Validation of the Modified Fatigue Impact Scale in mild to moderate traumatic brain injury.

OBJECTIVE: To evaluate the validity of the Modified Fatigue Impact Scale (MFIS) in veterans with a history of mild to moderate traumatic brain injury (TBI). PARTICIPANTS: Veterans (N = 106) with mild (92%) or moderate (8%) TBI. SETTING: Veterans Administration Health System. PROCEDURE: Factor structure, internal consistency, convergent validity, sensitivity, and specificity of the MFIS were examined. RESULTS: Principal component analysis identified 2 viable MFIS factors: a Cognitive subscale and a Physical/Activities subscale. Item analysis revealed high internal consistency of the MFIS Total scale and subscale items. Strong convergent validity of the MFIS scales was established with 2 Beck Depression Inventory II fatigue items. Receiver operating characteristic curve analysis revealed good to excellent accuracy of the MFIS in classifying fatigued versus nonfatigued individuals. CONCLUSION: The MFIS is a valid multidimensional measure that can be used to evaluate the impact of fatigue on cognitive and physical functioning in individuals with mild to moderate TBI. The psychometric properties of the MFIS make it useful for evaluating fatigue and provide the potential for improving research on fatigue in this population.

Altered insula activation during pain anticipation in individuals recovered from anorexia nervosa: evidence of interoceptive dysregulation.

OBJECTIVE: Recent evidence raises the possibility that symptoms of anorexia nervosa (AN) could be related to impaired interoception. Pain is an interoceptive process with well-characterized neuroanatomical pathways that may overlap to a large degree with neural systems that may be dysregulated in individuals with AN, such as the insula. METHOD: Functional magnetic resonance imaging (fMRI) was used to assess neural substrates of pain anticipation and processing in 10 healthy control women (CW) and 12 individuals recovered from AN (REC AN) in order to avoid the confounding effects of malnutrition. Painful heat stimuli were applied while different colors signaled the intensity of the upcoming stimuli. RESULTS: REC AN compared with CW showed greater activation within right anterior insula (rAI), dorsolateral prefrontal cortex (dlPFC) and cingulate during pain anticipation, and greater activation within dlPFC and decreased activation within posterior insula during painful stimulation. Greater anticipatory rAI activation correlated positively with alexithymic feelings in REC AN participants. DISCUSSION: REC AN showed a mismatch between anticipation and objective responses, suggesting altered integration and, possibly, disconnection between reported and actual interoceptive state. Alexithymia assessment provided additional evidence of an altered ability to accurately perceive bodily signals in women recovered from AN.

fMRI differences between subjects with low and high responses to alcohol during a stop signal task.

BACKGROUND: A low level of response (i.e., a low LR) to alcohol is a genetically influenced phenotype that predicts later alcoholism. While the low LR reflects, at least in part, a low brain response to alcohol, the physiological underpinnings of the low LR have only recently been addressed. METHODS: Forty-nine drinking but not yet alcoholic matched pairs of 18- to 25-year-old subjects (N = 98; 53% women) with low and high LRs as established in separate alcohol challenges were evaluated in 2 event-related functional magnetic resonance imaging (fMRI) sessions (placebo and approximately 0.7 ml/kg of alcohol) while performing a validated stop signal task. The high and low LR groups had identical blood alcohol levels during the alcohol session. RESULTS: Significant high versus low LR group and LR group × condition effects were observed in blood oxygen level-dependent (BOLD) signal during error and inhibitory processing, despite similar LR group performance on the task. In most clusters with significant (corrected p < 0.05, clusters > 1,344 µl) LR group × alcohol/placebo condition interactions, the low LR group demonstrated relatively less, whereas the high LR group demonstrated more, error and inhibition-related activation after alcohol compared with placebo. CONCLUSIONS: This is one of the first fMRI studies to demonstrate significant differences between healthy groups with different risks of a future life-threatening disorder. The results may suggest a brain mechanism that contributes to how a low LR might enhance the risk of future heavy drinking and alcohol dependence.

