Related Articles

Background

Increased activity of the habenula has been implicated in the etiology of major depressive disorder (MDD), in which reductions in habenula volume are present at postmortem. We conducted the first MRI analysis of habenula volume in MDD and bipolar disorder (BD).

Methods

High-resolution images (resolution≈0.4mm3) were acquired using a 3T scanner, and a pulse sequence optimized for tissue contrast resolution. The habenula was manually segmented by one rater blind to diagnosis. Seventy-four healthy controls (HC) were compared to both medicated (lithium/divalproex, n=15) and unmedicated, depressed BD (n=22) patients, unmedicated, depressed MDD patients (n=28), and unmedicated MDD patients in remission (RD, n=32).

Results

The unmedicated BD patients displayed significantly smaller absolute (p<0.01) and normalized (p<0.05) habenula volumes than the HC subjects. In post hoc assessments analyzing males and females separately, the currently-depressed females with MDD had smaller absolute (p<0.05) habenula volumes than the healthy control females. None of the other psychiatric groups differed significantly from the HC group.

Conclusions

We provide further evidence for the involvement of the habenula in affective illness, but suggest that a reduction in volume may be more pronounced in unmedicated, depressed BD subjects and female, currently depressed MDD subjects. The habenula plays major roles in the long-term modification of monoamine transmission and behavioral responses to stress, and in the suppression of dopamine cell activity following the absence of an expected reward. A reduction in habenula volume may thus have functional consequences which contribute to the risk for developing affective disease.

Objective

Gray matter loss in the limbic structures was found in recent onset post traumatic stress disorder (PTSD) patients. In the present study, we measured regional gray matter volume in trauma survivors to verify the hypothesis that stress may cause different regional gray matter loss in trauma survivors with and without recent onset PTSD.

Method

High resolution T1-weighted magnetic resonance imaging (MRI) were obtained from coal mine flood disaster survivors with (n = 10) and without (n = 10) recent onset PTSD and 20 no trauma exposed normal controls. The voxel-based morphometry (VBM) method was used to measure the regional gray matter volume in three groups, the correlations of PTSD symptom severities with the gray matter volume in trauma survivors were also analyzed by multiple regression.

Results

Compared with normal controls, recent onset PTSD patients had smaller gray matter volume in left dorsal anterior cingulate cortex (ACC), and non PTSD subjects had smaller gray matter volume in the right pulvinar and left pallidum. The gray matter volume of the trauma survivors correlated negatively with CAPS scores in the right frontal lobe, left anterior and middle cingulate cortex, bilateral cuneus cortex, right middle occipital lobe, while in the recent onset PTSD, the gray matter volume correlated negatively with CAPS scores in bilateral superior medial frontal lobe and right ACC.

Conclusion

The present study identified gray matter loss in different regions in recent onset PTSD and non PTSD after a single prolonged trauma exposure. The gray matter volume of left dorsal ACC associated with the development of PTSD, while the gray matter volume of right pulvinar and left pallidum associated with the response to the severe stress. The atrophy of the frontal and limbic cortices predicts the symptom severities of the PTSD.

Background

Controversy exists over the nature and origin of reduced regional brain volumes in post-traumatic stress disorder (PTSD). At issue is whether these reductions represent pre-existing vulnerability factors for developing PTSD upon traumatic exposure or acquired PTSD signs due to the traumatic stress that caused the PTSD and/or the chronic stress of having PTSD. We employed a case-control design in monozygotic twin pairs discordant for combat exposure to address the pre-existing vs. acquired origin of brain morphometric abnormalities in this disorder.

Method

We used voxel-based morphometry to search for gray matter density reductions in magnetic resonance imaging (MRI) data obtained in a previous study of combat-exposed Vietnam veteran twins with (n=18) vs. without (n=23) PTSD and their “high-risk” vs. “low-risk” (respectively), identical, combat-unexposed co-twins.

Results

Compared to the combat-exposed twins without PTSD, the combat-exposed twins with PTSD showed significant gray matter density reductions in four predicted brain regions: right hippocampus, pregenual anterior cingulate cortex (ACC), and left and right insulae. There was a significant PTSD Diagnosis × combat Exposure interaction in pregenual ACC, in which combat-exposed PTSD twins had lower gray matter density than their own combat-unexposed co-twins as well as than the combat-exposed twins without PTSD and their co-twins.

