Elbert Geuze | University Medical Center Utrecht ,The Netherlands (original) (raw)
Papers by Elbert Geuze
Psychological Medicine, 2021
BackgroundPost-traumatic stress disorder (PTSD), anxiety, and impulsive aggression are linked to ... more BackgroundPost-traumatic stress disorder (PTSD), anxiety, and impulsive aggression are linked to transdiagnostic neurocognitive deficits. This includes impaired inhibitory control over inappropriate responses. Prior studies showed that inhibitory control can be improved by modulating the right inferior frontal gyrus (IFG) with transcranial direct current stimulation (tDCS) in combination with inhibitory control training. However, its clinical potential remains unclear. We therefore aimed to replicate a tDCS-enhanced inhibitory control training in a clinical sample and test whether this reduces stress-related mental health symptoms.MethodsIn a preregistered double-blind randomized-controlled trial, 100 active-duty military personnel and post-active veterans with PTSD, anxiety, or impulsive aggression symptoms underwent a 5-session intervention where a stop-signal response inhibition training was combined with anodal tDCS over the right IFG for 20 min at 1.25 mA. Inhibitory control wa...
BMC Psychiatry, 2021
Background Noninvasive brain stimulation techniques like transcranial direct current stimulation ... more Background Noninvasive brain stimulation techniques like transcranial direct current stimulation (tDCS) offer potential new approaches to treat stress-related mental health disorders. While the acceptability of tDCS as a treatment tool plays a crucial role in its development and implementation, little is known about tDCS acceptability for users in mental healthcare, especially in the context of stress-related disorders. Methods Using a mixed-methods approach, we investigated tDCS acceptability among 102 active duty and post-active military patients with stress-related symptoms (posttraumatic stress disorder, anxiety and impulsive aggression) who participated in a 5-session tDCS intervention. Quantitative dropout and adverse effects data was collected for all patients involved in the sham-controlled tDCS intervention. We additionally explored perspectives on the acceptability of tDCS treatment via a theory-based semi-structured interview. A subgroup of patients as well as their careg...
Stress-related psychiatric disorders across the life spa
Additional file 2. Complete EWAS results for the Discovery Cohort.
IntroductionCortical thickness (CT) and surface area (SA) are established biomarkers of brain pat... more IntroductionCortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. The ENIGMA-PGC PTSD Working Group aggregated PTSD and control subjects’ data from 29 cohorts in five countries (n=3439).MethodsUsing Destrieux Atlas, we built SCNs and compared centrality measures between PTSD subjects and controls. Centrality is a graph theory measure derived using SCN.ResultsNotable nodes with higher CT-based centrality in PTSD compared to controls were left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. We found sex-based centrality differences in bilateral frontal lobe regions, left anterior cingulate, left superior occipital cortex and right ventromedial prefrontal cortex (vmPFC). Comor...
Frontiers in Virtual Reality, 2021
With the application of virtual reality (VR), tailored interventions can be created that mirror t... more With the application of virtual reality (VR), tailored interventions can be created that mirror the traumatic experiences of veterans with post-traumatic stress disorder (PTSD). Visual elements can be mimicked, and auditory and other senses stimulated. In doing so, the degree of immersion can be adjusted to optimize the therapeutic process. Objectively measuring the sensory immersion is key to keep subjects within their personal window of tolerance. Based on this information the therapist can decide manipulate the sensory stimulation embedded in the treatment. The objectives of this article are to explore the different immersive design aspects of VRET that can be modified to influence the experienced presence in veterans with PTSD, and to discuss possible methods of measuring the emotional response facilitated by immersive design aspects and experienced presence. Four design aspects are discussed: system, sensory cues, narrative and challenge. We also report on a user experiment in ...
Clinical Epigenetics, 2020
Background Epigenetic mechanisms have been suggested to play a role in the development of post-tr... more Background Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whether DNA methylation profiles are associated with the development of PTSD. A total of 123 PTSD cases and 143 trauma-exposed controls were included in the analyses. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis in a two-stage design. In stage one, we jointly analyzed data of two new cohorts (N = 126 and 78) for gene discovery, and sought to replicate significant findings in a third, previously published cohort (N = 62) to assess the robustness of our results. In stage 2, we aimed at maximizing power for gene discovery by combining all three cohorts in a meta-an...
