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Sleep Disturbance, Psychiatric, and Cognitive Functioning in Veterans with Mild to Moderate Traumatic Brain Injury

Henry J. Orff, Ph.D.1,2, Amy J. Jak, Ph.D.3,1,2, Amber M. Gregory4, Candice C. Col�n5, 
Dawn M. Schiehser, Ph.D.5,3,2, Sean P.A. Drummond 3,1,2, Ph.D. James B. Lohr, Ph.D.1,2, Elizabeth W. Twamley, Ph.D.1,2

1 Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, 
San Diego, CA
2 Department of Psychiatry, University of California, San Diego, CA 
3 Psychology Service, VA San Diego Healthcare System, San Diego, CA 
4 University of Alabama, Birmingham, Department of Psychology
5 Research Service, VA San Diego Healthcare System, San Diego, CA



Corresponding author:

Henry J. Orff, Ph.D.
VA San Diego Healthcare System
3350 La Jolla Village Dr. (9151B)
San Diego, CA 92161 USA
(858) 642-6492 (phone)
(858) 642-6340 (fax)
Email: horff@ucsd.edu


Key Words: Traumatic Brain Injury, Sleep Disturbance, Depression, PTSD, Post-concussive Symptoms; Neuropsychological Performance.
Abstract
Objective: For many Veterans, traumatic brain injury (TBI) can result in persistent post-concussive symptoms, of which sleep disturbances are among the most common. Sleep disturbances have been shown to increase risk and/or exacerbate psychiatric and physical health problems in many different populations. However, few studies have examined the relationships among sleep, psychiatric, and cognitive functioning in Veterans with TBI.

Methods: Retrospective chart reviews of 137 Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with a history of mild to moderate TBI referred for cognitive rehabilitation at the VA San Diego Healthcare System.

Results: 100% of Veterans reported clinically significant sleep disturbance (PSQI global scores >5). Veterans also reported clinically relevant impairments in sleep latency (50 minutes), total sleep time (5.5 hours), and sleep efficiency (77%). More severe sleep problems were related to greater endorsement of depressive, post-concussive, and PTSD symptomatology. Conversely, sleep disturbance showed limited associations with objective neuropsychological assessment. Overall measures of affective functioning were significantly associated with global measures of sleep quality, though such relationships were not observed for quantitative measures of sleep.

Conclusions: Veterans with mild to moderate TBI exhibit very high rates of sleep disturbance. Sleep disturbance is associated with higher levels of comorbid psychiatric symptomatology, particularly affective complaints. The high prevalence of sleep problems in Veterans with a history of TBI underscores a need to develop both a better understanding of etiologic mechanisms relating brain injury and sleep and a better clinical appreciation of the ramifications of sleep disturbance on daily functioning and recovery in individuals who experience TBI.
Introduction
Although TBI is common in the general population, there is increased clinical and research interest in TBI due to its high incidence in military personnel involved in recent wars. TBI has been identified as the �signature wound� of the Iraq and Afghanistan Wars, with increased rates of TBI attributed to blast-related injuries emanating from artillery, mortar, rocket shells, mines, bombs, grenades, and improvised explosive devices [ ADDIN EN.CITE <EndNote><Cite><Author>Gondusky</Author><Year>2005</Year><RecNum>1</RecNum><record><rec-number>1</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Gondusky, J. S.</author><author>Reiter, M. P.</author></authors></contributors><auth-address>1st Light Armored Reconnaissance Battalion, 1st Marine Division, Camp Pendleton, CA 92055, USA.</auth-address><titles><title>Protecting military convoys in Iraq: an examination of battle injuries sustained by a mechanized battalion during Operation Iraqi Freedom II</title><secondary-title>Mil Med</secondary-title></titles><periodical><full-title>Mil Med</full-title></periodical><pages>546-9</pages><volume>170</volume><number>6</number><keywords><keyword>Blast Injuries/prevention &amp; control</keyword><keyword>Delivery of Health Care/methods/statistics &amp; numerical data</keyword><keyword>Humans</keyword><keyword>Iraq</keyword><keyword>Military Personnel/*statistics &amp; numerical data</keyword><keyword>War</keyword><keyword>Wounds and Injuries/*classification/prevention &amp; control</keyword></keywords><dates><year>2005</year><pub-dates><date>Jun</date></pub-dates></dates><accession-num>16001610</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=16001610 </url></related-urls></urls></record></Cite></EndNote>1] Although precise rates of TBI in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans are difficult to determine, comprehensive surveys such as the RAND Corporation Study  ADDIN EN.CITE <EndNote><Cite><Author>Tanielian</Author><Year>2008</Year><RecNum>16</RecNum><record><rec-number>16</rec-number><ref-type name="Report">27</ref-type><contributors><authors><author>Tanielian, T.</author><author>Jaycox, L.H.</author></authors></contributors><titles><title>Invisible Wounds of War: Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery</title></titles><dates><year>2008</year></dates><pub-location>Santa Monica, CA</pub-location><publisher>RAND Corporation</publisher><urls></urls></record></Cite></EndNote>[2] have found that about 19% of returning service members report having experienced a TBI while deployed. Additionally, approximately 67% of OEF/OIF Veterans seen in VA Polytrauma settings show evidence of possible persistent post-concussive symptoms secondary to a TBI [ ADDIN EN.CITE <EndNote><Cite><Author>Lew</Author><Year>2009</Year><RecNum>11</RecNum><record><rec-number>11</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lew, H. L.</author><author>Otis, J. D.</author><author>Tun, C.</author><author>Kerns, R. D.</author><author>Clark, M. E.</author><author>Cifu, D. X.</author></authors></contributors><auth-address>Physical Medicine and Rehabilitation (PM&amp;R) Service, Department of Veterans Affairs (VA) Boston Healthcare System, 150 South Huntington Avenue, Boston, MA 02130, USA. henry.lew@va.gov</auth-address><titles><title>Prevalence of chronic pain, posttraumatic stress disorder, and persistent postconcussive symptoms in OIF/OEF veterans: polytrauma clinical triad</title><secondary-title>J Rehabil Res Dev</secondary-title></titles><periodical><full-title>J Rehabil Res Dev</full-title></periodical><pages>697-702</pages><volume>46</volume><number>6</number><keywords><keyword>Afghan Campaign 2001-</keyword><keyword>Blast Injuries/complications</keyword><keyword>Brain Injuries/complications/*epidemiology</keyword><keyword>Cohort Studies</keyword><keyword>Humans</keyword><keyword>Iraq War, 2003 -</keyword><keyword>Pain/*epidemiology/etiology</keyword><keyword>Post-Concussion Syndrome/*epidemiology/etiology</keyword><keyword>Prevalence</keyword><keyword>Retrospective Studies</keyword><keyword>Stress Disorders, Post-Traumatic/*epidemiology/etiology</keyword><keyword>Veterans/*statistics &amp; numerical data</keyword></keywords><dates><year>2009</year></dates><accession-num>20104399</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=20104399 </url></related-urls></urls></record></Cite></EndNote>3].

