Usual Care for Rural Veterans With Posttraumatic Stress Disorder.

PURPOSE: Community-Based Outpatient Clinics (CBOCs) provide primary-care-based mental health services to rural veterans who live long distances from Veterans Affairs (VA) hospitals. Characterizing the composition of usual care will highlight the need and potential strategies to improve access to and engagement in evidence-based psychotherapy for posttraumatic stress disorder (PTSD). METHOD: Veterans (N = 132) with PTSD recruited from 5 large- (5,000-10,000 patients) and 6 medium-sized (1,500-4,999) CBOCs were enrolled in the usual care arm of a randomized control trial for a PTSD collaborative care study. Chart review procedures classified all mental health encounters during the 1-year study period into 10 mutually exclusive categories (7 psychotherapy and 3 medication management). FINDINGS: Seventy-two percent of participants received at least 1 medication management encounter with 30% of encounters being delivered via interactive video. More than half of veterans (58.3%) received at least 1 session of psychotherapy. Only 12.1% received a session of therapy classified as an evidence-based psychotherapy for PTSD. The vast majority of psychotherapy encounters were delivered in group format and only a small proportion were delivered via interactive video. CONCLUSIONS: Findings suggest that veterans diagnosed with PTSD who receive their mental health treatment in large and medium CBOCs are likely to receive medication management, and very few veterans received evidence-based psychotherapy. There may be ways to increase access to evidence-based psychotherapy by expanding the use of interactive video to connect specialty mental health providers with patients, hosted either in CBOCs or in home-based care, and to offer more group-based therapies.

Differential abnormalities of functional connectivity of the amygdala and hippocampus in unipolar and bipolar affective disorders.

OBJECTIVE: The amygdala and hippocampus - two structures intimately associated with mood and cognition - have been reported to exhibit altered neural activity or volume in affective disorders. We hypothesized the amygdala and hippocampus would show altered and differential patterns of connectivity in patients with bipolar (BPs) and unipolar (UPs) disorder compared to healthy volunteers. METHOD: Thirty BPs, 34 UPs, and 66 healthy volunteers were imaged using F-18-fluorodeoxyglucose and positron emission tomography while performing an auditory continuous performance task (CPT). Normalized mean activity of the amygdala and hippocampus was correlated with the rest of the brain. RESULTS: In BPs, the amygdalae displayed exaggerated positive metabolic correlations with prefrontal and ventral striatal areas, while the hippocampus showed a paucity of normal inter-relations compared to controls. In contrast, in UPs the amygdala was significantly negatively correlated with prefrontal and anterior cingulate cortex, while the hippocampus was significantly more positively correlated to these same prefrontal areas. CONCLUSIONS: During a simple cognitive task, the functional connectivity of the amygdala and hippocampus, regions usually associated with emotion and memory regulation, was substantially different in affective illness compared to healthy controls whether or not there were baseline abnormalities in these areas. These striking differences in functional connectivity of amygdala and hippocampus should be further explored in ill and well states and using more specific emotion and cognitive evocative tasks.

The impact of Purple Heart commendation and PTSD on mortality rates in older veterans.

BACKGROUND: To determine whether having received a Purple Heart (PH) or having been diagnosed with posttraumatic stress disorder (PTSD) affected mortality in older veterans. METHODS: We compared mortality rates of older veterans with a PH but without PTSD (PH+/PTSD-) to veterans with a PH and PTSD (PH+/PTSD+), veterans without a PH but with PTSD (PH-/PTSD+), and a comparison group without a PH or PTSD (PH-/PTSD-). Administrative data from the Veterans Integrated Service Network 16 were collected between 10/01/97 and 09/30/99 for veterans who were 65 years or older. Proportional hazards regression was used to compare the survival times for the four groups (n = 10,255) from entry into the study until death or study termination (9/30/2008). The Charleson co-morbidity index was used to control for potential co-morbid illness burden differences between the groups. RESULTS: Older veterans with a PH (PH+/PTSD- and PH+/PTSD+) had significantly lower mortality rates than PH-/PTSD- veterans (hazard ratio [HR] = 0.6, 95% confidence interval [CI] 0.5 to 0.6, P<.0001; and HR = 0.5, 95% CI 0.4 to 0.7, P<.0001). The PH-/PTSD+ group had a higher mortality rate than the PH-/PTSD- group (HR = 1.1, 95% CI 1.0 to 1.2, P<.01). CONCLUSIONS: Veterans who had PH citations and survived into their seventh decade had half the mortality rate of veterans without PH citations with or without PTSD. Veterans with PTSD but without a PH had a significantly higher mortality rate compared to (PH-/PTSD-). Veterans who suffer combat injury without developing PTSD may provide a useful study population for determining the factors that confer resilience.

