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  • Addiction, Drugs
  • Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation

    540—Mood Disorders: Human Biomarkers and Treatment Studies

    Tuesday, November 12, 2013, 8:00 am - 12:00 noon

    540.09: The Additive Impact of Clinical Depression on white matter abnormalities in veterans with Co-morbid PTSD &Traumatic Brain Injury: A diffusion tensor imaging study

    Location: Halls B-H

    ">L. ISAAC1,2, K. MAIN1,2, S. SOMAN1, J. KONG1, I. H. GOTLIB2, A. J. FURST1, J. W. ASHFORD1,2,3, *P. J. BAYLEY1,2,3, M. M. ADAMSON1,2,3;
    1War Related Illness and Injury Study Ctr., VA Palo Alto Hlth. Care Syst., Palo Alto, CA; 2Stanford Univ., Stanford, CA; 3Stanford/Va Aging Clin. Res. Ctr., Palo Alto, CA

    Abstract Body: A significant proportion of military personnel deployed in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) have been exposed to war-zone events that are potentially associated with traumatic brain injury (TBI), major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). The co-occurrence of TBI, PTSD, and MDD in returning veterans and the symptom overlap among the three disorders has fueled both research and clinical interest in elucidating the unique and shared effects of such injuries. The purpose of this study was to test the hypothesis that white matter abnormalities are present in association fibers of the uncinate fasciculus (UF), a key fronto-temporal tract involved in mood regulation, and cingulum bundle (CB), a tract that connects to the hippocampus and is involved in memory integration to other parts of the brain. Both the UF and CB tracts, considered part of the limbic system, are posited to be involved in emotion processing, attention, and memory, all of which have been implicated in depression. We performed diffusion tensor imaging on 25 patients with a combination of PTSD, TBI and MDD and 20 patients with PTSD and TBI without MDD matched on age (M = 44.65, SD = 12.0), gender distribution (88% male), education (M = 13.96 , SD = 2.28), and deployment duration in years (M = 7.9, SD = 3.5). We measured the impact of clinical depression on white matter integrity by comparing these two patient groups, who were differentiated only with respect to the presence or absence of MDD. A hierarchical logistic regression model comparing fractional anisotropy (FA) values revealed that after controlling for age, the model correctly classified and distinguished 86.2% of patients who had PTSD, TBI and MDD from the patient group with PTSD and TBI alone. However, the model was able to correctly classify only 61.3% of the patients who had only PTSD and TBI. The regression coefficients indicated that both the right CB (β = 21.04, p = .05) and the left UF (β = 32.05, p = .045) were significant predictors of group assignment. Both the left UF and the right CB had significantly lower FA values in the group with MDD. Our findings provide new evidence of microstructural changes in white matter in Veterans with clinical depression. These results complement those obtained in previous work on depression and support the hypothesis that the disruption of cortical-subcortical circuit integrity is involved in the etiology of MDD. Thus, a detailed examination of the tracts that connect these regions has implications for the management, treatment, and pathophysiology of these commonly observed co-morbidities in the veteran population.

    Lay Language Summary: (Control Number: 10238)
    We found two white matter fiber tracts in the brain that showed more signs of pathology in Veterans with Major Depressive Disorder (MDD) suggesting that clinical depression is associated with compromised connections in the brain above and beyond Post-traumatic Stress Disorder (PTSD) and Traumatic Brain Injury (TBI). Current treatment interventions for Veterans returning from recent and previous conflicts only target PTSD and may be TBI. We show that both psychological conditions are deserving of early clinical attention and treatment opposed to an emphasis on only one condition which is often PTSD. Based on this knowledge, our bench-to-bed-side translational approach is the first to highlight a need to address both psychological conditions to adequately inform clinical research and practice.
    This study examined how MDD impacts the white matter fibers in the brain in Veterans with additional diagnoses of PTSD and TBI. We employed a sophisticated brain imaging technique, Diffusion Tensor Imaging (DTI), to map the diffusion process of water molecules in biological tissues. DTI has become one of the most popular techniques in brain research, as well as in clinical practice because it allows researchers to look at water molecule diffusion or flow patterns which can reveal details about the integrity of brain tissue. The integrity of white matter is especially important as a range of psychiatric and nervous system disorders are accompanied by abnormalities in white matter structure. MDD reduced two association fibers in the brain; one known as the uncinate facisculus involved in controlling emotions and mood and the other known as the cingulum bundle which is involved in memory. We can now visualize how the various regions of the brain are wired together or connected. To this end, we employed DTI to map the diffusion process of water molecules in the brain.
    A significant number of military personnel deployed in support of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) have been exposed to war-zone events potentially associated with traumatic brain injury, MDD and PTSD. The co-occurrence of TBI, PTSD and MDD in returning Veterans and the symptom overlap between the three disorders has fueled both research and clinical interest to better understand how these disorders are alike and how they are different. Our findings confirm what is known about changes in how the depressed brain is connected using DTI. However this is the first study to show these effects. Moreover, this is the first study to illustrate that depression has a detectible impact on the brain above and beyond what is seen in PTSD and TBI. Here, we have provided a first look into how Veterans are impacted by a combination of MDD, TBI and PTSD.
    Participants included 25 Veteran patients with a combination of PTSD, TBI and MDD and 20 Veteran patients with PTSD and TBI without MDD matched for age (mean = 44, SD = 12.0), gender distribution (88% male), education (mean = 13.96, SD = 2.28) and length of deployment in years (mean = 7.9, SD = 3.5). Participants represented a range of combat missions (OIF = 17, OEF = 7, Gulf War = 9, Vietnam = 7, Operation New Dawn = 4, and Korea = 1).
    The interruption of connections in the brain may be implicated in MDD. An examination of these brain tracts can increase our understanding of why people with depression experience certain symptoms such as sad mood, and how to better manage and treat these symptoms. Such knowledge argues for a broader conceptualization of the response to combat-related traumatic events.