Predictors of New-Onset Depression After Mild Traumatic Brain Injury

Back to table of contents Previous article Next article CLINICAL RESEARCH REPORTSFull AccessPredictors of New-Onset Depression After Mild Traumatic Brain InjuryVani Rao M.D.Melaine Bertrand M.P.H.Paul Rosenberg M.D.Michael Makley M.D.David J. Schretlen Ph.D.Jason Brandt Ph.D.Michelle M. Mielke Ph.D.Vani Rao M.D.Melaine Bertrand M.P.H.Paul Rosenberg M.D.Michael Makley M.D.David J. Schretlen Ph.D.Jason Brandt Ph.D.Michelle M. Mielke Ph.D.Published Online:1 Jan 2010AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail T raumatic brain injury (TBI) is a growing public health problem with an annual incidence of at least 1.4 million 1 ; of those incidents 75% are mild TBI. While 80%–90% of individuals with mild TBI usually make a good recovery, 2 10%–20% continue to have psychosocial problems, predominantly mood disorder. 3 – 6 Depression is quite common after mild TBI with a prevalence of 15.3% 7 and is a risk factor for poor recovery. 8 – 9 Remarkably enough, mild TBI subjects have higher rates of depression, postconcussive syndrome, and poor global outcome than those with more severe TBI. 10 There are only a few studies of clinical correlates of mild TBI and depression. Levin et al. 11 reported that risk factors for developing major depression in mild TBI within 3 months of injury include older age and abnormal computerized tomography (CT) scans, with an odds ratio of 7.8 for the latter. To our knowledge, no other studies have looked at preinjury and injury factors associated with the development of depression after mild TBI. This is an important area of study, as identifying people at risk to develop depression soon after the injury can help initiate treatment early on. We present here the preliminary results from an ongoing 1-year longitudinal study examining risk factors for depression after TBI. The current analysis focuses only on risk factors associated with the development of new-onset depression after mild TBI. Participants and ProceduresMild TBI patients were recruited from the trauma unit of the Johns Hopkins Hospital and the Brain Injury Unit of Kernan Hospital at the University of Maryland. The study was approved and overseen by the Johns Hopkins Institutional Review Board and the Kernan Hospital Medical Executive Committee. All participants gave written informed consent. All participants received two study evaluations within the first 3 months of the TBI. If participants were able to provide written informed consent within the first 2 weeks of trauma, the first evaluation (V0) was done within the first 2 weeks of TBI (assessing pre-TBI functioning) and the second evaluation (V1) was done around the third month of TBI to assess psychiatric problems and psychosocial functioning soon after TBI. However, for subjects who were unable to give consent within the first 2 weeks of trauma or unable to be contacted, both the pre-TBI (V0) and post-TBI (V1) status were assessed at the time they were contacted and able to provide informed consent, in either the second or third month posttrauma. Follow-up visits were done at 6 and 12 months posttrauma.Inclusion criteria included (a) first-time closed head injury; (b) clear history of altered mental status or Glasgow Coma Scale (GCS) score less than 15 soon after injury as assessed by the trauma staff or emergency room personnel; (c) admission to the inpatient trauma units for assessment of brain injury; (d) ability to provide consent; and (e) age at least 18 years old.Exclusion criteria included (a) prior TBI; (b) an open-head injury (e.g., a displaced skull fracture or a gun-shot wound); or (c) history of any other type of brain illness (e.g., stroke, seizure, encephalitis).As the focus of the analysis is to examine risk factors for new-onset depression after mild TBI, only patients with loss of consciousness less than 30 minutes and no past psychiatric history of mood disorder were included. The results presented here are preliminary and part of an ongoing study on risk factors for depression after TBI of all severities.MeasuresPsychiatric DiagnosisAll participants were