Post-traumatic Stress Disorder Pathology Research Articles

Emotional lability and affective synchrony in posttraumatic stress disorder pathology

This study examined the relations of PTSD pathology to both the lability of three specific emotions (anxiety, anger, self-conscious emotions [SCE]) and the extent to which changes in one emotional state co-occur with changes in another emotional state (i.e. affective synchrony). Moreover, given evidence that emotional responding in PTSD may be heightened in response to trauma-related cues, these relations were explored in the context of a trauma cue versus neutral cue. Trauma-exposed patients in residential substance use disorder treatment (N=157) completed a diagnostic interview and two laboratory sessions involving presentation of neutral and individualized trauma scripts. State anxiety, anger, and SCE were assessed at five points throughout each laboratory session. Hierarchical linear modeling indicated that participants (regardless of PTSD status) exhibited greater lability of all emotions following the trauma script versus neutral script. Only anger lability was elevated among those with (versus without) a current PTSD diagnosis following the neutral script. Results also revealed synchrony (i.e., positive covariation) between each possible pair of emotions, regardless of PTSD status. Findings suggest that concurrent changes in anxiety and anger may be especially relevant to PTSD symptom severity.

Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder.

Background:Posttraumatic stress disorder (PTSD) is a severe problem among soldiers with combating experience difficult to treat. The pathogenesis is still not fully understood at the psychological level. Therefore, genetic research became a focus of interest. The identification of single nucleotide polymorphisms (SNPs) may help to predict, which persons are at high risk to develop PTSD as a starting point to develop novel targeted drugs for treatment.Methods:We conducted a systematic review on SNPs in genes related to PTSD pathology and development of targeted pharmacological treatment options based on PubMed database searches. We focused on clinical trials with military personnel.Results:SNPs in 22 human genes have been linked to PTSD. These genes encode proteins acting as neurotransmitters and receptors, downstream signal transducers and metabolizing enzymes. Pharmacological inhibitors may serve as drug candidates for PTSD treatment, e.g. β2 adrenoreceptor antagonists, dopamine antagonists, partial dopamine D2 receptor agonists, dopamine β hydroxylase inhibitors, fatty acid amid hydrolase antagonists, glucocorticoid receptor agonists, tropomyosin receptor kinase B agonists, selective serotonin reuptake inhibitors, catechol-O-methyltransferase inhibitors, gamma-amino butyric acid receptor agonists, glutamate receptor inhibitors, monoaminoxidase B inhibitors, N-methyl-d-aspartate receptor antagonists.Conclusion:The combination of genetic and pharmacological research may lead to novel target-based drug developments with improved specificity and efficacy to treat PTSD. Specific SNPs may be identified as reliable biomarkers to assess individual disease risk. Focusing on soldiers suffering from PTSD will not only help to improve treatment options for this specific group, but for all PTSD patients and the general population.

Restless ‘rest’: intrinsic sensory hyperactivity and disinhibition in post-traumatic stress disorder

