heme irons simultaneously with evaluation of tissue neuronal density in the iron-rich basal ganglia. Our approach is based on the quantitative Gradient Recalled Echo (qGRE) MRI technique that allows separation of the total R2* metric characterizing decay of GRE signal into tissue-specific (R2t*) and the baseline blood oxygen level-dependent (BOLD) contributions. A combination with the QSM data (also available from the qGRE signal phase) allowed further separation of the tissue-specific R2t* metric in a cell-specific and non-heme-iron-specific contributions. It is shown that the non-heme iron contribution to R2t* relaxation can be described with the previously developed Gaussian Phase Approximation (GPA) approach. qGRE data were obtained from 22 healthy control participants (ages 26–63 years). Results suggest that the ferritin complexes are aggregated in clusters with an average radius about 100nm comprising approximately 2600 individual ferritin units. It is also demonstrated that the concentrations of heme and non-heme iron tend to increase with age. The strongest age effect was seen in the pallidum region, where the highest age-related non-heme iron accumulation was observed. © 2021 The Authors
Author Keywords
BOLD; Brain iron; Neuronal density; QSM; Quantitative gradient recalled echo MRI; R2*; R2t*
Funding details
National Institutes of HealthNIH20140257, R01AG054513
Document Type: Article
Publication Stage: Final
Source: Scopus
“Temporal modes of hub synchronization at rest” (2021) NeuroImage
Temporal modes of hub synchronization at rest
(2021) NeuroImage, 235, art. no. 118005, .
de Pasquale, F.a , Spadone, S.b , Betti, V.c d , Corbetta, M.e f g , Della Penna, S.b
a Faculty of Veterinary Medicine, University of Teramo, Teramo, Italy
b Department of Neuroimaging and Department of Neuroscience, Imaging and Clinical Sciences, Institute for Advanced Biomedical Technologies, “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy
c Department of Psychology, Sapienza University of Rome, Rome, 00185, Italy
d IRCCS Fondazione Santa Lucia, Rome, 00142, Italy
e Department of Neuroscience and Padova Neuroscience Center (PNC), University of Padua, Padua, Italy
f Venetian Institute of Molecular Medicine (VIMM), Padua, Italy
g Department of Neurology, Radiology, and Neuroscience, Washington University St. Louis
Abstract
The brain is a dynamic system that generates a broad repertoire of perceptual, motor, and cognitive states by the integration and segregation of different functional domains represented in large-scale brain networks. However, the fundamental mechanisms underlying brain network integration remain elusive. Here, for the first time to our knowledge, we found that in the resting state the brain visits few synchronization modes defined as clusters of temporally aligned functional hubs. These modes alternate over time and their probability of switching leads to specific temporal loops among them. Notably, although each mode involves a small set of nodes, the brain integration seems highly vulnerable to a simulated attack on this temporal synchronization mechanism. In line with the hypothesis that the resting state represents a prior sculpted by the task activity, the observed synchronization modes might be interpreted as a temporal brain template needed to respond to task/environmental demands. © 2021 The Author(s)
Funding details
Ministero dell’Istruzione, dell’Università e della RicercaMIUR
Università degli Studi G. d’Annunzio Chieti – PescaraUd’A
Document Type: Article
Publication Stage: Final
Source: Scopus
“Recognition memory and divergent cognitive profiles in prodromal genetic frontotemporal dementia” (2021) Cortex
Recognition memory and divergent cognitive profiles in prodromal genetic frontotemporal dementia
(2021) Cortex, 139, pp. 99-115.
Barker, M.S.a , Manoochehri, M.a , Rizer, S.J.a , Appleby, B.S.b , Brushaber, D.c , Dev, S.I.d , Devick, K.L.c , Dickerson, B.C.d , Fields, J.A.e , Foroud, T.M.f , Forsberg, L.K.g , Galasko, D.R.h , Ghoshal, N.i , Graff-Radford, N.R.j , Grossman, M.k , Heuer, H.W.l , Hsiung, G.-Y.m , Kornak, J.n , Litvan, I.h , Mackenzie, I.R.o , Mendez, M.F.p q , Pascual, B.r s , Rankin, K.P.l , Rascovsky, K.k , Staffaroni, A.M.l , Tartaglia, M.C.t , Weintraub, S.u , Wong, B.d , Boeve, B.F.g , Boxer, A.L.l , Rosen, H.J.l , Goldman, J.a v , Huey, E.D.a v w , Cosentino, S.a v x , ALLFTD consortiumy
a Taub Institute for Research on Alzheimer’s Disease and the Aging Brain Columbia University Medical Center, New York, NY, United States
b Department of Neurology, Case Western Reserve University, Cleveland, OH, United States
c Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States
d Department of Neurology, Frontotemporal Disorders Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
e Division of Neurocognitive Disorders, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States
f National Centralized Repository for Alzheimer’s Disease (NCRAD), Indiana University, Indianapolis, IN, United States
g Department of Neurology, Mayo Clinic, Rochester, MN, United States
h Department of Neuroscience, University of California, San Diego, San Diego, CA, United States
i Department of Neurology, Washington University, St. Louis, MO, United States
j Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
k Penn Frontotemporal Degeneration Center, Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
l Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, United States
m Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
n Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, United States
o Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
p Department of Neurology, University of California, Los Angeles, CA, United States
q Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, United States
r Nantz National Alzheimer Center, Houston Methodist Neurological Institute, Houston, TX, United States
s Weill Cornell MedicineNY, United States
t Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada
u Northwestern Feinberg School of Medicine, Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Northwestern University, Chicago, IL, United States
