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1.  PTSD symptom severity is associated with increased recruitment of top-down attentional control in a trauma-exposed sample☆ 
NeuroImage : Clinical  2014;7:19-27.
Recent neuroimaging work suggests that increased amygdala responses to emotional stimuli and dysfunction within regions mediating top down attentional control (dorsomedial frontal, lateral frontal and parietal cortices) may be associated with the emergence of anxiety disorders, including posttraumatic stress disorder (PTSD). This report examines amygdala responsiveness to emotional stimuli and the recruitment of top down attention systems as a function of task demands in a population of U.S. military service members who had recently returned from combat deployment in Afghanistan/Iraq. Given current interest in dimensional aspects of pathophysiology, it is worthwhile examining patients who, while not meeting full PTSD criteria, show clinically significant functional impairment.
Fifty-seven participants with sub-threshold levels of PTSD symptoms completed the affective Stroop task while undergoing fMRI. Participants with PTSD or depression at baseline were excluded.
Greater PTSD symptom severity scores were associated with increased amygdala activation to emotional, particularly positive, stimuli relative to neutral stimuli. Furthermore, greater PTSD symptom severity was associated with increased superior/middle frontal cortex response during task conditions relative to passive viewing conditions. In addition, greater PTSD symptom severity scores were associated with: (i) increased activation in the dorsolateral prefrontal, lateral frontal, inferior parietal cortices and dorsomedial frontal cortex/dorsal anterior cingulate cortex (dmFC/dACC) in response to emotional relative to neutral stimuli; and (ii) increased functional connectivity during emotional trials, particularly positive trials, relative to neutral trials between the right amygdala and dmFC/dACC, left caudate/anterior insula cortex, right lentiform nucleus/caudate, bilateral inferior parietal cortex and left middle temporal cortex.
We suggest that these data may reflect two phenomena associated with increased PTSD symptomatology in combat-exposed, but PTSD negative, armed services members. First, these data indicate increased emotional responsiveness by: (i) the positive relationship between PTSD symptom severity and amygdala responsiveness to emotional relative to neutral stimuli; (ii) greater BOLD response as a function of PTSD symptom severity in regions implicated in emotion (striatum) and representation (occipital and temporal cortices) during emotional relative to neutral conditions; and (iii) increased connectivity between the amygdala and regions implicated in emotion (insula/caudate) and representation (middle temporal cortex) as a function of PTSD symptom severity during emotional relative to neutral trials. Second, these data indicate a greater need for the recruitment of regions implicated in top down attention as indicated by (i) greater BOLD response in superior/middle frontal gyrus as a function of PTSD symptom severity in task relative to view conditions; (ii) greater BOLD response in dmFC/dACC, lateral frontal and inferior parietal cortices as a function of PTSD symptom severity in emotional relative to neutral conditions and (iii) greater functional connectivity between the amygdala and inferior parietal cortex as a function of PTSD symptom severity during emotional relative to neutral conditions.
•Greater PTSD symptoms associated with increased amygdala activation to emotional stimuli•PTSD symptoms associated with greater top down attention response in task and emotion conditions•PTSD symptoms were associated with slower reaction times.•Increased top down attention recruitment may compensate for heightened emotional responses.
PMCID: PMC4299952  PMID: 25610763
Post-traumatic stress disorder; Emotion attention; Amygdala; Top down attention
2.  Comparison of mental health between former child soldiers and children never conscripted by armed groups in Nepal 
JAMA : the journal of the American Medical Association  2008;300(6):10.1001/jama.300.6.691.
Despite child soldiers being considered in need of special mental health interventions, there is a lack of studies investigating the mental health of child soldiers compared with civilian children in armed conflicts.
To compare the mental health status of former child soldiers with children who have never been conscripts of armed groups.
Design, Setting, and Participants:
A matched-pair cohort study conducted from March through April 2007 in Nepal compared the mental health of 141 former child soldiers to 141 never conscripted children matched on age, sex, education, and ethnicity.
Outcome Measures:
Depression symptoms were assessed via the Depression Self Rating Scale (DSRS), anxiety symptoms via the Screen for Child Anxiety Related Emotional Disorders (SCARED-5), symptoms of posttraumatic stress disorder (PTSD) via the Child PTSD Symptom Scale (CPSS), general psychological difficulties via the Strength and Difficulties Questionnaire (SDQ), daily functioning via the Function Impairment (FI) tool, and exposure to traumatic events via Kiddie-Schedule of Affective Disorders and Schizophrenia (KIDDIE-SADS) PTSD Traumatic Event Checklist.
Participants were a mean of 15.75 years at the time of this study and child soldiers ranged in age from 5 to 16 years at the time of conscription. All participants experienced at least 1 type of trauma. Number (%) of child soldiers meeting cutoff scores were 75 (53.2%) for depression, 65 (46.1%) for anxiety, 78 (55.3%) for PTSD, 55 (39.0%) for psychological difficulties, and 88 (62.4%) for function impairment. Child soldiers had greater odds of meeting cutoff for depression (OR=3.56, 95% CI 2.33—5.43), PTSD (for which we employed stratified analyses because of sex interaction: boys’ OR=3.85, 95% CI 1.77—8.39; girls’ OR=6.33, 95% CI 2.64—15.17), psychological difficulties (OR=2.91, 95% CI=1.53—5.51), and function impairment (OR=2.04, 95% CI 1.41—2.96), but no difference for anxiety (OR=1.46, 95% CI 0.72—2.68). After adjusting for traumatic exposures, soldier status was no longer associated with psychological difficulties or function impairment but remained significantly associated with depression (OR=2.69, 95% CI 1.48—4.89) and PTSD among girls (OR=5.98, 95% CI 1.86—19.27), but not PTSD among boys (OR=2.38, 95% CI 0.87—6.50).
In Nepal, former child soldiers display greater severity of mental health problems compared with children never conscripted by armed groups, and this difference remains for depression and PTSD (the latter especially among girls) even after controlling for trauma exposure.