A multimodal imaging study in U.S. veterans of Operations Iraqi and Enduring Freedom with and without major depression after blast-related concussion.

Although the exact number of affected individuals is unknown, it has been estimated that approximately 20% of U.S. veterans of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) have experienced mild traumatic brain injury (mTBI) (i.e., concussion), which is defined as a brief loss or alteration of consciousness from a blow or jolt to the head. Blast exposure is among the most common causes of concussion in OEF-OIF warriors. Although the mechanism is unknown, major depressive disorder (MDD) after head injury is common. The purpose of this study was to use diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to examine the structural and functional neural correlates of MDD in OEF-OIF combat veterans with a self-reported history of blast-related concussion. We hypothesized that subjects in the MDD group (i.e., individuals with a history of blast-related concussion who were experiencing current MDD) relative to individuals in the non-MDD group (i.e., individuals with a history of blast-related concussion but no current or lifetime history of MDD) would show amygdala hyperactivity and disruption of white matter tracts connecting prefrontal and limbic brain regions. To test these hypotheses, 11 MDD and 11 non-MDD individuals underwent DTI and performed a validated emotional face matching task during fMRI. MDD relative to non-MDD individuals showed greater activity during fear matching trials in the amygdala and other emotion processing structures, lower activity during fear matching trials in emotional control structures such as the dorsolateral prefrontal cortex and lower fractional anisotropy (FA) in several white matter tracts including the superior longitudinal fasciculus (SLF). Greater depressive symptom severity correlated negatively with FA in the SLF. These results suggest a biological basis of MDD in OEF-OIF veterans who have experienced blast-related concussion, and may contribute to the development of treatments aimed at improving the clinical care of this unique population of wounded warriors.

Demand-specific alteration of medial prefrontal cortex response during an inhibition task in recovered anorexic women.

OBJECTIVE: It is well known that individuals with anorexia nervosa (AN) are inhibited and over-controlled. This study investigated a prefrontal-cingulate network that is involved in inhibitory control. METHOD: To avoid the confounds of malnutrition, 12 recovered (RAN) subjects were compared to 12 matched control women (CW) using a validated inhibition task (i.e., a stop signal task) during functional magnetic resonance imaging. RESULTS: Consistent with the a priori hypothesis, RAN subjects showed altered task-related activation in the medial prefrontal cortex (mPFC), a critical node of the inhibitory control network. Specifically, whereas RAN and CW showed similar mPFC activity during trials when inhibitory demand was low (i.e., easy trials), RAN relative to CW showed significantly less mPFC activation as inhibition trials became more difficult (i.e., hard trials), suggesting a demand-specific modulation of inhibitory control circuitry in RAN. DISCUSSION: These findings support a neural basis for altered impulse control symptoms in AN.

Alcohol attenuates activation in the bilateral anterior insula during an emotional processing task: a pilot study.

AIMS: Alcohol acutely reduces agitation and is widely used in social situations, but the neural substrates of emotion processing during its intoxication are not well understood. We examine whether alcohol's social stress dampening effect may be via reduced activity in the cortical systems that subserve awareness of bodily sensations, and are associated with affective distress. METHODS: Blood oxygen level-dependent activation was measured through 24 functional magnetic resonance imaging sessions in 12 healthy volunteers during an emotional face-processing task following ingestion of a moderate dose of alcohol and a placebo beverage. RESULTS: Results revealed that bilateral anterior insula response to emotional faces was significantly attenuated following consumption of alcohol, when compared with placebo (clusters >1472 µl; corrected P < 0.05). CONCLUSION: Attenuated response in the anterior insula after alcohol intake may explain some of the decreased interoceptive awareness described during intoxication.

Right anterior insula hypoactivity during anticipation of homeostatic shifts in major depressive disorder.