Comprehension of affective prosody in veterans with chronic posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is one of the few psychiatric conditions in which a subjective decrease in emotional range serves as a diagnostic criterion. In order to investigate whether veterans with chronic PTSD also experienced objective limitations in emotional perception, the authors administered the Aprosodia Battery to a group of 11 veterans with chronic PTSD, nine subjects with right hemisphere damage, seven subjects with left hemisphere damage, and 12 comparison subjects. The patients with PTSD displayed significant deficiencies in the comprehension and discriminative components of affective speech, similar in severity and performance profile on the Aprosodia Battery to the individuals with focal right hemisphere damage due to ischemic infarction.

Interregional cerebral metabolic associativity during a continuous performance task (Part II) : differential alterations in bipolar and unipolar disorders.

Unipolar and bipolar disorders have often been reported to exhibit abnormal regional brain activity in prefrontal cortex and paralimbic structures compared with healthy controls. We sought to ascertain how regions postulated to be abnormal in bipolar and unipolar disorders were functionally connected to the rest of the brain, and how this associativity differed from healthy controls. Thirty patients with bipolar disorder (BPs), 34 patients with unipolar disorder (UPs), and 66 healthy volunteers (Willis, M.W., Benson, B.E., Ketter, T.A., Kimbrell, T.A., George, M.S., Speer, A.M., Herscovitch, P., Post, R.M., 2008. Interregional cerebral metabolic associativity during a continuous performance task in healthy adults. Psychiatry Research: Neuroimaging 164 (1)) were imaged using F-18-fluorodeoxyglucose and positron emission tomography (FDG-PET) while performing an auditory continuous performance task (CPT). Five bilateral regions of interest (ROIs), namely dorsolateral prefrontal cortex (DLPFC), insula, inferior parietal cortex (INFP), thalamus and cerebellum, were correlated with normalized cerebral metabolism in the rest of the brain while covarying out Hamilton Depression Rating Scale Scores. In bipolar patients compared with controls, metabolism in the left DLPFC and INFP, and bilateral thalamus and insula had more positive and fewer negative metabolic correlations with other brain regions. In contrast, compared with controls, unipolar patients had fewer significant correlative relationships, either positive or negative. In common, bipolar and unipolar patients lacked the normal inverse relationships between the DLPFC and cerebellum, as well as relationships between the primary ROIs and other limbic regions (medial prefrontal cortex, anterior cingulate, and temporal lobes) compared with controls. Associations of DLPFC and INFP with other brain areas were different in each hemisphere in patients and controls. Bipolar patients exhibited exaggerated positive coherence of activity throughout the brain, while unipolar patients showed a paucity of normal interrelationships compared with controls. These abnormal patterns of metabolic associativity suggest marked interregional neuronal dysregulation in bipolar and unipolar illness exists beyond that of mere absolute regional differences from control levels, and provides rationale for using acute and long-term therapies that may re-establish and maintain normal associativity in these devastating illnesses.

Interregional cerebral metabolic associativity during a continuous performance task (Part I): healthy adults.

One emerging hypothesis regarding psychiatric illnesses is that they arise from the dysregulation of normal circuits or neuroanatomical patterns. In order to study mood disorders within this framework, we explored normal metabolic associativity patterns in healthy volunteers as a prelude to examining the same relationships in affectively ill patients (Part II). We applied correlational analyses to regional brain activity as measured with FDG-PET during an auditory continuous performance task (CPT) in 66 healthy volunteers. This simple attention task controlled for brain activity that otherwise might vary amongst affective and cognitive states. There were highly significant positive correlations between homologous regions in the two hemispheres in thalamic, extrapyramidal, orbital frontal, medial temporal and cerebellar areas. Dorsal frontal, lateral temporal, cingulate, and especially insula, and inferior parietal areas showed less significant homologous associativity, suggesting more specific lateralized function. The medulla and bilateral thalami exhibited the most diverse interregional associations. A general pattern emerged of cortical regions covarying inversely with subcortical structures, particularly the frontal cortex with cerebellum, amygdala and thalamus. These analytical data may help to confirm known functional and neuroanatomical relationships, elucidate others as yet unreported, and serve as a basis for comparison to patients with psychiatric illness.