Conclusion

The results point to gray matter volume diminutions in limbic and paralimbic structures in PTSD. The pattern of results obtained for pregenual ACC suggests that gray matter reduction in this region represents an acquired sign of PTSD that is consistent with stress-induced loss.

The habenula complex modulates the a ctivity of dopamine and serotonin systems in the brain. An important question remains whether there is a link between habenula dysfunction and monoamine-related disorders, such as schizophrenia. In this study, we describe an interaction between habenula lesions and stress that produces long-lasting effects on behavior. Mice received control lesions or bilateral electrolytic lesions of the habenula and were tested for fear-potentiated startle and freezing measures of conditioned fear. They w ere also tested for prepulse inhibition (PPI) and locomotor activity in the presence or absence of a dopaminergic agonist (apomorphine) or an atypical antipsychotic with mixed dopamine/serotonin antagonist properties (clozapine). There were no detectable effects of habenula lesions on fear conditioning and no effects on PPI in the absence o f stress. However, following conditioned fear stress, habenula-lesioned animals showed decreased PPI which normalized with clozapine. Lesioned animals also showed diminished activity at baseline, with hyperlocomotion following apomorphine. These data support the hypothesis that the habenula may be normally involved in stress-dependent regulation of monoamine systems.

Most of magnetic resonance imaging (MRI) studies about post-traumatic stress disorder (PTSD) focused primarily on measuring of small brain structure volume or regional brain volume changes. There were rare reports investigating cortical thickness alterations in recent onset PTSD. Recent advances in computational analysis made it possible to measure cortical thickness in a fully automatic way, along with voxel-based morphometry (VBM) that enables an exploration of global structural changes throughout the brain by applying statistical parametric mapping (SPM) to high-resolution MRI. In this paper, Laplacian method was utilized to estimate cortical thickness after automatic segmentation of gray matter from MR images under SPM. Then thickness maps were analyzed by SPM8. Comparison between 10 survivors from a mining disaster with recent onset PTSD and 10 survivors without PTSD from the same trauma indicates cortical thinning in the left parietal lobe, right inferior frontal gyrus, and right parahippocampal gyrus. The regional cortical thickness of the right inferior frontal gyrus showed a significant negative correlation with the CAPS score in the patients with PTSD. Our study suggests that shape-related cortical thickness analysis may be more sensitive than volumetric analysis to subtle alteration at early stage of PTSD.

Background

Neuroimaging studies have proved that hippocampus relate to the deficient of memory in patients with post-traumatic stress disorder (PTSD). Many studies in healthy subjects also shown that insular cortex (IC) be involved in the declarative memory. This study was designed to investigate whether insular cortex is involved in declarative memory deficits in patients with PTSD.

Methods

Twelve subjects with PTSD and 12 subjects without PTSD victims underwent functional magnetic resonance imaging and magnetic resonance imaging. All subjects performed encoding and retrieval memory tasks during the fMRI session. Voxel-based morphometry method was used to analyze gray-matter volume, and the Statistical Parametric Mapping (SPM2) was used to analyze activated brain areas when performing tasks.

Results

Grey matter volume was significantly reduced bilaterally in the insular cortex of PTSD subjects than non-PTSD. PTSD group also had lower level of activation in insular cortex when performing word encoding and retrieval tasks than non-PTSD group.

Conclusion

The study provides evidence on structural and function abnormalities of the insular cortex in patients with PTSD. Reduced grey-matter volume in insular cortex may be associated with declarative memory deficits in patients with PTSD.

Objective

Hippocampal volume is reduced in posttraumatic stress disorder (PTSD). In the present study, we sought to determine whether volume loss is homogenously distributed or confined to certain part of the structure.

Method

Twenty-two adult outpatients with PTSD (11 after prolonged prepubertal trauma and 11 after single adult trauma) and 22 matched healthy subjects were scanned at the National Institute of Mental Health using high-resolution 3T magnetic resonance imaging between September 2003 and August 2004. PTSD diagnosis was conferred using the Structured Clinical Interview for DSM-IV. Volumes of whole, anterior, and posterior hippocampus and subiculum were compared between groups.

Results

Total hippocampal volume was lower in patients with PTSD (p = .2), with a significant diagnosis by hippocampal-subregion interaction (p = .2). Post hoc analysis revealed significantly smaller posterior hippocampi in PTSD (p = .006), with no difference in the volumes of anterior hippocampus or subiculum. No volume differences were found between PTSD participants with prolonged childhood abuse compared to single adult trauma exposure.

