The Impact of Common Psychiatric and Behavioral Comorbidities on Functional Disability Across Time and Individuals in Post-9/11 Veterans.

Returning veterans often face multiple concurrent psychiatric and behavioral conditions that negatively impact reintegration into civilian life and are associated with functional disability. Understanding how conditions interact to negatively impact functioning is an important step toward developing holistic treatment approaches optimized for this population. This study utilized a cross-sectional and prospective longitudinal cohort design, applying regression algorithms to understand the relative contribution of common clinical issues to functional disability in U.S. veterans who served after the September 11, 2001 (9/11), terror attacks. Community-dwelling post-9/11 veterans (N = 397) completed detailed assessments, including common clinical condition diagnoses, combat experience, and demographics, which were used to predict functional disability (World Health Organization Disability Assessment Schedule); 205 participants were reassessed approximately 1-2 years after enrollment. Regression analyses showed a strong association between the predictor variables and functional disability, f 2 = 1.488. Validation analyses showed a high prediction ability of functional disability to independent samples, r = .719, and across time in the same individuals, r = .780. The strongest predictors included current posttraumatic stress disorder, depressive disorder, sleep disturbance, and pain diagnoses. These results demonstrate the importance of considering multiple common co-occurring conditions when assessing functional disability in post-9/11 veterans and suggest that certain syndromes contribute the most unique information to predicting functional disability with high confidence. As most U.S. veterans utilize private healthcare systems, these results have clinical utility for both Veterans Affairs and civilian healthcare practitioners in assessing and monitoring functional disability in post-9/11 veterans over time.

The Deployment Trauma Phenotype and Employment Status in Veterans of the Wars in Iraq and Afghanistan.

OBJECTIVES: To determine the prevalence of comorbid mild traumatic brain injury (mTBI), posttraumatic stress disorder (PTSD), and depression, termed the deployment trauma phenotype (DTP), and its constituent diagnoses' impact on unemployment status in a national cohort of veterans. SETTING: Retrospective analysis of the comprehensive TBI evaluation, a Veterans Affairs-wide protocol for assessing TBI, employment status, and psychiatric impressions. PARTICIPANTS: The final data set consisted of 48 821 veterans. MAIN OUTCOMES AND MEASURES: Frequency of mTBI, PTSD, and depression in isolation and combinations and their association with unemployment status. RESULTS: Age- and education-adjusted risk ratios (RRs) showed that the mTBI-only group was the least likely to be unemployed, RR = 0.65 (0.59-0.71). By contrast, the greatest likelihood of unemployment was associated with membership in the DTP group, RR = 1.45 (1.36-1.56), and the comorbid PTSD and depression group, RR = 1.39 (1.27-1.52). Furthermore, the DTP was nearly 3 times more prevalent (16.4%) in this sample compared with comorbid PTSD and depression (5.7%), indicating that the DTP conveys risk for unemployment to a significantly greater number of individuals. CONCLUSIONS AND RELEVANCE: The comorbid and interactive conditions of PTSD, depression, and mTBI, rather than mTBI in isolation, were linked to significant risk for unemployment in this veteran cohort. These findings suggest that multifaceted assessments and interventions to improve postdeployment reintegration are needed.

Associations Among Posttraumatic Stress Disorder Symptoms, Substance Use, and Affective Attentional Processing in OEF/OIF/OND Veterans.

The majority of research examining affective attentional bias in posttraumatic stress disorder (PTSD) has not examined the influence of co-occurring psychiatric disorders. This study examined the individual and interactive effects of PTSD symptoms and substance use disorders (SUDs) on affective attentional processing among 323 veterans deployed to Iraq or Afghanistan. Participants were divided into those with SUD (SUD+, n = 46) and those without (SUD-, n = 277). Substance use disorder was determined using the Structured Clinical Interview for DSM-IV. Posttraumatic stress disorder was measured using the Clinician Administered PTSD Scale. A computerized go/no-go task (Robbins et al., 1994, Robbins et al.,1998) assessed affective attentional processing. Relative to those without SUD, those with SUD showed a significant association between PTSD symptoms and increased omission and commission accuracy rates and decreased d prime. No effects of valence were found. Findings suggest the need to consider co-occurring SUD when investigating the effects of PTSD on attentional control.

Neurobiological indicators of disinhibition in posttraumatic stress disorder.