Post-traumatic stress disorder is characterized by exaggerated threat response, and theoretical accounts to date have focused on impaired threat processing and dysregulated prefrontal-cortex-amygdala circuitry. Nevertheless, evidence is accruing for broad, threat-neutral sensory hyperactivity in post-traumatic stress disorder. As low-level, sensory processing impacts higher-order operations, such sensory anomalies can contribute to widespread dysfunctions, presenting an additional aetiological mechanism for post-traumatic stress disorder. To elucidate a sensory pathology of post-traumatic stress disorder, we examined intrinsic visual cortical activity (based on posterior alpha oscillations) and bottom-up sensory-driven causal connectivity (Granger causality in the alpha band) during a resting state (eyes open) and a passive, serial picture viewing state. Compared to patients with generalized anxiety disorder (n = 24) and healthy control subjects (n = 20), patients with post-traumatic stress disorder (n = 25) demonstrated intrinsic sensory hyperactivity (suppressed posterior alpha power, source-localized to the visual cortex-cuneus and precuneus) and bottom-up inhibition deficits (reduced posterior→frontal Granger causality). As sensory input increased from resting to passive picture viewing, patients with post-traumatic stress disorder failed to demonstrate alpha adaptation, highlighting a rigid, set mode of sensory hyperactivity. Interestingly, patients with post-traumatic stress disorder also showed heightened frontal processing (augmented frontal gamma power, source-localized to the superior frontal gyrus and dorsal cingulate cortex), accompanied by attenuated top-down inhibition (reduced frontal→posterior causality). Importantly, not only did suppressed alpha power and bottom-up causality correlate with heightened frontal gamma power, they also correlated with increased severity of sensory and executive dysfunctions (i.e. hypervigilance and impulse control deficits, respectively). Therefore, sensory aberrations help construct a vicious cycle in post-traumatic stress disorder that is in action even at rest, implicating dysregulated triangular sensory-prefrontal-cortex-amygdala circuitry: intrinsic sensory hyperactivity and disinhibition give rise to frontal overload and disrupt executive control, fuelling and perpetuating post-traumatic stress disorder symptoms. Absent in generalized anxiety disorder, these aberrations highlight a unique sensory pathology of post-traumatic stress disorder (ruling out effects merely reflecting anxious hyperarousal), motivating new interventions targeting sensory processing and the sensory brain in these patients.

PTSD Symptom Severity and Emotion Regulation Strategy Use During Trauma Cue Exposure Among Patients With Substance Use Disorders: Associations With Negative Affect, Craving, and Cortisol Reactivity

The co-occurrence of posttraumatic stress disorder (PTSD) pathology with a substance use disorder (SUD) is associated with emotion regulation deficits. However, studies in this area generally rely on trait-based emotion regulation measures, and there is limited information on the relation of PTSD pathology to the use of specific emotion regulation strategies in response to trauma-related distress among SUD patients or the consequences of these strategies for trauma cue reactivity. This study examined the relation of PTSD symptom severity to the use of specific emotion regulation strategies during trauma cue exposure among trauma-exposed SUD patients, as well as the indirect relations of PTSD symptom severity to changes in negative affect, cravings, and cortisol levels pre- to posttrauma cue exposure through different emotion regulation strategies. Participants were 133 trauma-exposed SUD patients. Participants listened to a personalized trauma script and reported on emotion regulation strategies used during the script. Data on negative affect, cravings, and cortisol were collected pre- and postscript. PTSD symptom severity related positively to the use of more adaptive (e.g., distraction) and maladaptive (e.g., suppression) regulation strategies. Moreover, evidence for the indirect effects of PTSD symptom severity on negative affect and cortisol reactivity through both adaptive and maladaptive emotion regulation strategies was found. Implications of findings are discussed.

Anomalous gray matter structural networks in recent onset post-traumatic stress disorder.

Alterations of the topological organization of abnormal regions or network-level structural aberrations are still poorly understood for post-traumatic stress disorder (PTSD). Herein, we investigated brain structural networks in recent-onset PTSD patients, all affected by the coalmine-flood disaster. Cortical networks were studied in recent onset PTSD patients (n=15) and matched healthy controls (n=25). Cortical networks were constructed by thresholding correlation matrices of 150 regions and quantified using graph theoretical approaches. Contributions of high-degree nodes, and regional and global network measures, including degree and betweenness, were studied. Compared with healthy controls, PTSD patients showed altered quantitative values in global network properties, characterized by shorter path length and higher clustering. Moreover, PTSD patients exhibited decreased connectivity in the right lingual gyrus, parahippocampal gyrus, left supramarginal gyrus, parahippocampal gyrus, bilateral superior and inferior frontal gyrus, superior frontal gyrus, and posterior cingulate gyrus. Nodal centrality decreased predominantly in the occipital regions (lingual gyrus) and default-mode regions, while increased correlations and centralities were observed in the medial temporal lobe and posterior cingulate cortex. PTSD-related networks exhibited a less efficient organization and regional connectivity. According to these findings, we conclude that regional connections involving fear-processing and re-experiential-processing cortex may play a role in maintaining or adapting to PTSD pathology.

