Steven E. Bruce

Does Cognitive―Behavioral Therapy for PTSD Improve Perceived Health and Sleep Impairment?

There is a paucity of empirical study about the effects of evidence-based psychotherapy for posttraumatic stress disorder (PTSD) on concurrent health concerns including sleep impairment. This study compares the differential effects of cognitive processing therapy (CPT) and prolonged exposure (PE) on health-related concerns and sleep impairment within a PTSD sample of female, adult rape survivors (N = 108). Results showed that participants in both treatments reported lower health-related concerns over treatment and follow-up, but there were relatively more improvements in the CPT condition. Examination of sleep quality indicated significant improvement in both CPT and PE across treatment and follow-up and no significant differences between treatments. These results are discussed with regard to the different mechanisms thought to underlie the treatments and future innovations in PTSD treatment.

The relationship between early life stress and microstructural integrity of the corpus callosum in a non-clinical population

Background Previous studies have examined the impact of early life stress (ELS) on the gross morphometry of brain regions, including the corpus callosum. However, studies have not examined the relationship between ELS and the microstructural integrity of the brain. Methods In the present study we evaluated this relationship in healthy non-clinical participants using diffusion tensor imaging (DTI) and self-reported history of ELS. Results Regression analyses revealed significant reductions in fractional anisotropy (FA) within the genu of the corpus callosum among those exposed to the greatest number of early life stressors, suggesting reduced microstructural integrity associated with increased ELS. These effects were most pronounced in the genu of the corpus callosum compared to the body and splenium, and were evident for females rather than males despite no differences in total ELS exposure between the sexes. In addition, a further comparison of those participants who were exposed to no ELS vs. three or more ELS events revealed lower FA in the genu of the corpus callosum among the ELS-exposed group, with trends of FA reduction in the body and the whole corpus callosum. By contrast, there were no relationships between ELS and volumetric analysis of the CC regions. The two group did not differ significantly on measures of current depression, stress or anxiety. Conclusion Our results reveal that greater exposure to ELS is associated with microstructural alterations in the white matter in the absence of significant volumetric changes. Importantly, our results indicate that exposure to ELS is associated with abnormalities on DTI despite the absence of clinically significant psychiatric symptoms. Future studies are needed to determine whether specific types of ELS are more likely to impact brain structure and function.

Early Life Stress on Brain Structure and Function Across the Lifespan: A Preliminary Study

Previous studies have shown that exposure to early life stress (ELS) is associated with reduced volume of brain regions critical for information processing, memory and emotional function. Further, recent studies from our lab utilizing diffusion tensor imaging (DTI) have found alterations in the microstructural integrity of white matter pathways among adults exposed to ELS. However, it is not clear if these relationships extend to children and adolescents, and it is also unclear if these DTI abnormalities are associated with cognitive performance. The present study examined the relationship between ELS and the microstructural integrity of the corpus callosum among a sample of otherwise healthy controls between the ages of 8 and 73. The participants were subdivided into four age groups (8–12, 13–18, 19–50, 51–73). Individuals with three or more ELS events were compared to individuals with fewer than 3 ELS events on fractional anisotropy (FA) in the genu of the corpus callosum. Separate analyses examined the two groups on tests of verbal memory, information processing speed, psychomotor speed and cognitive flexibility. Results revealed that the youngest group and the oldest group of individuals with ELS exhibited significantly lower FA in the genu compared to individuals without ELS. However, there were no group differences on any of the cognitive tasks. Our results indicate that ELS is related to subtle alterations in brain structure, but not function. The effects found with regard to DTI occurred during periods of critical age-related developmental windows.

Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty

Depressive symptoms are common in multiple psychiatric disorders and are frequent sequelae of trauma. A dimensional conceptualization of depression suggests that symptoms should be associated with a continuum of deficits in specific neural circuits. However, most prior investigations of abnormalities in functional connectivity have typically focused on a single diagnostic category using hypothesis-driven seed-based analyses. Here, using a sample of 105 adult female participants from three diagnostic groups (healthy controls, n=17; major depression, n=38; and post-traumatic stress disorder, n=50), we examine the dimensional relationship between resting-state functional dysconnectivity and severity of depressive symptoms across diagnostic categories using a data-driven analysis (multivariate distance-based matrix regression). This connectome-wide analysis identified foci of dysconnectivity associated with depression severity in the bilateral amygdala. Follow-up seed analyses using subject-specific amygdala segmentations revealed that depression severity was associated with amygdalo-frontal hypo-connectivity in a network of regions including bilateral dorsolateral prefrontal cortex, anterior cingulate and anterior insula. In contrast, anxiety was associated with elevated connectivity between the amygdala and the ventromedial prefrontal cortex. Taken together, these results emphasize the centrality of the amygdala in the pathophysiology of depressive symptoms, and suggest that dissociable patterns of amygdalo-frontal dysconnectivity are a critical neurobiological feature across clinical diagnostic categories.

The Role of Rumination in Elevating Perceived Stress in Posttraumatic Stress Disorder

Rumination has been shown to be important in both the maintenance and severity of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Increased rumination has also been linked to perceptions of increased stress, which in turn are significantly associated with increased PTSD severity. The present study sought to examine this relationship in more detail by means of a mediation analysis. Forty-nine female survivors of interpersonal violence who met Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria for PTSD were administered the Clinician-Administered PTSD Scale (CAPS), the Ruminative Thought Style Questionnaire (RTS), the Perceived Stress Scale (PSS), and the Beck Depression Inventory–II (BDI-II). Results indicated that perceived stress mediates the relationship between rumination and PTSD, but did not do so after controlling for depression. Such results provide further evidence for the overlap between PTSD and MDD, and, in broader clinical practice, translate to a sharper focus on rumination and perceived stress as maintenance factors in both disorders.

Cognitive behavioral therapy increases amygdala connectivity with the cognitive control network in both MDD and PTSD

Background Both major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are characterized by alterations in intrinsic functional connectivity. Here we investigated changes in intrinsic functional connectivity across these disorders as a function of cognitive behavioral therapy (CBT), an effective treatment in both disorders. Methods 53 unmedicated right-handed participants were included in a longitudinal study. Patients were diagnosed with PTSD (n = 18) and MDD (n = 17) with a structured diagnostic interview and treated with 12 sessions of manualized CBT over a 12-week period. Patients received an MRI scan (Siemens 3 T Trio) before and after treatment. Longitudinal functional principal components analysis (LFPCA) was performed on functional connectivity of the bilateral amygdala with the fronto-parietal network. A matched healthy control group (n = 18) was also scanned twice for comparison. Results LFPCA identified four eigenimages or principal components (PCs) that contributed significantly to the longitudinal change in connectivity. The second PC differentiated CBT-treated patients from controls in having significantly increased connectivity of the amygdala with the fronto-parietal network following CBT. Limitations Analysis of CBT-induced amygdala connectivity changes was restricted to the a priori determined fronto-parietal network. Future studies are needed to determine the generalizability of these findings, given the small and predominantly female sample. Conclusion We found evidence for the hypothesis that CBT treatment is associated with changes in connectivity between the amygdala and the fronto-parietal network. CBT may work by strengthening connections between the amygdala and brain regions that are involved in cognitive control, potentially providing enhanced top-down control of affective processes that are dysregulated in both MDD and PTSD.

Improvements in concentration, working memory and sustained attention following consumption of a natural citicoline-caffeine beverage.

Abstract This study examined the neurocognitive and electrophysiological effects of a citicoline–caffeine-based beverage in 60 healthy adult participants enrolled in a randomized, double-blind, placebo-controlled trial. Measures of electrical brain activity using electroencephalogram (EEG) and neuropsychological measures examining attention, concentration and reaction time were administered. Compared to placebo, participants receiving the citicoline–caffeine beverage exhibited significantly faster maze learning times and reaction times on a continuous performance test, fewer errors in a go/no-go task and better accuracy on a measure of information processing speed. EEG results examining P450 event-related potentials revealed that participants receiving the citicoline–caffeine beverage exhibited higher P450 amplitudes than controls, suggesting an increase in sustained attention. Overall, these findings suggest that the beverage significantly improved sustained attention, cognitive effort and reaction times in healthy adults. Evidence of improved P450 amplitude indicates a general improvement in the ability to accommodate new and relevant information within working memory and overall enhanced brain activation.