Deficits in impulse control are increasingly recognized in association with posttraumatic stress disorder (PTSD). To our further understanding of the neurobiology of PTSD-related disinhibition, we examined alterations in brain morphology and network connectivity associated with response inhibition failures and PTSD severity. The sample consisted of 189 trauma-exposed Operation Enduring Freedom/Operation Iraqi Freedom veterans (89% male, ages 19-62) presenting with a range of current PTSD severity. Disinhibition was measured using commission errors on a Go/No-Go (GNG) task with emotional stimuli, and PTSD was assessed using a measure of current symptom severity. Whole-brain vertex-wise analyses of cortical thickness revealed two clusters associated with PTSD-related disinhibition (Monte Carlo cluster corrected P < 0.05). The first cluster included portions of right inferior and middle frontal gyri and frontal pole. The second cluster spanned portions of left medial orbital frontal, rostral anterior cingulate, and superior frontal gyrus. In both clusters, commission errors were associated with reduced cortical thickness at higher (but not lower) levels of PTSD symptoms. Resting-state functional magnetic resonance imaging analyses revealed alterations in the functional connectivity of the right frontal cluster. Together, study findings suggest that reductions in cortical thickness in regions involved in flexible decision-making, emotion regulation, and response inhibition contribute to impulse control deficits in PTSD. Furthermore, aberrant coupling between frontal regions and networks involved in selective attention, memory/learning, and response preparation suggest disruptions in functional connectivity may also play a role.

Correspondence of the Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) clinical interview and the VA TBI screen.

OBJECTIVE: Mild traumatic brain injury is the signature injury of Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND), yet its identification and diagnosis is controversial and fraught with challenges. SETTING: In 2007, the Department of Veterans Affairs (VA) implemented a policy requiring traumatic brain injury (TBI) screening on all individuals returning from deployment in the OEF/OIF/OND theaters of operation that lead to the rapid and widespread use of the VA TBI screen. The Boston Assessment of TBI-Lifetime (BAT-L) is the first validated, postcombat semistructured clinical interview to characterize head injuries and diagnose TBIs throughout the life span, including prior to, during, and post-military service. PARTICIPANTS: Community-dwelling convenience sample of 179 OEF/OIF/OND veterans. MAIN MEASURES: BAT-L, VA TBI screen. RESULTS: Based on BAT-L diagnosis of military TBI, the VA TBI screen demonstrated similar sensitivity (0.85) and specificity (0.82) when administered by research staff. When BAT-L diagnosis was compared with historical clinician-administered VA TBI screen in a subset of participants, sensitivity was reduced. CONCLUSIONS: The specificity of the research-administered VA TBI screen was more than adequate. The sensitivity of the VA TBI screen, although relatively high, suggests that it does not oversample or "catch all" possible military TBIs. Traumatic brain injuries identified by the BAT-L, but not identified by the VA TBI screen, were predominantly noncombat military injuries. There is potential concern regarding the validity and reliability of the clinician administered VA TBI screen, as we found poor correspondence between it and the BAT-L, as well as low interrater reliability between the clinician-administered and research-administered screen.

The Boston Assessment of Traumatic Brain Injury-Lifetime (BAT-L) semistructured interview: evidence of research utility and validity.

OBJECTIVE: Report the prevalence of lifetime and military-related traumatic brain injuries (TBIs) in Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) veterans and validate the Boston Assessment of TBI-Lifetime (BAT-L). SETTING: The BAT-L is the first validated, postcombat, semistructured clinical interview to characterize head injuries and diagnose TBIs throughout the life span. PARTICIPANTS: Community-dwelling convenience sample of 131 OEF/OIF veterans. DESIGN: TBI criteria (alteration of mental status, posttraumatic amnesia, and loss of consciousness) were evaluated for all possible TBIs, including a novel evaluation of blast exposure. MAIN MEASURES: BAT-L, Ohio State University TBI Identification Method (OSU-TBI-ID). RESULTS: About 67% of veterans incurred a TBI in their lifetime. Almost 35% of veterans experienced at least 1 military-related TBI; all were mild in severity, 40% of them were due to blast, 50% were due to some other (ie, blunt) mechanism, and 10% were due to both types of injuries. Predeployment TBIs were frequent (45% of veterans). There was strong correspondence between the BAT-L and the OSU-TBI-ID (Cohen κ = 0.89; Kendall τ-b = 0.95). Interrater reliability of the BAT-L was strong (κs >0.80). CONCLUSIONS: The BAT-L is a valid instrument with which to assess TBI across a service member's lifetime and captures the varied and complex nature of brain injuries across OEF/OIF veterans' life span.

PTSD modifies performance on a task of affective executive control among deployed OEF/OIF veterans with mild traumatic brain injury.