Sleep disturbances are frequently reported post-TBI sequelae. Research suggests that 25-70% of people experience sleep problems following a TBI and that these sleep disturbances often exacerbate other symptoms as well as impede the rehabilitation process and the ability to return to work [ ADDIN EN.CITE <EndNote><Cite><Author>Ouellet</Author><Year>2004</Year><RecNum>2</RecNum><record><rec-number>2</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ouellet, M. C.</author><author>Savard, J.</author><author>Morin, C. M.</author></authors></contributors><auth-address>Ecole de Psychologie, Centre d&apos;Etude des Troubles du Sommeil, Universite Laval, Quebec, Canada. mcouellet@psy.ulaval.ca &lt;mcouellet@psy.ulaval.ca&gt;</auth-address><titles><title>Insomnia following traumatic brain injury: a review</title><secondary-title>Neurorehabil Neural Repair</secondary-title></titles><periodical><full-title>Neurorehabil Neural Repair</full-title></periodical><pages>187-98</pages><volume>18</volume><number>4</number><keywords><keyword>Brain Injuries/*complications/*physiopathology/therapy</keyword><keyword>Humans</keyword><keyword>Sleep Initiation and Maintenance</keyword><keyword>Disorders/*etiology/*physiopathology/therapy</keyword></keywords><dates><year>2004</year><pub-dates><date>Dec</date></pub-dates></dates><accession-num>15669131</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=15669131 </url></related-urls></urls></record></Cite></EndNote>4]. A recent review reported that approximately 46% of all TBI patients with chronic post-injury symptoms have sleep disorders ADDIN EN.CITE <EndNote><Cite><Author>Castriotta</Author><RecNum>17</RecNum><record><rec-number>17</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Castriotta, R. J.</author><author>Murthy, J. N.</author></authors></contributors><auth-address>Division of Pulmonary, Critical Care and Sleep Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. Richard.J.Castriotta@uth.tmc.edu</auth-address><titles><title>Sleep disorders in patients with traumatic brain injury: a review</title><secondary-title>CNS Drugs</secondary-title></titles><periodical><full-title>CNS Drugs</full-title></periodical><pages>175-85</pages><volume>25</volume><number>3</number><keywords><keyword>Brain Injuries/*complications</keyword><keyword>Humans</keyword><keyword>Polysomnography</keyword><keyword>Sleep Disorders/diagnosis/*etiology/*physiopathology</keyword></keywords><dates><pub-dates><date>Mar 1</date></pub-dates></dates><accession-num>21062105</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=21062105 </url></related-urls></urls></record></Cite></EndNote> [5]. In this review, the authors concluded that over 50% of the patients who reported post-injury sleep disorders had symptoms consistent with a diagnosis of insomnia, 23% had sleep apnea, 11% post-traumatic hypersomnia, 7% periodic limb movements during sleep, and 6% narcolepsy. Additionally, in a recently-published meta-analysis, Mathias, et al. ADDIN EN.CITE <EndNote><Cite><Author>Mathias</Author><RecNum>50</RecNum><record><rec-number>50</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mathias, J. L.</author><author>Alvaro, P. K.</author></authors></contributors><auth-address>School of Psychology, University of Adelaide, Adelaide, SA 5005, Australia. jane.mathias@adelaide.edu.au</auth-address><titles><title>Prevalence of sleep disturbances, disorders, and problems following traumatic brain injury: a meta-analysis</title><secondary-title>Sleep Med</secondary-title></titles><periodical><full-title>Sleep Med</full-title></periodical><pages>898-905</pages><volume>13</volume><number>7</number><dates><pub-dates><date>Aug</date></pub-dates></dates><accession-num>22705246</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=22705246 </url></related-urls></urls></record></Cite></EndNote>[6] found that some form of sleep disturbance was reported in 25-29% of individuals following a TBI and that these patients were 2-4 times more likely than individuals in the general population to experience problems with sleep maintenance, sleep efficiency, nightmares, excessive sleepiness, early awakenings, and sleep walking. When examining the prevalence of sleep disturbance in Veteran patient samples, even higher levels of symptomatology have been observed relative to civilian patient surveys  ADDIN EN.CITE <EndNote><Cite><Author>Capaldi</Author><RecNum>185</RecNum><record><rec-number>185</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Capaldi, V. F., 2nd</author><author>Guerrero, M. L.</author><author>Killgore, W. D.</author></authors></contributors><auth-address>Walter Reed Army Medical Center, 6900 Georgia Avenue, NW, Washington, DC 20307, USA.</auth-address><titles><title>Sleep disruptions among returning combat veterans from Iraq and Afghanistan</title><secondary-title>Mil Med</secondary-title></titles><periodical><full-title>Mil Med</full-title></periodical><pages>879-88</pages><volume>176</volume><number>8</number><keywords><keyword>Adult</keyword><keyword>*Afghan Campaign 2001-</keyword><keyword>Brain Injuries/*epidemiology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Iraq War, 2003 -</keyword><keyword>Middle Aged</keyword><keyword>*Military Personnel</keyword><keyword>Polysomnography</keyword><keyword>Retrospective Studies</keyword><keyword>Sleep Apnea Syndromes/epidemiology</keyword><keyword>Sleep Apnea, Obstructive/epidemiology</keyword><keyword>Sleep Disorders/*epidemiology</keyword><keyword>Stress Disorders, Post-Traumatic/*epidemiology</keyword><keyword>United States/epidemiology</keyword><keyword>Young Adult</keyword></keywords><dates><pub-dates><date>Aug</date></pub-dates></dates><accession-num>21882777</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=21882777 </url></related-urls></urls></record></Cite></EndNote>[7]. For example, in a chart review of 200 OEF/OIF Veterans evaluated at a VA Polytrauma outpatient clinic, it was found that sleep disturbance following TBI (endorsed by 93.5% of sample) was even more prevalent than that observed in civilian studies  ADDIN EN.CITE <EndNote><Cite><Author>Lew</Author><RecNum>19</RecNum><record><rec-number>19</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lew, H. L.</author><author>Pogoda, T. K.</author><author>Hsu, P. T.</author><author>Cohen, S.</author><author>Amick, M. M.</author><author>Baker, E.</author><author>Meterko, M.</author><author>Vanderploeg, R. D.</author></authors></contributors><auth-address>Defense and Veterans Brain Injury Center, Richmond, Virginia 23219, USA.</auth-address><titles><title>Impact of the &quot;polytrauma clinical triad&quot; on sleep disturbance in a department of veterans affairs outpatient rehabilitation setting</title><secondary-title>Am J Phys Med Rehabil</secondary-title></titles><periodical><full-title>Am J Phys Med Rehabil</full-title></periodical><pages>437-45</pages><volume>89</volume><number>6</number><keywords><keyword>Adult</keyword><keyword>Afghan Campaign 2001-</keyword><keyword>Ambulatory Care</keyword><keyword>Cohort Studies</keyword><keyword>Combat Disorders/*complications/diagnosis/rehabilitation</keyword><keyword>Disability Evaluation</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Multiple Trauma/complications</keyword><keyword>Pain/*complications/diagnosis/rehabilitation</keyword><keyword>Prevalence</keyword><keyword>Retrospective Studies</keyword><keyword>Severity of Illness Index</keyword><keyword>Sleep Disorders/*epidemiology/*etiology/rehabilitation</keyword><keyword>Stress Disorders, Post-Traumatic/*complications/diagnosis/rehabilitation</keyword><keyword>United States</keyword><keyword>United States Department of Veterans Affairs</keyword><keyword>Veterans/statistics &amp; numerical data</keyword><keyword>War</keyword></keywords><dates><pub-dates><date>Jun</date></pub-dates></dates><accession-num>20489391</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=20489391 </url></related-urls></urls></record></Cite></EndNote>[8] Research also indicates that mild to moderate TBI is most frequently associated with sleep disturbance, as opposed to more severe TBI [ ADDIN EN.CITE <EndNote><Cite><Author>Mahmood</Author><Year>2004</Year><RecNum>8</RecNum><record><rec-number>8</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Mahmood, O.</author><author>Rapport, L. J.</author><author>Hanks, R. A.</author><author>Fichtenberg, N. L.</author></authors></contributors><auth-address>Department of Psychology, Wayne State University, 71 W. Warren Avenue, Detroit, MI 48202, USA.</auth-address><titles><title>Neuropsychological performance and sleep disturbance following traumatic brain injury</title><secondary-title>J Head Trauma Rehabil</secondary-title></titles><periodical><full-title>J Head Trauma Rehabil</full-title></periodical><pages>378-90</pages><volume>19</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Brain Injuries/*rehabilitation</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Psychological Tests</keyword><keyword>Regression Analysis</keyword><keyword>Sleep Disorders/psychology/*rehabilitation</keyword></keywords><dates><year>2004</year><pub-dates><date>Sep-Oct</date></pub-dates></dates><accession-num>15597029</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=15597029 </url></related-urls></urls></record></Cite><Cite><Author>Pillar</Author><Year>2003</Year><RecNum>12</RecNum><record><rec-number>12</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Pillar, G.</author><author>Averbooch, E.</author><author>Katz, N.</author><author>Peled, N.</author><author>Kaufman, Y.</author><author>Shahar, E.</author></authors></contributors><auth-address>Sleep Laboratory, Rambam Medical Center and Technion-IIT, Haifa, Israel.</auth-address><titles><title>Prevalence and risk of sleep disturbances in adolescents after minor head injury</title><secondary-title>Pediatr Neurol</secondary-title></titles><periodical><full-title>Pediatr Neurol</full-title></periodical><pages>131-5</pages><volume>29</volume><number>2</number><keywords><keyword>Adolescent</keyword><keyword>Body Mass Index</keyword><keyword>Case-Control Studies</keyword><keyword>Child</keyword><keyword>Craniocerebral Trauma/*complications</keyword><keyword>Educational Status</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Parents</keyword><keyword>Prevalence</keyword><keyword>Questionnaires</keyword><keyword>Risk Factors</keyword><keyword>Sleep Disorders/*epidemiology/*etiology</keyword></keywords><dates><year>2003</year><pub-dates><date>Aug</date></pub-dates></dates><accession-num>14580656</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=14580656 </url></related-urls></urls></record></Cite></EndNote>9, 10]. 