Measuring symptom exaggeration in veterans with chronic posttraumatic stress disorder.

Veteran subjects with chronic, combat-related posttraumatic stress disorder (PTSD) are frequently used as research subjects in the study of PTSD. However, questions have consistently been raised regarding PTSD symptom exaggeration in veteran populations due to the relationship between PTSD symptoms and disability payments within the Veterans Affairs (VA) system. We used a variety of standardized forensic instruments frequently utilized in measuring symptom exaggeration - including the MMPI-2, the Structured Interview for Reported Symptoms (SIRS), the Structured Inventory of Malingered Symptomatology (SIMS), and the Miller Forensic Assessment Test (MFAST) - to examine symptom report in a group of veterans presenting for treatment at a VA residential PTSD treatment program. The majority of Vietnam veteran subjects in our study (53%) exhibited clear symptom exaggeration by SIRS criteria. Within the entire subject group, total SIRS scores correlated significantly with reported PTSD symptom severity as measured by the Clinician Administered PTSD Scale (CAPS).

Evidence of resilience: neuroimaging in former prisoners of war.

In this study, single voxel proton magnetic resonance spectroscopic imaging ((1)H-MRS) and volumetric analysis of hippocampal magnetic resonance imaging (MRI) images were used to determine if any differences in hippocampal biochemistry or volume were present between former prisoners of war (POWs) with and without posttraumatic stress disorder (PTSD) and control subjects matched for age and education. This study did not find lower hippocampal concentrations of N-acetylaspartate (NAA), smaller hippocampal volumes, or more impaired memory function in older veterans with PTSD compared with a group matched for traumatic experience or a nontraumatized control group.

Preliminary findings of uncoupling of flow and metabolism in unipolar compared with bipolar affective illness and normal controls.

Cerebral metabolism (CMR for glucose or oxygen) and blood flow (CBF) have been reported to be closely correlated in healthy controls. Altered relationships between CMR and CBF have been reported in some brain disease states, but not others. This study examined relationships between global and regional CMRglu vs. CBF in controls and medication-free primary affective disorder patients. Nine bipolars, eight unipolars, and nine healthy controls had [15O]-water positron emission tomography (PET) scans at rest, and [18F]-fluorodeoxyglucose PET scans during an auditory continuous performance task. Patients had [15O]-water and FDG PET scans in tandem the same day; controls had an average of 45+/-27 days between scans. Maps of regional coupling were constructed for each subject group. In controls and bipolars, global and virtually all regional correlation coefficients for CMRglu and CBF were positive, albeit more robustly so in controls. However, correlative relationships in unipolars were qualitatively different, such that global and most regional measures of flow and metabolism were not positively related. Unipolars had significantly fewer positive regional correlation coefficients than healthy controls and bipolars. These were significantly different from controls in orbital cortex, anterior cingulate, posterior cingulate, and posterior temporal cortex, and different from bipolars in pregenual anterior cingulate. In unipolars, the degree of flow-metabolism uncoupling was inversely correlated with Hamilton depression scores, indicating the severity of uncoupling was directly related to the severity of depression. These preliminary data suggest abnormal relationships between cerebral metabolism and blood flow globally and regionally in patients with unipolar depression that warrant replication and extension to potential pathophysiological implications.

Relationship of in vivo medial temporal lobe magnetic resonance spectroscopy to documented combat exposure in veterans with chronic posttraumatic stress disorder.

Veterans diagnosed with combat-related posttraumatic stress disorder (PTSD) and comparison subjects underwent single voxel proton magnetic resonance spectroscopy (1H-MRS) of the medial temporal lobe (MTL). PTSD subjects were divided into combat and non-combat groups based on military records. Combat PTSD subjects did not have lower MTL levels of N-acetylaspartate compared with non-combat PTSD subjects.

Weight loss and PTSD symptom severity in former POWs.