interviewed with the Structured Clinical Interview for DSM-IV axis I disorders (SCID-IV). The SCID-IV was administered by a neuropsychiatrist (VR) at each visit. Patients were diagnosed with depression if they met the criteria for mood disorder secondary to general medical condition (TBI), major depressive-like episode, or other depressive symptoms.Clinical VariablesDemographic information was collected via interviews and review of medical records. Psychosocial functioning was also established using a semistructured interview using the Social Functioning Examination scale and the Social Ties Check List. Scores range from 0.00 to 1.00, with higher values indicating poorer levels of satisfaction. The Family Health Screen was used to collect lifetime psychiatric history of family members. Medical comorbidity was assessed using the General Medical Health Rating scale, a 4-item Likert scale with 4 indicating excellent health and 1 indicating poor health. In addition, the presence of nonhead injuries was captured as presence or absence of body injuries.Lesion LocationAssessment of lesion location was obtained via CT scans conducted as part of the clinical workup. The CT scans were done soon after injury. For the purpose of this analysis, results were characterized as presence or absence of contusion, intracerebral bleed, subarachnoid hemorrhage, epidural bleed, and subdural bleed in different brain regions grouped as frontal, temporal, parietal, occipital subcortical, and/or cerebellar sites.Cognitive TestsThe test battery included Mini-Mental State Examination (MMSE); National Adult Reading Test; verbal fluency (letters "s" and "p") and category (animals and supermarket); Hopkins Verbal Learning Test—Revised; Brief Visuospatial Memory Test—Revised; Trail Making test; Stroop Color and Word Test; Brief Test of Attention, and the Wisconsin Card Sorting Test.Statistical MethodsResults were analyzed used a nested case-control design. Cases were patients who were diagnosed with mood disorder due to general medical condition (TBI), major depressive-like episode, or other depressive-symptoms at any time over the follow-up (n=8), while comparison subjects had no depression diagnosis at any time (n=35). None of the cases had a pre-TBI lifetime history of major depression, minor depression, or any other depressive disorder. As there was little difference in results from parametric versus nonparametric tests, parametric tests were chosen. To compare dichotomous diagnostic groups, unpaired t tests were used for continuous variables and Fisher's exact test for dichotomous variables. The significance level was set a priori at p<0.05. After identifying group differences, logistic regression was used to examine the odds ratio of having a major depression diagnosis for variables that were statistically significant (p=0.05).RESULTSForty-three participants who completed at least one follow-up examination during the 1-year follow-up period were included in the present analysis. The mean age of the sample was 44.5 years old (SD=17.5) and mean education level was 12.9 years (SD=2.9). Fifty-four percent were males (n=23) and 56% were non-Caucasians (n=24). The majority (93%, n=40) lived with family/friends, were either married or had a partner (74%, n=32) and had a full time/part-time job (72%, n=31). Fifty-eight percent had an annual income of 20K or greater (n=25). Motor vehicle accidents were the most common cause (45%, n=20) of TBI, and falls and assaults each accounted for 25% (n=11).Incidence and Persistence of Post-TBI DepressionEight of the 43 participants (18.6%) met the diagnostic criterion for mood disorder due to general medical condition (mild TBI) during the first year of trauma. Of these, six participants (75%) met the diagnostic criterion for mood disorder due to general medical condition, major depressive-like episode, and two participants (25%) met criteria for mood disorder due to general medical condition, other depressive symptoms. Of these eight participants who had depression, seven were diagnosed at the first follow-up visit (V1, i.e., 2–3 months after trauma), and one was diagnosed for the first time at