v Department of Neurology, Columbia University Medical Center, New York, NY, United States
w Department of Psychiatry and New York Psychiatric Institute, Columbia University Medical Center, New York, United States
x Gertrude H. Sergievsky Center, Columbia University Medical Center, New York, NY, United States
Abstract
Although executive dysfunction is the characteristic cognitive marker of behavioral variant frontotemporal dementia (bvFTD), episodic memory deficits are relatively common, and may be present even during the prodromal disease phase. In a cohort of mutation carriers with mild behavioral and/or cognitive symptoms consistent with prodromal bvFTD, we aimed to investigate patterns of performance on an abbreviated list learning task, with a particular focus on recognition memory. We further aimed to characterize the cognitive prodromes associated with the three major genetic causes of frontotemporal dementia, as emerging evidence suggests there may be subtle differences in cognitive profiles among carriers of different genetic mutations. Participants included 57 carriers of a pathogenic mutation in microtubule-associated protein tau (MAPT, N = 23), or progranulin (GRN, N = 15), or a or a hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72, N = 19), with mild cognitive and/or behavioral symptoms consistent with prodromal bvFTD. Familial non-carriers were included as controls (N = 143). All participants completed a comprehensive neuropsychological examination, including an abbreviated list learning test assessing episodic memory recall and recognition. MAPT mutation carriers performed worse than non-carriers in terms of list recall, and had difficulty discriminating targets from distractors on the recognition memory task, primarily due to the endorsement of distractors as targets. MAPT mutation carriers also showed nonverbal episodic memory and semantic memory dysfunction (object naming). GRN mutation carriers were variable in performance and overall the most dysexecutive. Slowed psychomotor speed was evident in C9orf72 repeat expansion carriers. Identifying the earliest cognitive indicators of bvFTD is of critical clinical and research importance. List learning may be a sensitive cognitive marker for incipient dementia in MAPT and potentially a subset of GRN carriers. Our results highlight that distinct cognitive profiles may be evident in carriers of the three disease-causing genes during the prodromal disease stage. © 2021 Elsevier Ltd
Author Keywords
Behavioral variant frontotemporal dementia; Episodic memory; Genetic frontotemporal dementia; Neuropsychology; Prodromal disease
Funding details
1:15-cv-975
AG063911, RFA #1510130358
1:14-cv-00121, 1:14-cv-00686
National Institutes of HealthNIH1R21NS114764-01A1, 2R01AG038791-06A, 5P50AG005131-33, P20GM109025, R25NS098999, U01NS090259, U01NS100610, U01NS80818, U19 AG063911-1
Centers for Disease Control and PreventionCDC
National Institute on AgingNIA
National Institute of Neurological Disorders and StrokeNINDSU54 NS092089
Michael J. Fox Foundation for Parkinson’s ResearchMJFF
Mayo Clinic
Bristol-Myers SquibbBMS
Association for Frontotemporal DegenerationAFTD
Novartis
Roche
Biogen
National Center for Advancing Translational SciencesNCATSU01 AG045390
AbbVie
University of California, San DiegoUCSD
Parkinsonfonden
Parkinson Study GroupPSG
Quest Diagnostics
Rainwater Charitable FoundationRCF
Canadian Institutes of Health ResearchCIHR
Alzheimer Society
Eisai
Document Type: Article
Publication Stage: Final
Source: Scopus
“Evidence for dissociable cognitive and neural pathways from poverty versus maltreatment to deficits in emotion regulation” (2021) Developmental Cognitive Neuroscience
Evidence for dissociable cognitive and neural pathways from poverty versus maltreatment to deficits in emotion regulation
(2021) Developmental Cognitive Neuroscience, 49, art. no. 100952, .
Elsayed, N.M.a , Rappaport, B.I.a , Luby, J.L.b , Barch, D.M.a b c
a Department of Psychological & Brain Sciences at Washington University in St. Louis, United States
b Department of Psychiatry at Washington University in St. Louis, United States
c Department of Radiology at Washington University in St. Louis, United States
Abstract
Poverty and threat exposure (TE) predict deficits in emotion regulation (ER). Effective cognitive ER (i.e., reappraisal) may be supported by: (1) cognitive processes implicated in generating and implementing cognitive reappraisal, supported by activation in brain regions involved in cognitive control (e.g., frontal, insular, and parietal cortices) and (2) emotion processing and reactivity, involving identification, encoding, and maintenance of emotional states and related variation in brain activity of regions involved in emotional reactivity (i.e., amygdala). Poverty is associated with deficits in cognitive control, and TE with alterations in emotion processing and reactivity. Our goal was to identify dissociable emotional and cognitive pathways to ER deficits from poverty and TE. Measures of cognitive ability, emotional processing and reactivity, ER, and neural activity during a sadness ER task, were examined from a prospective longitudinal study of youth at risk for depression (n = 139). Both cognitive ability and left anterior insula extending into the frontal operculum activity during a sadness reappraisal task mediated the relationship between poverty and ER. Emotion processing/reactivity didn’t mediate the relationship of TE to ER. Findings support a cognitive pathway from poverty to ER deficits. They also underscore the importance of dissociating mechanisms contributing to ER impairments from adverse early childhood experiences. © 2021
Author Keywords
Emotion regulation; Language; Left anterior insula; Poverty
Funding details
National Science FoundationNSFDGE-1745038
Document Type: Article
Publication Stage: Final
Source: Scopus
“Brd4-bound enhancers drive cell-intrinsic sex differences in glioblastoma” (2021) Proceedings of the National Academy of Sciences of the United States of America
Brd4-bound enhancers drive cell-intrinsic sex differences in glioblastoma
(2021) Proceedings of the National Academy of Sciences of the United States of America, 118 (16), .