Molecular Psychiatry, 2019
Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stres... more Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like characteristics in a subset of mice, including persistently enhanced memory and heightened cFos in the basolateral amygdala complex (BLC) with retrieval of the remote (30-day-old) stress memory. Here, the contribution of BLC microRNAs (miRNAs) to stress-enhanced memory was investigated because of the molecular complexity they achieve through their ability to regulate multiple targets simultaneously. We performed small-RNA sequencing (smRNA-Seq) and quantitative proteomics on BLC tissue collected from mice 1 month after SEFL and identified persistently changed microRNAs, including mir-135b-5p, and proteins associated with PTSD-like heightened fear expression. Viral-mediated overexpression of mir-135b-5p in the BLC of stress-resilient animals enhanced remote fear memory expression and promoted spontaneous renewal 14 days after extinction. Conversely, inhibition of BLC mir-135b-5p in stress-susceptible animals had the opposite effect, promoting a resilient-like phenotype. mir-135b-5p is highly conserved across mammals and was detected in post mortem human amygdala, as well as human serum samples. The mir-135b passenger strand, mir-135b-3p, was significantly elevated in serum from PTSD military veterans, relative to combat-exposed control subjects. Thus, miR-135b-5p may be an important therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.
Social Cognitive and Affective Neuroscience, 2017
Impulsive aggression is common among military personnel after deployment and may arise because of... more Impulsive aggression is common among military personnel after deployment and may arise because of impaired top-down regulation of the amygdala by prefrontal regions. This study sought to further explore this hypothesis via resting-state functional connectivity analyses in impulsively aggressive combat veterans. Male combat veterans with (n ¼ 28) and without (n ¼ 30) impulsive aggression problems underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were conducted with the following seed-regions: basolateral amygdala (BLA), centromedial amygdala, anterior cingulate cortex (ACC), and anterior insular cortex (AIC). Regions-of-interest analyses focused on the orbitofrontal cortex and periaqueductal gray, and yielded no significant results. In exploratory cluster analyses, we observed reduced functional connectivity between the (bilateral) BLA and left dorsolateral prefrontal cortex in the impulsive aggression group, relative to combat controls. This finding indicates that combat-related impulsive aggression may be marked by weakened functional connectivity between the amygdala and prefrontal regions, already in the absence of explicit emotional stimuli. Group differences in functional connectivity were also observed between the (bilateral) ACC and left cuneus, which may be related to heightened vigilance to potentially threatening visual cues, as well as between the left AIC and right temporal pole, possibly related to negative memory association in impulsive aggression.
European Neuropsychopharmacology, 2017
Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucoco... more Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1 F region (GR-1 F) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1 F methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1 F methylation (52 loci) was quantified using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1 F methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1 F expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1 F methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self-Report Inventory for PTSD). Trauma exposure during deployment was associated with an increase in all methylation measures, but development of mental health problems 6 months after deployment was only significantly associated with an increased functional methylation. Emergence of post-deployment PTSD symptoms was not related to increased functional methylation over time. Pre-deployment methylation levels did not predict post-deployment psychopathology. To our knowledge, this is the first study to prospectively demonstrate trauma-related increases in GR-1 F methylation, and it shows that only increases at specific functionally relevant sites predispose for post-deployment psychopathology.