PMCID: PMC3842355  PMID: 18698067
3.  Attentional bias for trauma-related words: exaggerated emotional Stroop effect in Afghanistan and Iraq war veterans with PTSD 
BMC Psychiatry  2013;13:86.
Post-traumatic stress disorder (PTSD) involves debilitating symptoms that can disrupt cognitive functioning. The emotional Stroop has been commonly used to examine the impact of PTSD on attentional control, but no published study has yet used it with Afghanistan and Iraq war veterans, and only one previous study has compared groups on habituation to trauma-related words.
We administered the emotional Stroop, the Beck Depression Inventory (BDI), and the PTSD Checklist (PCL) to 30 veterans with PTSD, 30 military controls, and 30 civilian controls. Stroop word types included Combat, Matched-neutral, Neutral, Positive and Negative.
Compared to controls, veterans with PTSD were disproportionately slower in responding to Combat words. They were also slower and less accurate overall, did not show interference on Negative or Positive words relative to Neutral, and showed a trend for delayed but successful habituation to Combat words. Higher PCL and BDI scores also correlated with larger interference effects.
Because of its specificity in detecting attentional biases to trauma-related words, the emotional Stroop task may serve as a useful pre- and post task with intervention studies of PTSD patients.
PMCID: PMC3608167  PMID: 23496805
Posttraumatic stress disorder; PTSD; Stroop; Habituation; Trauma; Interference
4.  Sexual Violence and Mental Health Symptoms Among National Guard and Reserve Soldiers 
Reserve and National Guard (NG) soldiers report disproportionate mental health problems relative to active duty military upon returning from the Iraq and Afghanistan conflicts. However, few studies have examined whether exposure to particular types of traumatic events (e.g., lifetime sexual violence) is associated with this increased burden of psychopathology.
The current study examined the prevalence of lifetime sexual violence exposure as well as the adjusted odds and population attributable fraction of psychopathology associated with sexual violence in a large sample of male and female Reserve and NG soldiers.
Baseline structured telephone interviews were conducted in 2009.
1,030 Reserve (23 % female) and 973 NG (15 % female) soldiers.
Four items assessed lifetime and deployment-related sexual violence. Probable lifetime and past-year posttraumatic stress disorder (PTSD) and depression were assessed with the PTSD Checklist and the Patient Health Questionnaire, respectively.
Lifetime sexual violence prevalence was 37.4 % and 27.6 % among Reserve and NG women, and 4.3 % and 3.7 % among Reserve and NG men, respectively. Recent deployment-related sexual violence ranged from 1.4 to 2.6 % for women and 0 % for men. Regression analyses indicated that the adjusted odds of probable past-year and lifetime PTSD and depression were 1.2 to 3.5 times greater among those reporting sexual violence relative to non-victims. The proportion of probable lifetime PTSD and depression attributable to sexual violence was 45.2 % and 16.6 %, respectively, in the Reserves, and 10.3 % and 6.2 %, respectively, in the NG.
Lifetime sexual violence prevalence was high among female soldiers, with approximately one-third of Reserve and National Guard women reporting a history. The majority of sexual violence was not related to the most recent deployment; however, sexual violence contributed to a high burden of psychopathology. Findings emphasize a need to screen for lifetime sexual violence and associated mental disorders in military samples.
PMCID: PMC3889956  PMID: 23918158
reserve; national guard; sexual violence; PTSD; depression
5.  Childhood Trauma and PTSD Symptoms Increase the Risk of Cognitive Impairment in a Sample of Former Indentured Child Laborers in Old Age 
PLoS ONE  2013;8(2):e57826.
A growing body of evidence suggests a link between early childhood trauma, post-traumatic stress disorder (PTSD) and higher risk for dementia in old age. The aim of the present study was to investigate the association between childhood trauma exposure, PTSD and neurocognitive function in a unique cohort of former indentured Swiss child laborers in their late adulthood. To the best of our knowledge this is the first study ever conducted on former indentured child laborers and the first to investigate the relationship between childhood versus adulthood trauma and cognitive function. According to PTSD symptoms and whether they experienced childhood trauma (CT) or adulthood trauma (AT), participants (n = 96) were categorized as belonging to one of four groups: CT/PTSD+, CT/PTSD-, AT/PTSD+, AT/PTSD-. Information on cognitive function was assessed using the Structured Interview for Diagnosis of Dementia of Alzheimer Type, Multi-infarct Dementia and Dementia of other Etiology according to ICD-10 and DSM-III-R, the Mini-Mental State Examination, and a vocabulary test. Depressive symptoms were investigated as a potential mediator for neurocognitive functioning. Individuals screening positively for PTSD symptoms performed worse on all cognitive tasks compared to healthy individuals, independent of whether they reported childhood or adulthood adversity. When controlling for depressive symptoms, the relationship between PTSD symptoms and poor cognitive function became stronger. Overall, results tentatively indicate that PTSD is accompanied by cognitive deficits which appear to be independent of earlier childhood adversity. Our findings suggest that cognitive deficits in old age may be partly a consequence of PTSD or at least be aggravated by it. However, several study limitations need to considered. Consideration of cognitive deficits when treating PTSD patients and victims of lifespan trauma (even without a diagnosis of a psychiatric condition) is crucial. Furthermore, early intervention may prevent long-term deficits in memory function and development of dementia in adulthood.
PMCID: PMC3582641  PMID: 23469076
6.  A case–control study examining whether neurological deficits and PTSD in combat veterans are related to episodes of mild TBI 
BMJ Open  2012;2(2):e000312.
Mild traumatic brain injury (mTBI) is a common injury among military personnel serving in Iraq or Afghanistan. The impact of repeated episodes of combat mTBI is unknown.
To evaluate relationships among mTBI, post-traumatic stress disorder (PTSD) and neurological deficits (NDs) in US veterans who served in Iraq or Afghanistan.