OBJECTIVE: To use functional magnetic resonance imaging (fMRI) to examine how shifts in homeostatic state affect anticipatory insular activity in major depressive disorder (MDD). An intact ability to mount preparatory emotional, cognitive, and bodily responses to anticipated environmental change is necessary for adaptive responding. Although abnormal insula activity during aversive anticipation has been observed in individuals with MDD, the extent to which shifts in homeostatic state during anticipation affect insular activity in MDD subjects has not been reported. METHODS: Cued hot and warm stimuli were delivered as subjects either passively viewed a fixation cross or performed an attentional task during fMRI. The task was designed so that anticipatory brain activation related to the following three types of shifts could be measured: 1) anticipatory shifts in stimulus intensity; 2) anticipatory shifts in cognitive demand; and 3) dual anticipatory shifts (i.e., shifts in both stimulus intensity and cognitive demand). Brain activation related to each of these three contrasts was compared between 15 (12 females) unmedicated subjects with current MDD and 17 (10 females) age- and education-comparable healthy control (HC) subjects. RESULTS: MDD vs. HC subjects showed lower right anterior insula activity related to anticipatory shifts in stimulus intensity, and altered brain activation during anticipatory shifts in cognitive demand and dual anticipatory shifts. CONCLUSIONS: These results indicate that MDD individuals show altered brain responses to shifts in homeostatic state during anticipation, and may suggest that MDD is associated with an impaired ability to effectively prepare for changes in the environment.

Acute ethanol effects on brain activation in low- and high-level responders to alcohol.

BACKGROUND: A low level of response (LR) to alcohol is an important endophenotype associated with an increased risk of alcoholism. However, little is known about how neural functioning may differ between individuals with low and high LRs to alcohol. This study examined whether LR group effects on neural activity varied as a function of acute alcohol consumption. METHODS: A total of 30 matched high- and low-LR pairs (N = 60 healthy young adults) were recruited from the University of California, San Diego, and administered a structured diagnostic interview and laboratory alcohol challenge followed by two functional magnetic resonance imaging (fMRI) sessions under placebo and alcohol conditions, in randomized order. Task performance and blood oxygen level-dependent response contrast to high relative to low working memory load in an event-related visual working memory (VWM) task were examined across 120 fMRI sessions. RESULTS: Both LR groups performed similarly on the VWM task across conditions. A significant LR group by condition interaction effect was observed in inferior frontal and cingulate regions, such that alcohol attenuated the LR group differences found under placebo (p < 0.05). The LR group by condition effect remained even after controlling for cerebral blood flow, age, and typical drinking quantity. CONCLUSIONS: Alcohol had differential effects on brain activation for low- and high-LR individuals within frontal and cingulate regions. These findings represent an additional step in the search for physiological correlates of a low LR and identify brain regions that may be associated with the low LR response.

Escitalopram attenuates posterior cingulate activity during self-evaluation in healthy volunteers.

Medial cortex is critically involved in self-referential processing. Little is known about how selective serotonin reuptake inhibitors (SSRIs) affect medial cortical activity during self-assessment. We hypothesized that a 3-week oral course of escitalopram,10 mg/day, would alter activity related to self-referential processing in medial cortex. Fifteen healthy females performed a self-assessment task during functional magnetic resonance imaging on two occasions--once after 3 weeks of placebo and once at the end of 3 weeks of escitalopram. Task conditions involved responding "yes" or "no" to whether various positive and negative adjectives described the subject (i.e., "self" evaluation trials) or the subject's best friend (i.e., "other" evaluation trials), whereas the comparison condition involved responding whether the valence of various adjectives was positive or negative (i.e., "word" evaluation trials). Behaviorally after escitalopram, subjects less frequently endorsed that negative adjectives described themselves. Three main neuroimaging results were observed: (1) increased activation in medial prefrontal cortex and posterior cingulate related to self minus word evaluation trials, (2) increased activation in posterior cingulate related to escitalopram minus placebo for self and word evaluation trials, and (3) drug by task interactions in the insula, cerebellum and prefrontal cortex. These results show that SSRIs change medial cortical activity and may alter self-evaluation.

