White matter integrity alterations in post-traumatic stress disorder.
ABSTRACT: Post-traumatic stress disorder (PTSD) is a debilitating condition which can develop after exposure to traumatic stressors. Seventy-five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma-exposed age- and gender-matched controls. Participants underwent clinical assessment and magnetic resonance imaging. A previous voxel based morphometry (VBM) study using the same subject cohort identified decreased grey matter (GM) volumes within frontal/subcortical brain regions including the hippocampus, amygdala, and anterior cingulate cortex (ACC). This study examines the microstructural integrity of white matter (WM) tracts connecting the aforementioned regions/structures. Using diffusion tensor imaging, we investigated the integrity of frontal/subcortical WM tracts between all three subject groups. Trauma exposed subjects with and without PTSD diagnosis were identified to have significant disruption in WM integrity as indexed by decreased fractional anisotropy (FA) in the uncinate fasciculus (UF), cingulum cingulate gyrus (CCG), and corpus callosum (CC), when compared with healthy non-trauma-exposed controls. Significant negative correlations were found between total Clinician Administered PTSD scale (CAPS) lifetime clinical subscores and FA values of PTSD subjects in the right UF, CCG, CC body, and right superior longitudinal fasciculus (SLF). An analysis between UF and SLF FA values and VBM determined rostral ACC GM values found a negative correlation in PTSD subjects. Findings suggest that compromised WM integrity in important tracts connecting limbic structures such as the amygdala to frontal regions including the ACC (i.e., the UF and CCG) may contribute to impairments in threat/fear processing associated with PTSD.
Project description:Almost half of patients with major depressive disorder (MDD) also have clinically meaningful levels of anxiety. Anxious depression is a distinct clinical subtype of MDD, which has poor response to pharmacotherapy; however, the neural mechanisms behind are largely unknown. In the present study, we explored the white matter (WM) integrity traits of anxious depression in first-episode and medication-free (medication-naïve and medication washout) Chinese young adult patients by detecting differences in diffusion tensor imaging (DTI) with the tract-based spatial statistics (TBSS) method.DTI was obtained from 39 first-episode, medication-free anxious depressive patients, 45 nonanxious depressive patients, and 50 demographically similar healthy controls. All subjects underwent clinical assessments. TBSS was carried out to investigate the difference in WM integrity among three groups within DTI parameter maps. WM integrity was measured using fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity (RD). The correlations between WM integrity and clinical features were also computed.When compared with nonanxious patients, lower FA values in anxious depressive patients were found in multiple regions of the brain, mainly involving left uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), and forceps major and minor. Higher RD in forceps major and minor and SLF were also detected. The decreased FA values and increased RD values correlated with both anxiety level and depression level in the pooled depressive group.The anxious depressive patients had more abnormalities in WM integrity at the early phase than the nonanxious group. Alternations in WM integrity in fiber pathways, including SLF, UF, and forceps major and minor, may play a critical role in the neuropathology of anxious depression and might help to identify anxious MDD from nonanxious MDD. Further study with larger sample size, larger age range, and longitudinal design is needed to confer a robust inference to better understand the dynamic neurological change and neuropathology of WM integrity in anxious MDD.
Project description:Most studies of brain white matter (WM) in posttraumatic stress disorder (PTSD) have focused on combat trauma, and often were confounded by neurological and substance dependence comorbidity. This study used tract-based spatial statistics (TBSS) and probabilistic tractography to characterize WM microstructure in a mixed-sex community sample of PTSD patients exposed to diverse and multiple traumas, and in trauma-exposed normal comparison (TENC) subjects.TBSS compared diffusion measures between 20 adults with DSM-IV PTSD and 17 TENC, using a whole-brain voxel-wise approach. Probabilistic tractography using Freesurfer's TRACULA was employed to measure diffusion tensor imaging (DTI) metrics within anatomically defined pathways. DTI metrics were compared between groups and correlated with PTSD symptom severity and trauma load.Controlling for age, sex, and motion, PTSD subjects had significantly reduced fractional anisotropy (FA) in a left frontal lobe cluster compared with TENC, at p < .05, family-wise error corrected. Tractography identified significant group differences in the inferior longitudinal fasciculus (ILF), including lower FA and higher radial diffusivity in PTSD compared with TENC. Within the PTSD group, FA values were not correlated with symptom severity or trauma load. Results remained significant after removing participants using psychotropic medication or those with comorbid major depression.PTSD patients had reduced WM integrity in left hemisphere frontal WM and temporal-occipital WM tracts, compared to trauma-exposed controls. Reduced frontal FA is consistent with compromised top-down attentional control and emotion regulation in PTSD, while reduced ILF FA may be related to sensory processing and gating abnormalities in this disorder.