Conclusions

The posterior hippocampus has been associated with storage, processing, and retrieval of spatiotemporal memories, central to the protective function of fear conditioning. Volume deficit in the posterior hippocampus may indicate malfunction in this faculty, leading to the exaggerated conditioned fear response observed in PTSD.

Background

Several studies have investigated volumetric brain changes in patients with posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). Both groups exhibit volume reductions of the hippocampus and amygdala. Our aim was to investigate the influence of comorbid PTSD on hippocampus and amygdala volumes in patients with BPD.

Methods

We compared 2 groups of unmedicated female patients with BPD (10 with and 15 without comorbid PTSD) and 25 healthy female controls. We used T1- and T2-weighted magnetic resonance images for manual tracing and 3-dimensional reconstruction of the hippocampus and amygdala.

Results

Hippocampus volumes of patients with BPD and PTSD were smaller than those of healthy controls. However, there was no significant difference between patients with BPD but without PTSD and controls. Impulsiveness was positively correlated with hippocampus volumes in patients with BPD.

Limitations

Our study did not allow for disentangling the effects of PTSD and traumatization. Another limitation was the relatively small sample size.

Conclusion

Our findings highlight the importance of classifying subgroups of patients with BPD. Comorbid PTSD may be related to volumetric alterations in brain regions that are of central importance to our understanding of borderline psychopathology.

Objective

Exposure to parental verbal aggression (PVA) during childhood increases risk for the development of psychopathology, particularly mood and anxiety disorders. Other forms of childhood abuse have been found to be associated with alterations in brain structure. The aim of this study was to ascertain whether exposure to PVA was associated with discernible effects on brain morphology.

Methods

Optimized voxel based morphometry was performed on 21 unmedicated, right-handed subjects (18–25 years) with histories of PVA and 19 psychiatrically healthy controls of comparable age and gender. Group differences in gray matter volume (GMV) – covaried by age, gender, parental education, financial stress, and total GMV – were assessed using high-resolution, T1-weighted, volumetric MRI data sets (Siemens 3T trio scanner).

Results

GMV was increased by 14.1% in the left superior temporal gyrus (STG, BA 22) (P = 0.004, corrected cluster level). GMV in this cluster was associated most strongly with levels of maternal (β = 0.544, P < 0.0001) and paternal (β = 0.300, P < 0.02) verbal aggression and inversely associated with parental education (β = −0.577, P < 0.0001).

Conclusion

Previous studies have demonstrated an increase in STG GMV in children with abuse histories, and found a reduction in fractional anisotropy in the arcuate fasciculus connecting Wernicke’s and frontal areas in young adults exposed to PVA. These findings and the present results suggest that the development of auditory association cortex involved in language processing may be affected by exposure to early stress and/or emotionally-abusive language.

Several functional neuroimaging studies have implicated the cerebellar vermis in post-traumatic stress disorder (PTSD), but there have been no structural neuroimaging studies of this brain structure in PTSD. We utilized magnetic resonance imaging (MRI) with manual tracing to quantify the volumes of three divisions of the mid-sagittal vermis, and their total, within an identical, cotwin control design that employed Vietnam veterans discordant for combat exposure in Vietnam. Each structure’s volume was significantly correlated between twins, indicating a partial familial determination: for anterior superior vermis, r=0.73; for posterior superior vermis, r=0.47; for inferior posterior vermis, r=0.51; and for total vermis, r=0.57. There were no significant differences between the PTSD and non-PTSD veterans for any vermis volume, and no significant main effects or interactions when their non-combat-exposed co-twins were added to the analyses. Thus, the results do not support the structural abnormality of cerebellar vermis in combat-related PTSD.

MRI-based reports of both abnormally increased and decreased amygdala volume in bipolar disorder (BD) have surfaced in the literature. Two major methodological weaknesses characterizing extant studies are treatment with medication and inaccurate segmentation of the amygdala due to limitations in spatial and tissue contrast resolution. Here, we acquired high-resolution images (voxel size=0.55×0.55×0.60mm) using a GE 3T MRI scanner, and a pulse sequence optimized for tissue contrast resolution. The amygdala was manually segmented by one rater blind to diagnosis, using coronal images. Eighteen unmedicated (mean medication-free period 11±10 months) BD subjects were age and gender matched with 18 healthy controls, and 17 medicated (lithium or divalproex) subjects were matched to 17 different controls. The unmedicated BD patients displayed smaller left and right amygdala volumes than their matched control group (p<0.01). Conversely, the BD subjects undergoing medication treatment showed a trend towards greater amygdala volumes than their matched HC sample (p=0.051). Right and left amygdala volumes were larger (p<0.05) or trended larger, respectively, in the medicated BD sample compared with the unmedicated BD sample. The two control groups did not differ from each other in either left or right amygdala volume. BD patients treated with lithium have displayed increased gray matter volume of the cortex and hippocampus relative to untreated BD subjects in previous studies. Here we extend these results to the amygdala. We raise the possibility that neuroplastic changes in the amygdala associated with BD are moderated by some mood stabilizing medications.