Initial evidence of a failure to activate right anterior insula during affective set shifting in posttraumatic stress disorder.

OBJECTIVE: Interoception is the sense of one's internal physiological, sensory, and emotional status. Extensive evidence supports a link between interoception and subjective experience. An altered ability to monitor or modulate interoception as it relates to subjective experience may provide a mechanistic explanation for the development of some forms of psychiatric illness. METHODS: We investigated which neural networks are activated when anticipating a change in affective (and thus interoceptive) state, which we term "affective set-shifting," in 15 women with posttraumatic stress disorder (PTSD) related to intimate partner violence, and in 15 nontraumatized healthy volunteers. RESULTS: Although both groups activated the dorsolateral prefrontal cortex during affective set shifting, the PTSD group showed significantly less activation in the right anterior insula than did the controls. CONCLUSIONS: These findings may suggest that although individuals with PTSD are cognitively aware of the impending shift in interoceptive state, they fail to appropriately activate neural circuitry involved in modulating interoceptive responses.

Increased affective bias revealed using experimental graded heat stimuli in young depressed adults: evidence of "emotional allodynia".

OBJECTIVE: To examine the hypothesis that young adults with major depressive disorder (MDD) would show increased affective bias to painful and nonpainful experimental heat stimuli, as evidenced by an increased responsiveness to warm and hot temperatures. Pain and depression often occur together. Pain is both a sensation and an affective experience. Similarly, depression is associated frequently with somatic symptoms as well as emotional dysphoria. Existing evidence indicates that MDD may be associated with altered pain processing. However, the extent to which alterations in experimentally controlled heat pain sensations are related to increased affective bias in MDD is unknown. METHOD: Graded nonnoxious and noxious heat stimuli were delivered randomly with a thermode applied to the volar surface of the left arm of 15 unmedicated subjects with current MDD and 15 age- and gender-matched healthy comparison subjects. MDD and non-MDD subjects rated the intensity and unpleasantness of all stimuli. RESULTS: Two main results were observed. First, MDD relative to non-MDD subjects showed decreased heat pain thresholds. Second, a significantly increased affective bias (unpleasantness/intensity) was observed in subjects with MDD, particularly over the range of nonnoxious heat stimuli. This bias was independent of the change in sensory pain thresholds. CONCLUSION: These findings represent corroborative evidence of abnormal affective heat pain processing in young adults with MDD, and suggest that MDD is associated with "emotional allodynia," a qualitatively altered negative emotional response to normally nonaversive thermal stimuli.

Anxiety vulnerability is associated with altered anterior cingulate response to an affective appraisal task.

The anterior cingulate cortex (ACC) is critically involved not only in affective and anxiety processing, but also in error and conflict monitoring. To investigate how anxiety interacts with processing affective ambiguity, 15 anxious and 15 nonanxious individuals were scanned while performing a validated affective appraisal task, in which the fraction of faces of a particular affect or gender was parametrically controlled to provide various levels of ambiguity. The anxious group showed less ventral and greater dorsal ACC activation during ambiguous affective relative to ambiguous gender stimuli. For anxious individuals, dorsal ACC activation was related to a more biased response. Collectively, these data indicate that anxious individuals activate the dorsal and ventral components of the ACC differently during affective appraisal.

Intolerance of uncertainty correlates with insula activation during affective ambiguity.

Intolerance of uncertainty (IU), or the increased affective response to situations with uncertain outcomes, is an important component process of anxiety disorders. Increased IU is observed in panic disorder (PD), obsessive compulsive disorder (OCD) and generalized anxiety disorder (GAD), and is thought to relate to dysfunctional behaviors and thought patterns in these disorders. Identifying what brain systems are associated with IU would contribute to a comprehensive model of anxiety processing, and increase our understanding of the neurobiology of anxiety disorders. Here, we used a behavioral task, Wall of Faces (WOFs), during functional magnetic resonance imaging (fMRI), which probes both affect and ambiguity, to examine the neural circuitry of IU in 14 (10 females) college age (18.8 years) subjects. All subjects completed the Intolerance of Uncertainty Scale (IUS), Anxiety Sensitivity Index (ASI), and a measure of neuroticism (i.e. the NEO-N). IUS scores but neither ASI nor NEO-N scores, correlated positively with activation in bilateral insula during affective ambiguity. Thus, the experience of IU during certain types of emotion processing may relate to the degree to which bilateral insula processes uncertainty. Previously observed insula hyperactivity in anxiety disorder individuals may therefore be directly linked to altered processes of uncertainty.