Project description:<h4>Background</h4>Social anxiety disorder (SAD) is a mental illness with a complex, partially genetic background. Differences in characteristics of white matter (WM) microstructure have been reported in patients with SAD compared to healthy controls. Also, WM characteristics are moderately to highly heritable. Endophenotypes are measurable characteristics on the road from genotype to phenotype, putatively reflective of genetically based disease mechanisms. In search of candidate endophenotypes of SAD we used a unique sample of SAD patients and their family members of two generations to explore microstructure of WM tracts as candidate endophenotypes. We focused on two endophenotype criteria: co-segregation with social anxiety within the families, and heritability.<h4>Methods</h4>Participants (n = 94 from 8 families genetically vulnerable for SAD) took part in the Leiden Family Lab Study on Social Anxiety Disorder (LFLSAD). We employed tract-based spatial statistics to examine structural WM characteristics, being fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD), in three a-priori defined tracts of interest: uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF). Associations with social anxiety symptoms and heritability were estimated.<h4>Results</h4>Increased FA in the left and right SLF co-segregated with symptoms of social anxiety. These findings were coupled with decreased RD and MD. All characteristics of WM microstructure were estimated to be at least moderately heritable.<h4>Conclusion</h4>These findings suggest that alterations in WM microstructure in the SLF could be candidate endophenotypes of SAD, as they co-segregated within families genetically vulnerable for SAD and are heritable. These findings further elucidate the genetic susceptibility to SAD and improve our understanding of the overall etiology.
Project description:<b>Background:</b> Growing evidence suggests that cannabis and alcohol (and especially binge alcohol drinking) use independently alters neural structure and functioning, particularly during sensitive developmental time periods (e.g., emerging adulthood). However, few studies have investigated the effects of same-day use of these two substances. Here, white matter (WM) integrity was investigated in relation to binge alcohol drinking, cannabis, and same-day binge and cannabis co-use in adolescents and emerging adults. <b>Methods:</b> FreeSurfer's TRACULA was used to assess WM in emerging adults (<i>n</i>=75; 16-26 years old). Timeline Followback calculated past month cannabis use, binge episodes, and same-day cannabis and binge drinking co-use. Multiple regressions investigated WM by past month cannabis, binge, and co-use. <b>Results:</b> Results revealed co-use episodes were related to lower fractional anisotropy (FA), an overall measure of neuronal integrity, in three tracts (left inferior longitudinal fasciculus [ILF], <i>p</i>=0.02; right anterior thalamic radiation [ATR], <i>p</i>=0.01; and left cingulum cingulate gyrus [CCG], <i>p</i>=0.01); and lower axial diffusivity in left ILF (<i>p</i>=0.03). Cannabis use was significantly related to greater FA in left ILF (<i>p</i>=0.005), left ATR (<i>p</i>=0.02), right ATR (<i>p</i>=0.05), left CCG (<i>p</i>=0.006), right CCG (<i>p</i>=0.03), and right superior longitudinal fasciculus parietal (<i>p</i>=0.03). Binge episodes related to greater FA in right ATR (<i>p</i>=0.03). <b>Conclusions:</b> These findings suggest that co-use was associated with lower WM integrity across frontolimbic tracts. In addition, greater FA was related to greater cannabis use across several tracts and binge alcohol use in one tract. Co-users also appeared to be more severe substance users. Future research should investigate the potential independent and interactive effects of these substances on pre-clinical and clinical levels.