Background:

Post-traumatic stress disorder (PTSD) is a psychiatric sequel to a stressful event or situation of an exceptionally threatening or catastrophic nature. Cognitive behavioral therapy (CBT) has been used in the management of PTSD for many years. This paper reviews the effectiveness of CBT for the treatment of PTSD following various types of trauma, its potential to prevent PTSD, methods used in CBT, and reflects on the mechanisms of action of CBT in PTSD.

Methods:

Electronic databases, including PubMed, were searched for articles on CBT and PTSD. Manual searches were conducted for cross-references in the relevant journal sites.

Results:

The current literature reveals robust evidence that CBT is a safe and effective intervention for both acute and chronic PTSD following a range of traumatic experiences in adults, children, and adolescents. However, nonresponse to CBT by PTSD can be as high as 50%, contributed to by various factors, including comorbidity and the nature of the study population. CBT has been validated and used across many cultures, and has been used successfully by community therapists following brief training in individual and group settings. There has been effective use of Internet-based CBT in PTSD. CBT has been found to have a preventive role in some studies, but evidence for definitive recommendations is inadequate. The effect of CBT has been mediated mostly by the change in maladaptive cognitive distortions associated with PTSD. Many studies also report physiological, functional neuroimaging, and electroencephalographic changes correlating with response to CBT.

Conclusion:

There is scope for further research on implementation of CBT following major disasters, its preventive potential following various traumas, and the neuropsychological mechanisms of action.

Although positive reward prediction error, a key element in learning that is signaled by dopamine cells, has been extensively studied, little is known about negative reward prediction errors in humans. Detailed animal electrophysiology shows that the habenula, an integrative region involved in many processes including learning, reproduction, and stress responses, also encodes negative reward-related events such as negative reward prediction error signals. In humans, however, the habenula's extremely small size has prevented direct assessments of its function. We developed a method to functionally locate and study the habenula in humans using fMRI, based on the expected reward-dependent response phenomenology of habenula and striatum and, we provide conclusive evidence for activation in human habenula to negative reward prediction errors.

Introduction

Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after exposure to a life-threatening traumatic experience. Meta-analyses of the brainstem showed that midsagittal area of the pons was significantly reduced in patients with PTSD, suggesting a potential apoptosis in dorsal raphe nucleus after single-prolonged stress (SPS). The aim of this study is to investigate whether SPS induces apoptosis in dorsal raphe nucleus in PTSD rats, which may be a possible mechanism of reduced volume of pons and density of gray matter.

Methods

In this study, rats were randomly divided into 1d, 7d and 14d groups after SPS along with the control group. The apoptosis rate was determined using annexin V-FITC/PI double-labeled flow cytometry (FCM). Levels of Cytochrome c (Cyt-C) was examined by Western blotting. Expression of Cyt-C on mitochondria in the dorsal raphe nucleus neuron was determined by enzymohistochemistry under transmission electron microscopy (TEM). The change of thiamine monophosphatase (TMP) levels was assessed by enzymohistochemistry under light microscope and TEM. Morphological changes of the ultrastructure of the dorsal raphe nucleus neuron were determined by TEM.

Results

Apoptotic morphological alterations were observed in dorsal raphe nucleus neuron for all SPS-stimulate groups of rats. The apoptosis rates were significantly increased in dorsal raphe nucleus neuron of SPS rats, along with increased release of cytochrome c from the mitochondria into the cytoplasm, increased expression of Cyt-C and TMP levels in the cytoplasm, which reached to the peak of increase 7 days of SPS.

Conclusions

The results indicate that SPS induced Cyt-C released from mitochondria into cytosol and apoptosis in dorsal raphe nucleus neuron of rats. Increased TMP in cytoplasm facilitated the clearance of apoptotic cells. We propose that this presents one of the mechanisms that lead to reduced volume of pons and gray matter associated with PTSD.