This was a case–control study. From 2091 veterans screened for traumatic brain injury, the authors studied 126 who sustained mTBI with one or more episodes of loss of consciousness (LOC) in combat. Comparison groups: 21 combat veterans who had definite or possible episodes of mTBI without LOC and 21 veterans who sustained mTBI with LOC as civilians.
Among combat veterans with mTBI, 52% had NDs, 66% had PTSD and 50% had PTSD and an ND. Impaired olfaction was the most common ND, found in 65 veterans. The prevalence of an ND or PTSD correlated with the number of mTBI exposures with LOC. The prevalence of an ND or PTSD was >90% for more than five episodes of LOC. Severity of PTSD and impairment of olfaction increased with number of LOC episodes. The prevalence of an ND for the 34 combat veterans with one episode of LOC (4/34=11.8%) was similar to that of the 21 veterans of similar age and educational background who sustained civilian mTBI with one episode of LOC (2/21=9.5%, p-NS).
Impaired olfaction was the most frequently recognised ND. Repeated episodes of combat mTBI were associated with increased likelihood of PTSD and an ND. Combat setting may not increase the likelihood of an ND. Two possible connections between mTBI and PTSD are (1) that circumstances leading to combat mTBI likely involve severe psychological trauma and (2) that altered cerebral functioning following mTBI may increase the likelihood that a traumatic event results in PTSD.
Article summary
Article focus
Case–control study of mTBI associated with LOC among US veterans who were deployed to Iraq or Afghanistan during Operations Iraqi Freedom and Enduring Freedom.
Three study groups: (1) 126 veterans who had mTBI with LOC, (2) 21 OIF/OEF veterans who did not suffer mTBI with LOC and (3) 21 veterans who sustained mTBI with LOC in a civilian setting.
Evaluated NDs including a quantitative test of olfaction, PTSD with severity assessed using the PCL-M instrument and a cognitive function using the Montreal Cognitive Assessment Test.
Key messages
Olfaction was a sensitive test for neurological injury associated with mTBI with LOC.
More episodes of mTBI with LOC were associated with higher prevalence rates of NDs or of PTSD.
The severity of PTSD and extent of olfactory impairment increased with the number of episodes of LOC; cognitive function performance was inversely related to the number of episodes of LOC.
Strengths and limitations of this study
Case–control study of US combat veterans with mTBI who were assessed for NDs, PTSD and cognitive function.
Subjects and comparison groups had detailed assessments for NDs, and combat veterans were also assessed for PTSD.
The findings should be relevant to other groups of military personnel with combat mTBI.
The neurological examination was not blinded.
The selection of veterans in this study may be biased because veterans who do not have health issues may not seek care from the Department of Veterans Affairs.
The comparison groups were small.
The findings in veterans with mTBI with LOC may not apply to people with mTBI without LOC.
PMCID: PMC3312078  PMID: 22431700
7.  Concussive brain injury from explosive blast 
Explosive blast mild traumatic brain injury (mTBI) is associated with a variety of symptoms including memory impairment and posttraumatic stress disorder (PTSD). Explosive shock waves can cause hippocampal injury in a large animal model. We recently reported a method for detecting brain injury in soldiers with explosive blast mTBI using magnetic resonance spectroscopic imaging (MRSI). This method is applied in the study of veterans exposed to blast.
The hippocampus of 25 veterans with explosive blast mTBI, 20 controls, and 12 subjects with PTSD but without exposure to explosive blast were studied using MRSI at 7 Tesla. Psychiatric and cognitive assessments were administered to characterize the neuropsychiatric deficits and compare with findings from MRSI.
Significant reductions in the ratio of N-acetyl aspartate to choline (NAA/Ch) and N-acetyl aspartate to creatine (NAA/Cr) (P < 0.05) were found in the anterior portions of the hippocampus with explosive blast mTBI in comparison to control subjects and were more pronounced in the right hippocampus, which was 15% smaller in volume (P < 0.05). Decreased NAA/Ch and NAA/Cr were not influenced by comorbidities – PTSD, depression, or anxiety. Subjects with PTSD without blast had lesser injury, which tended to be in the posterior hippocampus. Explosive blast mTBI subjects had a reduction in visual memory compared to PTSD without blast.
The region of the hippocampus injured differentiates explosive blast mTBI from PTSD. MRSI is quite sensitive in detecting and localizing regions of neuronal injury from explosive blast associated with memory impairment.
PMCID: PMC4241796  PMID: 25493283
8.  PTSD, depression and anxiety among former abductees in Northern Uganda 
Conflict and Health  2011;5:14.
The population in Northern Uganda has been exposed to extreme levels of traumatic stress and thousands abducted forcibly became rebel combatants.
Using structured interviews, the prevalence and severity of posttraumatic stress disorder (PTSD), depression and anxiety was assessed in 72 former abducted adults, 62 of them being former child soldiers.
As retrospective reports of exposure to traumatic stress increased, anxiety and PTSD occurrence increased (r = .45). 49% of respondents were diagnosed with PTSD, 70% presented with symptoms of depression, and 59% with those of anxiety. In a multiple linear regression analysis four factors could best explain the development of PTSD symptoms: male respondents (sex) living in an IDP-Camp (location) with a kinship murdered in the war (family members killed in the war) and having experienced a high number of traumatic events (number of traumatic events) were more likely to develop symptoms of PTSD than others. In disagreement to a simple dose-response-effect though, we also observed a negative correlation between the time spent with the rebels and the PTSD symptom level.
Former abductees continue to suffer from severe mental ill-health. Adaptation to the living condition of rebels, however, may lower trauma-related mental suffering.
PMCID: PMC3171296  PMID: 21871069
9.  Resting-state hippocampal connectivity correlates with symptom severity in post-traumatic stress disorder 
NeuroImage : Clinical  2014;5:377-384.