the 12 month visit (V12). Of the seven, three were still depressed at the 12 month visit (V12), two were lost to follow-up, one had resolution of depression by the end of 12 months, and the other had not yet completed 1 year. Comparison of Depressed to Nondepressed Mild TBI Participants ( Table 1 ) The total sample was divided into two groups: those diagnosed with mood disorder due to general medical condition (depressed) at any time over the follow-up and those without (nondepressed). The only significant differences were the greater age and presence of frontal subdural hemorrhage in the depressed group. Lesion laterality could not be analyzed secondary to the small numbers. TABLE 1. Comparison of Depressed to Nondepressed on Demographic, Pre-TBI Clinical Variables, and Injury-Related FactorsTABLE 1. Comparison of Depressed to Nondepressed on Demographic, Pre-TBI Clinical Variables, and Injury-Related FactorsEnlarge tableThe two groups also did not differ on the cognitive tests at any of the follow-up periods. There were no differences in demographic or clinical variables between subjects with minor depression (n=2) and major depression (n=6).DISCUSSION Incident depression was found in 18% of patients up to a year after mild TBI. This rate is consistent with Rapoport et al. 7 who found a prevalence of 15% in the first 3 months after a mild TBI. On analysis of demographic variables, most preinjury clinical factors did not differ between depressed and nondepressed participants. The only significant differences were increased age and the presence of frontal subdural lesions in the depressed group. These findings are similar to the study by Levin et al. 11 who found increased age and presence of an abnormal CT scan done soon after mild TBI to predict the development of depression within the first 3 months after a TBI. The relationship between advanced age and the development of depression after mild TBI is controversial. While our findings support the findings of Levin et al., 11 Rapoport et al. 12 have found that older mild TBI patients are not at increased risk of developing depression in the immediate trauma period. Our study had longer duration of follow-up (1 year) and included participants with minor as well as major depression, which may be an equally important contributor to morbidity. 13 Jorge et al. 14 , 15 reported in two studies that major depression post-TBI is associated with left frontal abnormality. Our finding of the positive association between mild TBI depression and frontal subdural hemorrhages supports this association of lesion location with post-TBI depression and extends the results specifically to mild TBI. Strengths of our study include longitudinal design and use of well-validated psychiatric diagnostic and clinical measures. Limitations include the small sample size, which may have limited identifying other correlates of mild TBI depression, and the absence of more sensitive neuroimaging scans. It is also possible that some patients may have had preexisting microvascular ischemic lesions and executive functioning deficits that may have been misdiagnosed as minor depression. Another limitation is that assessment of pre-TBI status (V0) was done in the first 2 weeks of trauma in only those who could be contacted and/or who provided informed consent within the first 2 weeks of trauma. The rest had their pre-TBI status assessment at 2–3 months post trauma, which could be subject to recall bias.CONCLUSIONAs mild TBI is a growing public health concern and depression after mild TBI a common cause of morbidity, it is important to identify predictors so that treatment interventions can be instituted early on. The results of this study, though preliminary, suggest that there are at least two robust factors (age and frontal subdural lesions) of several possible predictive factors that are associated with mild TBI depression. Emergency room physicians and trauma clinicians can use these results to identify high-risk mild TBI patients and make appropriate referrals.Received June 7, 2008; revised September 2 and November 19, 2008; accepted December 9, 2008. Drs. Rao, Bertrand, Rosenberg, and