Objectives

This study had three objectives. Firstly, the prevalence of post-traumatic stress disorder (PTSD) and trauma exposure was compared between individuals with and without substance use disorder (SUD). Secondly, we compared self-rating of PTSD and clinical judgement. Thirdly, an analysis of the characteristics of SUD/PTSD patients was performed.

Methods

The sample consisted of 423 patients with SUD and 206 healthy controls. All individuals were screened on PTSD using the self-rating inventory for PTSD.

Results

Significantly higher numbers of PTSD and trauma exposure were found in the SUD group (resp. 36.6 and 97.4%). PTSD went frequently unnoticed when relying on clinical judgement alone. Patients with SUD/PTSD were significantly more often unemployed and had a lower educational level. Axis I comorbidity and especially depressive disorders were more common in the SUD/PTSD group.

Conclusion

It is concluded that patients with SUD/PTSD are a substantial and vulnerable subgroup in addiction treatment facilities and that a systematic screening for PTSD is required.

The comorbidity of pain syndromes and trauma related syndromes has been shown to be high. However, there have been limited data, especially in civilian medical populations, on the role of trauma related disorders such as Post Traumatic Stress Disorder (PTSD) on chronic pain and pain medication use. We analyzed 647 general hospital patients in primary care and obstetrics and gynecological waiting rooms for the experience of trauma and PTSD related stress disorders. PTSD symptoms were found to be significantly positively correlated with pain ratings (r=.282, p<.001) and pain related function impairment (r=.303, p<.001). Those with a current PTSD diagnosis had significantly higher subjective pain and pain related-impairment ratings than those with no PTSD. Furthermore, those with a current diagnosis of PTSD were significantly more likely to have used opioid analgesics for pain control compared to those without a diagnosis of PTSD (χ2=8.98, p=.011). When analyzing the separate PTSD symptom subclusters, (re-experiencing, avoidance and hyper-arousal), all symptom clusters were significantly related to pain and pain-related impairment ratings, but only the avoidance cluster was significantly related to prior opioid pain medication use. We conclude that PTSD and trauma-related disorders are common in impoverished medical populations and that their presence should be examined in patients with pain syndromes. Furthermore, these data suggest that PTSD and pain may share a vulnerability pathway including the endogenous opioid neurotransmission systems.

Background and methods

Factors contributing to posttraumatic stress disorder (PTSD) and comorbid major depression (MDD) were investigated among female victims of intimate partner violence (IPV).

Results

High levels of PTSD (75% of the sample) and MDD (54% of the sample) were observed. Individuals with both PTSD and MDD reported significantly greater levels of PTSD and depression symptoms than individuals with either PTSD alone or without major psychopathology. Individuals with comorbid PTSD and MDD had more maladaptive depressogenic cognitive styles than individuals without PTSD. The three groups were comparable in terms of pre-abuse mental health, childhood trauma history, and relationship violence variables and injuries. Maladaptive schemas did not contribute to the identification of comorbidity caseness, whereas PTSD severity and prior trauma did. Psychological aggression by an abuser and PTSD severity accounted for 52% of the variance in depressive symptoms.

Limitations

Cross-sectional design and lack of trauma-specific cognitive measures.

Conclusions

The findings confirm that comorbid PTSD and MDD is common among IPV victims. The mechanisms that contribute to comorbid depression, however, are unclear, and prospective studies are necessary to delineate the roles that psychological abuse, PTSD severity and prior trauma experiences may have in the development of depression following IPV.

Background

A central problem in posttraumatic stress disorder (PTSD) is a reduced capacity to suppress fear under safe conditions. Previously, we have shown that combat-related PTSD patients have impaired inhibition of fear-potentiated startle. Given the high comorbidity between PTSD and depression, our goal was to see whether this impairment is specific to PTSD, or a nonspecific symptom associated with both disorders.

Methods

Fear-potentiated startle (FPS) was assessed in 106 trauma-exposed individuals divided into four groups: a) No diagnosis control, b) PTSD only, c) major depression (MDD) only, and d) comorbid PTSD and MDD. We used a novel conditional discrimination procedure, in which one set of shapes (the danger signal) was paired with aversive airblasts to the throat, and different shapes (the safety signal) were presented without airblasts. The paradigm also included fear inhibition transfer test.

