Hope Center Member Publications

Transcranial focused ultrasound-induced blood‒brain barrier opening in mice without shaving hairs
(2023) Scientific Reports, 13 (1), art. no. 13500, . 

Xu, L.^a , Gong, Y.^a , Chien, C.-Y.^a , Leuthardt, E.^a b c , Chen, H.^a b

^a Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO 63130, United States
^b Department of Neurosurgery, Washington University School of Medicine, Saint Louis, MO 63110, United States
^c Center for Innovation in Neuroscience and Technology, Washington University School of Medicine, Saint Louis, MO 63110, United States

Abstract
Acoustic coupling through hairs remains a challenge to performing transcranial-focused ultrasound procedures. Here, we demonstrated that this challenge could be addressed by using oil as the coupling medium, leveraging oil’s high affinity to hairs due to their inherent hydrophobicity. We compared focused ultrasound-induced blood–brain barrier opening (FUS-BBBO) outcomes in mice under three coupling conditions: oil with hairs (“oil + hairs”), ultrasound gel with hair shaving (“ultrasound gel + no hair”), and ultrasound gel with hairs (“ultrasound gel + hairs”). The quality of the coupling was evaluated by T 2 -weighted magnetic resonance imaging (MRI) and passive cavitation detection (PCD). The outcome of FUS-BBBO was assessed by MRI contrast agent extravasation using in vivo T 1 -weighted contrast-enhanced MRI. It was also evaluated by ex vivo fluorescence imaging of the mouse brain after intravenous injection of a model drug, Evans blue. The results showed that “oil + hairs” consistently achieved high-quality acoustic coupling without trapping air bubbles. The FUS-BBBO outcome was not significantly different between the “oil + hairs” and the “ultrasound gel + no hair” groups. These two groups had significantly higher levels of BBB opening than the “ultrasound gel + hairs” group. This study demonstrated that oil could be a coupling medium for transcranial FUS procedures without shaving hairs. © 2023, Springer Nature Limited.

Funding details
National Institutes of HealthNIHR01CA276174, R01EB027223, R01EB030102, R01MH116981, R01NS128461
Office of Extramural Research, National Institutes of HealthOER
Office of Research Infrastructure Programs, National Institutes of HealthORIP, NIH, NIH-ORIP, ORIP

Document Type: Article
Publication Stage: Final
Source: Scopus

Reliability of diurnal salivary cortisol metrics: A meta-analysis and investigation in two independent samples
(2023) Comprehensive Psychoneuroendocrinology, 16, art. no. 100191, . 

Norton, S.A.^a , Baranger, D.A.^a , Young, E.S.^b , Voss, M.^a , Hansen, I.^a , Bondy, E.^a , Rodrigues, M.^a , Paul, S.E.^a , Edershile, E.^c , Hill, P.L.^a , Oltmanns, T.F.^a , Simpson, J.^c , Bogdan, R.^a

^a Washington University in St. Louis, Department of Psychological & Brain Sciences, United States
^b Utrecht University, Department of Psychology, Netherlands
^c University of Minnesota, Department of Psychology, United States

Abstract
Stress-induced dysregulation of diurnal cortisol is a cornerstone of stress-disease theories; however, observed associations between cortisol, stress, and health have been inconsistent. The reliability of diurnal cortisol features may contribute to these equivocal findings. Our meta-analysis (5 diurnal features from 11 studies; total participant n = 3307) and investigation (15 diurnal cortisol features) in 2 independent studies (St. Louis Personality and Aging Network [SPAN] Study, n = 147, ages 61–73; Minnesota Longitudinal Study of Risk and Adaptation [MLSRA] Study, n = 90, age 37) revealed large variability in the day-to-day test-retest reliability of diurnal features derived from salivary cortisol data (i.e., ICC = 0.00–0.75). Collectively, these data indicate that some commonly used diurnal cortisol features have poor reliability that is insufficient for individual differences research (e.g., cortisol awakening response) while others (e.g., area under the curve with respect to ground) have fair-to-good reliability that could support reliable identification of associations in well-powered studies. © 2023 The Authors

Author Keywords
Cortisol;  Reliability;  Stress;  Variability

Document Type: Article
Publication Stage: Final
Source: Scopus

Finding new and better treatments for psychiatric disorders
(2023) Neuropsychopharmacology, . 

Paul, S.M.^a , Potter, W.Z.^b

^a Karuna Therapeutics, Washington University School of Medicine, St. Louis, MO, United States
^b Independent Consultant, Philadelphia, PA, United States

Abstract
In contrast to most fields of medicine, progress to discover and develop new and improved psychiatric drugs has been slow and disappointing. The vast majority of currently prescribed drugs to treat schizophrenia, mood and anxiety disorders are arguably no more effective than the first generation of psychiatric drugs introduced well over 50 years ago. With only a few exceptions current psychiatric drugs work via the same fundamental mechanisms of action as first-generation agents. Here we describe the reasons for this slow progress and outline a number of areas of research that involve a greater reliance on experimental therapeutics utilizing recent advances in neuroscience to better understand disease biology. We exemplify the potential impact of these areas of research focus with several recent examples of novel agents that have emerged and which support our optimism that newer, more effective and better tolerated agents, are on the horizon. Together with existing drugs these newer agents and novel mechanisms could offer markedly improved functional outcomes for the millions of people still disabled by psychiatric disorders. © 2023, The Author(s).

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