Neuroinflammatory genes associated with post-traumatic stress disorder: implications for comorbidity.

Post-traumatic stress disorder (PTSD) is a debilitating condition that only occurs in the aftermath of traumatic event exposure and is characterized by an impaired stress response and chronic, low-grade inflammation. Dysregulation of the immune system may contribute towards central nervous system tissue damage and exacerbation of fear memories following trauma. Patients with PTSD often have comorbid psychiatric and somatic disorders that are of themselves associated with heightened inflammation. Several immune-related genes have been associated with PTSD and other co-occurring disorders. In this review, we propose that chronic inflammation, particularly neuroinflammation, is an important contributory factor towards PTSD comorbidity. Thus, novel treatments that target dysregulated inflammatory processes could provide symptomatic relief from PTSD and its comorbid disorders. This review investigates the intricate links between chronic stress, anxiety and neuroinflammation and the potential impact of increased neuroinflammation on PTSD pathology and comorbidity.

Morphovolumetric changes after EMDR treatment in drug-naïve PTSD patients.

Few studies have investigated the effects of efficacious psychotherapy on structural alterations of discrete brain regions associated with posttraumatic stress disorder (PTSD). We therefore proposed to evaluate the neurobiological effects of eye movement desensitization and reprocessing (EMDR) on 19 patients with drug-naïve PTSD without comorbidity, matched with 19 untreated healthy controls. We administered the Clinician Administered PTSD Scale (CAPS) and conducted brain MRI measurements (with Optimized Voxel-Based Morphometry). Patients received 12 EMDR sessions over three months. Then patients and controls were reassessed. At baseline, grey matter volume (GMV) differed significantly between patients and controls (F 1,35 =3.674; p=.008; η 2=.298). Analyses of 3-month scans showed no changes for controls, while significant changes were highlighted for patients post-EMDR, with a significant increase in GMV in left parahippocampal gyrus, and a significant decrease in GMV in the left thalamus region. The diagnosis of PTSD was effectively eliminated in 16 of 19 patients, reflected in a significant improvement on the CAPS (t(35)=2.132, p<.004). Results indicated post-EMDR changes for patients in brain morphology. We discuss whether EMDR’s mechanism of action may work at the level of the thalamus, an area implicated in PTSD pathology.

Combat PTSD and Implicit Behavioral Tendencies for Positive Affective Stimuli: A Brief Report.

Background: Prior cognitive research in posttraumatic stress disorder (PTSD) has focused on automatic responses to negative affective stimuli, including attentional facilitation or disengagement and avoidance action tendencies. More recent research suggests PTSD may also relate to differences in reward processing, which has lead to theories of PTSD relating to approach-avoidance imbalances. The current pilot study assessed how combat-PTSD symptoms relate to automatic behavioral tendencies to both positive and negative affective stimuli.Method: Twenty male combat veterans completed the approach-avoidance task (AAT), Clinician Administered PTSD Scale, Beck Depression Inventory-II, and State-Trait Anger Expression Inventory-II. During the AAT, subjects pulled (approach) or pushed (avoid) a joystick in response to neutral, happy, disgust, and angry faces based on border color. Bias scores were calculated for each emotion type (avoid-approach response latency differences). Main and interaction effects for psychological symptom severity and emotion type on bias score were assessed using linear mixed models.Results: There was a significant interaction between PTSD symptoms and emotion type, driven primarily by worse symptoms relating to a greater bias to avoid happy faces. Post hoc tests revealed that veterans with worse PTSD symptoms were slower to approach as well as quicker to avoid happy faces. Neither depressive nor anger symptoms related to avoid or approach tendencies of emotional stimuli.Conclusion: Posttraumatic stress disorder severity was associated with a bias for avoiding positive affective stimuli. These results provide further evidence that PTSD may relate to aberrant processing of positively valenced, or rewarding stimuli. Implicit responses to rewarding stimuli could be an important factor in PTSD pathology and treatment. Specifically, these findings have implications for recent endeavors in using computer-based interventions to influence automatic approach-avoidance tendencies.