Kfoury, N.a b , Qi, Z.c d , Prager, B.C.e f , Wilkinson, M.N.c d , Broestl, L.a g , Berrett, K.C.h , Moudgil, A.c d g , Sankararaman, S.c d , Chen, X.c d , Gertz, J.h , Rich, J.N.e i , Mitra, R.D.d j , Rubin, J.B.k l
a Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110
b Department of Neurological Surgery, University of California San Diego, La Jolla, CA, 92037, Italy
c Department of Genetics, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110
d Center for Genome Sciences and Systems Biology, Washington University in St. Louis, St. Louis, MO 63110
e Division of Regenerative Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, 92037, Italy
f Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195
g Medical Scientist Training Program, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110
h Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, United States
i Department of Neurosciences, University of California San Diego, La Jolla, CA, 92037, Italy
j Department of Genetics, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110; Rubin_J@kids.wustl.edu
k Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110; rmitra@wustl.edu Rubin_J@kids.wustl.edu
l Department of Neuroscience, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110
Abstract
Sex can be an important determinant of cancer phenotype, and exploring sex-biased tumor biology holds promise for identifying novel therapeutic targets and new approaches to cancer treatment. In an established isogenic murine model of glioblastoma (GBM), we discovered correlated transcriptome-wide sex differences in gene expression, H3K27ac marks, large Brd4-bound enhancer usage, and Brd4 localization to Myc and p53 genomic binding sites. These sex-biased gene expression patterns were also evident in human glioblastoma stem cells (GSCs). These observations led us to hypothesize that Brd4-bound enhancers might underlie sex differences in stem cell function and tumorigenicity in GBM. We found that male and female GBM cells exhibited sex-specific responses to pharmacological or genetic inhibition of Brd4. Brd4 knockdown or pharmacologic inhibition decreased male GBM cell clonogenicity and in vivo tumorigenesis while increasing both in female GBM cells. These results were validated in male and female patient-derived GBM cell lines. Furthermore, analysis of the Cancer Therapeutic Response Portal of human GBM samples segregated by sex revealed that male GBM cells are significantly more sensitive to BET (bromodomain and extraterminal) inhibitors than are female cells. Thus, Brd4 activity is revealed to drive sex differences in stem cell and tumorigenic phenotypes, which can be abrogated by sex-specific responses to BET inhibition. This has important implications for the clinical evaluation and use of BET inhibitors. Copyright © 2021 the Author(s). Published by PNAS.
Author Keywords
BET inhibitors; Brd4-bound enhancers; glioblastoma; sex differences; sex-specific transcriptional programs
Document Type: Article
Publication Stage: Final
Source: Scopus
“Bff: Bayesian, fiducial, and frequentist analysis of cognitive engagement among cognitively impaired older adults” (2021) Entropy
Bff: Bayesian, fiducial, and frequentist analysis of cognitive engagement among cognitively impaired older adults
(2021) Entropy, 23 (4), art. no. 428, .
Neupert, S.D.a , Growney, C.M.b , Zhu, X.a , Sorensen, J.K.a , Smith, E.L.a , Hannig, J.c
a Department of Psychology, North Carolina State University, Raleigh, NC 27695, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States
c Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
Abstract
Engagement in cognitively demanding activities is beneficial to preserving cognitive health. Our goal was to demonstrate the utility of frequentist, Bayesian, and fiducial statistical methods for evaluating the robustness of effects in identifying factors that contribute to cognitive engagement for older adults experiencing cognitive decline. We collected a total of 504 observations across two longitudinal waves of data from 28 cognitively impaired older adults. Participants’ systolic blood pressure responsivity, an index of cognitive engagement, was continuously sampled during cognitive testing. Participants reported on physical and mental health challenges and provided hair samples to assess chronic stress at each wave. Using the three statistical paradigms, we compared results from six model testing levels and longitudinal changes in health and stress predicting changes in cognitive engagement. Findings were mostly consistent across the three paradigms, providing additional confidence in determining effects. We extend selective engagement theory to cognitive impairment, noting that health challenges and stress appear to be important moderators. Further, we emphasize the utility of the Bayesian and fiducial paradigms for use with relatively small sample sizes because they are not based on asymptotic distributions. In particular, the fiducial paradigm is a useful tool because it provides more information than p values without the need to specify prior distributions, which may unduly influence the results based on a small sample. We provide the R code used to develop and implement all models. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
Bayesian; Cognitive engagement; Cognitive impairment; Fiducial paradigm; Frequentist
Funding details
National Science FoundationNSFDMS-1916115, IIS-1633074
National Institute on AgingNIAR01AG005552-28S1
Document Type: Article
Publication Stage: Final
Source: Scopus
“Impact of COVID-19 on the hospitalization, treatment, and outcomes of intracerebral and subarachnoid hemorrhage in the United States” (2021) PLoS ONE
Impact of COVID-19 on the hospitalization, treatment, and outcomes of intracerebral and subarachnoid hemorrhage in the United States
(2021) PLoS ONE, 16 (4 April), art. no. e0248728, .
Ravindra, V.M.a b , Grandhi, R.b , Delic, A.c , Hohmann, S.d , Shippey, E.d , Tirschwell, D.e , Frontera, J.A.f , Yaghi, S.f g , Majersik, J.J.c , Anadani, M.h , De Havenon, A.c
a Department of Neurosurgery, Naval Medical Center San Diego, San Diego, CA, United States
b Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, United States
c Department of Neurology, Clinical Neurosciences Center, University of Utah, Salt Lake City, UT, United States
d Research Analytics, Vizient Inc., Irving, TX, United States
e Department of Neurology, University of Washington, Seattle, WA, United States
f Department of Neurology, NYU Langone Health, New York, NY, United States
g Department of Neurology, Brown University, Providence, RI, United States
h Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Objective To examine the outcomes of adult patients with spontaneous intracranial and subarachnoid hemorrhage diagnosed with comorbid COVID-19 infection in a large, geographically diverse cohort. Methods We performed a retrospective analysis using the Vizient Clinical Data Base. We separately compared two cohorts of patients with COVID-19 admitted April 1-October 31, 2020- patients with intracerebral hemorrhage (ICH) and those with subarachnoid hemorrhage (SAH)-with control patients with ICH or SAH who did not have COVID-19 admitted at the same hospitals in 2019. The primary outcome was in-hospital death. Favorable discharge and length of hospital and intensive-care stay were the secondary outcomes. We fit multivariate mixed-effects logistic regression models to our outcomes. Results There were 559 ICH-COVID patients and 23,378 ICH controls from 194 hospitals. In the ICH-COVID cohort versus controls, there was a significantly higher proportion of Hispanic patients (24.5% vs. 8.9%), Black patients (23.3% vs. 20.9%), nonsmokers (11.5% vs. 3.2%), obesity (31.3% vs. 13.5%), and diabetes (43.4% vs. 28.5%), and patients had a longer hospital stay (21.6 vs. 10.5 days), a longer intensive-care stay (16.5 vs. 6.0 days), and a higher in-hospital death rate (46.5% vs. 18.0%). Patients with ICH-COVID had an adjusted odds ratio (aOR) of 2.43 [1.96-3.00] for the outcome of death and an aOR of 0.55 [0.44- 0.68] for favorable discharge. There were 212 SAH-COVID patients and 5,029 controls from 119 hospitals. The hospital (26.9 vs. 13.4 days) and intensive-care (21.9 vs. 9.6 days) length of stays and in-hospital death rate (42.9% vs. 14.8%) were higher in the SAH-COVID cohort compared with controls. Patients with SAH-COVID had an aOR of 1.81 [1.26-2.59] for an outcome of death and an aOR of 0.54 [0.37-0.78] for favorable discharge. Conclusions Patients with spontaneous ICH or SAH and comorbid COVID infection were more likely to be a racial or ethnic minority, diabetic, and obese and to have higher rates of death and longer hospital length of stay when compared with controls. © 2021 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Vigilance-Avoidance Toward Negative Faces in Social Anxiety With and Without Comorbid Depression” (2021) Frontiers in Psychiatry
Vigilance-Avoidance Toward Negative Faces in Social Anxiety With and Without Comorbid Depression
(2021) Frontiers in Psychiatry, 12, art. no. 636961, .