Results

Subjects with comorbid MDD and PTSD had higher FPS to the safety signal and to the transfer test compared to controls and MDD only subjects. In contrast to the control and MDD groups, the PTSD and comorbid PTSD and MDD groups did not show fear inhibition to safety cues.

Conclusions

These results suggest that impaired fear inhibition may be a specific biomarker of PTSD symptoms.

The present study describes Personality Assessment Inventory (PAI) profiles for women with posttraumatic stress disorder (PTSD). Four groups of women were sampled: single Axis I diagnosis of PTSD; PTSD and major depressive disorder (MDD); PTSD, MDD, at least one other Axis I disorder; and controls with no Axis I disorder. Higher comorbidity rates were associated with higher mean profile elevations and broader range of endorsed symptoms. The group with the highest rate of comorbidity produced profiles most similar to previously published reports of patients with PTSD. This is in contrast to women with a single diagnosis of PTSD, who produced relative mean elevations only on subscales measuring distress caused by trauma and physiological symptoms of depression. Thus, published profiles may be more reflective of PTSD with comorbidity than a single diagnosis of PTSD.

Over the past decade there has been consistent criticism of the diagnostic criteria of posttraumatic stress disorder (PTSD) because of its high comorbidity with other mental disorders. Part of the problem surrounding PTSD may be related to the heterogeneity of its symptoms. In fact, recent research has identified a subset of PTSD symptoms, including symptoms of numbing and dysphoria, that may explain much of the overlap between PTSD and major depressive disorder (MDD). The present study sought to extend prior work by investigating the various subsets of PTSD symptoms in individuals from all four diagnostic combinations of PTSD and MDD (no MDD-PTSD, MDD-only, PTSD-only, and comorbid MDD-PTSD). Consenting participants completed diagnostic interviews and were categorized into the four groups. Based on responses to a self-report measure of PTSD symptoms, participants with no MDD-PTSD reported the least severe symptoms while the participants with comorbid MDD-PTSD reported the most severe symptoms. Interesting, participants in the MDD-only and PTSD-only groups consistently reported similar scores across all PTSD symptom scales. These findings further highlight the problematic diagnostic criteria and comorbidity in PTSD and emphasize the need to incorporate transdiagnostic treatment practices that focus on the overlapping symptoms, rather than specific diagnostic categories.

Exposure to interparental violence is associated with negative outcomes, such as depression, post-traumatic stress disorder and reduced cognitive abilities. However, little is known about the potential effects of witnessing domestic violence during childhood on gray matter volume (GMV) or cortical thickness. High-resolution 3.0 T volumetric scans (Siemens Trio Scanner) were obtained on 52 subjects (18–25 years) including 22 (6 males/16 females) with a history of visually witnessing episodes of domestic violence, and 30 (8 males/22 females) unexposed control subjects, with neither a current nor past DSM-IV Axis I or II disorder. Potential confounding effects of age, gender, level of parental verbal aggression, parental education, financial stress, full scale IQ, and total GMV, or average thickness were modeled using voxel based morphometry and FreeSurfer. Witnessing domestic violence subjects had a 6.1% GMV reduction in the right lingual gyrus (BA18) (P = 0.029, False Discovery Rate corrected peak level). Thickness in this region was also reduced, as was thickness in V2 bilaterally and left occipital pole. Theses regions were maximally sensitive to exposure to witnessing domestic violence between 11–13 years of age. Regional reductions in GMV and thickness were observed in both susceptible and resilient witnessing domestic violence subjects. Results in subjects witnessing domestic violence were similar to previously reported results in subjects with childhood sexual abuse, as the primary region affected was visual cortex. Brain regions that process and convey the adverse sensory input of the abuse may be specifically modified by this experience, particularly in subjects exposed to a single type of maltreatment. Exposure to multiple types of maltreatment is more commonly associated with morphological alterations in corticolimbic regions. These findings fit with preclinical studies showing that visual cortex is a highly plastic structure.

Context

Most neuroimaging studies of posttraumatic stress disorder (PTSD) have focused on potential abnormalities in the whole hippocampus, but the subfields of this structure, which have distinctive histological characteristics and specialized functions, have not been investigated. Studies of individual subfields may clarify the role of the hippocampus in PTSD.

Objective

To determine if PTSD is associated with structural alterations in specific subfields of the hippocampus.

Design

Case-control study.