One of the most actively debated issues in the TBI literature in recent years is the etiology of post-concussive illness following TBI. Emanating from this research are two related, yet competing, hypotheses. The first suggests that TBI acts as a risk factor for development of psychiatric symptomatology, and that observed chronic post-concussive symptomatology results from presence of psychiatric illness (e.g., depression and PTSD). This hypothesis is supported by research that has shown that depression (along with PTSD and symptom exaggeration) is strongly associated with reports of post-concussive symptoms  ADDIN EN.CITE <EndNote><Cite ExcludeYear="1"><Author>Lange</Author><RecNum>285</RecNum><record><rec-number>285</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lange, R. T.</author><author>Brickell, T.</author><author>French, L. M.</author><author>Ivins, B.</author><author>Bhagwat, A.</author><author>Pancholi, S.</author><author>Iverson, G. L.</author></authors></contributors><auth-address>Defense and Veterans Brain Injury Center, North Bethesda, Maryland 20852, USA. rlange@dvbic.org</auth-address><titles><title>Risk factors for postconcussion symptom reporting after traumatic brain injury in U.S. military service members</title><secondary-title>J Neurotrauma</secondary-title></titles><periodical><full-title>J Neurotrauma</full-title></periodical><pages>237-46</pages><volume>30</volume><number>4</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Brain Injuries/*complications/*psychology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Military Personnel</keyword><keyword>Neuropsychological Tests</keyword><keyword>Post-Concussion Syndrome/*etiology/*psychology</keyword><keyword>Risk Factors</keyword><keyword>*Self Report</keyword><keyword>Young Adult</keyword></keywords><dates><pub-dates><date>Feb 15</date></pub-dates></dates><accession-num>23126461</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=23126461 </url></related-urls></urls></record></Cite></EndNote>[11] and through influential work by Hoge et al.  ADDIN EN.CITE <EndNote><Cite><Author>Hoge</Author><Year>2008</Year><RecNum>12</RecNum><record><rec-number>12</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hoge, C. W.</author><author>McGurk, D.</author><author>Thomas, J. L.</author><author>Cox, A. L.</author><author>Engel, C. C.</author><author>Castro, C. A.</author></authors></contributors><auth-address>Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, U.S. Army Medical Research and Materiel Command, Silver Spring, MD 20910, USA. charles.hoge@us.army.mil</auth-address><titles><title>Mild traumatic brain injury in U.S. Soldiers returning from Iraq</title><secondary-title>N Engl J Med</secondary-title></titles><periodical><full-title>N Engl J Med</full-title></periodical><pages>453-63</pages><volume>358</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Blast Injuries/complications</keyword><keyword>Brain Injuries/*complications/*epidemiology/psychology</keyword><keyword>Consciousness Disorders/complications/epidemiology</keyword><keyword>Data Collection</keyword><keyword>Depressive Disorder/complications</keyword><keyword>Female</keyword><keyword>Headache/etiology</keyword><keyword>Health Status</keyword><keyword>Humans</keyword><keyword>*Iraq War, 2003 -</keyword><keyword>Male</keyword><keyword>*Military Personnel</keyword><keyword>Post-Concussion Syndrome/*etiology</keyword><keyword>Prevalence</keyword><keyword>Stress Disorders, Post-Traumatic/*etiology</keyword><keyword>Trauma Severity Indices</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2008</year><pub-dates><date>Jan 31</date></pub-dates></dates><accession-num>18234750</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=18234750 </url></related-urls></urls></record></Cite></EndNote>[12], which found that PTSD and depression fully mediate the relationship between mTBI history and most subjective measures of health and psychosocial functioning (except head pain).