Kishimoto, T.a , Wen, X.b , Li, M.c , Zhang, R.-Y.d e , Yao, N.f , Huang, Y.b , Qian, M.b
a Department of Social Psychology, Zhou Enlai School of Government, Nankai University, Tianjin, China
b Beijing Key Laboratory for Behavior and Mental Health, School of Psychological and Cognitive Sciences, Peking University, Beijing, China
c George Warren Brown School of Social work, Washington University in St. Louis, Missouri, TX, United States
d Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
e Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai, China
f State Key Laboratory of Brain and Cognitive Science, Chinese Academy of Sciences (CAS), Center for Excellence in Brain Science and Intelligence Technology, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Abstract
Despite the growing evidence for the attentional bias toward emotional related stimuli in patients with social anxiety disorder (SAD), it remains unclear how the attentional bias manifests in normal individuals with SAD and/or depressive traits. To address this question, we recruited three groups of normal participants with different psychiatric traits—individuals with comorbid SAD and depression (SADd, N = 19), individuals with only SAD (SAD, N = 15), and healthy control individuals (HC, N = 19). In a dot-probe paradigm, participants view angry, disgusted, and sad face stimuli with durations ranging from very brief (i.e., 14ms) that renders stimuli completely intangible, to relatively long (i.e., 2000ms) that guarantees image visibility. We find significant early vigilance (i.e., on brief stimuli) and later avoidance (i.e., on long stimuli) toward angry faces in the SADd group. We also find vigilance toward angry and disgusted faces in the SAD group. To our best knowledge, this is the first study to unify both vigilance and avoidance within the same experimental paradigm, providing direct evidence for the “vigilance-avoidance” theory of comorbid SAD and depression. In sum, these results provide evidence for the potential behavioral differences induced by anxiety-depression comorbidity and a single trait in non-clinical populations, but the lack of a depression-only group cannot reveal the effects of high levels of depression on the results. The limitations are discussed. © Copyright © 2021 Kishimoto, Wen, Li, Zhang, Yao, Huang and Qian.
Author Keywords
attentional bias; comorbidity; depression; social anxiety disorder; vigilance-avoidance
Funding details
National Key Research and Development Program of ChinaNKRDPC2017YFB1002503
Document Type: Article
Publication Stage: Final
Source: Scopus
“Cannabis-Induced Hypodopaminergic Anhedonia and Cognitive Decline in Humans: Embracing Putative Induction of Dopamine Homeostasis” (2021) Frontiers in Psychiatry
Cannabis-Induced Hypodopaminergic Anhedonia and Cognitive Decline in Humans: Embracing Putative Induction of Dopamine Homeostasis
(2021) Frontiers in Psychiatry, 12, art. no. 623403, .
Blum, K.a b c d e f , Khalsa, J.g , Cadet, J.L.h , Baron, D.a , Bowirrat, A.i , Boyett, B.j , Lott, L.d , Brewer, R.c d , Gondré-Lewis, M.k , Bunt, G.l , Kazmi, S.m , Gold, M.S.n
a Western University Health Sciences, Pomona, CA, United States
b Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
c Division of Nutrigenomics, Precision Translational Medicine, LLC, San Antonio, TX, United States
d Division of Nutrigenomics, Genomic Testing Center, Geneus Health, LLC, San Antonio, TX, United States
e Department of Psychiatry, University of Vermont, Burlington, VT, United States
f Department of Psychiatry, Wright University Boonshoff School of Medicine, Dayton, OH, United States
g Department of Microbiology, Immunology and Tropical Medicine, George Washington University, School of Medicine, Washington, DC, United States
h Molecular Neuropsychiatry Research Branch, DHHS/NIH, NIDA Intramural Research Program, National Institutes of Health, Baltimore, MD, United States
i Department of Neuroscience, Interdisciplinary Center (IDC), Herzliya, Israel
j Bradford Health Services, Madison, AL, United States
k Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC, United States
l Good Samaritan/Day Top Treatment Center, NYU School of Medicine, New York, NY, United States
m College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United States
n Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
Abstract
Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young adults who use these cannabis products. Preliminary research suggests that it is possible to induce ‘dopamine homeostasis,’ that is, restore dopamine function with dopamine upregulation with the proposed compound and normalize behavior in chronic cannabis users with cannabis-induced hypodopaminergic anhedonia (depression) and cognitive decline. This psychological, neurobiological, anatomical, genetic, and epigenetic research also could provide evidence to use for the development of an appropriate policy regarding the decriminalization of cannabis for recreational use. © Copyright © 2021 Blum, Khalsa, Cadet, Baron, Bowirrat, Boyett, Lott, Brewer, Gondré-Lewis, Bunt, Kazmi and Gold.