Mielke are affiliated with the Division of Geriatric Psychiatry & Neuropsychiatry, Department of Psychiatry, at Johns Hopkins School of Medicine in Baltimore, Md.; Dr. Makley is affiliated with the Department of Neurology at the University of Maryland in Baltimore; Dr. Schretlen is affiliated with the Division of Medical Psychology, Department of Psychiatry, at Johns Hopkins School of Medicine in Baltimore; Dr. Brandt is affiliated with the Division of Medical Psychology, Department of Psychiatry & Department of Neurology, at Johns Hopkins School of Medicine in Baltimore. Address correspondence to Vani Rao, M.D., Division of Geriatric Psychiatry & Neuropsychiatry, Department of Psychiatry, Johns Hopkins University, 5300 Alpha Commons Dr., 4th Floor, # 444, Baltimore, MD 21224; [email protected] (e-mail).Copyright © 2010 American Psychiatric Publishing, Inc.References1. Langlois JA, Rutland-Brown W, Thomas KE: Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations, and Deaths. Atlanta, Ga, Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2006Google Scholar2. Ruff R: Two decades of advances in understanding of mild traumatic brain injury. J Head Trauma Rehabil 2005; 20:5–18Google Scholar3. Emanuelson I, Holmkvist A, Bjorklund R, et al: Quality of life and postconcussion symptoms in adults after mild traumatic brain injury: a population-based study in western Sweden. Acta Neurologica Scandinavica 2003; 108:332–338Google Scholar4. Wood RL: Understanding the "miserable minority": a diathesis-stress paradigm for postconcussional syndrome. Brain Inj 2004; 18:1135–1153Google Scholar5. Carroll L, Cassidy JD, Holm L, et al: Methodological issues and research recommendations for mild traumatic brain injury: WHO Collaborating Centre Task Force on Mild Traumatic Brain Injury. J Rehabil Med 2004; (suppl 43):S113–S125Google Scholar6. Bazarian J, McClung J, Shah M, et al: Mild traumatic brain injury in the US, 1998–2000. Brain Inj 2005; 19:85–91Google Scholar7. Rapoport MJ, McCullagh S, Streiner D, et al: The clinical significance of major depression following mild traumatic brain injury. Psychosomatics 2003; 44:31–37Google Scholar8. Mooney G, Speed J: The association between mild traumatic brain injury and psychiatric conditions. Brain Inj 2001; 15:865–877Google Scholar9. Guskiewicz KM, Marshall SW, Bailes J, et al: Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc 2007; 39:903–909Google Scholar10. Alexander MP: Neuropsychiatric correlates of persistent postconcussive syndrome. J Head Trauma Rehabil 1992; 7:60–69Google Scholar11. Levin HS, McCauley SR, Josic CP, et al: Predicting depression following mild traumatic brain injury. Arch Gen Psychiatry 2005; 62:523–528Google Scholar12. Rapoport MJ, McCullagh S, Streiner D, et al: Age and major depression after mild traumatic brain injury. Am J Geriatr Psychiatry 2003; 11:365–369Google Scholar13. Beekman AT, Deeg DJ, Braam AW, et al: Consequences of major and minor depression in later life: a study of disability, well-being, and service utilization. Psychol Med 1997; 27:1397–1409Google Scholar14. Jorge RE, Robinson RG, Arndt SV, et al: Depression following traumatic brain injury: a 1 year longitudinal study. J Affect Disord 1993; 27:233–243Google Scholar15. Jorge RE, Robinson RG, Moser D, et al: Major depression following traumatic brain injury. Arch Gen Psychiatry 2004; 61:42–50Google Scholar FiguresReferencesCited byDetailsCited byLongitudinal Trajectories of Post-Concussive Symptoms Following Mild Traumatic Brain Injury5 February 2023 | Brain InjurySynergistic effect of mild traumatic brain injury and alcohol aggravates neuroinflammation, amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations: Impact on psychological stressExperimental Neurology, Vol. 358Prevalence and Correlates of Depressive Symptoms Within 6 Months After First-Time Mild Traumatic Brain InjuryDurga Roy, M.D., M.S., Anjik Ghosh, B.S., Haijuan Yan, Ph.D., M.H.S., Jeannie-Marie Leoutsakos, Ph.D., Vani Rao, M.D., Matthew E. Peters, M.D., Timothy E. Van Meter, Ph.D., Haris Sair, M.D., Hayley Falk, Sc.M., Frederick K. Korley, M.D., Ph.D., Kathleen T. Bechtold, Ph.D.21 March 