Alternatively, several studies have suggested that post-concussive symptoms, such as sleep disturbance, may actually precede and/or exist independently of psychiatric illness following TBI. For example, after controlling for other psychiatric conditions, Vanderploeg et al.  ADDIN EN.CITE <EndNote><Cite><Author>Vanderploeg</Author><Year>2009</Year><RecNum>268</RecNum><record><rec-number>268</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vanderploeg, R. D.</author><author>Belanger, H. G.</author><author>Curtiss, G.</author></authors></contributors><auth-address>Department of Mental Health and Behavioral Sciences and Defense and Veterans Brain Injury Center, James A. Haley Veterans Affairs Medical Center, Tampa, FL 33612, USA. Rodney.Vanderploeg@va.gov</auth-address><titles><title>Mild traumatic brain injury and posttraumatic stress disorder and their associations with health symptoms</title><secondary-title>Arch Phys Med Rehabil</secondary-title></titles><periodical><full-title>Arch Phys Med Rehabil</full-title></periodical><pages>1084-93</pages><volume>90</volume><number>7</number><keywords><keyword>Adult</keyword><keyword>Brain Injuries/complications/*physiopathology</keyword><keyword>Cohort Studies</keyword><keyword>Cross-Sectional Studies</keyword><keyword>*Health Status</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Mental Disorders/complications/physiopathology</keyword><keyword>Post-Concussion Syndrome/physiopathology</keyword><keyword>Prevalence</keyword><keyword>Risk Factors</keyword><keyword>Severity of Illness Index</keyword><keyword>Socioeconomic Factors</keyword><keyword>Stress Disorders, Post-Traumatic/complications/*physiopathology</keyword><keyword>United States</keyword><keyword>*Veterans</keyword></keywords><dates><year>2009</year><pub-dates><date>Jul</date></pub-dates></dates><accession-num>19577020</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=19577020 </url></related-urls></urls></record></Cite></EndNote>[13] found that mTBI may still be significantly associated with headaches, sleep problems, and memory difficulties for years after the injury. Furthermore, persistent post-concussive symptoms in Veterans with deployment related TBI have been shown to mediate the relationship between TBI and psychopathologies such as depression  ADDIN EN.CITE <EndNote><Cite><Author>Macera</Author><Year>2103</Year><RecNum>269</RecNum><record><rec-number>269</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Macera, C. A.</author><author>Aralis, H. J.</author><author>Rauh, M. J.</author><author>MacGregor, A. J.</author></authors></contributors><auth-address>Department of Warfighter Performance, Naval Health Research Center, San Diego, CA 92106-5122, USA. carol.macera@med.navy.mil</auth-address><titles><title>Do sleep problems mediate the relationship between traumatic brain injury and development of mental health symptoms after deployment?</title><secondary-title>Sleep</secondary-title></titles><periodical><full-title>Sleep</full-title></periodical><pages>83-90</pages><volume>36</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Afghan Campaign 2001-</keyword><keyword>Brain Injuries/diagnosis/*epidemiology</keyword><keyword>Causality</keyword><keyword>Combat Disorders/diagnosis/*epidemiology</keyword><keyword>Comorbidity</keyword><keyword>Depressive Disorder/diagnosis/*epidemiology</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Iraq War, 2003 - 2011</keyword><keyword>Kuwait</keyword><keyword>Male</keyword><keyword>Mental Disorders/diagnosis/*epidemiology</keyword><keyword>Military Personnel/*statistics &amp; numerical data</keyword><keyword>Prospective Studies</keyword><keyword>Questionnaires</keyword><keyword>Risk Factors</keyword><keyword>Stress Disorders, Post-Traumatic/diagnosis/*epidemiology</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2103</year><pub-dates><date>Jan</date></pub-dates></dates><accession-num>23288974</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=23288974 </url></related-urls></urls></record></Cite><Cite ExcludeYear="1"><Author>Morissette</Author><RecNum>270</RecNum><record><rec-number>270</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Morissette, S. B.</author><author>Woodward, M.</author><author>Kimbrel, N. A.</author><author>Meyer, E. C.</author><author>Kruse, M. I.</author><author>Dolan, S.</author><author>Gulliver, S. B.</author></authors></contributors><auth-address>Department of Veterans Affairs VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, Texas, USA. sandra.morissette@va.gov</auth-address><titles><title>Deployment-related TBI, persistent postconcussive symptoms, PTSD, and depression in OEF/OIF veterans</title><secondary-title>Rehabil Psychol</secondary-title></titles><periodical><full-title>Rehabil Psychol</full-title></periodical><pages>340-50</pages><volume>56</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>*Afghan Campaign 2001-</keyword><keyword>Brain Concussion/epidemiology/psychology</keyword><keyword>Brain Injuries/epidemiology/*psychology</keyword><keyword>Depressive Disorder/epidemiology/*psychology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Interview, Psychological</keyword><keyword>*Iraq War, 2003 - 2011</keyword><keyword>Male</keyword><keyword>Military Personnel/*psychology/statistics &amp; numerical data</keyword><keyword>Stress Disorders, Post-Traumatic/epidemiology/*psychology</keyword><keyword>Veterans/*psychology/statistics &amp; numerical data</keyword></keywords><dates><pub-dates><date>Nov</date></pub-dates></dates><accession-num>22121940</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=22121940 </url></related-urls></urls></record></Cite></EndNote>[14, 15]. As well, one recent investigation found sleep disturbance to be an independent and early indicator of risk for depression and/or PTSD  ADDIN EN.CITE <EndNote><Cite><Author>Macera</Author><Year>2103</Year><RecNum>269</RecNum><record><rec-number>269</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Macera, C. A.</author><author>Aralis, H. J.</author><author>Rauh, M. J.</author><author>MacGregor, A. J.</author></authors></contributors><auth-address>Department of Warfighter Performance, Naval Health Research Center, San Diego, CA 92106-5122, USA. carol.macera@med.navy.mil</auth-address><titles><title>Do sleep problems mediate the relationship between traumatic brain injury and development of mental health symptoms after deployment?</title><secondary-title>Sleep</secondary-title></titles><periodical><full-title>Sleep</full-title></periodical><pages>83-90</pages><volume>36</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Afghan Campaign 2001-</keyword><keyword>Brain Injuries/diagnosis/*epidemiology</keyword><keyword>Causality</keyword><keyword>Combat Disorders/diagnosis/*epidemiology</keyword><keyword>Comorbidity</keyword><keyword>Depressive Disorder/diagnosis/*epidemiology</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Iraq War, 2003 - 2011</keyword><keyword>Kuwait</keyword><keyword>Male</keyword><keyword>Mental Disorders/diagnosis/*epidemiology</keyword><keyword>Military Personnel/*statistics &amp; numerical data</keyword><keyword>Prospective Studies</keyword><keyword>Questionnaires</keyword><keyword>Risk Factors</keyword><keyword>Stress Disorders, Post-Traumatic/diagnosis/*epidemiology</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2103</year><pub-dates><date>Jan</date></pub-dates></dates><accession-num>23288974</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=23288974 </url></related-urls></urls></record></Cite></EndNote>[14].
In an attempt to further explore these complex relationships, this investigation examined the sleep disturbance and post-concussive functioning in OEF/OIF Veterans with a history of mild to moderate TBI, who were referred for evaluation and treatment at the VA San Diego Healthcare System (VASDHS) TBI Cognitive Rehabilitation Clinic. We sought to describe the sleep characteristics of this sample and hypothesized that: 
OEF/OIF Veterans who had sustained a mild to moderate TBI would show high prevalence of self-reported sleep disturbance;
Severity of psychiatric symptoms, post-concussive symptoms, and cognitive impairment, would be associated with severity of sleep disturbance;
In a multivariate context, severity of both post-concussive and psychiatric symptoms would show a strong association with both qualitative and quantitative measures of sleep disturbance.
Methods
Subjects
Archival data from 137 OEF/OIF Veterans with a history of mild to moderate TBI referred for cognitive rehabilitation services at the VASDHS between April 2009 and June 2013 were evaluated. Mild TBI was defined as loss of consciousness (LOC) < 30 minutes and/or post-traumatic amnesia (PTA) < 1 day and moderate TBI was defined as LOC < 24 hours and/or PTA < 7 days  ADDIN EN.CITE <EndNote><Cite><Author>Group</Author><Year>2009</Year><RecNum>65</RecNum><record><rec-number>65</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Management of Concussion/mTBI Working Group</author></authors></contributors><titles><title>VA/DoD clinical practice guideline for management of concussion/mild traumatic brain injury</title><secondary-title>J Rehabil Res Dev</secondary-title></titles><periodical><full-title>J Rehabil Res Dev</full-title></periodical><pages>703-716</pages><volume>46</volume><dates><year>2009</year></dates><urls></urls></record></Cite></EndNote>[16]. As Glasgow Coma Scale scores and neuroimaging results were not available for most Veterans, these measures were not used in the evaluation of TBI severity in this study. Veterans who were clinically determined to have invalid neuropsychological test results as measured by performance below standard cutoffs on either of two symptom validity measures (Trial 2 and/or Delayed Recall (percent accuracy) on the Test of Memory Malingering (TOMM)  ADDIN EN.CITE <EndNote><Cite><Author>Tombaugh</Author><Year>1996</Year><RecNum>37</RecNum><record><rec-number>37</rec-number><ref-type name="Generic">13</ref-type><contributors><authors><author>Tombaugh, T.N.</author></authors></contributors><titles><title>Test of Memory Malingering (TOMM)</title></titles><dates><year>1996</year></dates><pub-location>San Antonio, TX</pub-location><publisher>Pearson Education, Inc.</publisher><urls></urls></record></Cite></EndNote>[17] and/or total score on the Forced Choice Recognition portion of the California Verbal Learning Test II (CVLT-II)  ADDIN EN.CITE <EndNote><Cite><Author>Delis</Author><Year>2000</Year><RecNum>31</RecNum><record><rec-number>31</rec-number><ref-type name="Generic">13</ref-type><contributors><authors><author>Delis, D.C.</author><author>Kramer, J.H.</author><author>Kaplan, E.</author><author>Ober, B.A.</author></authors></contributors><titles><title>California Verbal Learning Test � Second Edition (CVLT �II)</title></titles><dates><year>2000</year></dates><pub-location>San Antonio, TX</pub-location><publisher>Pearson Education, Inc</publisher><urls></urls></record></Cite></EndNote>[18] results were not included in the study.

Retrospective chart reviews of the Veterans� Polytrauma, neuropsychological, and mental health visits were conducted. Information obtained for this archival investigation was primarily gathered from each Veteran�s neuropsychological assessment report and, when necessary, from notes entered by other providers seen by the Veteran in the context of their medical care at the VASDHS. Given that patient assessments were not systematized in terms of how and what information was collected, the quality of data and availability of information often varied considerably from patient to patient. Nonetheless, for many Veterans data that included measures of personal demographics, TBI history, measures of sleep and post-concussive functioning, psychiatric history (including diagnoses and self-reported psychiatric symptom severity measures), and comprehensive neuropsychological test data were available and therefore included in this study. Demographic data of interest that was consistently available for the majority of the sample included age, gender, years of formal education, and TBI history (including mechanism of injury, number of TBIs, and length of LOC and PTA). This study was approved by the University of California, San Diego IRB and VASDHS Research and Development Committee.