Post-traumatic stress disorder (PTSD) is a serious mental health injury which can manifest after experiencing a traumatic life event. The disorder is characterized by symptoms of re-experiencing, avoidance, emotional numbing and hyper-arousal. Whilst its aetiology and resultant symptomology are better understood, relatively little is known about the underlying cortical pathophysiology, and in particular whether changes in functional connectivity may be linked to the disorder. Here, we used non-invasive neuroimaging with magnetoencephalography to examine functional connectivity in a resting-state protocol in the combat-related PTSD group (n = 23), and a military control group (n = 21). We identify atypical long-range hyperconnectivity in the high-gamma-band resting-state networks in a combat-related PTSD population compared to soldiers who underwent comparable environmental exposure but did not develop PTSD. Using graph analysis, we demonstrate that apparent network connectivity of relevant brain regions is associated with cognitive-behavioural outcomes. We also show that left hippocampal connectivity in the PTSD group correlates with scores on the well-established PTSD Checklist (PCL). These findings indicate that atypical synchronous neural interactions may underlie the psychological symptoms of PTSD, whilst also having utility as a potential biomarker to aid in the diagnosis and monitoring of the disorder.
Graphical abstract
•Soldiers with PTSD display increased connectivity in high gamma resting state.•Left frontal, temporal and hippocampus regions show hyperconnectivity in PTSD.•Emotionally-salient stimuli induced increased connectivity in soldiers without PTSD.•Connectivity strength in left hippocampus correlates with PTSD symptom severity.
PMCID: PMC4145533  PMID: 25180157
Post-traumatic stress disorder; Magnetoencephalography (MEG); Resting-state; Functional connectivity; Neural network
10.  Validation of the Pittsburgh Sleep Quality Index Addendum for Posttraumatic Stress Disorder (PSQI-A) in Male Military Veterans 
Journal of traumatic stress  2013;26(2):192-200.
Sleep disturbances are core symptoms of posttraumatic-stress disorder (PTSD), yet they bear less stigma than other PTSD symptoms. Given the growing number of returning military veterans, brief, valid assessments that identify PTSD in a minimally stigmatizing way may be highly useful in both research and clinical practice. The Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A) was examined for the ability to identify cases of PTSD among male military veterans. Male military veterans (N = 119) completed the PSQI-A, as well as measures of sleep quality, combat exposure, posttraumatic stress, depression, and anxiety. Veterans with PTSD had higher PSQI-A identified disruptive nocturnal behaviors than veterans without PTSD. The PSQI-A had good internal consistency and had convergent validity with sleep quality, combat exposure, PTSD symptoms, depression, and anxiety. A cutoff score ≥ 4 provided an area-under-the-curve = .81, with 71% sensitivity, 82% specificity, and 60% positive and 83% negative predictive value for a clinical diagnosis of PTSD; correct classification was 74%. The PSQI-A is a valid measure to possibly detect PTSD among male military veterans without directly probing trauma reactions. Assessment of disruptive nocturnal behaviors may provide a cost-effective, non-stigmatizing approach to PTSD screening among male military veterans.
PMCID: PMC3746481  PMID: 23512653
Nightmares; Psychometric; Trauma; Military; Combat; PTSD
11.  The Influence of Depressive Symptoms on Suicidal Ideation Among U.S. Vietnam-Era and Afghanistan/Iraq-Era Veterans With Posttraumatic Stress Disorder 
Journal of traumatic stress  2012;25(5):578-582.
Major depressive disorder (MDD) co-occurs frequently with posttraumatic stress disorder (PTSD), and both disorders are linked to suicidal ideation. An emergent literature examines suicidal ideation in U.S. Afghanistan/Iraq-era veterans. Little research, however, has studied the role of PTSD and comorbid MDD on suicidal ideation across service eras. Therefore, this study aimed to examine the impact of depression on suicidal ideation in Afghanistan/Iraq-era and Vietnam-era veterans with PTSD. The sample included 164 Vietnam and 98 Afghanistan/Iraq veterans diagnosed with PTSD at a VA outpatient PTSD Clinic. Using structured interviews, 63% of the Vietnam sample and 45% of the Afghanistan/Iraq sample were diagnosed with comorbid current MDD. Measures included self-report assessments of PTSD and depressive symptoms and the Personality Assessment Inventory. Results of analyses suggested that in veterans of both eras, PTSD, MDD, and their interaction were significantly related to suicidal ideation (PTSD: η2 = .01; MDD: η2 = .10; PTSD × MDD: η2 = .02). For veterans reporting greater depressive symptoms, there was a stronger relationship between PTSD symptoms and suicidal ideation. These results suggest that veterans from both eras display a similar clinical presentation and highlight the need to consider depressive symptoms when assessing veterans with PTSD. Future research should examine suicidal ideation and behaviors as they change over time in these two cohorts.
PMCID: PMC3752899  PMID: 23047458
12.  Psychopathological status, behavior problems, and family adjustment of Kuwaiti children whose fathers were involved in the first gulf war 
Following the end of the Gulf War that resulted in the liberation of Kuwait, there are no reports on the impact of veterans' traumatic exposure and posttraumatic stress disorder (PTSD) on their children. We compared the severity of anxiety, depression, deviant behavior and poor family adjustment among the children of a stratified random sample of four groups of Kuwaiti military men, viz: the retired; an active -in-the-army group (AIA) (involved in duties at the rear); an in-battle group (IB) (involved in combat); and a prisoners -of- war (POWs) group. Also, we assessed the association of father's PTSD/combat status and mother's characteristics with child psychosocial outcomes.
Subjects were interviewed at home, 6 years after the war, using: the Child Behavior Index to assess anxiety, depression, and adaptive behavior; Rutter Scale A2 for deviant behavior; and Family Adjustment Device for adjustment at home. Both parents were assessed for PTSD.