Iron-induced neuronal damage in a rat model of post-traumatic stress disorder

Previous studies have shown that iron redistribution and deposition in the brain occurs in some neurodegenerative diseases, and oxidative damage due to abnormal iron level is a primary cause of neuronal death. In the present study, we used the single prolonged stress (SPS) model to mimic post-traumatic stress disorder (PTSD), and examined whether iron was involved in the progression of PTSD. The anxiety-like behaviors of the SPS group were assessed by the elevated plus maze (EPM) and open field tests, and iron levels were measured by inductively coupled plasma optical emission spectrometer (ICP-OES). Expression of glucocorticoid receptors and transferrin receptor 1 (TfR1) and ferritin (Fn) was detected by Western blot and immunohistochemistry in selected brain areas; TfR1 and Fn mRNA expression were detected by quantitative-polymerase chain reaction (Q-PCR). Ultrastructures of the hippocampus were observed under a transmission electron microscope. Our results showed that SPS exposure induced anxiety-like symptoms and increased the level of serum cortisol and the concentration of iron in key brain areas such as the hippocampus, prefrontal cortex, and striatum. The stress induced region-specific changes in both protein and mRNA levels of TfR1 and Fn. Moreover, swelling mitochondria and cell apoptosis were observed in neurons in brain regions with iron accumulation. We concluded that SPS stress increased iron in some cognition-related brain regions and subsequently cause neuronal injury, indicating that the iron may function in the pathology of PTSD.

Abnormal Functional Connectivity Density in Post-traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that occurs in individuals who have experienced life-threatening mental traumas. Previous neuroimaging studies have indicated that the pathology of PTSD may be associated with the abnormal functional integration among brain regions. In the current study, we used functional connectivity density (FCD) mapping, a novel voxel-wise data-driven approach based on graph theory, to explore aberrant FC through the resting-state functional magnetic resonance imaging of the PTSD. We calculated both short- and long-range FCD in PTSD patients and healthy controls (HCs). Compared with HCs, PTSD patients showed significantly increased long-range FCD in the left dorsolateral prefrontal cortex (DLPFC), but no abnormal short-range FCD was found in PTSD. Furthermore, seed-based FC analysis of the left DLPFC showed increased connectivity in the left superior parietal lobe and visual cortex of PTSD patients. The results suggested that PTSD patients experienced a disruption of intrinsic long-range functional connections in the fronto-parietal network and visual cortex, which are associated with attention control and visual information processing.

Gray matter volume alterations related to trait dissociation in PTSD and traumatized controls

This study used voxel-based morphometry (VBM) to investigate brain structural alterations related to trait dissociation and its relationship with post-traumatic stress disorder (PTSD). Thirty-two subjects either developing (N = 15) or non-developing (N = 17) PTSD underwent MRI scanning and were assessed with the Dissociative Experience Scale (DES), subscales for pathological (DES-T) and non-pathological trait (DES-A) dissociation, and other clinical measures. Gray matter volume (GMV) was analyzed using VBM as implemented in SPM. PTSD and non-PTSD subjects were compared to assess brain alterations related to PTSD pathology, whereas correlation analyses between dissociation measures and GMV were performed on the whole sample (N = 32), irrespective of PTSD diagnosis, to identify alterations related to trait dissociation. As compared to traumatized controls, PTSD subjects showed reduced GMV in the prefrontal cortex, hippocampus and lingual gyrus. Correlations with dissociation measures (DES, DES-T, and DES-A) consistently showed increased GMV in the medial and lateral prefrontal, orbitofrontal, parahippocampal, temporal polar, and inferior parietal cortices. PTSD and dissociation seem to be associated with opposite volumetric patterns in the prefrontal cortex. Trait dissociation appears to involve increased GMV in prefrontal, paralimbic, and parietal cortices, with negligible differences between pathological and non-pathological dissociation.