A Critical Review of Negative Affect and the Application of CBT for PTSD.

Forms of cognitive and behavioral therapies (CBTs), including prolonged exposure and cognitive processing therapy, have been empirically validated as efficacious treatments for posttraumatic stress disorder (PTSD). However, the assumption that PTSD develops from dysregulated fear circuitry possesses limitations that detract from the potential efficacy of CBT approaches. An analysis of these limitations may provide insight into improvements to the CBT approach to PTSD, beginning with an examination of negative affect as an essential component to the conceptualization of PTSD and a barrier to the implementation of CBT for PTSD. As such, the literature regarding the impact of negative affect on aspects of cognition (i.e., attention, processing, memory, and emotion regulation) necessary for the successful application of CBT was systematically reviewed. Several literature databases were explored (e.g., PsychINFO and PubMed), resulting in 25 articles that met criteria for inclusion. Results of the review indicated that high negative affect generally disrupts cognitive processes, resulting in a narrowed focus on stimuli of a negative valence, increased rumination of negative autobiographical memories, inflexible preservation of initial information, difficulty considering counterfactuals, reliance on emotional reasoning, and misinterpretation of neutral or ambiguous events as negative, among others. With the aim to improve treatment efficacy of CBT for PTSD, suggestions to incorporate negative affect into research and clinical contexts are discussed.

Improvements in quantitative EEG following consumption of a natural citicoline-enhanced beverage

The present study examined the impact of a taurine-free drink enhanced with citicoline and other natural ingredients on electrophysiological markers of mental alertness. Ten healthy adult participants enrolled in a double-blind, placebo-controlled crossover study and were randomized to receive either placebo or the citicoline supplement on the first visit. Measures of electrical brain activity using electroencephalogram (EEG) were collected 30 min after consuming the beverage. Seven days after the initial assessment participants completed the alternative condition (placebo or citicoline beverage). Compared to placebo, significant improvements were found in frontal alpha EEG and N100 event related potentials (ERP) associated with the citicoline-enhanced supplement. These preliminary findings suggest that a novel brain drink containing compounds known to increase choline in the brain significantly improved attention as measured by ERP and EEG. These findings suggest that a viable and alternative brain supplement without potential compounds such as taurine may augment attentional mechanisms in healthy individuals.

Cognitive Behavioral Therapy Is Associated With Enhanced Cognitive Control Network Activity in Major Depression and Posttraumatic Stress Disorder

BACKGROUND Both major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are characterized by depressive symptoms, abnormalities in brain regions important for cognitive control, and response to cognitive behavioral therapy (CBT). However, whether a common neural mechanism underlies CBT response across diagnoses is unknown. METHODS Brain activity during a cognitive control task was measured using functional magnetic resonance imaging in 104 participants: 28 patients with MDD, 53 patients with PTSD, and 23 healthy control subjects; depression and anxiety symptoms were determined on the same day. A patient subset (n = 31) entered manualized CBT and, along with controls (n = 19), was rescanned at 12 weeks. Linear mixed effects models assessed the relationship between depression and anxiety symptoms and brain activity before and after CBT. RESULTS At baseline, activation of the left dorsolateral prefrontal cortex was negatively correlated with Montgomery–Åsberg Depression Rating Scale scores across all participants; this brain–symptom association did not differ between MDD and PTSD. Following CBT treatment of patients, regions within the cognitive control network, including ventrolateral prefrontal cortex and dorsolateral prefrontal cortex, showed a significant increase in activity. CONCLUSIONS Our results suggest that dimensional abnormalities in the activation of cognitive control regions were associated primarily with symptoms of depression (with or without controlling for anxious arousal). Furthermore, following treatment with CBT, activation of cognitive control regions was similarly increased in both MDD and PTSD. These results accord with the Research Domain Criteria conceptualization of mental disorders and implicate improved cognitive control activation as a transdiagnostic mechanism for CBT treatment outcome.