Author Keywords
anhedonia; cannabis use disorder; depression; dopamine homeostasis; genetic testing; neuroanatomic alterations; pro-dopamine regulation; reward deficiency syndrome
Funding details
National Institutes of HealthNIH
U.S. Department of Health and Human ServicesHHS
National Institute on Drug AbuseNIDA
Howard University
Document Type: Article
Publication Stage: Final
Source: Scopus
“Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain” (2021) Genetics in Medicine
Variants in PRKAR1B cause a neurodevelopmental disorder with autism spectrum disorder, apraxia, and insensitivity to pain
(2021) Genetics in Medicine, .
Marbach, F.a , Stoyanov, G.b , Erger, F.b c , Stratakis, C.A.d , Settas, N.d , London, E.d , Rosenfeld, J.A.e f , Torti, E.g , Haldeman-Englert, C.h , Sklirou, E.i , Kessler, E.i , Ceulemans, S.j , Nelson, S.F.k , Martinez-Agosto, J.A.k , Palmer, C.G.S.k l m , Signer, R.H.k , Acosta, M.T.q , Adam, M.r , Adams, D.R.q , Agrawal, P.B.s , Alejandro, M.E.t , Alvey, J.u , Amendola, L.r , Andrews, A.u , Ashley, E.A.v , Azamian, M.S.t , Bacino, C.A.t , Bademci, G.w , Baker, E.q , Balasubramanyam, A.t , Baldridge, D.x y , Bale, J.u , Bamshad, M.r , Barbouth, D.w , Bayrak-Toydemir, P.u , Beck, A.r , Beggs, A.H.s , Behrens, E.z , Bejerano, G.v , Bennett, J.r , Berg-Rood, B.r , Bernstein, J.A.v , Berry, G.T.s , Bican, A.aa , Bivona, S.w , Blue, E.r , Bohnsack, J.u , Bonnenmann, C.q , Bonner, D.v , Botto, L.u , Boyd, B.r , Briere, L.C.s , Brokamp, E.aa , Brown, G.ab , Burke, E.A.q , Burrage, L.C.t , Butte, M.J.ab , Byers, P.r , Byrd, W.E.ac , Carey, J.u , Carrasquillo, O.w , Chang, T.C.P.w , Chanprasert, S.r , Chao, H.-T.t , Clark, G.D.t , Coakley, T.R.v , Cobban, L.A.s , Cogan, J.D.aa , Coggins, M.s , Cole, F.S.x , Colley, H.A.q , Cooper, C.M.s , Cope, H.ad , Craigen, W.J.t , Crouse, A.B.ac , Cunningham, M.r , D’Souza, P.q , Dai, H.t , Dasari, S.ae , Davis, J.q , Daya, J.G.q , Deardorff, M.z , Dell’Angelica, E.C.ab , Dhar, S.U.t , Dipple, K.r , Doherty, D.r , Dorrani, N.ab , Doss, A.L.q , Douine, E.D.ab , Draper, D.D.q , Duncan, L.aa , Earl, D.r , Eckstein, D.J.q , Emrick, L.T.t , Eng, C.M.af , Esteves, C.ag , Falk, M.z , Fernandez, L.v , Ferreira, C.q , Fieg, E.L.s , Findley, L.C.q , Fisher, P.G.v , Fogel, B.L.ab , Forghani, I.w , Fresard, L.v , Gahl, W.A.q , Glass, I.r , Gochuico, B.q , Godfrey, R.A.q , Golden-Grant, K.r , Goldman, A.M.t , Goldrich, M.P.q , Goldstein, D.B.ah , Grajewski, A.w , Groden, C.A.q , Gutierrez, I.ab , Hahn, S.r , Hamid, R.aa , Hanchard, N.A.t , Hassey, K.z , Hayes, N.x , High, F.s , Hing, A.r , Hisama, F.M.r , Holm, I.A.s , Hom, J.v , Horike-Pyne, M.r , Huang, A.ab , Huang, Y.v , Huryn, L.q , Isasi, R.w , Jamal, F.t , Jarvik, G.P.r , Jarvik, J.r , Jayadev, S.r , Karaviti, L.t , Kennedy, J.aa , Kiley, D.x , Kohane, I.S.ag , Kohler, J.N.v , Korrick, S.s , Kozuira, M.aa , Krakow, D.ab , Krasnewich, D.M.q , Kravets, E.v , Krier, J.B.s , LaMoure, G.L.q , Lalani, S.R.t , Lam, B.w , Lam, C.r , Lanpher, B.C.ae , Lanza, I.R.ae , Latham, L.q , LeBlanc, K.ag , Lee, B.H.t , Lee, H.ab , Levitt, R.w , Lewis, R.A.t , Lincoln, S.A.s , Liu, P.af , Liu, X.Z.w , Longo, N.u , Loo, S.K.ab , Loscalzo, J.s , Maas, R.L.s , MacDowall, J.q , MacRae, C.A.s , Macnamara, E.F.q , Maduro, V.V.q , Majcherska, M.M.v , Mak, B.C.ab , Malicdan, M.C.V.q , Mamounas, L.A.q , Manolio, T.A.q , Mao, R.u , Maravilla, K.r , Markello, T.C.q , Marom, R.t , Marth, G.u , Martin, B.A.v , Martin, M.G.ab , Martinez-Agosto, J.A.ab , Marwaha, S.v , McCauley, J.w , McConkie-Rosell, A.ad , McCormack, C.E.v , McCray, A.T.ag , McGee, E.ab , Mefford, H.r , Merritt, J.L.r , Might, M.ac , Mirzaa, G.r , Morava, E.ae , Moretti, P.M.t , Moretti, P.u , Mosbrook-Davis, D.q , Mulvihill, J.J.q , Murdock, D.R.t , Nagy, A.ag , Nakano-Okuno, M.ac , Nath, A.q , Nelson, S.F.ab , Newman, J.H.aa , Nicholas, S.K.t , Nickerson, D.r , Nieves-Rodriguez, S.ab , Novacic, D.q , Oglesbee, D.ae , Orengo, J.P.t , Pace, L.u , Pak, S.y , Pallais, J.C.s , Palmer, C.G.S.ab , Papp, J.C.ab , Parker, N.H.ab , Phillips, J.A., IIIaa , Posey, J.E.t , Potocki, L.t , Power, B.q , Pusey, B.N.q , Quinlan, A.u , Raja, A.N.v , Rao, D.A.s , Raskind, W.r , Renteria, G.ab , Reuter, C.M.v , Rives, L.aa , Robertson, A.K.aa , Rodan, L.H.s , Rosenfeld, J.A.t , Rosenwasser, N.r , Rossignol, F.q , Ruzhnikov, M.v , Sacco, R.w , Sampson, J.B.v , Samson, S.L.t , Saporta, M.w , Schaechter, J.w , Schedl, T.y , Schoch, K.ad , Scott, C.R.q , Scott, D.A.t , Shashi, V.ad , Shin, J.y , Signer, R.H.ab , Silverman, E.K.s , Sinsheimer, J.S.ab , Sisco, K.x , Smith, E.C.ad , Smith, K.S.v , Solem, E.aa , Solnica-Krezel, L.y , Ben Solomonq , Spillmann, R.C.ad , Stoler, J.M.s , Sullivan, J.A.ad , Sullivan, K.z , Sun, A.r , Sutton, S.v , Sweetser, D.A.s , Sybert, V.r , Tabor, H.K.v , Tan, A.L.M.ag , Tan, Q.K.-G.ad , Tekin, M.w , Telischi, F.w , Thorson, W.w , Thurm, A.q , Tifft, C.J.q , Toro, C.q , Tran, A.A.t , Tucker, B.M.v , Urv, T.K.q , Vanderver, A.z , Velinder, M.u , Viskochil, D.u , Vogel, T.P.t , Wahl, C.E.q , Walker, M.s , Wallace, S.r , Walley, N.M.ad , Walsh, C.A.s , Wambach, J.x , Wan, J.ab , Wang, L.-K.ab , Wangler, M.F.ai , Ward, P.A.af , Wegner, D.x , Wener, M.r , Wenger, T.r , Perry, K.W.ab , Westerfield, M.aj , Wheeler, M.T.v , Whitlock, J.ac , Wolfe, L.A.q , Woods, J.D.ab , Yamamoto, S.ai , Yang, J.q , Yousef, M.q , Zastrow, D.B.v , Zein, W.q , Zhao, C.v , Zuchner, S.w , Andrews, M.V.n , Grange, D.K.n , Willaert, R.f , Person, R.g , Telegrafi, A.g , Sievers, A.a , Laugsch, M.a , Theiß, S.a , Cheng, Y.Z.o , Lichtarge, O.e , Katsonis, P.e , Stocco, A.p , Schaaf, C.P.a c e , Undiagnosed Diseases Networkak