Individuals with post-traumatic stress disorder (PTSD) show a cognitive bias for threatening information, reflecting dysregulated executive control for affective stimuli. This study examined whether comorbid mild Traumatic Brain Injury (mTBI) with PTSD exacerbates this bias. A computer-administered Affective Go/No-Go task measured reaction times (RTs) and errors of omission and commission to words with a non-combat-related positive or negative valence in 72 deployed United States service members from the wars in Iraq and Afghanistan. Incidents of military-related mTBI were measured with the Boston Assessment of Traumatic Brain Injury-Lifetime. PTSD symptoms were measured with the Clinician-Administered PTSD Scale. Participants were divided into those with (mTBI+, n = 34) and without a history of military-related mTBI (mTBI-, n = 38). Valence of the target stimuli differentially impacted errors of commission and decision bias (criterion) in the mTBI+ and mTBI- groups. Specifically, within the mTBI+ group, increasing severity of PTSD symptoms was associated with an increasingly liberal response pattern (defined as more commission errors to negative distractors and greater hit rate for positive stimuli) in the positive compared to the negative blocks. This association was not observed in the mTBI- group. This study underscores the importance of considering the impact of a military-related mTBI and PTSD severity upon affective executive control.

A recommended scale for cognitive screening in clinical trials of Parkinson's disease.

Cognitive impairment is common in Parkinson's disease (PD). There is a critical need for a brief, standard cognitive screening measure for use in PD trials whose primary focus is not on cognition. The Parkinson Study Group (PSG) Cognitive/Psychiatric Working Group formed a Task Force to make recommendations for a cognitive scale that could screen for dementia and mild cognitive impairment in clinical trials of PD where cognition is not the primary outcome. This Task Force conducted a systematic literature search for cognitive assessments previously used in a PD population. Scales were then evaluated for their appropriateness to screen for cognitive deficits in clinical trials, including brief administration time (<15 minutes), assessment of the major cognitive domains, and potential to detect subtle cognitive impairment in PD. Five scales of global cognition met the predetermined screening criteria and were considered for review. Based on the Task Force's evaluation criteria the Montreal Cognitive Assessment (MoCA), appeared to be the most suitable measure. This Task Force recommends consideration of the MoCA as a minimum cognitive screening measure in clinical trials of PD where cognitive performance is not the primary outcome measure. The MoCA still requires further study of its diagnostic utility in PD populations but appears to be the most appropriate measure among the currently available brief cognitive assessments. Widespread adoption of a single instrument such as the MoCA in clinical trials can improve comparability between research studies on PD.

Contrast sensitivity in Parkinson's disease patients with subthalamic nucleus deep brain stimulation.

This study examined whether deep brain stimulation (DBS) would affect the contrast sensitivity (CS) curve in patients with PD. CS was tested in 12 nondemented PD patients treated with bilateral subthalamic nucleus DBS on and off stimulation and medications. Neither stimulation condition (on vs. off) nor medications altered CS performance in this group of patients. However, collapsed across conditions, patients with bipolar stimulation in this study had significantly poorer CS at higher spatial frequencies (12 and 18 cycles per degree) than patients with monopolar stimulation. This suggests that CS deficits in PD may possibly be influenced by DBS polarity and merits further study.

Role of a lateralized parietal-basal ganglia circuit in hierarchical pattern perception: evidence from Parkinson's disease.

The role of corticostriatal circuits in hierarchical pattern perception was examined in Parkinson's disease. The hypothesis was tested that patients with right-side onset of motor symptoms (RPD, left hemisphere dysfunction) would be impaired at local level processing because the left posterior temporoparietal junction (TP) emphasizes processing of local information. By contrast, left-side onset patients (LPD; right hemisphere dysfunction) would show impaired global processing because right TP emphasizes global processing. Participants identified targets at local or global levels without and with attention biased toward those levels. Despite normal attentional control between levels, LPD patients showed a single dissociation, demonstrating abnormal global level processing under all conditions, whereas RPD patients showed abnormal local level processing mainly when attention was biased toward the local level. These findings link side of motor symptom onset to visuospatial cognitive abilities that depend upon the contralateral TP, highlighting that side of onset can predict visuospatial impairments, and provide evidence that an inferior parietal-basal ganglia pathway involving the caudate head and the hemispherically asymmetrical TP region is necessary for hierarchical pattern perception.

Rhinorrhea is increased in Parkinson's disease.

