Melynda D. Casement

Hippocampal hyperperfusion in Alzheimer's disease.

Many of the regions with the earliest atrophy in Alzheimers Disease (AD) do not show prominent deficits on functional imaging studies of flow or metabolism. This paradox may provide unique insights into the pathophysiology of AD. We sought to examine the relationship between function and atrophy in AD using MRI blood flow and anatomic imaging. 22 subjects diagnosed with AD, mean Mini Mental State Exam (MMSE) score 22.2, and 16 healthy elderly controls were imaged with a volumetric arterial spin labeling blood flow MRI technique and an anatomical imaging method using the identical spatial resolution, image orientation, and spatial encoding strategy. Cerebral blood flow (CBF) and gray matter (GM) maps derived from the imaging were transformed to a standard anatomical space. GM and CBF maps were tested for significant differences between groups. Additionally, images were tested for regions with significant mismatch of the CBF and GM differences between groups. CBF was significantly lower in the bilateral precuneus, parietal association cortex and the left inferior temporal lobe but was non-significantly increased in the hippocampus and other medial temporal structures. After correction for GM loss, CBF was significantly elevated in the hippocampus and other medial temporal structures. The hippocampus and other regions affected early in AD are characterized by elevated atrophy-corrected perfusion per cm(3) of tissue. This suggests compensatory or pathological elevation of neural activity, inflammation, or elevated production of vasodilators.

A meta-analysis of imagery rehearsal for post-trauma nightmares: effects on nightmare frequency, sleep quality, and posttraumatic stress.

This meta-analysis evaluates the efficacy of imagery rehearsal as a treatment for nightmares, general sleep disturbance, and symptoms of post-traumatic stress. Bibliographic databases and cited references were searched to identify clinical trials of imagery rehearsal in individuals with post-trauma nightmares. Thirteen studies met inclusion criteria and reported sleep and post-traumatic stress outcomes in sufficient detail to calculate effect sizes. Results indicate that imagery rehearsal had large effects on nightmare frequency, sleep quality, and PTSD symptoms from the initial to post-treatment assessments. These effects were sustained through 6 to 12 months follow-up. Furthermore, interventions that included both imagery rehearsal and cognitive behavioral therapy for insomnia resulted in greater treatment-related improvement in sleep quality than imagery rehearsal alone. Combined treatment did not improve outcomes for PTSD or nightmares. Notably, effect sizes were small in the single study that included an active-treatment control condition. Future research should identify necessary and sufficient components of interventions for trauma-related sleep disturbance and post-traumatic stress (e.g., exposure, cognitive reappraisal, sleep and circadian regulation).

Conditional risk for PTSD among Latinos: A systematic review of racial/ethnic differences and sociocultural explanations

Conditional risk for Posttraumatic Stress Disorder (PTSD)--defined as prevalence, onset, persistence, or severity of PTSD after traumatic exposure--appears to be higher among Latinos relative to non-Latinos after accounting for sociodemographic factors. This systematic review focuses on differences in conditional risk for PTSD between Latinos and non-Latinos (White, Black, or combined) and across Latino subgroups in studies that adjust for trauma exposure. We discuss methodological characteristics of existing articles and sociocultural explanatory factors. Electronic bibliographic searches were conducted for English-language articles published in peer-reviewed journals between 1991 and 2012. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-eight articles met inclusion criteria. Consistent support was found for elevated rates of PTSD onset and PTSD severity among Latinos relative to non-Latino Whites. The evidence on racial/ethnic differences in conditional risk for PTSD prevalence and PTSD persistence is mixed. Twenty-four articles evaluated sociocultural explanations, with the strongest support found for racial/ethnic variation in peri-traumatic responses and structure of PTSD. There were also consistent main effects for social disadvantage in studies that simultaneously adjusted for effects of race/ethnicity. Future research should use theoretically-driven models to formally test for interactions between sociocultural factors, race/ethnicity, and PTSD probability.