The 489 offspring (250 m, 239 f; mean age 13.8 yrs) belonged to 166 father-mother pairs. Children of POWs tended to have higher anxiety, depression, and abnormal behavior scores. Those whose fathers had PTSD had significantly higher depression scores. However, children of fathers with both PTSD and POW status (N = 43) did not have significantly different outcome scores than the other father PTSD/combat status groups. Mother's PTSD, anxiety, depression and social status were significantly associated with all the child outcome variables. Parental age, child's age and child's level of education were significant covariates. Although children with both parents having PTSD had significantly higher anxiety/depression scores, the mother's anxiety was the most frequent and important predictor of child outcome variables. The frequency of abnormal test scores was: 14% for anxiety/depression, and 17% for deviant behavior.
Our findings support the impression that child emotional experiences in vulnerable family situations transcend culture and are associated with the particular behavior of significant adults in the child's life. The primacy of the mother's influence has implications for interventions to improve the psychological functioning of children in such families. Mental health education for these families has the potential to help those in difficulty.
PMCID: PMC2423353  PMID: 18510770
13.  Combat Posttraumatic Stress Disorder, Substance Use Disorders, and Traumatic Brain Injury 
Journal of addiction medicine  2009;3(4):179-188.
Among both civilian and veteran populations, substance use disorders (SUDs) and anxiety disorders frequently co-occur. One of the most common comorbid anxiety disorder is posttraumatic stress disorder (PTSD), a condition which may develop after exposure to traumatic events, such as military combat. In comparison with the general population, rates of both SUDs and PTSD are elevated among veterans. Recent data show that soldiers returning from Iraq and Afghanistan demonstrate high rates of co-occurring SUDs, PTSD, and traumatic brain injury. Careful assessment of these conditions is critical and may be complicated by symptom overlap. More research targeting integrated interventions for these conditions is needed to establish optimal treatments.
PMCID: PMC4124907  PMID: 21769015
posttraumatic stress disorder; PTSD; substance use disorders; combat; TBI
14.  The role of major depression in neurocognitive functioning in patients with posttraumatic stress disorder 
European Journal of Psychotraumatology  2013;4:10.3402/ejpt.v4i0.19979.
Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) frequently co-occur after traumatic experiences and share neurocognitive disturbances in verbal memory and executive functioning. However, few attempts have been made to systematically assess the role of a comorbid MDD diagnosis in neuropsychological studies in PTSD.
The purpose of the current study is to investigate neurocognitive deficits in PTSD patients with and without MDD. We hypothesized that PTSD patients with comorbid MDD (PTSD+MDD) would have significantly lower performance on measures of verbal memory and executive functioning than PTSD patients without MDD (PTSD–MDD).
Participants included in this study were 140 treatment-seeking outpatients who had a diagnosis of PTSD after various single traumatic events and participated in a randomized controlled trial comparing different treatment types. Baseline neuropsychological data were compared between patients with PTSD+MDD (n=84) and patients with PTSD–MDD (n=56).
The PTSD+MDD patients had more severe verbal memory deficits in learning and retrieving words than patients with PTSD alone. There were no differences between the groups in recall of a coherent paragraph, recognition, shifting of attention, and cognitive interference.
The results of this study suggest that a more impaired neurocognitive profile may be associated with the presence of comorbid MDD, with medium-sized group differences for verbal memory but not for executive functioning. From a clinical standpoint, being aware that certain verbal memory functions are more restricted in patients with comorbid PTSD and MDD may be relevant for treatment outcome of trauma-focused psychotherapy.
PMCID: PMC3644057  PMID: 23671761
neuropsychology; cognitive functioning; PTSD; major depressive disorder; comorbidity
15.  Working memory processing of traumatic material in women with posttraumatic stress disorder 
Posttraumatic stress disorder (PTSD) is associated with medial frontal and amygdala functional alterations during the processing of traumatic material and frontoparietal dysfunctions during working memory tasks. This functional magnetic resonance imaging (fMRI) study investigated the effects of trauma-related words processing on working memory in patients with PTSD.
We obtained fMRI scans during a 3-back task and an identity task on both neutral and trauma-related words in women with PTSD who had been sexually abused and in healthy, nonexposed pair-matched controls.
Seventeen women with PTSD and 17 controls participated in the study. We found no behavioural working memory deficit for the PTSD group. In both tasks, deactivation of posterior parietal midline regions was more pronounced in patients than controls. Additionally, patients with PTSD recruited the left dorsolateral frontal sites to a greater extent during the processing of trauma-related material than neutral material.
This study included only women and did not include a trauma-exposed non-PTSD control group; the results may, therefore, have been influenced by sex or by effects specific to trauma exposure.
Our results broadly confirm frontal and parietal functional variations in women with PTSD and suggest a compensatory nature of these variations with regard to the retreival of traumatic memories and global attentional deficits, respectively, during cognitively challenging tasks.
PMCID: PMC3297067  PMID: 21971161
16.  Altered functional connectivity in posttraumatic stress disorder with versus without comorbid major depressive disorder: a resting state fMRI study 
F1000Research  2014;2:289.
Posttraumatic stress disorder (PTSD) is an anxiety disorder that is often diagnosed with comorbid depressive disorder. Therefore, neuroimaging studies investigating PTSD typically include both patients with and without comorbid depression. Differences in activity of the anterior cingulate cortex (ACC) and insula have been shown to differentiate PTSD patients with and without major depressive disorder (MDD). Whether or not comorbid MDD affects resting state functional connectivity of PTSD patients has not been investigated to our knowledge. Here, resting state functional connectivity of PTSD patients with (PTSD+MDD; n=27) and without (PTSD-MDD; n=23) comorbid MDD was investigated. The subgenual ACC and insula were investigated as seed regions. Connectivity between the subgenual ACC and perigenual parts of the ACC was increased in PTSD+MDD versus PTSD-MDD, which may reflect the presence of depressive specific symptoms such as rumination. Functional connectivity of the subgenual ACC with the thalamus was reduced, potentially related to more severe deficits in executive functioning in the PTSD+MDD group versus the PTSD-MDD group. In addition, the PTSD+MDD group showed reduced functional connectivity of the insula with the hippocampus compared to the PTSD-MDD group. However, this cluster was no longer significantly different when PTSD patients that were using medication were excluded from analyses. Thus, resting state functional connectivity of the subgenual ACC can distinguish PTSD+MDD from PTSD-MDD, and this may therefore be used as a neurobiological marker for comorbid MDD in the presence of PTSD. As PTSD+MDD are more treatment resistant, these findings can also guide treatment development, for example by targeting the subgenual ACC network with treatment.