To determine the relationship between weight loss suffered by former prisoners of war during captivity during World War II and the Korean Conflict and current posttraumatic stress disorder (PTSD) symptoms, the Clinician-Administered PTSD Symptom Scale, a lifetime stressor checklist, and the Structured Clinical Interview for DSM-IV were administered to 102 former prisoners of war. Preconfinement and postconfinement weights and length of confinement were obtained from military medical records. Percentage of body weight lost during captivity was significantly higher in those subjects with PTSD and correlated with current PTSD symptom severity. Length of confinement was not associated with current PTSD symptoms.

Bupropion and venlafaxine responders differ in pretreatment regional cerebral metabolism in unipolar depression.

BACKGROUND: Pretreatment functional brain imaging was examined for never-hospitalized outpatients with unipolar depression compared with control subjects in a crossover treatment trial involving bupropion or venlafaxine monotherapy. METHODS: Patients (n = 20) with unipolar depression received baseline (medication-free) fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) scan and then at least 6 weeks of bupropion or venlafaxine monotherapy in a single-blind crossover trial. Age-matched healthy control subjects (n = 20) also received baseline FDG PET scans. For each medication PET data from patients compared with control subjects was analyzed as a function of treatment response (defined as moderate to marked improvement on the Clinical Global Impression Scale). RESULTS: Treatment response rates were similar for buproprion (32%) and venlafaxine (33%). Compared with control subjects, responders but not nonresponders, to both drugs demonstrated frontal and left temporal hypometabolism. Selectively, compared with control subjects bupropion responders (n = 6) also had cerebellar hypermetabolism, whereas venlafaxine responders (n = 7) showed bilateral temporal and basal ganglia hypometabolism. CONCLUSIONS: These data suggest that pretreatment frontal and left temporal hypometabolism in never-hospitalized depressed outpatients compared with control subjects is linked to positive antidepressant response and that additional alterations in regional metabolism may be linked to differential responsivity to bupropion and venlafaxine monotherapy.

Neuropsychiatric associations of apolipoprotein E alleles in subjects with combat-related posttraumatic stress disorder.

Previous studies have reported associations between apolipoprotein E (APOE) genotype, cognitive function, and psychopathology in psychiatric populations. The authors investigated the associations between APOE allele status, memory function, and posttraumatic stress disorder (PTSD) symptom severity in PTSD subjects. Presence of the APOE 2 allele was associated with significantly worse reexperiencing symptoms and impaired memory function in this population.

Relationship of alcohol craving to symptoms of posttraumatic stress disorder in combat veterans.

To examine the relationship of alcohol craving to symptoms of posttraumatic stress disorder (PTSD), 129 male veterans with chronic PTSD were asked to complete the Obsessive Compulsive Drinking Scale (OCDS), the Mississippi Scale for combat-related PTSD symptoms, and other instruments to assess general psychopathology and lifetime alcohol and substance use. No correlations were found between current PTSD symptoms and alcohol craving, although significant correlations were found between the OCDS and measures of lifetime alcohol and substance use.

In vivo proton magnetic resonance spectroscopy of the medial temporal lobes of former prisoners of war with and without posttraumatic stress disorder.

Proton magnetic resonance spectroscopy was used to compare medial temporal lobe (MTL) concentrations of N-acetylaspartate and choline between former prisoners of war (POWs) with and without posttraumatic stress disorder (PTSD). MTL N-acetylaspartate and reexperiencing symptoms correlated strongly in the POW subjects with PTSD, suggesting a relationship between reexperiencing symptoms and the integrity of MTL structures.

A survey of gun collection and use among three groups of veteran patients admitted to veterans affairs hospital treatment programs.

BACKGROUND: An important risk factor for suicide is psychiatric illness, but only a limited amount of work has been directed at assessing the use of firearms and other weapons by select psychiatric populations at high risk for violent acts. METHOD: Patients with combat-related posttraumatic stress disorder (PTSD), patients with schizophrenia, and patients undergoing rehabilitation for substance abuse were asked to complete a weapons-use survey and measures of psychopathology. RESULTS: The PTSD patients surveyed related owning more than four times as many firearms as other subjects and reported significantly higher levels of potentially dangerous firearm-related behaviors than the other psychiatric subjects surveyed. CONCLUSION: High levels of aggression, impulsive and dangerous weapon use, and ready weapon availability may be significant factors in gun-related violence in the PTSD patient population. Additional prospective research is needed to determine whether gun ownership or certain types of weapon use in this population is associated with future acts of violence.