Changes in 5-HT1A receptor expression in the oculomotor nucleus in a rat model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after exposure to a life-threatening traumatic experience. Mental disorder appears after the traumatic stress incident and affects the movement of the eye muscle dominated by the oculomotor nucleus, an important nuclear group of the brainstem. It has been reported that dysfunction of the neurotransmitter 5-hydroxytryptamine (5-HT) can lead to the instability of the internal environment in response to stress and plays an important role in the pathology of PTSD and that the 5-HT1A receptor (5-HT1AR) is critically involved in regulating mood and anxiety levels. In this study, the 5-HT1AR expression in the oculomotor nucleus was examined in rats with single-prolonged stress (SPS), a well established post-traumatic stress disorder animal model. Our results show that the expression of 5-HT1AR in the oculomotor nucleus neurons gradually increased 1, 4, and 7 days after exposure to SPS in comparison to the normal control group, measured by immunohistochemistry, western blotting, and reverse transcription polymerase chain reaction (RT-PCR). The expression of 5-HT1AR reached its peak 7 days after the SPS exposure and then decreased 14 days after. There is also a change in the ultrastructure in the oculomotor nucleus neuron upon SPS treatment which was observed by transmission electron microscopy. These results suggest that SPS can induce a change of the 5-HT1AR expression in the oculomotor nucleus, which may be one of the molecular mechanisms that lead to PTSD.

Single prolonged stress induces changes in the expression of mineralocorticoid receptor in the medial prefrontal cortex in a rat model of post-traumatic stress disorder

It is not clear whether or not the mineralocorticoid receptor (MR) is involved in post-traumatic stress disorder (PTSD). The purpose of this study was to provide novel insights into the mechanism(s) through which the medial prefrontal cortex (mPFC) plays a role in PTSD by investigating MR expression in the mPFC of rats exposed to single prolonged stress (SPS), which is an established animal model for PTSD. A total of 90 healthy, male Wistar rats were selected for this study and randomly divided into normal control and SPS groups of 1, 7, 14 and 28 days. This study investigated the changes in MR expression in the mPFC of rats after SPS, which revealed pathogenetic mechanisms. The expression of MR in the mPFC was examined by immunofluorescence, western blotting and reverse transcription-polymerase chain reaction (RT-PCR). SPS exposure resulted in a significant change in MR expression in the SPS model groups compared with the normal control group. The MR protein was found to be localized in the cytoplasm and its expression levels were significantly increased in SPS rats, peaking at SPS 7 days, followed by a gradual decrease; however, a positive expression revealed a restoratory increase in the SPS-28 day group. The results suggest that MR plays an important role in the pathology of PTSD.

Single-prolonged stress induces increased phosphorylation of extracellular signal-regulated kinase in a rat model of post-traumatic stress disorder

The extracellular signal-regulated kinase (ERK) signaling transduction pathway has been implicated in multiple physiological processes. It is not clear whether the ERK1/2 pathway participates in post-traumatic stress disorder (PTSD). The aim of this study was to provide novel insights into the mechanisms of how the amygdala participates in PTSD by investigating changes in the ERK1/2 pathway induced by single prolonged stress (SPS). The level of phosphorylated ERK1/2 (pERK1/2) protein was defined in a single-prolonged stress (SPS) animal model of post-traumatic stress disorder. A total of 100 male Wistar rats were randomly divided into a normal control group and SPS groups of 0, 30, 60 and 120 min. pERK1/2 distribution in the amygdala neurons was observed using immune electron microscopy. The expression of pERK1/2 was examined by immunohistochemistry and Western blotting. The pERK protein was located in some cell organelles, such as the mitochondria and neuraxon. Quantitatively, the expression of pERK protein level was significantly increased in the SPS rats. The results suggest that the ERK signal transduction pathway may play a crucial role in the pathology of PTSD.