Measures 
Symptom severity measures included self-report assessments of:
Sleep: Pittsburgh Sleep Quality Inventory (PSQI)  ADDIN EN.CITE <EndNote><Cite><Author>Buysse</Author><Year>1989</Year><RecNum>22</RecNum><record><rec-number>22</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Buysse, D. J.</author><author>Reynolds, C. F., 3rd</author><author>Monk, T. H.</author><author>Berman, S. R.</author><author>Kupfer, D. J.</author></authors></contributors><auth-address>Department of Psychiatry, University of Pittsburgh School of Medicine, PA.</auth-address><titles><title>The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research</title><secondary-title>Psychiatry Res</secondary-title></titles><periodical><full-title>Psychiatry Res</full-title></periodical><pages>193-213</pages><volume>28</volume><number>2</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Depression/*psychology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Psychological Tests</keyword><keyword>Psychometrics</keyword><keyword>Sleep Initiation and Maintenance Disorders/*diagnosis/psychology</keyword><keyword>*Sleep Stages</keyword></keywords><dates><year>1989</year><pub-dates><date>May</date></pub-dates></dates><accession-num>2748771</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=2748771 </url></related-urls></urls></record></Cite></EndNote>[19]. The PSQI is a self-rated questionnaire that assesses sleep quality and disturbances over a 1-month interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score.
Post-concussive symptoms: Neurobehavioral Symptom Inventory (NSI)  ADDIN EN.CITE <EndNote><Cite><Author>Cicerone</Author><Year>1995</Year><RecNum>29</RecNum><record><rec-number>29</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Cicerone, K.D.</author><author>Kalmar, K.</author></authors></contributors><titles><title>Persistent postconcussion syndrome: The structure of subjective complaints after mild traumatic brain injury.</title><secondary-title>The Journal of Head Trauma Rehabilitation</secondary-title></titles><periodical><full-title>The Journal of Head Trauma Rehabilitation</full-title></periodical><pages>1-17</pages><volume>10</volume><number>3</number><dates><year>1995</year></dates><urls></urls></record></Cite></EndNote>[20]. The NSI is a 22-item assessment commonly used to measure post-concussive symptoms. In addition to total score, the NSI can be evaluated on three component scales: affective, cognitive, and somatic per Caplan, et al.  ADDIN EN.CITE <EndNote><Cite><Author>Caplan</Author><Year>2010</Year><RecNum>64</RecNum><record><rec-number>64</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Caplan, LJ</author><author>Ivins, B</author><author>Poole, JH</author><author>Vanderploeg, RD</author><author>Jaffee, MS</author><author>Schwab, K</author></authors></contributors><titles><title>The Structure of Postconcussive Symptoms in 3 US Military Samples</title><secondary-title>Journal of Head Trauma Rehabilitation</secondary-title></titles><periodical><full-title>Journal of Head Trauma Rehabilitation</full-title></periodical><pages>447-458</pages><volume>25</volume><number>6</number><dates><year>2010</year><pub-dates><date>November/December 2010</date></pub-dates></dates><urls></urls></record></Cite></EndNote>[21].
Depression: Beck Depression Inventory (BDI-II)  ADDIN EN.CITE <EndNote><Cite><Author>Beck</Author><Year>1961</Year><RecNum>2</RecNum><record><rec-number>2</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Beck, A. T.</author><author>Ward, C. H.</author><author>Mendelson, M.</author><author>Mock, J.</author><author>Erbaugh, J.</author></authors></contributors><titles><title>An inventory for measuring depression</title><secondary-title>Arch Gen Psychiatry</secondary-title></titles><periodical><full-title>Arch Gen Psychiatry</full-title></periodical><pages>561-71</pages><volume>4</volume><keywords><keyword>Depression/*psychology</keyword><keyword>*Psychological Tests</keyword></keywords><dates><year>1961</year><pub-dates><date>Jun</date></pub-dates></dates><accession-num>13688369</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=13688369 </url></related-urls></urls></record></Cite></EndNote>[22] The BDI-II is a 21-item depression scale used to measure the severity of depressive symptoms.
Post-traumatic Stress: PTSD Checklist (PCL-S)  ADDIN EN.CITE <EndNote><Cite><Author>Weathers</Author><Year>1993</Year><RecNum>23</RecNum><record><rec-number>23</rec-number><ref-type name="Conference Proceedings">10</ref-type><contributors><authors><author>Weathers, F.W.</author><author>Litz, B.T.</author><author>Herman, D.S.</author><author>Huska, J.A.</author><author>Keane, T.M.</author></authors></contributors><titles><title>The PTSD checklist: reliability, validity, &amp; diagnostic utility.</title><secondary-title>Ninth Annual Meeting of the International Society for Traumatic Stress Studies</secondary-title></titles><dates><year>1993</year></dates><pub-location>San Antonio</pub-location><urls></urls></record></Cite></EndNote>[23]. The PCL-S assesses PTSD symptoms in relation to an identified traumatic event.
Alcohol abuse: Alcohol Use Identification Test-Consumption Questions (AUDIT-C)  ADDIN EN.CITE <EndNote><Cite><Author>Bush</Author><Year>1998</Year><RecNum>24</RecNum><record><rec-number>24</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bush, K.</author><author>Kivlahan, D. R.</author><author>McDonell, M. B.</author><author>Fihn, S. D.</author><author>Bradley, K. A.</author></authors></contributors><auth-address>Health Services Research and Development, the Center of Excellence for Substance Abuse Treatment and Education, VA Puget Sound Health Care System, Seattle Division, Wash 98108, USA.</auth-address><titles><title>The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test</title><secondary-title>Arch Intern Med</secondary-title></titles><periodical><full-title>Arch Intern Med</full-title></periodical><pages>1789-95</pages><volume>158</volume><number>16</number><keywords><keyword>Aged</keyword><keyword>*Alcohol Drinking</keyword><keyword>Alcohol-Related Disorders/*diagnosis</keyword><keyword>Diagnosis, Differential</keyword><keyword>Female</keyword><keyword>Hospitals, Veterans</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Predictive Value of Tests</keyword><keyword>*Questionnaires</keyword><keyword>ROC Curve</keyword><keyword>Reproducibility of Results</keyword></keywords><dates><year>1998</year><pub-dates><date>Sep 14</date></pub-dates></dates><accession-num>9738608</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=9738608 </url></related-urls></urls></record></Cite></EndNote>[24]. The AUDIT-C is a ten-question screening test developed by the World Health Organization to determine if a person's alcohol consumption may be harmful.
Data were also collected from each Veteran�s comprehensive clinical neuropsychological assessment. Neuropsychological measures examined represented major domains of cognitive functioning including: attention and working memory (Digit Span from the Wechsler Adult Intelligence Scale IV [WAIS-IV]) [ ADDIN EN.CITE <EndNote><Cite><Author>Wechsler</Author><Year>2008</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Generic">13</ref-type><contributors><authors><author>Wechsler, D.</author></authors></contributors><titles><title>Wechsler Adult Intelligence Scale�Fourth Edition (WAIS�IV)</title></titles><dates><year>2008</year></dates><pub-location>San Antonio, TX</pub-location><publisher>Pearson Education, Inc</publisher><urls></urls></record></Cite></EndNote>25]; verbal fluency (Letter and Category Fluency from the Delis-Kaplan Executive Function System [D-KEFS]) [ ADDIN EN.CITE <EndNote><Cite><Author>Delis</Author><Year>2001</Year><RecNum>34</RecNum><record><rec-number>34</rec-number><ref-type name="Generic">13</ref-type><contributors><authors><author>Delis, D.C.</author><author>Kaplan, E.</author><author>Kramer, J.H.</author></authors></contributors><titles><title>Delis�Kaplan Executive Function System (D�KEFS)</title></titles><dates><year>2001</year></dates><pub-location>San Antonio, TX</pub-location><publisher>Pearson Education, Inc.</publisher><urls></urls></record></Cite></EndNote>26]; learning and memory (Trials 1-5 Total and Long Delay Free Recall from the California Verbal Learning Test-II [CVLT-II])  ADDIN EN.CITE <EndNote><Cite><Author>Delis</Author><Year>2000</Year><RecNum>31</RecNum><record><rec-number>31</rec-number><ref-type name="Generic">13</ref-type><contributors><authors><author>Delis, D.C.</author><author>Kramer, J.H.</author><author>Kaplan, E.</author><author>Ober, B.A.</author></authors></contributors><titles><title>California Verbal Learning Test � Second Edition (CVLT �II)</title></titles><dates><year>2000</year></dates><pub-location>San Antonio, TX</pub-location><publisher>Pearson Education, Inc</publisher><urls></urls></record></Cite></EndNote>[18] and Logical Memory I and II from the Wechsler Memory Scale IV [WMS-IV])  ADDIN EN.CITE <EndNote><Cite><Author>Wechsler</Author><Year>2009</Year><RecNum>49</RecNum><record><rec-number>49</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author>Wechsler, D.</author></authors></contributors><titles><title>Wechsler Memory Scale � Fourth Edition (WMS-IV)</title></titles><dates><year>2009</year></dates><pub-location>San Antonio, TX</pub-location><publisher>Pearson Education, Inc.</publisher><urls></urls></record></Cite></EndNote>[27]; visuospatial construction (Block Design from the WAIS-IV)  ADDIN EN.CITE <EndNote><Cite><Author>Wechsler</Author><Year>2008</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Generic">13</ref-type><contributors><authors><author>Wechsler, D.</author></authors></contributors><titles><title>Wechsler Adult Intelligence Scale�Fourth Edition (WAIS�IV)</title></titles><dates><year>2008</year></dates><pub-location>San Antonio, TX</pub-location><publisher>Pearson Education, Inc</publisher><urls></urls></record></Cite></EndNote>[25]; motor functioning (Grooved Pegboard from the Halstead-Reitan Neuropsychological Battery)  ADDIN EN.CITE <EndNote><Cite><Author>Reitan</Author><Year>1993</Year><RecNum>48</RecNum><record><rec-number>48</rec-number><ref-type name="Book">6</ref-type><contributors><authors><author>Reitan, R.M.</author><author>Wolfson, D.</author></authors></contributors><titles><title>The Halstead-Reitan Neuropsychological Test Battery: Theory and clinical interpretation</title></titles><edition>2</edition><dates><year>1993</year></dates><pub-location>Tucson, AZ: </pub-location><publisher>Neuropsychology Press</publisher><urls></urls></record></Cite></EndNote>[28]; executive functioning (Trail Making Test, Number-Letter Switching condition and Color-Word Interference Test, Inhibition and Inhibition/Switching conditions, from the D-KEFS)  ADDIN EN.CITE <EndNote><Cite><Author>Delis</Author><Year>2001</Year><RecNum>34</RecNum><record><rec-number>34</rec-number><ref-type name="Generic">13</ref-type><contributors><authors><author>Delis, D.C.</author><author>Kaplan, E.</author><author>Kramer, J.H.</author></authors></contributors><titles><title>Delis�Kaplan Executive Function System (D�KEFS)</title></titles><dates><year>2001</year></dates><pub-location>San Antonio, TX</pub-location><publisher>Pearson Education, Inc.</publisher><urls></urls></record></Cite></EndNote>[26]; and processing speed (Digit Symbol Coding and Symbol Search from the WAIS-IV Processing Speed Index)  ADDIN EN.CITE <EndNote><Cite><Author>Wechsler</Author><Year>2008</Year><RecNum>30</RecNum><record><rec-number>30</rec-number><ref-type name="Generic">13</ref-type><contributors><authors><author>Wechsler, D.</author></authors></contributors><titles><title>Wechsler Adult Intelligence Scale�Fourth Edition (WAIS�IV)</title></titles><dates><year>2008</year></dates><pub-location>San Antonio, TX</pub-location><publisher>Pearson Education, Inc</publisher><urls></urls></record></Cite></EndNote>[25].

