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2017 Research Articles

2017 VISN 20 MIRECC Staff Research Articles and Presentations

The findings of NW MIRECC research are disseminated through MIRECC Presents, lectures and presentations, and publications. Below is a list of publications and presentations by VISN 20 NW MIRECC researchers and fellowship program faculty that were published in 2017. 

Callahan, M., Binder, L., O’Neil, M., Zaccari, B., Roost, M., Golshan, S., … & Storzbach, D. (2017). Sensory sensitivity
in operation enduring freedom/operation Iraqi freedom veterans with and without blast exposure and mild traumatic brain injury. Applied Neuropsychology: Adult, 24, 1-11. doi:10.1080/23279095.2016.1261867

ABSTRACT: To examine factors associated with noise and light sensitivity among returning Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with a self-reported history of mild traumatic brain injury (mTBI) due to blast exposure, we compared the self-report of noise and light sensitivity of 42 OEF/OIF Veterans diagnosed with mTBI resulting from combat blast-exposure to that of 36 blast-exposed OEF/OIF Veterans without a history of mTBI. Results suggest a statistically significant difference between Veterans with and without a history of mTBI in the experience of noise and light sensitivity, with sensory symptoms reported most frequently in the mTBI group.

Cao, J., Gaamouch, F., Meabon, J., Meeker, K., Zhu, L., Zhong, M., … & Cai, D. (2017). ApoE4-associated
phospholipid dysregulation contributes to development of Tau hyper-phosphorylation after traumatic brain injury. Scientific Reports, 7(1), 11372. doi:10.1038/s41598-017-11654-7

ABSTRACT: The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer's Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP2) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP2 degrading enzyme, synaptojanin 1 (synj1). In contrast, hippocampal PIP2 levels in ApoE4 mice did not increase after blast TBI.

Cline, M., Yumul, J., Hysa, L., Murra, D., Garwin, G., Cook, D. G., … & Cross, D. (2017). Novel application of a Radial
Water Tread maze can distinguish cognitive deficits in mice with traumatic brain injury. Brain Research, 1657, 140-147. doi:10.1016/j.brainres.2016.11.027

ABSTRACT: The use of forced-swim, rat-validated cognition tests in mouse models of traumatic brain injury (TBI) raises methodological concerns; such models are vulnerable to a number of confounding factors including impaired motor function and stress-induced non-compliance (failure to swim). This study evaluated the ability of a Radial Water Tread (RWT) maze, designed specifically for mice, that requires no swimming to distinguish mice with controlled cortical impact (CCI) induced TBI and Sham controls.

Danziger, S., Miller, L., Singh, K., Whitney, G., Peskind, E. R., Li, G., … & Smith, J. (2017). An indicator cell assay
for blood-based diagnostics. PLOS ONE, 12(6), e0178608. doi:10.1371/journal.pone.0178608

ABSTRACT: We have established proof of principle for the Indicator Cell Assay Platform™ (iCAP™), a broadly applicable tool for blood-based diagnostics that uses specifically-selected, standardized cells as biosensors, relying on their innate ability to integrate and respond to diverse signals present in patients’ blood. To develop an assay, indicator cells are exposed in vitro to serum from case or control subjects and their global differential response patterns are used to train reliable, disease classifiers based on a small number of features. In a feasibility study, the iCAP detected pre-symptomatic disease in a murine model of amyotrophic lateral sclerosis (ALS) with 94% accuracy (p-Value = 3.81E-6) and correctly identified samples from a murine Huntington’s disease model as non-carriers of ALS.

Demidenko, M. I., Dobscha, S. K., Morasco, B. J., Meath, T. H. A., Ilgen, M. A., & Lovejoy, T. I. (2017). Suicidal ideation
and suicidal self-directed violence following clinician-initiated prescription opioid discontinuation among long-term opioid users. General Hospital Psychiatry, 47, 29-35.