PMCID: PMC4184309  PMID: 25309726
17.  A Prospective Study of PTSD and Early-Age Heart Disease Mortality Among Vietnam Veterans: Implications for Surveillance and Prevention 
Psychosomatic medicine  2008;70(6):668-676.
To examine prospectively early-age heart disease (HD) among a national random sample of 4328 male Vietnam veterans, who did not have HD at baseline in 1985. Studies have suggested that posttraumatic stress disorder (PTSD) may result in cardiovascular disease. However, many past studies had important methodological limitations to their designs.
Using Cox regressions, we assessed PTSD, age, race, intelligence, family history, obesity, smoking, alcohol abuse, antisocial personality, and depression in predicting HD mortality at follow-up in December 31, 2000. The men were <65 years old at follow-up.
Using two PTSD measures, a Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition (DSM-III) measure (D-PTSD) and one developed by Keane (K-PTSD), we found that among Vietnam theater and era veterans combined (era veterans had no Vietnam service), having PTSD was associated with HD mortality for D-PTSD (hazard ratio (HR) = 2.25, p = .045) and approached significance for K-PTSD (HR = 2.16, p = .066). However, having higher PTSD symptoms on either scale was associated with mortality, with a 5-point increase associated with ~20% increase in mortality risk (all p < .05). Controlling for lifetime depression only slightly altered the results. The effects for theater veterans alone were stronger (D-PTSD: HR = 2.58, p = .025; K-PTSD: HR = 2.73, p = .022). Among theater veterans, controlling for lifetime depression or combat exposure made little difference.
PTSD was prospectively associated with HD mortality among veterans free of HD at baseline. This study suggests that early-age HD may be an outcome after military service among PTSD-positive veterans.
PMCID: PMC3552245  PMID: 18596248
posttraumatic stress disorder; cardiovascular disease; survival analysis; depression; veterans
18.  Objective Neuropsychological Deficits in Post-Traumatic Stress Disorder and Mild Traumatic Brain Injury: What Remains Beyond Symptom Similarity? 
Behavioral Sciences  2014;4(4):471-486.
This exploratory study intends to characterize the neuropsychological profile in persons with post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) using objective measures of cognitive performance. A neuropsychological battery of tests for attention, memory and executive functions was administered to four groups: PTSD (n = 25), mTBI (n = 19), subjects with two formal diagnoses: Post-traumatic Stress Disorder and Mild Traumatic Brain Injury (mTBI/PTSD) (n = 6) and controls (n = 25). Confounding variables, such as medical, developmental or neurological antecedents, were controlled and measures of co-morbid conditions, such as depression and anxiety, were considered. The PTSD and mTBI/PTSD groups reported more anxiety and depressive symptoms. They also presented more cognitive deficits than the mTBI group. Since the two PTSD groups differ in severity of PTSD symptoms but not in severity of depression and anxiety symptoms, the PTSD condition could not be considered as the unique factor affecting the results. The findings underline the importance of controlling for confounding medical and psychological co-morbidities in the evaluation and treatment of PTSD populations, especially when a concomitant mTBI is also suspected.
PMCID: PMC4287701  PMID: 25469837
neuropsychological deficits; PTSD; mTBI; comorbidity; symptom similarity
19.  Posttraumatic Stress Disorder: Diagnostic Data Analysis by Data Mining Methodology 
Croatian medical journal  2007;48(2):185-197.
To use data mining methods in assessing diagnostic symptoms in posttraumatic stress disorder (PTSD)
The study included 102 inpatients: 51 with a diagnosis of PTSD and 51 with psychiatric diagnoses other than PTSD. Several models for predicting diagnosis were built using the random forest classifier, one of the intelligent data analysis methods. The first prediction model was based on a structured psychiatric interview, the second on psychiatric scales (Clinician-administered PTSD Scale – CAPS, Positive and Negative Syndrome Scale – PANSS, Hamilton Anxiety Scale – HAMA, and Hamilton Depression Scale – HAMD), and the third on combined data from both sources. Additional models placing more weight on one of the classes (PTSD or non-PTSD) were trained, and prototypes representing subgroups in the classes constructed.
The first model was the most relevant for distinguishing PTSD diagnosis from comorbid diagnoses such as neurotic, stress-related, and somatoform disorders. The second model pointed out the scores obtained on the Clinician-administered PTSD Scale (CAPS) and additional Positive and Negative Syndrome Scale (PANSS) scales, together with comorbid diagnoses of neurotic, stress-related, and somatoform disorders as most relevant. In the third model, psychiatric scales and the same group of comorbid diagnoses were found to be most relevant. Specialized models placing more weight on either the PTSD or non-PTSD class were able to better predict their targeted diagnoses at some expense of overall accuracy. Class subgroup prototypes mainly differed in values achieved on psychiatric scales and frequency of comorbid diagnoses.
Our work demonstrated the applicability of data mining methods for the analysis of structured psychiatric data for PTSD. In all models, the group of comorbid diagnoses, including neurotic, stress-related, and somatoform disorders, surfaced as important. The important attributes of the data, based on the structured psychiatric interview, were the current symptoms and conditions such as presence and degree of disability, hospitalizations, and duration of military service during the war, while CAPS total scores, symptoms of increased arousal, and PANSS additional criteria scores were indicated as relevant from the psychiatric symptom scales.