Noradrenergic enhancement of reconsolidation in the amygdala impairs extinction of conditioned fear in rats-a possible mechanism for the persistence of traumatic memories in PTSD

Posttraumatic stress disorder (PTSD) is associated with enhanced noradrenergic activity. Animal and human studies demonstrate that noradrenergic stimulation augments consolidation of fear learning. Retrieval of well-established memories by presenting a learned fear cue triggers reconsolidation processes during which memories may be updated, weakened, or strengthened. We previously reported that noradrenergic blockade in the rat amygdala impairs reconsolidation of fear memories. Here we investigated the effects of noradrenergic enhancement on reconsolidation of learned fear. Using auditory fear conditioning in rats, we tested the effects of postretrieval intraamygdala infusion of the β-adrenergic receptor agonist isoproterenol or the antagonist propranolol on conditioned fear in the amygdala. A single intraamygdala infusion of isoproterenol following a retrieval of a well-consolidated memory enhanced fear memory elicited by the learned fear stimulus and impaired extinction of this memory 48 hr later. Intraamygdala infusion of the β-adrenergic receptor antagonist propranolol following a consecutive retrieval trial blocked the enhancing effects of isoproterenol on fear memory. Postretrieval β-adrenergic stimulation in the amygdala enhances reconsolidation of fear memories, making them resistant to extinction. Noradrenergic augmentation during retrieval of fear memories may thus contribute to persistence and severity of traumatic memories. Reconsolidation may be a useful tool in understanding the pathology of PTSD and may thus help in developing new and in modifying existing treatments of traumatic memories.

Acupuncture for Posttraumatic Stress Disorder: Conceptual, Clinical, and Biological Data Support Further Research

Posttraumatic stress disorder (PTSD) is common, debilitating, and has highly heterogeneous clinical and biological features. With the exception of one published preliminary clinical trial, rationale in support of the efficacy of acupuncture, a modality of Chinese medicine (CM), for PTSD has not been well described. This is a focused review of conceptual and clinical features of PTSD shared by modern western medicine (MWM) and CM, and of biological mechanisms of acupuncture that parallel known PTSD pathology. MWM and CM both recognize individual developmental variables and interactions between external conditions and internal responses in the genesis of PTSD. There is one published and one unpublished clinical trial that preliminarily support the efficacy of acupuncture for PTSD. Although there have been no mechanistic studies of acupuncture in human PTSD, extant research shows that acupuncture has biological effects that are relevant to PTSD pathology. Conceptual, clinical, and biological data support possible efficacy of acupuncture for PTSD. However, further definitive research about simultaneous clinical and biological effects is needed to support the use of acupuncture for PTSD in health care systems.

Increased serum cortisol and growth hormone levels in earthquake survivors with PTSD or subclinical PTSD

Alteration of neuroendocrine systems has been demonstrated to be involved in the pathology of posttraumatic stress disorder (PTSD). Three months after an earthquake in Northern China, cortisol, growth hormone (GH) and prolactin (PRL) levels were assessed in 34 earthquake survivors with PTSD (according to DSM-IV criteria), 30 earthquake survivors with subclinical PTSD and 34 normal controls. Only earthquake survivors diagnosed with PTSD had significantly higher serum GH levels. Also, we found that earthquake survivors (either with PTSD or subclinical PTSD) had significantly higher serum cortisol levels. We concluded that PTSD might be associated with an increased level of serum GH and traumatic survivors might be associated with a higher level of serum cortisol.