ABSTRACT: Little is known about patient outcomes following discontinuation of opioid therapy, which may include suicidal ideation and suicidal self-directed violence. Five hundred-nine Veterans Health Administration (VHA) patients whose clinicians discontinued them from LTOT were selected from a national cohort of Veterans Health Administration (VHA) patients who discontinued opioids in 2012. The purpose of this study was to examine correlates of suicidal ideation and non-fatal suicidal self-directed violence in a sample of patients discontinued from long-term opioid therapy. Read full research: Suicidal ideation and suicidal self-directed violence following clinician-initiated prescription opioid discontinuation among long-term opioid users

Durazzo, T., Meyerhoff, D. J., Yoder, K. K., & Murray, D. (2017). Cigarette smoking is associated with amplified age-related
volume loss in subcortical brain regions. Drug and Alcohol Dependence, 177, 228-236. DOI: 10.1016/j.drugalcdep.2017.04.012

ABSTRACT: Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers.

Frank, J. W., Lovejoy, T. I., Becker, W. C., Morasco, B. J., Koenig, C. J., Hoffecker, L., ... Krebs, E. E. (2017). Patient
outcomes in dose reduction or discontinuation of long-term opioid therapy A systematic review. Annals of Internal Medicine, 167(3), 181-191.

ABSTRACT: Expert guidelines recommend reducing or discontinuing long-term opioid therapy (LTOT) when risks outweigh benefits, but evidence on the effect of dose reduction on patient outcomes has not been systematically reviewed. The purpose of this study is to synthesize studies of the effectiveness of strategies to reduce or discontinue LTOT and patient outcomes after dose reduction among adults prescribed LTOT for chronic pain. Read full research article: Patient outcomes in dose reduction or discontinuation of long-term opioid therapy A systematic review

Gonzales, R., & Rasmussen, D. D. (2017). The neglected catecholamine: Noradrenergic mechanisms in regulation of alcohol-
related behaviors. Alcoholism, Clinical and Experimental Research, 41(S1), 13A.

Hoggatt, K., Lehavot, K., Krenek, M., Schweizer, C., & Simpson, T. L. (2017). Prevalence of substance misuse among US
veterans in the general population. The American Journal on Addictions, 26(4), 357-365. doi:10.1111/ajad.12534

ABSTRACT: Epidemiologic data on substance misuse prevalence among US Veterans are crucial to plan for Veterans' future healthcare needs. We estimated US Veterans' age-specific, overall, and age-adjusted prevalence of substance misuse, assessed whether prevalence differed between Veterans and civilians, and examined temporal trends in prevalence.

Kruse, L., Schindler, A., Williams, R., Weber, S., & Clark, J. (2017). Maladaptive decision making in adults with a
history of adolescent alcohol use, in a preclinical model, is attributable to the compromised assignment of incentive value during stimulus-reward learning. Frontiers in Behavioral Neuroscience, 11, 134. doi:10.3389/fnbeh.2017.00134

ABSTRACT: According to recent WHO reports, alcohol remains the number one substance used and abused by adolescents, despite public health efforts to curb its use. Adolescence is a critical period of biological maturation where brain development, particularly the mesocorticolimbic dopamine system, undergoes substantial remodeling. These circuits are implicated in complex decision making, incentive learning and reinforcement during substance use and abuse. An appealing theoretical approach has been to suggest that alcohol alters the normal development of these processes to promote deficits in reinforcement learning and decision making, which together make individuals vulnerable to developing substance use disorders in adulthood. Previously we have used a preclinical model of voluntary alcohol intake in rats to show that use in adolescence promotes risky decision making in adulthood that is mirrored by selective perturbations in dopamine network dynamics.

Lehavot, K., Blosnich, J., Glass, J., & Williams, E. (2017). Alcohol use and receipt of alcohol screening and brief
intervention in a representative sample of sexual minority and heterosexual adults receiving health care. Drug and Alcohol Dependence, 179, 240-246. doi:10.1016/j.drugalcdep.2017.07.003

ABSTRACT: Despite evidence of alcohol disparities between sexual minority and heterosexual individuals in the general population, research has not examined whether there are disparities in receipt of alcohol screening and brief intervention - together considered one of the highest prevention priorities for US adults. This study examined differences in alcohol use and receipt of alcohol screening and brief intervention across sexual minority status.