Statistical Analyses
Standardized, published normative scores corrected for age, gender, and/or education (where applicable) were used for neuropsychological variables, with higher scores indicating better performance. It should be noted that the data available for each patient varied as a result of the clinical assessment and/or referral question. All data were checked for normality prior to conducting analyses; log transformations were needed for self-reported sleep latency (SL) and total sleep time (TST) as well as measures of injury, including number of TBIs, LOC, and PTA.

Descriptive statistics were evaluated for sample demographic information. Frequency analyses were conducted to detail the pattern of responses to items on the PSQI Component Scales. Bivariate correlations were performed to compare PSQI Global Scores and self-reported measures of SL, TST, and sleep efficiency (SE) with measures of psychiatric and neuropsychological functioning. To examine the unique contribution of psychiatric and post-concussive factors on sleep disruption, a forward stepwise multiple regression analysis was performed utilizing BDI total score, NSI total score, and PCL total score as independent variables and PSQI total score as the dependent variable. We next ran the same analyses removing the sleep-related items from the BDI-II (question #16), NSI (question #18), and PCL (question #13) to adjust for potential bias in the results due to redundancy between the sleep items on these measures. Lastly, to fully explore the relationships in the data, other dependent measures of sleep disturbance (self-reported TST and SL, as well as the calculated SE from the PSQI) were examined using the same analytic approach noted above. Bonferroni corrections were employed to adjust for multiple comparisons.



Results
Veterans in this sample had a mean age of 31.7, a mean education level of 13.3 years, and a median of 2 TBIs, with their most severe injuries having a median LOC of 42 seconds and a median length of PTA of 0 minutes. Most (86%) of the TBIs in the sample were classified as mild and 14% were classified as moderate. Clinical diagnoses based on the comprehensive neuropsychological assessment included Cognitive Disorder, NOS (53%), cognitively normal (43%), and other diagnoses (4%, e.g., learning disorder) as defined by DSM-IV-TR criteria. The sample had moderate levels of self-reported psychiatric symptomatology, including PTSD symptoms, depressive symptoms, and post-concussive symptoms. See Table 1 for details.

Table 1 about here.

Self-Reported Sleep Impairment and TBI History. 100% of Veterans in the sample reported clinically significant sleep disturbance (PSQI global score >5), including SL averaging 50 (+/- 44) minutes, TST averaging 5.5 (+/- 1.3) hours, and SE averaging 77% (+/- 17%). On the PSQI component scales, 42% of Veterans rated sleep latency problems as �severe,� and 35% of Veterans rated sleep duration problems as �severe.�  However, sleep disturbance was the most commonly reported sleep complaint overall, rated as �moderate� or �severe� in severity by 71% of Veterans. Please see Figure 1.

Figure 1 about here.

Global score on the PSQI was not significantly correlated with LOC, PTA, or number of TBIs (all rs < 0.073, all ps >0.410) and there were no significant differences in reported sleep complaints between those with a mild versus moderate TBI (t(135)=.735, p=0.463). Additionally, sleep complaints did not differ significantly between those Veterans diagnosed as cognitively normal versus those diagnosed with Cognitive Disorder NOS and/or Veterans diagnosed with other cognitive conditions (F(15, 121) = 0.661, p= 0.817). 

Self-Reported Sleep Impairment and Symptom Severity. As shown in Table, 2, poorer sleep as measured by the PSQI global score was significantly correlated with greater levels of post-concussive (NSI), mood (BDI-II), and PTSD (PCL symptomatology, but not alcohol use (AUDIT-C). As expected, depressive symptoms were significantly correlated with longer self-reported sleep latencies, less total sleep times, and poorer sleep efficiencies. Total score on the NSI was found to be significantly correlated with less total sleep times and longer self-reported sleep latencies, while PCL total score was score was only found to be significantly correlated with less total sleep time.. Please see Table 2 for details.

Table 2 About Here

Self-Reported Sleep Impairment and Neuropsychological Functioning. Bivariate correlations between the PSQI global score and patient-reported measures of SL, TST, and SE with an array of neuropsychological measures revealed a significant correlation between PSQI global score and performance on Digits Forward and Backward (r= -0.237, p= .007 and r= -0.204, p= 0.020, respectively) and between patient-reported SL and DKEFS Color/Word Inhibition Switching (r= - 0.251, p= 0.006). However, these results failed to retain significance following statistical corrections for multiple comparisons (p < .005).

Relationship between psychiatric, post-concussive sleep disturbance measures: As noted above, we observed highly significant correlations between NSI, BDI-II, and PCL scores with PSQI global score and self-reported measures of TST, SL, and SE. In an attempt to more fully explore these relationships, we performed several stepwise multiple regressions. As the NSI instrument is comprised of items addressing multiple areas of post-concussive functioning, we separated the NSI into cognitive, somatic, and affective factors prior to performing the regression analyses. In the first model, we regressed BDI-II total score, NSI cognitive, somatic, and affective scores, and PCL total score on PSQI global score. In this analysis, only BDI-II total score was significantly associated with PSQI global score (F (1, 74) = 12.78, R2 = .147, B=.384, p= .001), with all other measures excluded from the model (all p�s> .106). In a second model we re-ran the analyses after removing the sleep items from each of the independent measures. Results of these analyses proved similar to those from model 1, as only BDI-II total score was significantly associated with PSQI global score (F (1, 72) = 10.27, R2 = .125, B=.353, p= .002), with all other measures excluded from the model (all p�s> .141). Lastly, we re-ran model 2 using SL, TST, and SE as the dependent variables. In these analyses, none of the predictor variables iwere found to be significantly associated with any of the dependent measures. 

Discussion
This investigation evaluated the prevalence of sleep disturbance and its relationship to psychiatric symptomatology and neuropsychological performance in a large clinically-referred sample of OEF/OIF Veterans with a history of mild to moderate TBI. In this study a high percentage of Veterans with mild to moderate TBI endorsed disrupted sleep at the time of their evaluation. The high prevalence rates of sleep disturbance seen in this study and other published reports provide evidence to suggest that a relationship exists between TBI and seep disturbance in Veterans. Additionally, in this investigation, sleep disturbance was found to be significantly correlated with psychiatric symptomatology, but not with cognitive performance. Overall, variance in global qualitative measures of sleep (i.e., PSQl global score) showed a significant association with depressive symptoms (as opposed to PTSD symptomatology or other post-concussive symptoms), however these relationships were not observed for quantitatively derived measures of sleep (SL, SE, TST).