Principal components of the Beck Depression Inventory and regional cerebral metabolism in unipolar and bipolar depression.

BACKGROUND: We determined clustering of depressive symptoms in a combined group of unipolar and patients with bipolar disorder using Principle Components Analysis of the Beck Depression Inventory. Then, comparing unipolars and bipolars, these symptom clusters were examined for interrelationships, and for relationships to regional cerebral metabolism for glucose measured by positron emission tomography. METHODS: [18F]-fluoro-deoxyglucose positron emission tomography scans and Beck Depression Inventory administered to 31 unipolars and 27 bipolars, all medication-free, mildly-to-severely depressed. BDI component and total scores were correlated with global cerebral metabolism for glucose, and voxel-by-voxel with cerebral metabolism for glucose corrected for multiple comparisons. RESULTS: In both unipolars and bipolars, the psychomotor-anhedonia symptom cluster correlated with lower absolute metabolism in right insula, claustrum, anteroventral caudate/putamen, and temporal cortex, and with higher normalized metabolism in anterior cingulate. In unipolars, the negative cognitions cluster correlated with lower absolute metabolism bilaterally in frontal poles, and in right dorsolateral frontal cortex and supracallosal cingulate. CONCLUSIONS: Psychomotor-anhedonia symptoms in unipolar and bipolar depression appear to have common, largely right-sided neural substrates, and these may be fundamental to the depressive syndrome in bipolars. In unipolars, but not bipolars, negative cognitions are associated with decreased frontal metabolism. Thus, different depressive symptom clusters may have different neural substrates in unipolars, but clusters and their substrates are convergent in bipolars.

Age, sex and laterality effects on cerebral glucose metabolism in healthy adults.

Normal cerebral glucose metabolism (CMRglc) was assessed with positron emission tomography in 66 healthy adults (28 women, 38 men; mean age 39, range 20--69 years) to determine effects of age, sex and laterality on CMRglc using statistical parametric mapping. Significant age-related decreases in global metabolism (gCMRglc) were noted in the entire sample and in both sexes, as well as widespread and bilateral decreases in cortical absolute regional metabolism (rCMRglc) and more focal anterior paralimbic normalized rCMRglc. However, significant positive correlations of age with normalized rCMRglc were observed in cerebellum, thalamus and occipital areas. Although the declines in gCMRglc and rCMRglc with age did not significantly differ between sexes, men compared with women had significantly lower gCMRglc and widespread decreased cortical and subcortical absolute rCMRglc. In the entire sample, and similarly in both sexes, left greater than right asymmetry was observed in medial frontal gyrus, posterior thalamus, lingual gyrus, cuneus and superior cingulate. The opposite laterality appeared in mesio-anterior cerebellum, and lateral frontal and temporal regions. Few regions showed significant interactions of metabolic laterality with either age or sex. These findings contribute toward a convergence in the literature, and the regression models of CMRglc vs. age serve as a normative database to which patients may be compared.

Regional cerebral glucose utilization in patients with a range of severities of unipolar depression.

BACKGROUND: Patients with unipolar depression are most often reported to have decreased regional cerebral glucose metabolism (rCMRglu) in dorsal prefrontal and anterior cingulate cortices compared with healthy control subjects, often correlating inversely with severity of depression. METHODS: We measured rCMRglu with fluorine-18 deoxyglucose positron emission tomography (PET) in 38 medication-free patients with unipolar depression and 37 healthy control subjects performing an auditory continuous performance task to further investigate potential prefrontal and anterior paralimbic rCMRglu abnormalities in patients attending to this task. RESULTS: Compared with control subjects, the subgroup of patients with Hamilton depression scores of 22 or greater demonstrated decreased absolute rCMRglu in right prefrontal cortex and paralimbic/amygdala regions as well as bilaterally in the insula and temporoparietal cortex (right > left); they also exhibited increased normalized metabolic activity bilaterally in the cerebellum, lingula/cuneus, and brain stem. Severity of depression negatively correlated with absolute rCMRglu in almost the entire extent of the right cingulate cortex as well as bilaterally in prefrontal cortex, insula, basal ganglia, and temporoparietal cortex (right > left). CONCLUSIONS: Areas of frontal, cingulate, insula, and temporal cortex appear hypometabolic in association with different components of the severity and course of illness in treatment-resistant unipolar depression.