Lehavot, K., Katon, J., Simpson, T. L., & Shipherd, J. (2017). Transgender veterans’ satisfaction with care and unmet
health needs. Medical Care, 55, S90-S96. doi:10.1097/MLR.0000000000000723

ABSTRACT: Transgender individuals are overrepresented among Veterans. However, little is known regarding their satisfaction with Veterans Administration (VA) care and unmet health needs. This study examined transgender Veterans' satisfaction with VA medical and mental health care, prevalence of delaying care, and correlates of these outcomes.

Lehavot, K., Litz, B., Millard, S., Hamilton, A., Sadler, A., & Simpson, T. L. (2017). Study adaptation, design, and
methods of a web-based PTSD intervention for women Veterans. Contemporary Clinical Trials, 53, 68-79. doi:10.1016/j.cct.2016.12.002

ABSTRACT: Women Veterans are a rapidly growing population with high risk of exposure to potentially traumatizing events and PTSD diagnoses. Despite the dissemination of evidence-based treatments for PTSD in the VA, most women Veteran VA users underutilize these treatments. Web-based PTSD treatment has the potential to reach and engage women Veterans with PTSD who do not receive treatment in VA settings. Our objective is to modify and evaluate Delivery of Self Training and Education for Stressful Situations (DESTRESSS), a web-based cognitive-behavioral intervention for PTSD, to target PTSD symptoms among women Veterans.

Li, G., Mayer, C., Morelli, D., Millard, S., Raskind, W., Petrie, E., … & Peskind, E. R. (2017). Effect of simvastatin
on CSF Alzheimer disease biomarkers in cognitively normal adults. Neurology, 89(12), 1251-1255. doi:10.1212/WNL.0000000000004392

ABSTRACT: To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure.

Li, G., Shofer, J., Petrie, E., Yu, C., Wilkinson, C., Figlewicz, D., … & Peskind, E. R. (2017). Cerebrospinal fluid
biomarkers for Alzheimer's and vascular disease vary by age, gender, and APOE genotype in cognitively normal adults. Alzheimer's Research & Therapy, 9(1), 48. doi:10.1186/s13195-017-0271-9

ABSTRACT: This study sought to evaluate gender and APOE genotype-related differences in the concentrations of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) and cerebrovascular injury across the life span of cognitively normal adults.

Lovejoy, T., Demidenko, M., Morasco, B., Meath, T., & Dobscha, S. (2017). (242) Suicidal ideation and behaviors
following clinician-initiated prescription opioid discontinuation among long-term opioid users. Journal of Pain, 18, S36.

ABSTRACT: Rates of clinician-initiated discontinuation of long-term opioid therapy (LTOT) for chronic pain are increasing, particularly for patients who may be considered "complex" given significant medical, mental health, and substance use disorder comorbidities. Although it is unclear if opioid therapy discontinuation leads to exacerbation of pain... Read full research article: Suicidal ideation and behaviors following clinician-initiated prescription opioid discontinuation among long-term opioid users

Lovejoy, T. I., Morasco, B. J., Demidenko, M. I., Meath, T. H. A., Frank, J. W., & Dobscha, S. K. (2017). Reasons for
discontinuation of long-term opioid therapy in patients with and without substance use disorders. Pain (03043959), 158(3), 526-534.

ABSTRACT: Several factors may accelerate opioid discontinuation rates, including lack of information about the long-term effectiveness of opioids for chronic pain, heightened awareness about opioid-related adverse events, closer monitoring of patients for opioid-related aberrant behaviors, and greater restrictions around opioid prescribing. Rates of discontinuation may be most pronounced in patients deemed to be at "high risk." The purpose of this study was to compare reasons for discontinuation of long-term opioid therapy between patients with and without Substance Use Disorder diagnoses. This retrospective cohort study assembled a cohort of Veterans Health Administration patients prescribed opioid therapy for at least 12 consecutive months... Read full research article: Reasons for discontinuation of long-term opioid therapy in patients with and without substance use disorders

Morasco, B. J., Yarborough, B. J., Smith, N. X., Dobscha, S. K., Deyo, R. A., Perrin, N. A., & Green, C. A. (2017). Higher
prescription opioid dose is associated with worse patient-reported pain outcomes and more health care utilization. Journal of Pain, 18(4), 437-445.