2022 | The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 34, No. 4Traumatic Brain Injury and Risk of Alzheimer's Disease and Related Dementias in the PopulationJournal of Alzheimer's Disease, Vol. 88, No. 3Depression in patients with traumatic brain injury - Prevalence and association with cognitive and physical function1 April 2019 | Current Psychology, Vol. 40, No. 6Diffusion tensor imaging findings and neuropsychological performance in adults with TBI across the spectrum of severity in the chronic-phase17 February 2021 | Brain Injury, Vol. 35, No. 5A Role for the Amygdala in Impairments of Affective Behaviors Following Mild Traumatic Brain Injury4 March 2021 | Frontiers in Behavioral Neuroscience, Vol. 15Increase in Seizure Susceptibility After Repetitive Concussion Results from Oxidative Stress, Parvalbumin-Positive Interneuron Dysfunction and Biphasic Increases in Glutamate/GABA Ratio17 July 2020 | Cerebral Cortex, Vol. 30, No. 12Neuroimaging and Psychometric Assessment of Mild Cognitive Impairment After Traumatic Brain Injury7 July 2020 | Frontiers in Psychology, Vol. 11Characterizing the Risk of Depression Following Mild Traumatic Brain Injury: A Meta-Analysis of the Literature Comparing Chronic mTBI to Non-mTBI Populations19 May 2020 | Frontiers in Neurology, Vol. 11Prevalence of depression after moderate to severe traumatic brain injury among adolescents and young adults: A systematic review26 November 2019 | Scandinavian Journal of Psychology, Vol. 61, No. 2PLOS ONE, Vol. 14, No. 9Depression and anxiety across the first 4 years after mild traumatic brain injury: findings from a community-based study29 October 2018 | Brain Injury, Vol. 32, No. 13-14Epidemiology and Natural History of Psychiatric Disorders After TBIJennie Ponsford, M.A. (Clin Neuropsych), Ph.D., Yvette Alway, B.Psych. (Hons), D.Psych. (Clinical Psychology), Kate Rachel Gould, BBNSc (Hons), D.Psych. (Clinical Neuropsychology)25 June 2018 | The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 30, No. 4Journal of Clinical Nursing, Vol. 27, No. 7-8Journal for Specialists in Pediatric Nursing, Vol. 23, No. 2Neural Regeneration Research, Vol. 13, No. 10Prevention Strategies in Post-TBI Depression in Older AdultsProfessional Case Management, Vol. 22, No. 6Caring for Patients with traumatic brain injury: a survey of nurses' perceptions20 March 2017 | Journal of Clinical Nursing, Vol. 26, No. 11-12Brain Injury, Vol. 31, No. 5Brain Injury, Vol. 31, No. 5Sleep, Vol. 40, No. 6Annals of Rehabilitation Medicine, Vol. 41, No. 2Nurses' Beliefs About Caring for Patients With Traumatic Brain Injury9 July 2016 | Western Journal of Nursing Research, Vol. 38, No. 9A Practical Concussion Physical Examination Toolbox28 March 2016 | Sports Health: A Multidisciplinary Approach, Vol. 8, No. 3Quality of Life Research, Vol. 25, No. 8European Journal of Radiology, Vol. 85, No. 1Psychological Medicine, Vol. 46, No. 6Health Care for Women International, Vol. 37, No. 1Neuropsychiatric and Psychiatric Symptoms after Traumatic Brain Injury9 February 2015Behavioural Brain Research, Vol. 279Behavioural Brain Research, Vol. 279Brain Injury, Vol. 29, No. 7-8Preinjury Coping, Emotional Functioning, and Quality of Life Following Uncomplicated and Complicated Mild Traumatic Brain InjuryJournal of Head Trauma Rehabilitation, Vol. 29, No. 5Neuroscience & Biobehavioral Reviews, Vol. 47Journal of Neurochemistry, Vol. 129, No. 6Brain Injury, Vol. 28, No. 1International Journal of Molecular Sciences, Vol. 16, No. 1Diffusion Tensor Imaging Atlas-Based Analyses in Major Depression After Mild Traumatic Brain InjuryVani Rao, M.D., Michelle Mielke, Ph.D., Xin Xu, M.S., Gwenn S. Smith, Ph.D., Una D. McCann, M.D., Alyssa Bergey, M.S., Vishal Doshi, M.D., Dzung L. Pham, Ph.D., David Yousem, M.D., M.B.A., and Susumi Mori, Ph.D.1 July 2012 | The Journal of Neuropsychiatry and Clinical Neurosciences, Vol. 24, No. 3Journal of Affective Disorders, Vol. 138, No. 1-2Current Problems in Pediatric and Adolescent Health Care, Vol. 40, No. 7 Volume 22Issue 1 Winter, 2010Pages 100-104 Metrics PDF download History Published online 1 January 2010 Published in print 1 January 2010