Our results demonstrate a significant relationship between sleep disturbance and psychiatric disturbance (particularly depressive symptoms). In fact, the etiology of sleep and psychiatric disturbance post�TBI is currently one of the most actively debated issues in the TBI literature. This debate has led to the development of competing hypotheses. Some suggest that TBI is a risk factor for the development of psychiatric symptomatology, and that observed chronic post-concussive symptomatology results from the presence of psychiatric illness (e.g., depression and PTSD). This hypothesis is supported by research that has shown that depression (along with PTSD) is strongly associated with reports of post-concussive symptoms  ADDIN EN.CITE <EndNote><Cite ExcludeYear="1"><Author>Lange</Author><RecNum>285</RecNum><record><rec-number>285</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lange, R. T.</author><author>Brickell, T.</author><author>French, L. M.</author><author>Ivins, B.</author><author>Bhagwat, A.</author><author>Pancholi, S.</author><author>Iverson, G. L.</author></authors></contributors><auth-address>Defense and Veterans Brain Injury Center, North Bethesda, Maryland 20852, USA. rlange@dvbic.org</auth-address><titles><title>Risk factors for postconcussion symptom reporting after traumatic brain injury in U.S. military service members</title><secondary-title>J Neurotrauma</secondary-title></titles><periodical><full-title>J Neurotrauma</full-title></periodical><pages>237-46</pages><volume>30</volume><number>4</number><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Brain Injuries/*complications/*psychology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Military Personnel</keyword><keyword>Neuropsychological Tests</keyword><keyword>Post-Concussion Syndrome/*etiology/*psychology</keyword><keyword>Risk Factors</keyword><keyword>*Self Report</keyword><keyword>Young Adult</keyword></keywords><dates><pub-dates><date>Feb 15</date></pub-dates></dates><accession-num>23126461</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=23126461 </url></related-urls></urls></record></Cite></EndNote>[11] and through work by Hoge et al.  ADDIN EN.CITE <EndNote><Cite><Author>Hoge</Author><Year>2008</Year><RecNum>12</RecNum><record><rec-number>12</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hoge, C. W.</author><author>McGurk, D.</author><author>Thomas, J. L.</author><author>Cox, A. L.</author><author>Engel, C. C.</author><author>Castro, C. A.</author></authors></contributors><auth-address>Division of Psychiatry and Neuroscience, Walter Reed Army Institute of Research, U.S. Army Medical Research and Materiel Command, Silver Spring, MD 20910, USA. charles.hoge@us.army.mil</auth-address><titles><title>Mild traumatic brain injury in U.S. Soldiers returning from Iraq</title><secondary-title>N Engl J Med</secondary-title></titles><periodical><full-title>N Engl J Med</full-title></periodical><pages>453-63</pages><volume>358</volume><number>5</number><keywords><keyword>Adult</keyword><keyword>Blast Injuries/complications</keyword><keyword>Brain Injuries/*complications/*epidemiology/psychology</keyword><keyword>Consciousness Disorders/complications/epidemiology</keyword><keyword>Data Collection</keyword><keyword>Depressive Disorder/complications</keyword><keyword>Female</keyword><keyword>Headache/etiology</keyword><keyword>Health Status</keyword><keyword>Humans</keyword><keyword>*Iraq War, 2003 -</keyword><keyword>Male</keyword><keyword>*Military Personnel</keyword><keyword>Post-Concussion Syndrome/*etiology</keyword><keyword>Prevalence</keyword><keyword>Stress Disorders, Post-Traumatic/*etiology</keyword><keyword>Trauma Severity Indices</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2008</year><pub-dates><date>Jan 31</date></pub-dates></dates><accession-num>18234750</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=18234750 </url></related-urls></urls></record></Cite></EndNote>[12], which found that PTSD and depression fully mediate the relationship between TBI history and most subjective measures of health and psychosocial functioning (except headache pain). Alternatively, other studies have suggested that post-concussive symptoms may actually precede and/or exist independently of psychiatric illness following TBI. For example, after controlling for other psychiatric conditions, Vanderploeg and colleagues  ADDIN EN.CITE <EndNote><Cite><Author>Vanderploeg</Author><Year>2009</Year><RecNum>268</RecNum><record><rec-number>268</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vanderploeg, R. D.</author><author>Belanger, H. G.</author><author>Curtiss, G.</author></authors></contributors><auth-address>Department of Mental Health and Behavioral Sciences and Defense and Veterans Brain Injury Center, James A. Haley Veterans Affairs Medical Center, Tampa, FL 33612, USA. Rodney.Vanderploeg@va.gov</auth-address><titles><title>Mild traumatic brain injury and posttraumatic stress disorder and their associations with health symptoms</title><secondary-title>Arch Phys Med Rehabil</secondary-title></titles><periodical><full-title>Arch Phys Med Rehabil</full-title></periodical><pages>1084-93</pages><volume>90</volume><number>7</number><keywords><keyword>Adult</keyword><keyword>Brain Injuries/complications/*physiopathology</keyword><keyword>Cohort Studies</keyword><keyword>Cross-Sectional Studies</keyword><keyword>*Health Status</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Mental Disorders/complications/physiopathology</keyword><keyword>Post-Concussion Syndrome/physiopathology</keyword><keyword>Prevalence</keyword><keyword>Risk Factors</keyword><keyword>Severity of Illness Index</keyword><keyword>Socioeconomic Factors</keyword><keyword>Stress Disorders, Post-Traumatic/complications/*physiopathology</keyword><keyword>United States</keyword><keyword>*Veterans</keyword></keywords><dates><year>2009</year><pub-dates><date>Jul</date></pub-dates></dates><accession-num>19577020</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=19577020 </url></related-urls></urls></record></Cite></EndNote>[13] found that TBI may still be significantly associated with headaches, sleep problems, and memory difficulties for years after the injury. Furthermore, persistent post-concussive symptoms in Veterans with deployment-related TBI have been shown to mediate the relationship between TBI and psychopathologies such as depression  ADDIN EN.CITE <EndNote><Cite><Author>Macera</Author><Year>2103</Year><RecNum>269</RecNum><record><rec-number>269</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Macera, C. A.</author><author>Aralis, H. J.</author><author>Rauh, M. J.</author><author>MacGregor, A. J.</author></authors></contributors><auth-address>Department of Warfighter Performance, Naval Health Research Center, San Diego, CA 92106-5122, USA. carol.macera@med.navy.mil</auth-address><titles><title>Do sleep problems mediate the relationship between traumatic brain injury and development of mental health symptoms after deployment?</title><secondary-title>Sleep</secondary-title></titles><periodical><full-title>Sleep</full-title></periodical><pages>83-90</pages><volume>36</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Afghan Campaign 2001-</keyword><keyword>Brain Injuries/diagnosis/*epidemiology</keyword><keyword>Causality</keyword><keyword>Combat Disorders/diagnosis/*epidemiology</keyword><keyword>Comorbidity</keyword><keyword>Depressive Disorder/diagnosis/*epidemiology</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Iraq War, 2003 - 2011</keyword><keyword>Kuwait</keyword><keyword>Male</keyword><keyword>Mental Disorders/diagnosis/*epidemiology</keyword><keyword>Military Personnel/*statistics &amp; numerical data</keyword><keyword>Prospective Studies</keyword><keyword>Questionnaires</keyword><keyword>Risk Factors</keyword><keyword>Stress Disorders, Post-Traumatic/diagnosis/*epidemiology</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2103</year><pub-dates><date>Jan</date></pub-dates></dates><accession-num>23288974</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=23288974 </url></related-urls></urls></record></Cite><Cite ExcludeYear="1"><Author>Morissette</Author><RecNum>270</RecNum><record><rec-number>270</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Morissette, S. B.</author><author>Woodward, M.</author><author>Kimbrel, N. A.</author><author>Meyer, E. C.</author><author>Kruse, M. I.</author><author>Dolan, S.</author><author>Gulliver, S. B.</author></authors></contributors><auth-address>Department of Veterans Affairs VISN 17 Center of Excellence for Research on Returning War Veterans, Waco, Texas, USA. sandra.morissette@va.gov</auth-address><titles><title>Deployment-related TBI, persistent postconcussive symptoms, PTSD, and depression in OEF/OIF veterans</title><secondary-title>Rehabil Psychol</secondary-title></titles><periodical><full-title>Rehabil Psychol</full-title></periodical><pages>340-50</pages><volume>56</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>*Afghan Campaign 2001-</keyword><keyword>Brain Concussion/epidemiology/psychology</keyword><keyword>Brain Injuries/epidemiology/*psychology</keyword><keyword>Depressive Disorder/epidemiology/*psychology</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Interview, Psychological</keyword><keyword>*Iraq War, 2003 - 2011</keyword><keyword>Male</keyword><keyword>Military Personnel/*psychology/statistics &amp; numerical data</keyword><keyword>Stress Disorders, Post-Traumatic/epidemiology/*psychology</keyword><keyword>Veterans/*psychology/statistics &amp; numerical data</keyword></keywords><dates><pub-dates><date>Nov</date></pub-dates></dates><accession-num>22121940</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=22121940 </url></related-urls></urls></record></Cite></EndNote>[14, 15]. As well, one recent investigation found sleep disturbance to be an independent and early indicator of risk for depression and/or PTSD  ADDIN EN.CITE <EndNote><Cite><Author>Macera</Author><Year>2103</Year><RecNum>269</RecNum><record><rec-number>269</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Macera, C. A.</author><author>Aralis, H. J.</author><author>Rauh, M. J.</author><author>MacGregor, A. J.</author></authors></contributors><auth-address>Department of Warfighter Performance, Naval Health Research Center, San Diego, CA 92106-5122, USA. carol.macera@med.navy.mil</auth-address><titles><title>Do sleep problems mediate the relationship between traumatic brain injury and development of mental health symptoms after deployment?</title><secondary-title>Sleep</secondary-title></titles><periodical><full-title>Sleep</full-title></periodical><pages>83-90</pages><volume>36</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Afghan Campaign 2001-</keyword><keyword>Brain Injuries/diagnosis/*epidemiology</keyword><keyword>Causality</keyword><keyword>Combat Disorders/diagnosis/*epidemiology</keyword><keyword>Comorbidity</keyword><keyword>Depressive Disorder/diagnosis/*epidemiology</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Iraq War, 2003 - 2011</keyword><keyword>Kuwait</keyword><keyword>Male</keyword><keyword>Mental Disorders/diagnosis/*epidemiology</keyword><keyword>Military Personnel/*statistics &amp; numerical data</keyword><keyword>Prospective Studies</keyword><keyword>Questionnaires</keyword><keyword>Risk Factors</keyword><keyword>Stress Disorders, Post-Traumatic/diagnosis/*epidemiology</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2103</year><pub-dates><date>Jan</date></pub-dates></dates><accession-num>23288974</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=23288974 </url></related-urls></urls></record></Cite></EndNote>[14]. 