Decreased functional coupling of the amygdala and supragenual cingulate is related to increased depression in unmedicated individuals with current major depressive disorder.

BACKGROUND: Individuals with major depressive disorder (MDD) show abnormal functional coupling (FC) between several nodes of a widely distributed cortico-limbic network that includes the amygdala and anterior cingulate. The aim of this study was to examine the degree to which alterations in amygdala-cingulate FC relate to severity of current depressive symptoms in a group of depressed individuals without significant co-morbidities. METHODS: Fifteen young, unmedicated subjects with current MDD and 16 healthy controls (HC) with no lifetime history of psychiatric illness performed a validated emotional face-matching task during functional magnetic resonance imaging. Amygdala activity and strength of amygdala-cingulate FC during emotional face processing were contrasted between the groups. RESULTS: Although both groups activated the extended amygdala (EA) during emotion processing, the MDD relative to the HC group showed more task-related co-activation of the subgenual cingulate, which is involved in processing negative self-referential information; and less co-activation of the supragenual cingulate, which is involved in the cognitive control of emotion. Greater depressive symptom severity correlated positively with decreased FC between bilateral EA and supragenual cingulate in MDD subjects. LIMITATIONS: This study included a demographically homogeneous population of subjects, which may limit the generalizability of the findings. CONCLUSIONS: These results elaborate current neurobiological models of MDD by providing unique evidence that decreased FC between the EA and supragenual cingulate is related to increased severity of current depressive symptoms. We speculate that the clinical manifestations of MDD may result in part from a failed ability to co-activate a cognitive control network during emotion processing.

In-Home Sleep Recordings in Military Veterans With Posttraumatic Stress Disorder Reveal Less REM and Deep Sleep <1 Hz.

Veterans with posttraumatic stress disorder (PTSD) often report suboptimal sleep quality, often described as lack of restfulness for unknown reasons. These experiences are sometimes difficult to objectively quantify in sleep lab assessments. Here, we used a streamlined sleep assessment tool to record in-home 2-channel electroencephalogram (EEG) with concurrent collection of electrodermal activity (EDA) and acceleration. Data from a single forehead channel were transformed into a whole-night spectrogram, and sleep stages were classified using a fully automated algorithm. For this study, 71 control subjects and 60 military-related PTSD subjects were analyzed for percentage of time spent in Light, Hi Deep (1-3 Hz), Lo Deep (<1 Hz), and rapid eye movement (REM) sleep stages, as well as sleep efficiency and fragmentation. The results showed a significant tendency for PTSD sleepers to spend a smaller percentage of the night in REM (p < 0.0001) and Lo Deep (p = 0.001) sleep, while spending a larger percentage of the night in Hi Deep (p < 0.0001) sleep. The percentage of combined Hi+Lo Deep sleep did not differ between groups. All sleepers usually showed EDA peaks during Lo, but not Hi, Deep sleep; however, PTSD sleepers were more likely to lack EDA peaks altogether, which usually coincided with a lack of Lo Deep sleep. Linear regressions with all subjects showed that a decreased percentage of REM sleep in PTSD sleepers was accounted for by age, prazosin, SSRIs and SNRIs (p < 0.02), while decreased Lo Deep and increased Hi Deep in the PTSD group could not be accounted for by any factor in this study (p < 0.005). Linear regression models with only the PTSD group showed that decreased REM correlated with self-reported depression, as measured with the Depression, Anxiety, and Stress Scales (DASS; p < 0.00001). DASS anxiety was associated with increased REM time (p < 0.0001). This study shows altered sleep patterns in sleepers with PTSD that can be partially accounted for by age and medication use; however, differences in deep sleep related to PTSD could not be linked to any known factor. With several medications [prazosin, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs); p < 0.03], as well as SSRIs were associated with less sleep efficiency (b = -3.3 ± 0.95; p = 0.0005) and more sleep fragmentation (b = -1.7 ± 0.51; p = 0.0009). Anti-psychotics were associated with less sleep efficiency (b = -4.9 ± 1.4; p = 0.0004). Sleep efficiency was negatively impacted by SSRIs, antipsychotic medications, and depression (p < 0.008). Increased sleep fragmentation was associated with SSRIs, SNRIs, and anxiety (p < 0.009), while prazosin and antipsychotic medications correlated with decreased sleep fragmentation (p < 0.05).