Project description:Marijuana (MJ) use and post-traumatic stress disorder (PTSD) have both been associated with abnormalities in brain white matter tracts, including the cingulum and the anterior thalamic radiations (ATR), which project from subcortical regions to frontal cortex. Studies have not assessed the integrity of these tracts in patients with comorbid PTSD and MJ use. To examine effects of PTSD and MJ use on brain structure, we performed diffusion tensor imaging scans on seventy-two trauma-exposed participants, categorized into four groups: those with PTSD who used MJ at least weekly (PTSD+MJ; n?=?20), those with PTSD with no regular MJ use (PTSD; n?=?19), trauma-exposed controls without PTSD who used MJ (TEC+MJ; n?=?14) and trauma-exposed controls with no PTSD or MJ use (TEC; n?=?19). White matter integrity was evaluated by calculating fractional anisotropy (FA). Results showed that while FA values in the right ATR and the cingulum differed across groups, there were no significant interactions between PTSD and MJ in any white matter tracts, indicating that MJ exposure neither normalizes nor worsens white matter abnormalities in those with PTSD. Further study is needed to evaluate the impact of MJ use on other neurobiological markers of PTSD.
Project description:Compared to healthy controls, spinal cord injury (SCI) patients demonstrate white matter (WM) abnormalities in the brain. However, little progress has been made in comparing cerebral WM differences between SCI-subgroups. The purpose of this study was to investigate WM microstructure differences between paraplegia and quadriplegia using tract-based spatial statistics (TBSS) and atlas-based analysis methods. Twenty-two SCI patients (11 cervical SCI and 11 thoracic SCI) and 22 age- and sex-matched healthy controls were included in this study. TBSS and atlas-based analyses were performed between SCI and control groups and between SCI-subgroups using multiple diffusion metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Compared to controls, SCI patients had decreased FA and increased MD and RD in the corpus callosum (CC; genu and splenium), superior longitudinal fasciculus (SLF), corona radiata (CR), posterior thalamic radiation (PTR), right cingulum (cingulate gyrus; CCG) and right superior fronto-occipital fasciculus (SFOF). Cervical SCI patients had lower FA and higher RD in the left PTR than thoracic SCI patients. Time since injury had a negative correlation with FA within the right SFOF (<i>r</i> = -0.452, <i>p</i> = 0.046) and a positive association between the FA of left PTR and the American Spinal Injury Association (ASIA) sensory score (<i>r</i> = 0.428, <i>p</i> = 0.047). In conclusion, our study suggests that multiple cerebral WM tracts are damaged in SCI patients, and WM disruption in cervical SCI is worse than thoracic injury level, especially in the PTR region.
Project description:Anhedonia emerges in some people after psychological trauma, reflected by a loss of interest, diminished affect, and detachment. Structural abnormalities in specific neural pathways at the time of trauma may influence the development of these posttraumatic anhedonia (PTA) symptoms. In this prospective study, we determined whether white matter connectivity at around one month post-trauma predicts PTA and other PTSD symptoms at six months post-trauma. Thirty men and women aged 19-62 were recruited from the emergency department of a Level I trauma center. Participants received diffusion tensor imaging at approximately one month post-trauma and clinical assessments at one and six months post-trauma. Probabilistic tractography was used to examine connectivity of select pathways. A replication sample (N?=?57) in an independent, cross-sectional dataset of traumatized women was similarly analyzed. Logistic regression results indicated that, after accounting for early PTSD symptoms (at one month) and other clinical risk factors, the integrity of the uncinate fasciculus (UF) uniquely predicted the presence of PTA at six months post-trauma (Beta?=?-225.6, p?<?.05). Together, these factors contributed to 76% of the variance in PTA. Integrity of the UF also predicted re-experiencing PTSD symptoms at six months post-trauma. These results were supported in our replication analyses. Our findings indicate that the integrity of the UF around 1 month post-trauma affects vulnerability for the development of anhedonic PTSD symptoms as well as re-experiencing symptoms. Connectivity of this amygdala-ventromedial prefrontal pathway appears to be a salient predictor of anhedonia, above and beyond clinical risk factors.