Biological Psychology, 2017
Psychoneuroendocrinology, 2016
Journal of Psychiatric Research, 2016
Health care providers need to be aware that stress complaints that result from deployment can eme... more Health care providers need to be aware that stress complaints that result from deployment can emerge even after many years. This has important implications for health care policies. The main aim of this study is to investigate the relation between the development of posttraumatic stress and other mental health complaints and the burden on (mental) health care after a deployment. For this study we used data from a large prospective cohort study on stress-factors related to deployment in 1007 Dutch soldiers, who were deployed to Afghanistan. Participants were assessed at six follow up times up until five years after deployment. In a Generalized Estimated Equations model we estimated the relation between mental health complaints and the utilization of psychological treatment and a general practitioner, respectively. Moreover, we studied the relation between mental health complaints and health care costs using bootstrap techniques. The results showed that higher scores for PTSD, depression and fatigue relate to increased use of a psychologist. And lower PTSD scores and higher depression, anxiety and somatization scores relate to increased odds to visit a GP. Furthermore, mental health complaints relate to higher costs. In conclusion, monitoring soldiers is important in order to be informed on the current demand for (mental) health care to satisfy the health care need of veterans. Early treatment, which is enabled by lowering barriers to care, relates to positive results and therefore, lower health care costs.
Additional file 3. Replication of top EWAS resultsin the PFC of the Brain Bank Cohort.
Biological Psychiatry, 2020
We integrated small-RNA sequencing (smRNA-Seq) with quantitative proteomics on BLC tissue collect... more We integrated small-RNA sequencing (smRNA-Seq) with quantitative proteomics on BLC tissue collected from mice one month after SEFL. In vivo functional manipulation of a candidate miRNA was performed in SEFL mice to delineate the miRNA's role in persistent, stress-enhanced memory. Levels of the miRNA were also measured in postmortem human amygdala tissue and in serum samples from military personnel with a PTSD diagnosis. Results: mir-135b-5p was identified as a persistently altered miRNA that bidirectionally modulated stress-associated remote memory in stress susceptible and resilient mice, without impacting anxiety-like behaviors. mir-135b-5p is expressed in human amygdala and its passenger strand was elevated in military personnel diagnosed with PTSD. Integration of smRNA-Seq with quantitative proteomics following intra-BLC mir-135b-5p overexpression or SEFL identified potential mir-135b-5p target proteins and pathways mediating PTSD-like heightened fear expression. Conclusions: miR-135b-5p is a promising therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.
Brain Structure and Function, 2019
Aggression after military deployment is a common occurrence in veterans. Neurobiological research... more Aggression after military deployment is a common occurrence in veterans. Neurobiological research has shown that aggression is associated with a dysfunction in a network connecting brain regions implicated in threat processing and emotion regulation. However, aggression may also be related to deficits in networks underlying communication and social cognition. The uncinate and arcuate fasciculi are integral to these networks, thus studying potential abnormalities in these white matter connections can further our understanding of anger and aggression problems in military veterans. Here, we use diffusion tensor imaging tractography to investigate white matter microstructural properties of the uncinate fasciculus and the arcuate fasciculus in veterans with and without anger and aggression problems. A control tract, the parahippocampal cingulum was also included in the analyses. More specifically, fractional anisotropy (FA) estimates are derived along the trajectory from all fiber pathwa...
Macroscale white matter pathways form the infrastructure for large-scale communication in the hum... more Macroscale white matter pathways form the infrastructure for large-scale communication in the human brain, a prerequisite for healthy brain function. Conversely, disruptions in the brain’s connectivity architecture are thought to play an important role in a wide range of psychiatric and neurological brain disorders. Here we show that especially connections important for global communication and network integration are involved in a wide range of brain disorders. We report on a meta-analytic connectome study comprising in total 895 patients and 1,016 controls across twelve neurological and psychiatric disorders. We extracted disorder connectome fingerprints for each of these twelve disorders, which were then combined into a cross-disorder disconnectivity involvement map, representing the involvement of each brain pathway across brain disorders. Our findings show connections central to the brain’s infrastructure are disproportionally involved across a wide range of disorders. Connecti...