Multimodal canonical correlation reveals converging neural circuitry across trauma-related disorders of affect and cognition.

Trauma-related disorders of affect and cognition (TRACs) are associated with a high degree of diagnostic comorbidity, which may suggest that these disorders share a set of underlying neural mechanisms. TRACs are characterized by aberrations in functional and structural circuits subserving verbal memory and affective anticipation. Yet, it remains unknown how the neural circuitry underlying these multiple mechanisms contribute to TRACs. Here, in a sample of 47 combat Veterans, we measured affective anticipation using functional magnetic resonance imaging (fMRI), verbal memory with fluorodeoxyglucose positron emission tomography (FDG-PET), and grey matter volume with structural magnetic resonance imaging (sMRI). Using a voxel-based multimodal canonical correlation analysis (mCCA), the set of neural measures were statistically integrated, or fused, with a set of TRAC symptom measures including mild traumatic brain injury (mTBI), posttraumatic stress, and depression severity. The first canonical correlation pair revealed neural convergence in clusters encompassing the middle frontal gyrus and supplemental motor area, regions implicated in top-down cognitive control and affect regulation. These results highlight the potential of leveraging multivariate neuroimaging analysis for linking neurobiological mechanisms associated with TRACs, paving the way for transdiagnostic biomarkers and targets for treatment.

Increased amygdala activation is related to heart rate during emotion processing in adolescent subjects.

Emotions have been conceptualized as representations of bodily responses to a stimulus that critically involves the autonomic nervous system (ANS). An association between amygdala activation and ANS activity has been shown in adults. However, to date, no studies have demonstrated this association in adolescents. Examining the interaction between the ANS and amygdala in healthy adolescents may provide information about age-related changes in the association between amygdala activation and ANS measures. Therefore, the aim of this study was to examine the relationship between amygdala activation and heart rate in normal adolescents. Eighteen 12- to 17-year old adolescents participated. Heart rate data was collected during functional magnetic resonance imaging while subjects performed a facial expression matching task that reliably activates the amygdala. Adolescents showed significant amygdala activation for all facial expressions relative to the shape-matching, control task. Moreover, the degree of activation in the right amygdala for Fearful faces was significantly correlated with heart rate (Spearman's rho=0.55, p=0.018, two-tailed). This study shows that amygdala activity is related to heart rate in healthy adolescents. Thus, similar to adults, adolescents show a coupling between processing emotional events and adjusting the ANS accordingly. Furthermore, this study confirms previous adolescent studies showing amygdala activation to Fearful, Angry, and Happy faces. Finally, the results of the present study lay the foundation for future research to investigate whether adolescents with mood or anxiety disorders show an altered coupling between processing emotionally salient events and ANS activity.

Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects.