Participants

A total of 17 male veterans with combat trauma and PTSD (mean [SD] age, 41[12] years) and 19 age-matched male veterans without PTSD who were recruited from the outpatient mental health clinic of the San Francisco Veterans Affairs Medical Center and by advertising in the community.

Interventions

High-resolution magnetic resonance imaging at 4 T.

Main Outcome Measure

Volumes of hippocampal subfields.

Results

Posttraumatic stress disorder was associated with 11.4%(1.5%) (P = .02) smaller mean (SD) cornu ammonis 3 (CA3)/dentate gyrus subfield volumes, irrespective of age-related alterations, whereas other subfields were spared. Age was associated with reduced volume of the CA1 subfield (P = .03). Total hippocampal volume was also reduced in PTSD by a mean (SD) of 6.5%(0.6%) but, related to both PTSD (P = .05) and age (P = .01), was consistent with the measurements in the subfields.

Conclusions

The findings indicate for the first time in humans that PTSD is associated with selective volume loss of the CA3/dentate gyrus subfields, consistent with animal studies, implying that chronic stress suppresses neurogenesis and dendritic branching in these structures.

Abstract

Objective

The subgenual cingulate (SGC) cortex has been implicated in the pathophysiology of mood disorders. We sought to study morphometric characteristics of the SGC in pediatric subjects with familial bipolar disorder (BD) compared with healthy controls.

Method

Twenty children and adolescents with BD (mean age = 14.6 years, 4 females) and 20 healthy age-, gender-, and intelligence quotient-matched controls underwent high-resolution anatomical magnetic resonance imaging. Patients were primarily euthymic and most were taking medications. SGC cortex volumes were determined by manual tracings from a reliable rater, blinded to diagnosis. Analyses of covariance were performed with total cerebral gray matter and age as covariates.

Results

No differences were found in SGC volumes between BD subjects and healthy controls. Further analysis revealed that BD subjects with past mood stabilizer exposure had significantly increased SGC volumes compared with BD subjects without mood stabilizer exposure, and compared with controls. The increase was driven by larger bilateral posterior SGC volumes.

Conclusions

Youth with familial BD do not appear to have abnormalities in SGC volume. Mood stabilizer exposure, however, may be correlated with increases in SGC volume.

The aim of this study was to assess eventual differences in serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, LDL-C/HDL-C ratio between veterans with combat-related posttraumatic stress disorder (PTSD) only or comorbid with major depressive disorder (MDD), veterans with combat experiences with MDD, and healthy control group. PTSD and/ or MDD were diagnose according to structured clinical interview based on DSM-IV criteria. Additional criteria to diagnose PTSD were Clinician Administered PTSD Scale (CAPS), and to diagnose MDD Montgomery-Asberg Depression Rating Scale (MADRAS). Serum lipid concentrations were determined by using the enzyme-assay method. Veterans with combat-related PTSD as well as veterans with combat-related PTSD comorbid with MDD showed significantly higher concentrations of cholesterol (F=9.858, p<0.01), triglycerides (F=10.112, p<0.01), LDL-C (F=11.145, p<0.01), and LDL-C/HDL-C ratio (F=8.346, p<0.01) vs. veterans with MDD or healthy control group. Contrary healthy control group and veterans with MDD showed significantly higher concentrations of HDL-C (F=8.421, p<0.01), vs. veterans with PTSD or PTSD comorbid with MDD. In conclusion, there are no differences in serum lipid concentrations between veterans with combat-related PTSD and PTSD comorbid with MDD, but they have higher lipid concentrations than veterans with MDD or healthy control subjects.

Although prolonged exposure (PE) has received the most empirical support of any treatment for post-traumatic stress disorder (PTSD), clinicians are often hesitant to use PE due to beliefs that it is contraindicated for many patients with PTSD. This is especially true for PTSD patients with comorbid problems. Because PTSD has high rates of comorbidity, it is important to consider whether PE is indeed contraindicated for patients with various comorbid problems. Therefore, in this study, we examine the evidence for or against the use of PE with patients with problems that often co-occur with PTSD, including dissociation, borderline personality disorder, psychosis, suicidal behavior and non-suicidal self-injury, substance use disorders, and major depression. It is concluded that PE can be safely and effectively used with patients with these comorbidities, and is often associated with a decrease in PTSD as well as the comorbid problem. In cases with severe comorbidity, however, it is recommended to treat PTSD with PE while providing integrated or concurrent treatment to monitor and address the comorbid problems.