Psychological Medicine, 2021
BackgroundPost-traumatic stress disorder (PTSD), anxiety, and impulsive aggression are linked to ... more BackgroundPost-traumatic stress disorder (PTSD), anxiety, and impulsive aggression are linked to transdiagnostic neurocognitive deficits. This includes impaired inhibitory control over inappropriate responses. Prior studies showed that inhibitory control can be improved by modulating the right inferior frontal gyrus (IFG) with transcranial direct current stimulation (tDCS) in combination with inhibitory control training. However, its clinical potential remains unclear. We therefore aimed to replicate a tDCS-enhanced inhibitory control training in a clinical sample and test whether this reduces stress-related mental health symptoms.MethodsIn a preregistered double-blind randomized-controlled trial, 100 active-duty military personnel and post-active veterans with PTSD, anxiety, or impulsive aggression symptoms underwent a 5-session intervention where a stop-signal response inhibition training was combined with anodal tDCS over the right IFG for 20 min at 1.25 mA. Inhibitory control wa...
BMC Psychiatry, 2021
Background Noninvasive brain stimulation techniques like transcranial direct current stimulation ... more Background Noninvasive brain stimulation techniques like transcranial direct current stimulation (tDCS) offer potential new approaches to treat stress-related mental health disorders. While the acceptability of tDCS as a treatment tool plays a crucial role in its development and implementation, little is known about tDCS acceptability for users in mental healthcare, especially in the context of stress-related disorders. Methods Using a mixed-methods approach, we investigated tDCS acceptability among 102 active duty and post-active military patients with stress-related symptoms (posttraumatic stress disorder, anxiety and impulsive aggression) who participated in a 5-session tDCS intervention. Quantitative dropout and adverse effects data was collected for all patients involved in the sham-controlled tDCS intervention. We additionally explored perspectives on the acceptability of tDCS treatment via a theory-based semi-structured interview. A subgroup of patients as well as their careg...
Stress-related psychiatric disorders across the life spa
Additional file 2. Complete EWAS results for the Discovery Cohort.
IntroductionCortical thickness (CT) and surface area (SA) are established biomarkers of brain pat... more IntroductionCortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. The ENIGMA-PGC PTSD Working Group aggregated PTSD and control subjects’ data from 29 cohorts in five countries (n=3439).MethodsUsing Destrieux Atlas, we built SCNs and compared centrality measures between PTSD subjects and controls. Centrality is a graph theory measure derived using SCN.ResultsNotable nodes with higher CT-based centrality in PTSD compared to controls were left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. We found sex-based centrality differences in bilateral frontal lobe regions, left anterior cingulate, left superior occipital cortex and right ventromedial prefrontal cortex (vmPFC). Comor...
Frontiers in Virtual Reality, 2021
With the application of virtual reality (VR), tailored interventions can be created that mirror t... more With the application of virtual reality (VR), tailored interventions can be created that mirror the traumatic experiences of veterans with post-traumatic stress disorder (PTSD). Visual elements can be mimicked, and auditory and other senses stimulated. In doing so, the degree of immersion can be adjusted to optimize the therapeutic process. Objectively measuring the sensory immersion is key to keep subjects within their personal window of tolerance. Based on this information the therapist can decide manipulate the sensory stimulation embedded in the treatment. The objectives of this article are to explore the different immersive design aspects of VRET that can be modified to influence the experienced presence in veterans with PTSD, and to discuss possible methods of measuring the emotional response facilitated by immersive design aspects and experienced presence. Four design aspects are discussed: system, sensory cues, narrative and challenge. We also report on a user experiment in ...
Clinical Epigenetics, 2020
Background Epigenetic mechanisms have been suggested to play a role in the development of post-tr... more Background Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whether DNA methylation profiles are associated with the development of PTSD. A total of 123 PTSD cases and 143 trauma-exposed controls were included in the analyses. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis in a two-stage design. In stage one, we jointly analyzed data of two new cohorts (N = 126 and 78) for gene discovery, and sought to replicate significant findings in a third, previously published cohort (N = 62) to assess the robustness of our results. In stage 2, we aimed at maximizing power for gene discovery by combining all three cohorts in a meta-an...