BACKGROUND: Anticipation is a critical component of affective processing in general and for anxiety in particular. Prior research suggests that the right insula plays an important role in anticipation of affective processing during aversive images. This study aimed to test the hypothesis that individuals with increased anxiety-related temperamental traits (anxiety-prone [AP]) relative to anxiety-normative (AN) subjects would show an exaggerated insula response during anticipation of an aversive image. METHODS: 16 AP and 16 AN individuals performed a task in the functional magnetic resonance imaging scanner, during which they viewed pictures of spiders and snakes. Subjects were prompted 4-6 sec before the onset of each aversive image. Blood oxygenation level-dependent signal was contrasted during cued anticipation of images versus non-anticipatory task performance as well as viewing images. RESULTS: As hypothesized, AP subjects showed greater response than AN subjects in the bilateral insula during anticipation. In addition, these individuals had lower activity within the superior/medial frontal gyrus. During the image presentation phase, AN subjects showed greater activation than AP subjects in the bilateral temporal lobes and left superior frontal gyrus. Moreover, bilateral temporal lobe activation during image presentation was inversely correlated with bilateral insula activation during anticipation both within groups and in the combined group. CONCLUSIONS: These data suggest that greater activation of the insula during visual anticipation is associated with visual processing of aversive stimuli in AP individuals. Insula hyperactivity might be a common feature in persons with elevated trait anxiety and, as such, might be a neuroimaging marker for anxiety proneness.

A randomized controlled trial of gabapentin for chronic low back pain with and without a radiating component.

Gabapentin is prescribed for analgesia in chronic low back pain, yet there are no controlled trials supporting this practice. This randomized, 2-arm, 12-week, parallel group study compared gabapentin (forced titration up to 3600 mg daily) with inert placebo. The primary efficacy measure was change in pain intensity from baseline to the last week on treatment measured by the Descriptor Differential Scale; the secondary outcome was disability (Oswestry Disability Index). The intention-to-treat analysis comprised 108 randomized patients with chronic back pain (daily pain for ≥6 months) whose pain did (43%) or did not radiate into the lower extremity. Random effects regression models which did not impute missing scores were used to analyze outcome data. Pain intensity decreased significantly over time (P < 0.0001) with subjects on gabapentin or placebo, reporting reductions of about 30% from baseline, but did not differ significantly between groups (P = 0.423). The same results pertained for disability scores. In responder analyses of those who completed 12 weeks (N = 72), the proportion reporting at least 30% or 50% reduction in pain intensity, or at least "Minimal Improvement" on the Physician Clinical Global Impression of Change did not differ significantly between groups. There were no significant differences in analgesia between participants with radiating (n = 46) and nonradiating (n = 62) pain either within or between treatment arms. There was no significant correlation between gabapentin plasma concentration and pain intensity. Gabapentin appears to be ineffective for analgesia in chronic low back pain with or without a radiating component.

Depressive symptoms are associated with increased systemic vascular resistance to stress.

OBJECTIVE: The deleterious effects of major depressive disorder on cardiovascular (CV) functioning are well known. However, the etiologic mechanisms underlying this association are incompletely understood. In the current study, subjects with varying degrees of depressive symptoms performed a stress task while CV reactivity was measured. We hypothesized that high levels of depressive symptoms would be associated with altered CV reactivity. METHODS: Ninety-one healthy volunteer subjects performed reactivity testing while measures of impedance cardiography and autonomic nervous system function were obtained. Subjects completed the Center for Epidemiological Studies Depression Scale (CES-D) and were categorized into either the high depressive (i.e., CES-D > or =16) or low depressive (i.e., CES-D <16) symptoms group. RESULTS: Task performance was associated with increases in systemic vascular resistance (SVR) (p = .001), mean arterial pressure (p = .001), and heart rate (p = .005), and decreases in cardiac output (p = .001), heather index (p = .001), and stroke volume (p = .05). After controlling for screening mean arterial pressure, an interaction effect of stress by mood group on SVR (p = .01) was observed; subjects with high amounts of depressive symptoms manifested significantly greater SVR at baseline and in response to a stressor task than did subjects with low amounts of depressive symptoms. CONCLUSIONS: These results suggest a mechanism that may partially explain the increased CV morbidity associated with depressive symptoms. In future studies, it may be useful to examine if treatment of depressive symptoms alters CV reactivity.