ABSTRACT: Some previous research has examined pain-related variables on the basis of prescription opioid dose, but data from studies involving patient-reported outcomes have been limited. This study examined the relationships between prescription opioid dose and self-reported pain intensity, function, quality of life, and mental health. Read full research article: Higher prescription opioid dose is associated with worse patient-reported pain outcomes and more health care utilization

Nugent, S., Dobscha, S., Morasco, B., Demidenko, M., Meath, T., Frank, J., ... Lovejoy, T. I. (2017). Substance Use
Disorder treatment following clinician-initiated discontinuation of long-term opioid therapy resulting from an aberrant urine drug test. JGIM: Journal of General Internal Medicine, 32(10), 1076-1082. doi:10.1007/s11606-017-4084-0

OBJECTIVE: To describe the proportion of patients who were referred to, and engaged in, substance use disorder (SUD) treatment following long-term opioid therapy (LTOT) discontinuation and to examine differences in substance use disorder (SUD) treatment referral and engagement based on the substances that led to discontinuation. Read full research article: Substance Use Disorder treatment following clinician-initiated discontinuation of long-term opioid therapy resulting from an aberrant urine drug test

Nugent, S. M., Morasco, B. J., O'Neil, M. E., Freeman, M., Low, A., Kondo, K., ... Kansagara, D. (2017). The effects
of cannabis among adults with chronic pain and an overview of general harms: A systematic review. Annals of Internal Medicine, 167(5), 319-331.

ABSTRACT: Cannabis is increasingly available for the treatment of chronic pain, yet its efficacy remains uncertain. The purpose of this study is To review the benefits of plant-based cannabis preparations for treating chronic pain in adults and the harms of cannabis use in chronic pain and general adult populations. Read full research article: The effects of cannabis among adults with chronic pain and an overview of general harms: A systematic review

O’Neil, M. E., Nugent, S. M., Morasco, B. J., Freeman, M., Low, A., Kondo, K., ... Kansagara, D. (2017). Benefits and
harms of plant-based cannabis for posttraumatic stress disorder: A systematic review. Annals of Internal Medicine, 167(5), 332-340.

ABSTRACT: Cannabis is available from medical dispensaries for treating posttraumatic stress disorder (PTSD) in many states of the union, yet its efficacy in treating PTSD symptoms remains uncertain. The purpose of this study is to identify ongoing studies and review existing evidence regarding the benefits and harms of plant-based cannabis preparations in treating PTSD in adults. Read full research article: Benefits and harms of plant-based cannabis for posttraumatic stress disorder: A systematic review

Pagulayan, K. F., O'Neil, M., Williams, R. M., Turner, A. P., Golshan, S., Roost, M. S., … & Twamley, E. W. (2017).
Mental health does not moderate compensatory cognitive training efficacy for Veterans with a history of mild Traumatic Brain Injury. Archives of Physical Medicine and Rehabilitation, 98(9), 1893-1896. doi:10.1016/j.apmr.2017.04.009

ABSTRACT: To examine the potential moderating effects of mental health symptoms on the efficacy of compensatory cognitive training (CCT) for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans with a history of mild traumatic brain injury (mTBI). DESIGN: Secondary analysis of a randomized controlled trial of CCT. Posttraumatic stress disorder, depression, and substance dependence symptom severity were examined as potential moderators of CCT efficacy for subjective cognitive complaints, use of cognitive strategies, and objective neurocognitive performance.

Pottiez, G., Yang, L., Stewart, T., Song, N., Aro, P., Galasko, D., … & Zhang, J. (2017). Mass-spectrometry-based method
to quantify in parallel tau and amyloid ß 1–42 in CSF for the diagnosis of Alzheimer’s disease. Journal of Proteome Research, 16(3), 1228-1238. doi:10.1021/acs.jproteome.6b00829

ABSTRACT: Alzheimer's disease (AD), the most common form of dementia, afflicts about 50 million people worldwide. Currently, AD diagnosis is primarily based on psychological evaluation and can only be confirmed post-mortem. Reliable and objective biomarkers for prognosis and diagnosis have been sought for years. Together, tau and amyloid β 1-42 (Aβ42) in cerebrospinal fluid (CSF) have been shown to provide good diagnostic sensitivity and specificity. Additionally, phosphorylated forms of tau, such as tau pS181, have also shown promising results. However, the measurement of such markers currently relies on antibody-based immunoassays that have shown variability, leading to discrepant results across laboratories.