PMCID: PMC2080528  PMID: 17436383
20.  Examining the Relation Between Posttraumatic Stress Disorder and Suicidal Ideation, in an OEF/OIF Veteran Sample 
Journal of anxiety disorders  2010;25(1):12-18.
This study examined the relation between posttraumatic stress disorder (PTSD) and suicidal ideation among U.S. military veterans deployed during Operation Enduring Freedom and/or Operation Iraqi Freedom. Specific aims included investigation of (1) whether PTSD was associated with suicidal ideation after controlling for combat exposure and history of suicide attempt(s), (2) whether PTSD was associated with suicidal ideation absent a co-occurring depressive disorder (MDD) or alcohol use disorder (AUD), (3) whether co-occurring MDD or AUD increased risk of suicidal ideation among those with PTSD, and (4) whether PTSD/MDD symptom clusters were differentially associated with suicidal ideation. Results pointed to unique effects associated with prior suicide attempt(s), PTSD, and MDD. PTSD-diagnosed participants with co-occurring MDD or AUD were not significantly more likely to endorse suicidal ideation than PTSD-diagnosed participants without such comorbidity. The ‘emotional numbing’ cluster of PTSD symptoms and the ‘cognitive-affective’ cluster of MDD symptoms were uniquely associated with suicidal ideation.
PMCID: PMC3635678  PMID: 20709493
posttraumatic stress disorder; trauma; suicide; OEF-OIF; military
21.  Serotonin transporter gene polymorphisms and brain function during emotional distraction from cognitive processing in posttraumatic stress disorder 
BMC Psychiatry  2011;11:76.
Serotonergic system dysfunction has been implicated in posttraumatic stress disorder (PTSD). Genetic polymorphisms associated with serotonin signaling may predict differences in brain circuitry involved in emotion processing and deficits associated with PTSD. In healthy individuals, common functional polymorphisms in the serotonin transporter gene (SLC6A4) have been shown to modulate amygdala and prefrontal cortex (PFC) activity in response to salient emotional stimuli. Similar patterns of differential neural responses to emotional stimuli have been demonstrated in PTSD but genetic factors influencing these activations have yet to be examined.
We investigated whether SLC6A4 promoter polymorphisms (5-HTTLPR, rs25531) and several downstream single nucleotide polymorphisms (SNPs) modulated activity of brain regions involved in the cognitive control of emotion in post-9/11 veterans with PTSD. We used functional MRI to examine neural activity in a PTSD group (n = 22) and a trauma-exposed control group (n = 20) in response to trauma-related images presented as task-irrelevant distractors during the active maintenance period of a delayed-response working memory task. Regions of interest were derived by contrasting activation for the most distracting and least distracting conditions across participants.
In patients with PTSD, when compared to trauma-exposed controls, rs16965628 (associated with serotonin transporter gene expression) modulated task-related ventrolateral PFC activation and 5-HTTLPR tended to modulate left amygdala activation. Subsequent to combat-related trauma, these SLC6A4 polymorphisms may bias serotonin signaling and the neural circuitry mediating cognitive control of emotion in patients with PTSD.
The SLC6A4 SNP rs16965628 and 5-HTTLPR are associated with a bias in neural responses to traumatic reminders and cognitive control of emotions in patients with PTSD. Functional MRI may help identify intermediate phenotypes and dimensions of PTSD that clarify the functional link between genes and disease phenotype, and also highlight features of PTSD that show more proximal influence of susceptibility genes compared to current clinical categorizations.
PMCID: PMC3112079  PMID: 21545724
PTSD; imaging genetics; ventrolateral PFC; amygdala; SLC6A4; rs16965628; working memory; emotion processing; cognitive control
22.  Association of Variant rs4790904 in Protein Kinase C Alpha with Posttraumatic Stress Disorder in a U.S. Caucasian and African-American Veteran Sample 
Journal of depression & anxiety  2013;2(1):S4-001-.
Posttraumatic stress sisorder (PTSD) is a complex anxiety disorder that can develop after traumatic event exposure. Genetic factors have been associated with PTSD risk. Recently a variant rs4790904 in the protein kinase C alpha (PRKCA) gene has been shown to be associated with PTSD risk. The objective of this study was to replicate this association in a sample of U.S. Afghanistan/Iraq era veterans.
The genotypes of rs4790904 were evaluated in all trauma-exposed veterans. The sample of U.S. veterans included 428 Caucasians and 533 African-Americans. The statistical analysis was conducted independently in the Caucasian and African-American subjects to evaluate the association with PTSD symptom clusters of B symptoms (re-experiencing), C symptoms (avoidance and numbing), D symptoms (hyperarousal), and with current PTSD diagnosis.
The sample was comprised of 428 Caucasians (186 with current PTSD diagnosis, 242 trauma-exposed controls; median age, 35 years; 15% female) and 533 African-Americans (205 with current PTSD diagnosis, 328 trauma-exposed controls; median age, 41 years; 31% female). We observed a significant correlation between rs4790904 and all three PTSD symptom clusters in the Caucasian population, but no significant association with current PTSD diagnosis. However, these significant associations were with the G allele, rather than the A allele, that was previously reported by de Quervain. A significant association of this variant with current PTSD diagnosis (p=0.046) was detected in the African-American veterans.
We confirmed the correlation between rs4790904 and all three PTSD symptom clusters in the Caucasian but not the African-American population. A significant association with a current diagnosis of PTSD was found in the African-American veterans.
PMCID: PMC4021713  PMID: 24839585
Posttraumatic stress disorder; single nucleotide polymorphism (SNP); Variant rs4790904
23.  Risk Factors for Posttraumatic Stress Disorder Among Deployed US Male Marines 
BMC Psychiatry  2010;10:52.