We have observed that rhinorrhea is increased in people with Parkinson's disease (PD) but only a single publication supports this. We performed two separate case control studies to assess the prevalence of rhinorrhea in PD in Rhode Island. One was cross-sectional and the other in consecutive de novo patients. We further questioned subjects as to whether rhinorrhea might be associated with olfactory impairment. We found that rhinorrhea affects about half of PD patients in Rhode Island, is an early feature, being present at the time of presentation, was significantly more common than in controls and was associated with self-perceived reduced olfaction. These observations confirm that rhinorrhea is a common problem and raise the questions as to whether some olfactory impairment found in PD could be confounded by rhinorrhea and also whether rhinorrhea may be a premotor symptom.

Computerized maze navigation and on-road performance by drivers with dementia.

This study examined the ability of computerized maze test performance to predict the road test performance of cognitively impaired and normal older drivers. The authors examined 133 older drivers, including 65 with probable Alzheimer disease, 23 with possible Alzheimer disease, and 45 control subjects without cognitive impairment. Subjects completed 5 computerized maze tasks employing a touch screen and pointer as well as a battery of standard neuropsychological tests. Parameters measured for mazes included errors, planning time, drawing time, and total time. Within 2 weeks, subjects were examined by a professional driving instructor on a standardized road test modeled after the Washington University Road Test. Road test total score was significantly correlated with total time across the 5 mazes. This maze score was significant for both Alzheimer disease subjects and control subjects. One maze in particular, requiring less than 2 minutes to complete, was highly correlated with driving performance. For the standard neuropsychological tests, highest correlations were seen with Trail Making A (TrailsA) and the Hopkins Verbal Learning Tests Trial 1 (HVLT1). Multiple regression models for road test score using stepwise subtraction of maze and neuropsychological test variables revealed significant independent contributions for total maze time, HVLT1, and TrailsA for the entire group; total maze time and HVLT1 for Alzheimer disease subjects; and TrailsA for normal subjects. As a visual analog of driving, a brief computerized test of maze navigation time compares well to standard neuropsychological tests of psychomotor speed, scanning, attention, and working memory as a predictor of driving performance by persons with early Alzheimer disease and normal elders. Measurement of maze task performance appears to be useful in the assessment of older drivers at risk for hazardous driving.

HIV infection affects parietal-dependent spatial cognition: evidence from mental rotation and hierarchical pattern perception.

Human immunodeficiency virus (HIV) in the asymptomatic phase of the infection impairs some aspects of cognition, but little is known about how visuospatial functions are affected. In the present study, performance on tasks of mental rotation and hierarchical pattern perception was investigated in 14 HIV-positive men and 12 age- and education-matched HIV-negative men. Processes related to mental rotation of objects and hands were impaired in HIV-positive participants as compared to the HIV-negative group. The HIV-positive group was also impaired on hierarchical pattern perception of local targets under global biasing conditions. Consistent with these results, the HIV-positive participants showed impaired performance on standard clinical neuropsychological tests of visuospatial function. These findings indicate that the detrimental effects of HIV on cognition appear even in asymptomatic individuals and affect diverse visuospatial functions that depend upon the integrity of parietal brain regions.

Frontostriatal circuits are necessary for visuomotor transformation: mental rotation in Parkinson's disease.

The mental rotation of objects requires visuospatial functions mediated by the parietal lobes, whereas the mental rotation of hands also engages frontal motor-system processes. Nondemented patients with Parkinson's disease (PD), a frontostriatal disorder, were predicted to be impaired on mentally rotating hands. Side of PD motor symptom onset was investigated because the left motor cortices likely have a causal role in hand mental rotation. The prediction was that patients with right-side onset (RPD, greater left-hemisphere dysfunction) would commit more errors rotating hands than patients with left-side onset (LPD). Fifteen LPD, 12 RPD, and 13 normal control adults (NC) made same/different judgments about pairs of rotated objects or hands. There were no group differences with objects. When rotating hands, RPD, but not LPD, made more errors than the NC group. A control experiment evaluated whether visual field of presentation explained differences between PD subgroups. In the first experiment (1A), the hand to be mentally rotated was presented in the right visual field, but here (1B) it was presented in the left visual field. Only the LPD group made more errors than the NC group. The evidence suggests a double dissociation for the RPD and LPD groups between tasks differing in visual-field presentation. The findings indicate that hemifield location of a to-be-rotated hand stimulus can cause the hemispheric frontoparietal networks to be differentially engaged. Moreover, frontostriatal motor systems and the parietal lobes play a necessary role during the mental rotation of hands, which requires integrating visuospatial cognition with motor imagery.

Non-motor aspects of Parkinson's disease.