Girls’ Challenging Social Experiences in Early Adolescence Predict Neural Response to Rewards and Depressive Symptoms

Highlights • Adolescent psychosocial stress prospectively predicted neural response to potential rewards.• Low parental warmth predicted increased reward response in the mPFC, striatum, and amygdala.• Peer victimization predicted decreased reward response in the mPFC.• Stress-related neural response to potential rewards was correlated with depressive symptoms.• Results support reward-focused neurodevelopmental models of depression in girls.

Change in sleep symptoms across Cognitive Processing Therapy and Prolonged Exposure: a longitudinal perspective.

Sleep disturbance is a core component in posttraumatic stress disorder (PTSD). Although cognitive-behavioral treatments for PTSD reduce the severity of sleep symptoms, they do not lead to complete remission. The present study examines the impact of Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) on subjective measures of sleep disturbance from treatment randomization through long-term follow-up (LTFU). Participants were 171 female rape victims with PTSD who were randomly assigned to CPT, PE, or Minimal Attention (MA). After 6-weeks, the MA group was randomized to CPT or PE. Sleep symptoms were assessed at baseline, post-MA, post-treatment, 3-months, 9-months and LTFU using the Pittsburgh Sleep Quality Index (PSQI) and nightmare and insomnia items from the Clinician Administered PTSD Scale. Change in sleep during MA, from pre- to post-treatment for CPT and PE, and from post-treatment through LTFU was assessed using piecewise hierarchical linear modeling with the intent-to-treat sample. Controlling for medication, sleep improved during CPT and PE compared to MA, and treatment gains were maintained through LTFU. CPT and PE were equally efficacious and improvements persist over LTFU, yet, neither produced remission of sleep disturbance. Overall, sleep symptoms do not remit and may warrant sleep-specific treatments.

Associations between Pittsburgh Sleep Quality Index factors and health outcomes in women with posttraumatic stress disorder

OBJECTIVE The Pittsburgh Sleep Quality Index (PSQI) is a widely used measure of subjective sleep disturbance in clinical populations, including individuals with posttraumatic stress disorder (PTSD). Although the severity of sleep disturbance is generally represented by a global symptom score, recent factor analytic studies suggest that the PSQI is better characterized by a two- or three-factor model than a one-factor model. This study examined the replicability of two- and three-factor models of the PSQI, as well as the relationship between PSQI factors and health outcomes, in a female sample with PTSD. METHODS The PSQI was administered to 319 women with PTSD related to sexual or physical assault. Confirmatory factor analyses tested the relative fit of one-, two-, and three-factor solutions. Bivariate correlations were performed to examine the shared variance between PSQI sleep factors and measures of PTSD, depression, anger, and physical symptoms. RESULTS Confirmatory factor analyses supported a three-factor model with Sleep Efficiency, Perceived Sleep Quality, and Daily Disturbances as separate indices of sleep quality. The severity of symptoms represented by the PSQI factors was positively associated with the severity of PTSD, depression, and physical symptoms. However, these health outcomes correlated as much or more with the global PSQI score as with PSQI factor scores. CONCLUSIONS These results support the multidimensional structure of the PSQI. Despite this, the global PSQI score has as much or more explanatory power as individual PSQI factors in predicting health outcomes.

The contribution of sleep to improvements in working memory scanning speed: A study of prolonged sleep restriction

Working memory scanning and motor response speeds were assessed in chronically sleep restricted participants using the Sternberg item recognition paradigm (SIRP). Twenty-two healthy volunteers (ages 21-30) living in a controlled hospital environment were allowed either 4h of sleep opportunity (50% of habitual sleep) or 8h of sleep opportunity (100% of habitual sleep) for 12 days. Working memory scanning efficiency (time taken to access an item in working memory) was tested for the first 9 days of sleep restriction and improved over time in participants permitted an 8h sleep period, but did not change significantly in participants permitted a 4h sleep period. Speed of motor response (reaction time independent of cognitive processing) did not change significantly in either group. These results indicate that the efficiency of working memory scanning can improve with repeated practice given sufficient sleep, and that prolonged sleep restriction to 50% of habitual sleep prevents this improvement.

Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence

Stressful life events increase vulnerability to problematic alcohol use, and they may do this by disrupting reward-related neural circuitry. This is particularly relevant for adolescents because alcohol use rises sharply after mid-adolescence and alcohol abuse peaks at age 20. Adolescents also report more stressors compared with children, and neural reward circuitry may be especially vulnerable to stressors during adolescence because of prefrontal cortex remodeling. Using a large sample of male participants in a longitudinal functional magnetic resonance imaging study (N = 157), we evaluated whether cumulative stressful life events between the ages of 15 and 18 were associated with reward-related brain function and problematic alcohol use at age 20 years. Higher cumulative stressful life events during adolescence were associated with decreased response in the medial prefrontal cortex (mPFC) during monetary reward anticipation and following the receipt of monetary rewards. Stress-related decreases in mPFC response during reward anticipation and following rewarding outcomes were associated with the severity of alcohol dependence. Furthermore, mPFC response mediated the association between stressful life events and later symptoms of alcohol dependence. These data are consistent with neurobiological models of addiction that propose that stressors during adolescence increase risk for problematic alcohol use by disrupting reward circuit function.

Chronic stress is prospectively associated with sleep in midlife women: The SWAN sleep study

STUDY OBJECTIVES Evaluate whether levels of upsetting life events measured over a 9-y period prospectively predict subjective and objective sleep outcomes in midlife women. DESIGN Prospective cohort study. SETTING Four sites across the United States. PARTICIPANTS 330 women (46-57 y of age) enrolled in the Study of Womens Health Across the Nation (SWAN) Sleep Study. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Upsetting life events were assessed annually for up to 9 y. Trajectory analysis applied to life events data quantitatively identified three distinct chronic stress groups: low stress, moderate stress, and high stress. Sleep was assessed by self-report and in-home polysomnography (PSG) during the ninth year of the study. Multivariate analyses tested the prospective association between chronic stress group and sleep, adjusting for race, baseline sleep complaints, marital status, body mass index, symptoms of depression, and acute life events at the time of the Sleep Study. Women characterized by high chronic stress had lower subjective sleep quality, were more likely to report insomnia, and exhibited increased PSG-assessed wake after sleep onset (WASO) relative to women with low to moderate chronic stress profiles. The effect of chronic stress group on WASO persisted in the subsample of participants without baseline sleep complaints. CONCLUSIONS Chronic stress is prospectively associated with sleep disturbance in midlife women, even after adjusting for acute stressors at the time of the sleep study and other factors known to disrupt sleep. These results are consistent with current models of stress that emphasize the cumulative effect of stressors on health over time.

Adolescent girls’ neural response to reward mediates the relation between childhood financial disadvantage and depression

BACKGROUND Children who experience socioeconomic disadvantage are at heightened risk for developing depression; however, little is known about neurobiological mechanisms underlying this association. Low socioeconomic status (SES) during childhood may confer risk for depression through its stress-related effects on the neural circuitry associated with processing monetary rewards. METHODS In a prospective study, we examined the relationships among the number of years of household receipt of public assistance from age 5-16 years, neural activation during monetary reward anticipation and receipt at age 16, and depression symptoms at age 16 in 123 girls. RESULTS Number of years of household receipt of public assistance was positively associated with heightened response in the medial prefrontal cortex during reward anticipation, and this heightened neural response mediated the relationship between socioeconomic disadvantage and current depression symptoms, controlling for past depression. CONCLUSIONS Chronic exposure to socioeconomic disadvantage in childhood may alter neural circuitry involved in reward anticipation in adolescence, which in turn may confer risk for depression.