تاثیر افسردگی بر روی جانبازان مبتلا به اختلال استرس پس از حادثه و آسیب تروماتیک مغز: یک مطالعه تصویربرداری تانسور دیفیوژن

A significant proportion of military personnel deployed in support of Operation Enduring Freedom and Operation Iraqi Freedom were exposed to war-zone events associated with traumatic brain injury (TBI), depression (DEP) and posttraumatic stress disorder (PTSD). The co-occurrence of TBI, PTSD and DEP in returning Veterans has recently increased research and clinical interest. This study tested the hypothesis that white matter abnormalities are further impacted by depression. Of particular relevance is the uncinate fasciculus (UF), which is a key fronto-temporal tract involved in mood regulation, and the cingulum; a tract that connects to the hippocampus involved in memory integration. Diffusion tensor imaging (DTI) was performed on 25 patients with a combination of PTSD, TBI and DEP and 20 patients with PTSD and TBI (no DEP). Microstructural changes of white matter were found in the cingulum and UF. Fractional anisotropy (FA) was lower in Veterans with DEP compared to those without DEP.

Returning Veterans from Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) have high rates of psychiatric illness (Tanielian & Jaycox, 2008). Combat elevates the risk of both physical and psychological injuries (Hoge et al., 2004). Compared to civilians, Veterans have a higher incidence of co-morbid posttraumatic stress disorder (PTSD) (Richardson et al., 2010 and Sutker and Allain, 1996) and depression (DEP) (Bombardier et al., 2010 and Brown et al., 2000), present with more anger and hostility and have higher rates of completed suicides (Zivin et al., 2007). Evidence indicates military-related, delayed-onset (>6 months) PTSD is associated with higher chronicity, poorer prognosis, and resistance to treatments (Brewin et al., 2012 and Horesh et al., 2013). Traumatic brain injury (TBI) is also a contributing factor. Rates of psychiatric disturbance following TBI are higher in military personnel than in the general population. This risk remains elevated for several decades (Ashman et al., 2004 and Benotsch et al., 2000). The co-occurrence of TBI, PTSD and DEP in returning Veterans has fueled both clinical concern and research interest. A better understanding of the unique and shared effects of these conditions could guide clinical best practices. For example, despite advances in our understanding of emotion (Gross, 2008, Gross, 2013, Joormann and Gotlib, 2010 and Runnals et al., 2013) little is known about the effects of war-related illnesses on emotion regulation. Research on Veteran psychiatric illness is grossly underrepresented compared to civilians, especially in the neuroimaging literature. We propose that studying DEP, PTSD, and TBI in Veterans presents a unique opportunity to learn how combat-specific psychiatric illness is distinct from civilian cases (Runnals et al., 2013). The neurological interaction between PTSD, DEP and TBI remains largely unknown. No empirical work exists that comprehensively evaluates the unique or shared brain impairments associated with combat-related DEP-PTSD-TBI. Our research here aimed to study the neurological profile of these co-morbid illnesses in Veterans. We used diffusion tensor imaging (DTI), neuropsychological data, behavioral assessments, and medical history to assess the unique effect of DEP in Veterans also diagnosed with PTSD and TBI. We specifically asked: Does depression have an added impact on neuroanatomical integrity beyond that caused by PTSD and TBI? 1.1. Depression and DTI Structural and functional neuroimaging studies in humans have identified an emotional brain network. They have also contributed greatly to an understanding of emotion regulatory mechanisms. Broadly defined, emotion dysregulation is high sensitivity to emotional stimuli, high emotional intensity, and a slow return of arousal to baseline. This heightened state may be driven by cognitive processes of negative appraisal or selective attention to negative environmental cues. Emotional dysregulation is a common denominator in psychiatric illnesses like mood and anxiety disorder. Patient studies addressing the interaction between cognition and emotion agree that DEP impairs emotion regulation (Demeyer and De Raedt, 2013 and Kircanski et al., 2012). Magnetic resonance imaging (MRI) studies support this as well. Researchers studying DEP have found a number of brain regions implicated in mood regulation, including prefrontal areas, limbic structures, and subcortical gray matter (Canli et al., 2004, Drevets et al., 1997 and Hamilton et al., 2013). Reduced cortical volumes, for example, have been documented in regions such as the anterior cingulate (Schecklmann et al., 2011), orbitofrontal (Bremner et al., 2002), anterior insular (Horn et al., 2010), and prefrontal (Schecklmann et al., 2011) cortices of patients with depression. A developing MRI technique, diffusion tensor imaging (DTI), will likely advance these findings. DTI capitalizes on physical properties inherent in the diffusion of water molecules to assess the location, directionality, and integrity of brain white matter pathways (Assaf & Pasternak, 2008). DTI provides measures of white matter microstructure and can potentially differentiate healthy and diseased brains. One such metric is fractional anisotropy (FA). FA values quantify the direction of water's diffusion in white matter fascicles. High FA values indicate directional diffusion through structurally intact fibers. Low FA values below a certain threshold from healthy controls signals areas of clinical concern, locations where myelin and other cellular architecture have been disturbed due to shearing or degeneration. FA then serves as a potential neurocorrelate for cognitive impairment and psychological trauma. DTI is ideally suited to evaluate the health of brain tracts and certain pathways play an important role in the pathogenesis of DEP. Specifically, loss of integrity in key cortical–subcortical tracts can lead to a “disconnection syndrome”, where communication between cortical and subcortical regions is disrupted. Data from TBI patients, for example, indicates that frontal axonal injuries predispose them to emotional disinhibition and impulsive aggression (Bigler, 2008). Using voxel or region-based analyses, several DTI studies have revealed frontal and temporal white matter abnormalities in both DEP and PTSD patients (Nobuhara et al., 2006, Shimony et al., 2009 and Wu et al., 2011). For example, lower FA has been reported in frontal, temporal, and parietal regions of first-episode, young adults with DEP (Ma et al., 2007). Such white matter abnormalities may be potential biomarkers of DEP pathology especially those fiber structures that are pertinent to emotion regulatory systems such as the uncinate fasciculus and the cingulum (Liao et al., 2012). Previous findings have implicated both the uncinate fasciculus and the cingulum in depression neuropathology (Zhang et al., 2008, Zhang et al., 2010a and Zhang et al., 2010b) given that both of these tracts are considered part of the limbic system and are thought to be involved in emotion processing, attention, and memory. White matter loss in the left uncinate fasciculus appears to be associated with early onset depression opposed to mid-and late-onset depression (Taylor, MacFall, Gerig, & Krishnan, 2007). Thus, a detailed examination of these tracts will likely augment our understanding of depression.

Neuropsychological results revealed that group differences existed only on the digit span-backward (p = .05) and digit span-sequencing (p = .046) tasks, used to measure attention and working memory capacity. The group with depression scored significantly lower on both tasks (DSB: M = 4.6, SD = 1.8; DSS: M = 5.1, SD = 1.6) than the group without depression (DSB: M = 5.8, SD = 1.9; DSS: M = 6.2, SD = 1.3) suggesting that the additive impact of depression impairs attention and working memory. Note that while a statistically significant difference emerged on this measure of attention and working memory, further work is required to assert clinical significance. No other group differences were found on measures of neuropsychological function (all p values >.05). Group differences were not observed on measures of learning and memory (low average; Index score range = 82–87), and estimated verbal intelligence (average; Index score range = 92–107). Participants were all fully oriented to time and place as measured by the orientation subtest of the Mini Mental State Exam (MMSE = 99.6% for both groups). No subjects were excluded on the basis of cognitive effort, see Table 1.