Project description:We examined the relationship among white matter (WM) tract integrity, WM hyperintensities (WMH), lobar gray matter (GM) volumes, and cognition in the cross-sectional Framingham Offspring Study. Six hundred eighty participants (71.7 ± 7.7 years) completed cognitive testing and magnetic resonance imaging. Diffusion tensor imaging probabilistic tractography was used to reconstruct major WM tracts. We computed tract-specific mean fractional anisotropy (FA) and tract-specific WMH ratio. Linear regressions identified relations between tracts and lobar GM volumes. Partial least squares regression examined associations between integrity of combined tracts, lobar GM volumes and cognition, including scores of memory and processing speed. Five tracts were particularly vulnerable to WMH, and tract-specific WMH volumes were inversely associated with tract-specific FA (p values < 0.05). Tract-specific FA related to lobar GM volumes. Memory was associated with lobar GM, while processing speed related to both tract integrity and lobar GM volumes. We conclude that subtle microstructural WM tract degeneration relates to specific lobar GM atrophy. The integrity of associated WM tracts and GM lobes differentially impacts memory and processing speed.
Project description:Although epidemiological studies provide strong support for demographic and environmental risk factors in psychotic disorders, few data examine how these risk factors relate to the putative aberrant neurodevelopment associated with illness. The present study examined how the accumulation of risk factors including low IQ, low parental socioeconomic status (SES), history of adolescent cannabis use and childhood trauma, and high levels of subclinical psychotic-like experiences (PLEs) contributed to aberrant neurodevelopmental outcomes in 112 otherwise healthy adults recruited from the community. Participants were studied with diffusion tensor imaging (DTI), and voxel-wise statistical analysis of fractional anisotropy (FA) using tract-based spatial statistics (TBSS) was used to examine the relation between cumulative risk (CR) for psychosis and white matter (WM) integrity across the whole brain. Analyses revealed that higher CR was significantly associated with lower FA in a cluster in the left superior longitudinal fasciculus (SLF). These results suggest that risk factors previously associated with psychotic disorders are associated with WM integrity even in otherwise healthy adults and may provide insight into how previously identified risk factors contribute to the structural brain abnormalities associated with psychotic illness. Prospective longitudinal studies examining the effect of risk factors on the developmental trajectory of brain WM are warranted.
Project description:Diffusion tensor imaging (DTI) can noninvasively quantify white matter (WM) integrity. Although its application in adult traumatic brain injury (TBI) is common, few studies in children have been reported. The purposes of this study were to examine the alteration of fractional anisotropy (FA) in children with TBI experienced during early childhood and to quantify the association between FA and injury severity.FA was assessed in 9 children with TBI (age = 7.89 +/- 1.00 years; Glasgow Coma Scale [GCS] = 10.11 +/- 4.68) and a control group of 12 children with orthopedic injuries without central nervous system involvement (age = 7.51 +/- 0.95 years). All of the subjects were at minimum 12 months after injury. We examined group differences in a series of predetermined WM regions of interest with t test analysis. We subsequently conducted a voxel-wise comparison with Spearman partial correlation analysis. Correlations between FA and injury severity were also calculated on a voxel-wise basis.FA values were significantly reduced in the TBI group in genu of corpus callosum (CC), posterior limb of internal capsule (PLIC), superior longitudinal fasciculus (SLF), superior fronto-occipital fasciculus (SFO), and centrum semiovale (CS). GCS scores were positively correlated with FA in several WM areas including CC, PLIC, SLF, CS, SFO, and inferior fronto-occipital fasciculus (IFO).This DTI study provides evidence that WM integrity remains abnormal in children with moderate-to-severe TBI experienced during early childhood and that injury severity correlated strongly with FA.