Based on the literature, it seems reasonable to assume that multiple causal pathways may relate sleep disturbance to other post-concussive symptoms following TBI. For example, 1) TBI may directly cause problems such as sleep and/or mood disturbance, 2) TBI may exacerbate pre-existing sleep and/or mood disturbance, leading to greater post-injury impairment caused by these factors, and/or 3) TBI may cause post-concussive problems such as sleep disturbance, which if left untreated lead to real/perceived functional impairment, which in turn may result in more severe psychiatric morbidity (e.g., depression) in at-risk individuals. Our cross-sectional study cannot determine causal pathways, but the findings do support the concept that sleep and comorbid psychiatric disturbance are important factors that need to be concurrently addressed in this patient population. Furthermore, our findings suggest that the relationship between sleep and psychiatric measures may depend to a large degree on the questions being asked of patients. For example, our results found that if patients were evaluated on global and/or qualitative aspects of their sleep, the influence of psychiatric (i.e., mood) factors was significant. However, contrary to our expectations, when patients were evaluated on specific and/or quantitative measures of sleep (e.g., SL, TST, SE), the effects of psychopathology appeared to be nonsignificant. Hence, asking patients how �well� they slept appeared to differentially produce a response set associated significantly with psychopathology in a way not observed when asking patients how �much� they slept.

Another important aspect of this investigation was an attempt to evaluate whether sleep problems in Veterans in the post-acute period following TBI were associated with objective cognitive performance. In general, our results failed to find evidence that sleep played a significant role in objective neuropsychological performance. Failure to find evidence of a relationship between sleep disturbance cognitive impairment in this study may have resulted from limitations in the measures used to assess patients as part of the clinical evaluation, which, although useful for clinical diagnoses of cognitive functioning, may not be sufficiently challenging to show altered performance due to sleep disturbance. Alternatively, the lack of association between sleep disturbance and cognitive functioning may be consistent with recent findings, as reports demonstrate that  some sources of sleep disturbances (i.e., insomnia) are not associated with deficits on objective NP assessments  ADDIN EN.CITE <EndNote><Cite><Author>Shekleton</Author><RecNum>38</RecNum><record><rec-number>38</rec-number><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shekleton, J. A.</author><author>Rogers, N. L.</author><author>Rajaratnam, S. M.</author></authors></contributors><auth-address>School of Psychology, Psychiatry and Psychological Medicine, Monash University, Building 17, Clayton Campus, Victoria 3800, Australia.</auth-address><titles><title>Searching for the daytime impairments of primary insomnia</title><secondary-title>Sleep Med Rev</secondary-title></titles><periodical><full-title>Sleep Med Rev</full-title></periodical><pages>47-60</pages><volume>14</volume><number>1</number><keywords><keyword>Attention</keyword><keyword>Brain/metabolism/physiopathology</keyword><keyword>*Circadian Rhythm</keyword><keyword>Disorders of Excessive Somnolence/epidemiology/physiopathology</keyword><keyword>Electroencephalography</keyword><keyword>Humans</keyword><keyword>Memory, Short-Term</keyword><keyword>Psychomotor Performance/physiology</keyword><keyword>Sleep Initiation and Maintenance</keyword><keyword>Disorders/*diagnosis/epidemiology/*physiopathology</keyword><keyword>Time Factors</keyword><keyword>Wakefulness/physiology</keyword></keywords><dates><pub-dates><date>Feb</date></pub-dates></dates><accession-num>19963414</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;dopt=Citation&amp;list_uids=19963414 </url></related-urls></urls></record></Cite></EndNote>[29-30]. 

Despite limitations in the science of TBI and its relationship to sleep and psychiatric and cognitive functioning, ultimately the overarching implications of this report (and other published work) underscore the need for clinical interventions in this patient population. From a clinical perspective, recognition of sleep disturbance as an independent, treatable problem may allow for more rapid intervention with behavioral and/or pharmacological approaches that may reduce patient symptomatology following brain injury. In addition to ameliorating sleep complaints, sleep interventions may also have indirect beneficial effects on many of the other post-concussive psychiatric symptoms, thereby leading to enhanced recovery outcomes. Clinical interventional work with TBI patients may also inform current treatment options (e.g., Cognitive Behavioral Therapy for Insomnia [CBT-I]) within this particular patient population, leading to modifications that might improve treatment effectiveness (e.g., adding CBT-I to other empirically supported interventions as a means of improving treatment outcomes).  

In summary, Veterans with a history of mild to moderate TBI in this investigation had high rates of sleep disruption following their brain injuries. Sleep problems appeared to be most strongly associated with mood disturbance, and to a lesser extent, PTSD, post-concussive symptoms, and cognitive functioning. Potential limitations to these findings include use of an archival clinical data set and the select nature of the clinical sample studied in this investigation. Additionally, our participants did not have objective sleep data. Future studies should aim to correct these limitations by utilizing a more diverse population of TBI patients and incorporating multiple objective measures of sleep (e.g., actigraphy, polysomnograhpy, and sleep diaries), psychological and daytime functioning, and quality of life, as these issues appear to be prominent concerns in this population. As well, implementation of longitudinal studies may help better determine the causal relationships between TBI and sleep disturbance in this patient population. As noted in published comments [31-32] there is a growing appreciation of the high prevalence of sleep problems in this population and a clear need for a better understanding of the ramifications of sleep disturbance on daily functioning and recovery as well as the potential benefits of treating sleep disturbance in these individuals. Therefore, future investigations should consider incorporating sleep interventions with concurrent assessment of the effects of treatment on overall functioning. 
References

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Running head: Sleep Disturbance and Traumatic Brain Injury


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