Combat exposure has been reported as one of the strongest risk factors for postdeployment posttraumatic stress disorder (PTSD) among military service members. Determining the impact of specific deployment-related exposures on the risk of developing PTSD has not been fully explored. Our study objective was to explore the relationship between specific combat exposures and other life experiences with postdeployment PTSD.
This study consisted of male Marines who completed a Recruit Assessment Program (RAP) survey during recruit training at the Marine Corps Recruit Depot in San Diego, California as well as a follow-up survey several years after recruit training. Study participants included those Marines who deployed to the current operations in Iraq or Afghanistan between the baseline and follow-up surveys. Multivariable logistic regression was performed to determine which significant exposures and experiences were associated with postdeployment PTSD.
Of the 706 study participants, 10.8% screened positive for postdeployment PTSD. Those who reported feeling in great danger of death (odds ratio [OR] = 4.63, 95% confidence interval [CI]: 2.46-8.73), were shot or seriously injured (OR = 3.51, 95% CI: 1.58-7.77), saw someone wounded or killed (OR = 2.47, 95% CI: 1.08-5.67), and baseline (before recruit training) prior violence exposures (OR = 2.99, 95% CI: 1.46-6.10) were at increased odds for reporting PTSD symptoms. Number of deployments, number of close friends or relatives reported at follow-up, and enlisted pay grade were also significantly associated with postdeployment PTSD.
Combat exposures, specifically the threat of death, serious injury, and witnessing injury or death are significant risk factors for screening positive for postdeployment PTSD among male Marines as well as violence exposures prior to entering the Marine Corps, which are independent of future combat exposures. A thorough history of lifetime violence exposures should be pursued when considering a clinical diagnosis of PTSD.
PMCID: PMC2912797  PMID: 20579379
24.  Colour or shape: examination of neural processes underlying mental flexibility in posttraumatic stress disorder 
Translational Psychiatry  2014;4(8):e421-.
Posttraumatic stress disorder (PTSD) is a mental disorder that stems from exposure to one or more traumatic events. While PTSD is thought to result from a dysregulation of emotional neurocircuitry, neurocognitive difficulties are frequently reported. Mental flexibility is a core executive function that involves the ability to shift and adapt to new information. It is essential for appropriate social-cognitive behaviours. Magnetoencephalography (MEG), a neuroimaging modality with high spatial and temporal resolution, has been used to track the progression of brain activation during tasks of mental flexibility called set-shifting. We hypothesized that the sensitivity of MEG would be able to capture the abnormal neurocircuitry implicated in PTSD and this would negatively impact brain regions involved in set-shifting. Twenty-two soldiers with PTSD and 24 matched control soldiers completed a colour–shape set-shifting task. MEG data were recorded and source localized to identify significant brain regions involved in the task. Activation latencies were obtained by analysing the time course of activation in each region. The control group showed a sequence of activity that involved dorsolateral frontal cortex, insula and posterior parietal cortices. The soldiers with PTSD showed these activations but they were interrupted by activations in paralimbic regions. This is consistent with models of PTSD that suggest dysfunctional neurocircuitry is driven by hyper-reactive limbic areas that are not appropriately modulated by prefrontal cortical control regions. This is the first study identifying the timing and location of atypical neural responses in PTSD with set-shifting and supports the model that hyperactive limbic structures negatively impact cognitive function.
PMCID: PMC4150239  PMID: 25093599
25.  Internet-Based Early Intervention to Prevent Posttraumatic Stress Disorder in Injury Patients: Randomized Controlled Trial 
Posttraumatic stress disorder (PTSD) develops in 10-20% of injury patients. We developed a novel, self-guided Internet-based intervention (called Trauma TIPS) based on techniques from cognitive behavioral therapy (CBT) to prevent the onset of PTSD symptoms.
To determine whether Trauma TIPS is effective in preventing the onset of PTSD symptoms in injury patients.
Adult, level 1 trauma center patients were randomly assigned to receive the fully automated Trauma TIPS Internet intervention (n=151) or to receive no early intervention (n=149). Trauma TIPS consisted of psychoeducation, in vivo exposure, and stress management techniques. Both groups were free to use care as usual (nonprotocolized talks with hospital staff). PTSD symptom severity was assessed at 1, 3, 6, and 12 months post injury with a clinical interview (Clinician-Administered PTSD Scale) by blinded trained interviewers and self-report instrument (Impact of Event Scale—Revised). Secondary outcomes were acute anxiety and arousal (assessed online), self-reported depressive and anxiety symptoms (Hospital Anxiety and Depression Scale), and mental health care utilization. Intervention usage was documented.
The mean number of intervention logins was 1.7, SD 2.5, median 1, interquartile range (IQR) 1-2. Thirty-four patients in the intervention group did not log in (22.5%), 63 (41.7%) logged in once, and 54 (35.8%) logged in multiple times (mean 3.6, SD 3.5, median 3, IQR 2-4). On clinician-assessed and self-reported PTSD symptoms, both the intervention and control group showed a significant decrease over time (P<.001) without significant differences in trend. PTSD at 12 months was diagnosed in 4.7% of controls and 4.4% of intervention group patients. There were no group differences on anxiety or depressive symptoms over time. Post hoc analyses using latent growth mixture modeling showed a significant decrease in PTSD symptoms in a subgroup of patients with severe initial symptoms (n=20) (P<.001).
Our results do not support the efficacy of the Trauma TIPS Internet-based early intervention in the prevention of PTSD symptoms for an unselected population of injury patients. Moreover, uptake was relatively low since one-fifth of individuals did not log in to the intervention. Future research should therefore focus on innovative strategies to increase intervention usage, for example, adding gameplay, embedding it in a blended care context, and targeting high-risk individuals who are more likely to benefit from the intervention.
Trial Registration
International Standard Randomized Controlled Trial Number (ISRCTN): 57754429; (Archived by WebCite at
PMCID: PMC3742408  PMID: 23942480
early intervention; prevention; Internet; posttraumatic stress disorder; cognitive behavior therapy

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