a Institute of Human Genetics, Heidelberg University, Heidelberg, Germany
b Faculty of Medicine, University of Cologne, Cologne, Germany
c Institute of Human Genetics, University Hospital Cologne, Cologne, Germany
d Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, United States
e Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States
f Baylor Genetics Laboratory, Houston, TX, United States
g GeneDX, Gaithersburg, MD, United States
h Mission Fullerton Genetics Center, Asheville, NC, United States
i Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
j Genetics/Dysmorphology, Rady Children’s Hospital, San Diego, CA, United States
k Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
l Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
m Institute for Society and Genetics, UCLA, Los Angeles, CA, United States
n Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, Saint Louis, MO, United States
o Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Biomedicine West Wing, International Centre for Life, Times Square, Newcastle upon Tyne, United Kingdom
p INTEGRIS Pediatric Neurology, Oklahoma City, OK, United States
q National Institutes of Health, Undiagnosed Diseases Program Clinical Site, Bethesda, MD, United States
r University of Washington and Seattle Children’s Hospital Clinical Site, Seattle, WA, United States
s Harvard-affiliated Boston Children’s Hospital, Massachusetts General Hospital, Brigham and Women’s Hospital, and Brigham Genomics Medicine Clinical Site, Boston, MA, United States
t Baylor College of Medicine, Clinical Site, Houston, TX, United States
u University of Utah Clinical Site, Salt Lake City, UT, United States
v Stanford University Clinical Site, Stanford, CA, United States
w University of Miami Clinical Site, Miami, FL, United States
x Washington University of Saint Louis, Clinical Site, Saint Louis, MO, United States
y Washington University of Saint Louis, Model Organism Screening Center, Saint Louis, MO, United States
z Children’s Hospital of Philadelphia or University of Pennsylvania Clinical Site, Philadelphia, PA, United States
aa Vanderbilt University Clinical Site, Nashville, TN, United States
ab University of California, Los Angeles, Clinical Site, Los Angeles, CA, United States
ac University of Alabama Coordinating Center, Birmingham, AL, United States
ad Duke University Clinical Site, Durham, NC, United States
ae Mayo Clinic Metabolomics Core, Rochester, MN, United States
af Baylor Genetics Sequencing Core, Houston, TX, United States
ag Harvard Medical School Coordinating Center, Boston, MA, United States
ah Columbia University Clinical Site, New York City, NY, United States
ai Baylor College of Medicine, Model Organism Screening Center, Houston, TX, United States
aj University of Oregon, Model Organism Screening Center, Eugene, OR, United States
Abstract
Purpose: We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability and autism spectrum disorder who carry heterozygous missense variants of the PRKAR1B gene, which encodes the R1β subunit of the cyclic AMP-dependent protein kinase A (PKA). Methods: Variants of PRKAR1B were identified by single- or trio-exome analysis. We contacted the families and physicians of the six individuals to collect phenotypic information, performed in vitro analyses of the identified PRKAR1B-variants, and investigated PRKAR1B expression during embryonic development. Results: Recent studies of large patient cohorts with neurodevelopmental disorders found significant enrichment of de novo missense variants in PRKAR1B. In our cohort, de novo origin of the PRKAR1B variants could be confirmed in five of six individuals, and four carried the same heterozygous de novo variant c.1003C>T (p.Arg335Trp; NM_001164760). Global developmental delay, autism spectrum disorder, and apraxia/dyspraxia have been reported in all six, and reduced pain sensitivity was found in three individuals carrying the c.1003C>T variant. PRKAR1B expression in the brain was demonstrated during human embryonal development. Additionally, in vitro analyses revealed altered basal PKA activity in cells transfected with variant-harboring PRKAR1B expression constructs. Conclusion: Our study provides strong evidence for a PRKAR1B-related neurodevelopmental disorder. © 2021, The Author(s).