Molecular Psychiatry, 2019
Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stres... more Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like characteristics in a subset of mice, including persistently enhanced memory and heightened cFos in the basolateral amygdala complex (BLC) with retrieval of the remote (30-day-old) stress memory. Here, the contribution of BLC microRNAs (miRNAs) to stress-enhanced memory was investigated because of the molecular complexity they achieve through their ability to regulate multiple targets simultaneously. We performed small-RNA sequencing (smRNA-Seq) and quantitative proteomics on BLC tissue collected from mice 1 month after SEFL and identified persistently changed microRNAs, including mir-135b-5p, and proteins associated with PTSD-like heightened fear expression. Viral-mediated overexpression of mir-135b-5p in the BLC of stress-resilient animals enhanced remote fear memory expression and promoted spontaneous renewal 14 days after extinction. Conversely, inhibition of BLC mir-135b-5p in stress-susceptible animals had the opposite effect, promoting a resilient-like phenotype. mir-135b-5p is highly conserved across mammals and was detected in post mortem human amygdala, as well as human serum samples. The mir-135b passenger strand, mir-135b-3p, was significantly elevated in serum from PTSD military veterans, relative to combat-exposed control subjects. Thus, miR-135b-5p may be an important therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.
Social Cognitive and Affective Neuroscience, 2017
Impulsive aggression is common among military personnel after deployment and may arise because of... more Impulsive aggression is common among military personnel after deployment and may arise because of impaired top-down regulation of the amygdala by prefrontal regions. This study sought to further explore this hypothesis via resting-state functional connectivity analyses in impulsively aggressive combat veterans. Male combat veterans with (n ¼ 28) and without (n ¼ 30) impulsive aggression problems underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were conducted with the following seed-regions: basolateral amygdala (BLA), centromedial amygdala, anterior cingulate cortex (ACC), and anterior insular cortex (AIC). Regions-of-interest analyses focused on the orbitofrontal cortex and periaqueductal gray, and yielded no significant results. In exploratory cluster analyses, we observed reduced functional connectivity between the (bilateral) BLA and left dorsolateral prefrontal cortex in the impulsive aggression group, relative to combat controls. This finding indicates that combat-related impulsive aggression may be marked by weakened functional connectivity between the amygdala and prefrontal regions, already in the absence of explicit emotional stimuli. Group differences in functional connectivity were also observed between the (bilateral) ACC and left cuneus, which may be related to heightened vigilance to potentially threatening visual cues, as well as between the left AIC and right temporal pole, possibly related to negative memory association in impulsive aggression.
European Neuropsychopharmacology, 2017
Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucoco... more Several cross-sectional studies have demonstrated the relevance of DNA methylation of the glucocorticoid receptor exon 1 F region (GR-1 F) for trauma-related psychopathology. We conducted a longitudinal study to examine GR-1 F methylation changes over time in relation to trauma exposure and the development of post-deployment psychopathology. GR-1 F methylation (52 loci) was quantified using pyrosequencing in whole blood of 92 military men 1 month before and 6 months after a 4-month deployment period to Afghanistan. GR-1 F methylation overall (mean methylation and the number of methylated loci) and functional methylation (methylation at loci associated with GR exon 1 F expression) measures were examined. We first investigated the effect of exposure to potentially traumatic events during deployment on these measures. Subsequently, changes in GR-1 F methylation were related to changes in mental health problems (total Symptom Checklist-90 score) and posttraumatic stress disorder (PTSD) symptoms (Self-Report Inventory for PTSD). Trauma exposure during deployment was associated with an increase in all methylation measures, but development of mental health problems 6 months after deployment was only significantly associated with an increased functional methylation. Emergence of post-deployment PTSD symptoms was not related to increased functional methylation over time. Pre-deployment methylation levels did not predict post-deployment psychopathology. To our knowledge, this is the first study to prospectively demonstrate trauma-related increases in GR-1 F methylation, and it shows that only increases at specific functionally relevant sites predispose for post-deployment psychopathology.