Rasmussen, D. D. (2017). Variability in alcohol drinking responses to suppression of noradrenergic signaling in outbred
rats. Alcoholism, Clinical and Experimental Research, 41(S1), 236.

Rasmussen, D. D., Kincaid, C. L., & Froehlich, J. C. (2017). Prazosin prevents increased anxiety behavior that occurs in
response to stress during alcohol deprivations. Alcohol and Alcoholism (Oxford, Oxfordshire), 52(1), 5-11. DOI: 10.1093/alcalc/agw082

ABSTRACT: Stress-induced anxiety is a risk factor for relapse to alcohol drinking. The aim of this study was to test the hypothesis that the central nervous system (CNS)-active α1-adrenergic receptor antagonist, prazosin, would block the stress-induced increase in anxiety that occurs during alcohol deprivations.

Rau, H., Hendrickson, R. C., Roggenkamp, H., Peterson, S., Parmenter, B., Cook, D. G., … & Pagulayan, K. F. (2017). Fatigue,
but not mTBI history, PTSD, or sleep quality –directly contributes to prospective memory performance in Iraq and Afghanistan era Veterans. The Clinical Neuropsychologist, 13, 1-18. doi:10.1080/13854046.2017.1381277

Schindler, A., Meabon, J., Pagulayan, K. F., Hendrickson, R. C., Meeker, K., Cline, M., … & Cook, D. G. (2017). Blast–related
disinhibition and risk seeking in mice and combat Veterans: Potential role for dysfunctional phasic dopamine release. Neurobiology of Disease, 106, 23-34. doi:10.1016/j.nbd.2017.06.004

Schmidt, N. B., Norr, A. M., Allan, N. P., Raines, A. M., & Capron, D. W. (2017). A randomized clinical trial targeting
anxiety sensitivity for patients with suicidal ideation. Journal of Consulting and Clinical Psychology, 85(6), 596-610. doi:10.1037/ccp0000195

Simpson, T. L., Lehavot, K., & Petrakis, I. (2017). No wrong doors: Findings from a critical review of behavioral randomized
clinical trials for individuals with co-occurring alcohol/drug problems and posttraumatic stress disorder. Alcoholism: Clinical and Experimental Research, 41(4), 681-702. doi:10.1111/acer.13325

Storzbach, D., Twamley, E. W., Roost, M. S., Golshan, S., Williams, R. M., O’Neil, M., … & Huckans, M. (2017). Compensatory
cognitive training for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) veterans with mild traumatic brain injury. Journal of Head Trauma Rehabilitation, 32(1), 16-24. doi:10.1097/HTR.0000000000000228

Szot, P., Franklin, A., Figlewicz, D., Beuca, T., Bullock, K., Hansen, K., … Peskind, E. R. (2017). Multiple lipopolysaccharide
(LPS) injections alter interleukin 6 (IL-6), IL-7, IL-10 and IL-6 and IL-7 receptor mRNA in CNS and spleen. Neuroscience, 355, 9-21. doi:10.1016/j.neuroscience.2017.04.028

Wilson, S., Krenek, M., Dennis, P., Yard, S. S., Browne, K., & Simpson, T. L. (2017). Daily associations between PTSD,
drinking, and self-appraised alcohol-related problems. Psychology of Addictive Behaviors, 31(1), 27-35. doi:10.1037/adb0000238

Zaccari, B., Layne, W., Loftis, J., & Penn, P. (2017). The participant’s voice: A mixed-method evaluation of a mixed-gender
seeking safety group. Alcoholism Treatment Quarterly, 35(3), 213-231. doi:10.1080/07347324.2017.1322416

Zou, Y., Murray, D., Durazzo, T., Schmidt, T. P., Murray, T. A., & Meyerhoff, D. J. (2017). Effects of abstinence and chronic
cigarette smoking on white matter microstructure in alcohol dependence: diffusion tensor imaging at 4 Tesla. Drug and Alcohol Dependence, 175, 42-50.

NW MIRECC Research Articles:   In Press | 2019 | 2018 | 2017 | 2016 | 2015 | 2014


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