Funding details
U01HG007703
National Institutes of HealthNIH
University of California, Los AngelesUCLA
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Everyday Emotional Experiences in Current and Remitted Major Depressive Disorder: An Experience-Sampling Study” (2021) Clinical Psychological Science
Everyday Emotional Experiences in Current and Remitted Major Depressive Disorder: An Experience-Sampling Study
(2021) Clinical Psychological Science, .
Thompson, R.J., Bailen, N.H., English, T.
Department of Psychological & Brain Sciences, Washington University in St. Louis, United States
Abstract
The emotional experiences of people with major depressive disorder (MDD) are characterized by emotional disturbances. We examined whether these patterns characterize people with MDD in remission. Participants included individuals who had experienced at least two major depressive episodes (remitted-MDD group; n = 80), had current MDD (current-MDD group; n = 48), or were control participants (n = 87). Participants reported their momentary affect five times per day for 14 days, from which we computed the mean (i.e., intensity), standard deviation (i.e., variability), and autocorrelation (i.e., inertia). Negative affect (NA) intensity and variability, but not inertia, differed between groups; the current-MDD group had the highest levels, the control group had the lowest, and the remitted-MDD group fell in between. Differences in NA variability held after accounting for mean NA. The only significant group difference for positive affect (PA) was that PA intensity was lower in the current-MDD group compared with the other two groups. Emotional disturbances of participants with remitted MDD appear limited to NA. © The Author(s) 2021.
Author Keywords
affect; emotion; inertia; instability; major depressive disorder
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Dysfunction in interpersonal neural synchronization as a mechanism for social impairment in autism spectrum disorder” (2021) Autism Research
Dysfunction in interpersonal neural synchronization as a mechanism for social impairment in autism spectrum disorder
(2021) Autism Research, .
Quiñones-Camacho, L.E.a , Fishburn, F.A.b , Belardi, K.c , Williams, D.L.d , Huppert, T.J.e , Perlman, S.B.a
a Department of Psychiatry, Washington University, St. Louis, MO, United States
b Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
c School of Health and Rehabilitation Sciences, University of Pittsburgh, Pittsburgh, PA, United States
d Department of Communication Sciences and Disorders, The Pennsylvania State University, State College, PA, United States
e Department of Electrical and Computer Engineering, University of Pittsburgh, Pittsburgh, PA, United States
Abstract
Social deficits in autism spectrum disorder (ASD) have been linked to atypical activation of the mentalizing network. This work, however, has been limited by a focus on the brain activity of a single person during computerized social tasks rather than exploring brain activity during in vivo interactions. The current study assessed neural synchronization during a conversation as a mechanism for social impairment in adults with ASD (n = 24) and matched controls (n = 26). Functional near-infrared spectroscopy (fNIRS) data were collected from the prefrontal cortex (PFC) and tempoparietal junction (TPJ). Participants self-reported on their social communication and videos of the interaction were coded for utterances and conversational turns. As expected, controls showed more neural synchrony than participants with ASD in the TPJ. Also as expected, controls showed less social communication impairment than participants with ASD. However, participants with ASD did not have fewer utterances compared with control subjects. Overall, less neural synchrony in the TPJ was associated with higher social impairment and marginally fewer utterances. Our findings advance our understanding of social difficulties in ASD by linking them to decreased neural synchronization of the TPJ. Lay Summary: The coordination of brain responses is important for efficient social interactions. The current study explored the coordination of brain responses in neurotypical adults and adults with ASD to investigate if difficulties in social interactions are related to difficulties coordinating brain responses in ASD. We found that participants with ASD had more difficulties coordinating brain responses during a conversation with an interacting partner. Additionally, we found that the level of coordination in brain responses was linked to problems with social communication. © 2021 International Society for Autism Research and Wiley Periodicals LLC.
Author Keywords
ASD; neural synchrony; social communication impairment; social deficits; TPJ
Funding details
National Institute of Mental HealthNIMHR01 MH107540, T32 MH100019‐06
Brain and Behavior Research FoundationBBRF
National Alliance for Research on Schizophrenia and DepressionNARSAD
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Course of Tic Disorders Over the Lifespan” (2021) Current Developmental Disorders Reports
Course of Tic Disorders Over the Lifespan
(2021) Current Developmental Disorders Reports, .