Parkinson's disease is primarily considered to be a movement disorder and is defined by its motor signs. Yet, the behavioral manifestations of the disease are often more debilitating than its motor complications. This review will focus on the non-motor aspects of Parkinson's disease, including mood, psychosis, cognitive, sleep, fatigue, apathy, delirium, and repetitive disorders, that may occur. The phenomenology, pathology, and treatment of the behavioral symptoms of Parkinson's disease will be discussed.

Deep brain stimulation surgery for Parkinson's disease: the role of neuropsychological assessment.

Neuropsychological assessment has two primary roles in the DBS process. First, assessment of cognitive and emotional functioning ensures that only appropriate candidates undergo this surgical procedure. Patients with dementia, cognitive performance suggestive of an additional neuropathological process, or significant psychiatric impairments should not undergo DBS. Second, neuropsychological assessment is essential to determine the cognitive and emotional outcomes following surgery. At the present time, a disruption in verbal fluency is the only consistent cognitive decline associated with DBS. While worsening of depression and the development of symptoms of mania are potential side effects from DBS, more studies find that DBS is associated with improvements in emotional functioning. Based on the growing understanding of the risk factors and potential side effects to DBS, neuropsychological assessment is necessary to ensure that patients selected to undergo this surgical intervention will likely have positive cognitive and emotional outcomes, in addition to the expected benefits in motor functioning.

Feasibility of use of probabilistic reversal learning and serial reaction time tasks in clinical trials of Parkinson's disease.

INTRODUCTION: The aim of this study was to investigate the feasibility of using two computer-administered neuropsychological tasks in a clinical trial involving participants with Parkinson's disease without dementia. The tasks, probabilistic reversal learning (PRL) and serial reaction time (SRT), target dorsolateral prefrontal cortex (SRT) and ventral striatal-orbitofrontal (PRL) functioning respectively. METHODS: Participants were 53 adults with idiopathic Parkinson's disease who completed both the SRT and PRL tasks at baseline in a clinical trial. Repeated measures were examined only for the placebo group (n = 20). RESULTS: No participants were removed from analyses due to inability to complete the tasks, and most had fewer than 10% of trials culled due to slow reaction times. Response accuracy on PRL was 81.98% and 66.65% for the two stages of the task respectively. Disease duration was associated with SRT relearning. Disease duration and stage were associated with initial learning on PRL, and there was a trend towards disease stage predicting greater errors on PRL. Among participants in the placebo group, practice effects were seen on PRL (Phase 1 errors) and SRT (relearning). CONCLUSIONS: These results provide initial evidence for the clinical feasibility of computerized PRL and SRT tasks in clinical trials in Parkinson's disease.

Visual processing of rapidly presented stimuli is normalized in Parkinson's disease when proximal stimulus strength is enhanced.

Deficient perception and cognition in Parkinson's disease (PD) has been attributed to slow information processing, but an alternative explanation may be reduced signal strength. In 18 nondemented individuals with PD and 15 healthy adults, we enhanced the contrast level of rapidly flashed masked letters. The PD group required significantly higher contrast to reach criterion (80% accuracy). Normal motion detection in these participants indicated no gross, general dysfunction of the dorsal visual processing stream. These results suggest that putatively slowed processing in PD may be an artifact of reduced signal strength arising from depletion of dopamine in retina or cortical visual areas.

Poor performance validity predicts clinical characteristics and cognitive test performance of OEF/OIF/OND Veterans in a research setting.

This study examined the performance of 198 Veteran research participants deployed during Operation Enduring Freedom, Operation Iraqi Freedom, and/or Operation New Dawn (OEF/OIF/OND) on four measures of performance validity: the Medical Symptom Validity Test (MSVT), California Verbal Learning Test: Forced Choice Recognition (FCR), Reliable Digit Span (RDS), and TOVA Symptom Exaggeration Index (SEI). Failure on these performance validity tests (PVTs) ranged from 4% to 9%. The overall base rate of poor performance validity, as measured by failure of the MSVT in conjunction with an embedded PVT (FCR, RDS, SEI), was 5.6%. Regression analyses revealed that poor performance validity predicted cognitive test performance and self-reported psychological symptom severity. Furthermore, a greater prevalence of traumatic brain injury (TBI), Post-Traumatic Stress Disorder (PTSD), co-morbid TBI/PTSD, and other Axis I diagnoses, was observed among participants with poor effort. Although poor performance validity is relatively uncommon in a research setting, these findings demonstrate that clinicians should be cautious when interpreting psychological symptoms and neuropsychological test performance of Veteran participants who fail effort measures.