Biological Psychology, 2017
Psychoneuroendocrinology, 2016
Journal of Psychiatric Research, 2016
Health care providers need to be aware that stress complaints that result from deployment can eme... more Health care providers need to be aware that stress complaints that result from deployment can emerge even after many years. This has important implications for health care policies. The main aim of this study is to investigate the relation between the development of posttraumatic stress and other mental health complaints and the burden on (mental) health care after a deployment. For this study we used data from a large prospective cohort study on stress-factors related to deployment in 1007 Dutch soldiers, who were deployed to Afghanistan. Participants were assessed at six follow up times up until five years after deployment. In a Generalized Estimated Equations model we estimated the relation between mental health complaints and the utilization of psychological treatment and a general practitioner, respectively. Moreover, we studied the relation between mental health complaints and health care costs using bootstrap techniques. The results showed that higher scores for PTSD, depression and fatigue relate to increased use of a psychologist. And lower PTSD scores and higher depression, anxiety and somatization scores relate to increased odds to visit a GP. Furthermore, mental health complaints relate to higher costs. In conclusion, monitoring soldiers is important in order to be informed on the current demand for (mental) health care to satisfy the health care need of veterans. Early treatment, which is enabled by lowering barriers to care, relates to positive results and therefore, lower health care costs.
Additional file 3. Replication of top EWAS resultsin the PFC of the Brain Bank Cohort.
Biological Psychiatry, 2020
We integrated small-RNA sequencing (smRNA-Seq) with quantitative proteomics on BLC tissue collect... more We integrated small-RNA sequencing (smRNA-Seq) with quantitative proteomics on BLC tissue collected from mice one month after SEFL. In vivo functional manipulation of a candidate miRNA was performed in SEFL mice to delineate the miRNA's role in persistent, stress-enhanced memory. Levels of the miRNA were also measured in postmortem human amygdala tissue and in serum samples from military personnel with a PTSD diagnosis. Results: mir-135b-5p was identified as a persistently altered miRNA that bidirectionally modulated stress-associated remote memory in stress susceptible and resilient mice, without impacting anxiety-like behaviors. mir-135b-5p is expressed in human amygdala and its passenger strand was elevated in military personnel diagnosed with PTSD. Integration of smRNA-Seq with quantitative proteomics following intra-BLC mir-135b-5p overexpression or SEFL identified potential mir-135b-5p target proteins and pathways mediating PTSD-like heightened fear expression. Conclusions: miR-135b-5p is a promising therapeutic target for dampening persistent, stress-enhanced memory and its passenger strand a potential biomarker for responsivity to a mir-135-based therapeutic.
Brain Structure and Function, 2019
Aggression after military deployment is a common occurrence in veterans. Neurobiological research... more Aggression after military deployment is a common occurrence in veterans. Neurobiological research has shown that aggression is associated with a dysfunction in a network connecting brain regions implicated in threat processing and emotion regulation. However, aggression may also be related to deficits in networks underlying communication and social cognition. The uncinate and arcuate fasciculi are integral to these networks, thus studying potential abnormalities in these white matter connections can further our understanding of anger and aggression problems in military veterans. Here, we use diffusion tensor imaging tractography to investigate white matter microstructural properties of the uncinate fasciculus and the arcuate fasciculus in veterans with and without anger and aggression problems. A control tract, the parahippocampal cingulum was also included in the analyses. More specifically, fractional anisotropy (FA) estimates are derived along the trajectory from all fiber pathwa...
Macroscale white matter pathways form the infrastructure for large-scale communication in the hum... more Macroscale white matter pathways form the infrastructure for large-scale communication in the human brain, a prerequisite for healthy brain function. Conversely, disruptions in the brain’s connectivity architecture are thought to play an important role in a wide range of psychiatric and neurological brain disorders. Here we show that especially connections important for global communication and network integration are involved in a wide range of brain disorders. We report on a meta-analytic connectome study comprising in total 895 patients and 1,016 controls across twelve neurological and psychiatric disorders. We extracted disorder connectome fingerprints for each of these twelve disorders, which were then combined into a cross-disorder disconnectivity involvement map, representing the involvement of each brain pathway across brain disorders. Our findings show connections central to the brain’s infrastructure are disproportionally involved across a wide range of disorders. Connecti...