Computational Modeling: A Tool for New Psychiatric Medication Development

&lt;p&gt;Computational models are being used in a variety of medical applications, including drug discovery research, where genomic and proteomic software tools facilitate modeling complex intracellular pathways. Increasing understanding of brain functioning due to advances in basic neuroscience techniques and imaging modalities has led to the emergence of computational modeling as an important tool for studying brain mechanisms and circuits. Recent advances in the areas of cellular neurophysiology and synaptic plasticity permit the development of biophysically realistic models that more closely approximate learning, both at the network and membrane levels. Such models have the potential to enhance a psychiatrist’s understanding of brain circuits with applicability to a range of phenomena from the mechanism of action of drugs to the neural basis of mental illness. An example case is provided in the fear circuit to illustrate the ability of a model to provide insights into possible sites for the storage of auditory fear and extinction memories. Since disruption of the fear circuit is thought to underlie the pathology of posttraumatic stress disorder (PTSD) and other anxiety disorders, such a model could potentially provide ideas and approaches for the development of new medications.&lt;/p&gt; &lt;h4&gt;ABOUT THE AUTHORS&lt;/h4&gt; &lt;p&gt;Guoshi Li, PhD candidate, and Satish S. Nair, PhD, are with the Department of Electrical and Computer Engineering, University of Missouri-Columbia. Jyotsna Nair, MD, is with the Department of Psychiatry, University of Missouri-Columbia. Gregory J. Quirk, PhD, is with the Department of Psychiatry, University of Puerto Rico School of Medicine, San Juan.&lt;/p&gt; &lt;p&gt;Address correspondence to: Satish S. Nair, PhD, &lt;a href="mailto:nairs@missouri.edu" target="_new"&gt;nairs@missouri.edu&lt;/a&gt;.&lt;/p&gt; &lt;p&gt;Mr. Li, Dr. Satish Nair, Dr. Jyotsna Nair, and Dr. Quirk have disclosed no relevant financial information.&lt;/p&gt;

Voxel-based diffusion tensor analysis reveals aberrant anterior cingulum integrity in posttraumatic stress disorder due to terrorism

Recent functional neuroimaging work has suggested that interregional functional connectivity between the anterior cingulate cortex (ACC), other limbic, and prefrontal regions may be involved in the pathophysiology of posttraumatic stress disorder (PTSD). However, less attention has been paid to the white matter network. Voxel-based analysis enables an exploration of morphological or functional changes throughout the entire brain. Here we undertook the first application of this technology to diffusion tensor data in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based analysis showed a significant fractional anisotropy increase in the left anterior cingulum, subjacent to the left ACC gray matter where we previously found a volume decrement, in PTSD subjects. Moreover, the severity was positively, but not significantly associated with the fractional anisotropy of the left anterior cingulum in the victims with PTSD, using the region of interest defined in the native space with the inverse normalization technique. The present study demonstrated further evidence of abnormalities of both the ACC, a structure that is pivotally involved in attention, emotional regulation, and fear conditioning, and of subjacent white matter in the pathology of PTSD.

Delayed-onset PTSD: A prospective study of injury survivors

Background Recent studies have indicated that delayed-onset posttraumatic stress disorder (PTSD) (i.e., the development of PTSD more than 6 months posttrauma) is generally characterised by subsyndromal diagnoses within the first 6 months. This study sought to examine the relationship between sub-clinical levels of PTSD symptoms at 3 months posttrauma and delayed onset PTSD at 12 months in a large sample of traumatic injury survivors. Methods Three hundred and one consecutively admitted injury survivors were assessed at 3 and 12 months posttrauma. PTSD was diagnosed according to DSM-IV criteria, while partial and subsyndromal diagnoses were based on recent definitions developed by Mylle and Maes [Mylle, J., Maes, M., 2004. Partial posttraumatic stress disorder revisited. J. Affect. Disord. 78, 37–48]. Results Eight percent of participants was diagnosed with 3-month PTSD while 10% was diagnosed with 12-month PTSD. Nearly half (47%) of 12-month PTSD cases were of delayed onset. The majority of those with delayed-onset were diagnosed with partial or subsyndromal PTSD at 3 months. Ten percent of delayed onset cases did not meet partial or subsyndromal criteria. Limitations As symptoms were not assessed at 6 months (the DSM cut-off for delayed PTSD), it could not be conclusively determined that delayed-onset cases had not developed PTSD between 3 and 6 months posttrauma. Conclusion A considerable proportion of 12-month PTSD diagnoses was delayed in onset. While most demonstrated 3-month morbidity in the form of partial and subsyndromal diagnoses, a minority did not. Thus, clinicians should consider subthreshold diagnoses as potential risk factors for delayed-onset PTSD. Future research is required to identify factors that may predict delayed-onset PTSD in trauma survivors without evidence of prior PTSD pathology.