Black, K.J.a b c d , Kim, S.a , Yang, N.Y.a , Greene, D.J.e
a Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States
b Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States
c Department of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States
d Department of Neuroscience, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, United States
e Department of Cognitive Science, University of California San Diego, San Diego, La Jolla, CA 92093, United States
Abstract
Purpose of Review: To summarize and update information on the course of tic disorders from childhood through later life. Recent Findings: Tics tend to improve substantially over the first year after they appear. However, contrary to widespread opinion, tics usually last longer than 1 year, though usually at minimal severity. Tics often wane to clinical insignificance over the teen years, possibly resurging occasionally over the lifespan. However, in an important minority of patients, tics remain clinically relevant throughout life. Tics rarely first come to clinical attention later in adulthood, but new reports describe additional such cases. Summary: Recent publications have shown tics to persist past a few months more often than previously thought, though often at minimal severity, and recurrence after an asymptomatic period is common. The safety and efficacy of behavior therapy for tics, together with prospective indicators of early prognosis, make feasible the possibility of bettering the lifetime course of tic disorders with early intervention. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Author Keywords
Adult; Outcome; Prognosis; Provisional tic disorder; Recurrence; Spontaneous remission; Tic disorders; Tourette syndrome
Funding details
National Institutes of HealthNIHR01MH104030, R01MH118217
National Institute of Mental HealthNIMH
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Sex and race-ethnic disparities in door-to-ct time in acute ischemic stroke: The florida stroke registry” (2021) Journal of the American Heart Association
Sex and race-ethnic disparities in door-to-ct time in acute ischemic stroke: The florida stroke registry
(2021) Journal of the American Heart Association, 10 (7), art. no. e017543, .
Polineni, S.P.a , Perez, E.J.b , Wang, K.a , Gutierrez, C.M.a , Walker, J.c , Foster, D.c , Dong, C.a , Asdaghi, N.a , Romano, J.G.a , Sacco, R.L.a , Rundek, T.a , Florida Stroke Registryd
a Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, United States
b Department of Neurology, Washington University, St. Louis, MO, United States
c American Heart Association Southeast, Marietta, GA, United States
Abstract
BACKGROUND: Less than 40% of acute stroke patients have computed tomography (CT) imaging performed within 25 minutes of hospital arrival. We aimed to examine the race-ethnic and sex differences in door-to-CT (DTCT) ≤25 minutes in the FSR (Florida Stroke Registry). METHODS AND RESULTS: Data were collected from 2010 to 2018 for 63 265 patients with acute ischemic stroke from the FSR and secondary analysis was performed on 15 877 patients with intravenous tissue plasminogen activator-treated ischemic stroke. Generalized estimating equation models were used to determine predictors of DTCT ≤25. DTCT ≤25 was achieved in 56% of cases of suspected acute stroke, improving from 36% in 2010 to 72% in 2018. Women (odds ratio [OR], 0.90; 95% CI, 0.87–0.93) and Black (OR, 0.88; CI, 0.84–0.94) patients who had strokes were less likely, and Hispanic patients more likely (OR, 1.07; CI, 1.01–1.14), to achieve DTCT ≤25. In a secondary analysis among intravenous tissue plasminogen activatortreated patients, 81% of patients achieved DTCT ≤25. In this subgroup, women were less likely to receive DTCT ≤25 (0.85, 0.77–0.94) whereas no significant differences were observed by race or ethnicity. CONCLUSIONS: In the FSR, there was considerable improvement in acute stroke care metric DTCT ≤25 in 2018 in comparison to 2010. However, sex and race-ethnic disparities persist and require further efforts to improve performance and reduce these disparities. © 2021 The Authors.
Author Keywords
Disparities; Ethnicity; Ischemic stroke; Race; Sex
Funding details
1U24 NS107267, R01 MD012467, R01 NS029993, R01 NS040807
National Institutes of HealthNIH
National Institute of Neurological Disorders and StrokeNINDSU54-NS081763
National Center for Advancing Translational SciencesNCATSKL2 TR002737, UL1 TR002736
Florida Department of HealthCOHAN-A1
Document Type: Article
Publication Stage: Final
Source: Scopus
“Personality traits as markers of psychosis risk in Kenya: Assessment of temperament and character” (2020) Schizophrenia Bulletin Open
Personality traits as markers of psychosis risk in Kenya: Assessment of temperament and character
(2020) Schizophrenia Bulletin Open, 1 (1), art. no. sgaa051, .
Mamah, D.a , Cloninger, C.R.a , Mutiso, V.N.b , Gitonga, I.b , Tele, A.b , Ndetei, D.M.b c
a Department of Psychiatry, Washington University Medical School, St. Louis, MO, United States
b Africa Mental Health Research and Training Foundation, Nairobi, Kenya
c Department of Psychiatry, University of Nairobi, Nairobi, Kenya
Abstract
Specific personality traits have been proposed as a schizophrenia-related endophenotype and confirmed in siblings at risk for psychosis. The relationship of temperament and character with psychosis has not been previously investigated in Africa. The study was conducted in Kenya, and involved participants at clinical high-risk (CHR) for psychosis (n = 268) and controls (n = 251), aged 15-25 years. CHR status was estimated using the Structured Interview of Psychosis-Risk Syndromes (SIPS) and the Washington Early Psychosis Center Affectivity and Psychosis (WERCAP) Screen. Student’s t-tests were used to assess group differences on the Temperament and Character Inventory (TCI). Neurocognitive functioning, stress severity, and substance use were correlated with the TCI, correcting for psychosis severity. CHR participants were more impulsive (ie, higher novelty seeking [NS]) and asocial (ie, lower reward dependence) than controls. They were also more schizotypal (ie, high self-transcendence [ST] and lower self-directedness [SD] and cooperativeness [CO] than controls). CO was related to logical reasoning, abstraction, and verbal memory. Stress severity correlated with high HA and schizotypal character traits. Lifetime tobacco use was related to NS, and lifetime marijuana use to high NS, low SD and high ST. Temperament and character of Kenyan CHR youth is similar to that observed in schizophrenia. Psychosis risk in Kenya is associated with impulsive, asocial, and schizotypal traits. CHR adolescents and young adults with schizophrenia-specific personality traits may be most at risk for developing a psychotic disorder and to require early intervention to improve outcomes. © The Author(s) 2020. Published by Oxford University Press on behalf of the University of Maryland’s school of medicine, Maryland
Author Keywords
Character/psychos is; Personality; Risk; TCI; Temperament
Funding details
National Institute of Mental HealthNIMHR56 MH111300
University of WashingtonUW
Document Type: Article
Publication Stage: Final
Source: Scopus