Aims Recent research has revealed that early life trauma (ELS), including abuse (sexual and/or physical) and neglect, produce lasting changes in the CNS. We posited that cognitive deficits, often observed in psychiatric patients, result, in part, due to the neurobiological consequences of ELS. Additionally, we hypothesized that the nature and magnitude of cognitive deficits would differ according to the subtype of ELS experienced. Method The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess neurocognitive functioning in 93 subjects (60 with ELS and 33 without). In the patients with a history of ELS, 35% and 16.7%, respectively, met criteria for current major depression and PTSD. Results Significant associations between ELS status and CANTAB measures of memory and executive and emotional functioning were found. Conclusions These data suggest that exposure to ELS results in a cascade of neurobiological changes associated with cognitive deficits in adulthood that vary according to the type of trauma experienced.

Objective: Neurocognitive studies of HIV typically target executive functions dependent on frontostriatal circuitry. The integrity of medial temporal systems has received considerably less attention despite high hippocampal viral load. Studies also predominately involve HIVϩ men, though HIVϩ women may be at increased risk for cognitive dysfunction due to the high prevalence of psychosocial/mental health problems and lower educational attainment. Our aim was to conduct a preliminary investigation of episodic memory and its neural correlates in HIV-infected and at-risk uninfected women.Methods: Participants included 54 HIVϩ and 12 HIVϪ women (mean age ϭ 43 years; 86% African American) recruited from the Chicago site of the Women's Interagency HIV Study. Participants completed standardized tests of verbal and visual episodic memory, working memory, and executive function. A subset of 11 women also underwent functional MRI during a delayed verbal episodic memory task.Results: HIV serostatus predicted significantly lower immediate and delayed verbal episodic memory, working memory, and visual memory. Preliminary neuroimaging findings revealed group differences in bilateral hippocampal function, with HIVϩ women showing decreased activation during encoding and increased activation during delayed recognition. These alterations correlated with worse episodic verbal memory. Conclusions:Verbal episodic memory deficits are evident in HIVϩ women and may be associated with hippocampal dysfunction at both encoding and retrieval. Neurology Until recently, the functional integrity of medial temporal systems in neuroAIDS has received little attention despite considerable evidence of hippocampal injury associated with HIV. Brain viral loads of HIV are particularly high in the hippocampus.1,2 Postmortem evidence of neuroinflammation by microglial/macrophage activation was found to be high in the hippocampus of HIVϩ individuals treated with highly active antiretroviral therapy (HAART), higher even than levels found in pre-HAART neuropathologic studies.3 Regional neurodegeneration of hippocampus and putamen each contributed unique variance in prediction of antemortem neurocognitive status in HIV. 4 A functional MRI (fMRI) study of well-educated HIVϩ men demonstrated reduced signal intensity in right posterior hippocampus, right inferior frontal gyrus, and left lingual gyrus during encoding of scenes.5 Further detailed multimodal investiga-

Objective Self-assessment deficits, often referred to as impaired insight or unawareness of illness, are well established in people with schizophrenia. There are multiple levels of awareness, including awareness of symptoms, functional deficits, cognitive impairments, and the ability to monitor cognitive and functional performance in an ongoing manner. The present study aimed to evaluate the comparative predictive value of each aspect of awareness on the levels of everyday functioning in people with schizophrenia. Method We examined multiple aspects of self-assessment of functioning in 214 people with schizophrenia. We also collected information on everyday functioning rated by high contact clinicians and examined the importance of self-assessment for the prediction of real world functional outcomes. The relative impact of performance based measures of cognition, functional capacity, and metacognitive performance on everyday functioning was also examined. Results Misestimation of ability emerged as the strongest predictor of real world functioning and exceeded the influences of cognitive performance, functional capacity performance, and performance-based assessment of metacognitive monitoring. The relative contribution of the factors other than self-assessment varied according to which domain of everyday functioning was being examined, but in all cases, accounted for less predictive variance. Conclusions These results underscore the functional impact of misestimating one’s current functioning and relative level of ability. These findings are consistent with the use of insight-focused treatments and compensatory strategies designed to increase self-awareness in multiple functional domains.

Social deficits are common in people with schizophrenia and the treatment of deficits in social competence has been a long-time treatment strategy. However, negative symptoms and social cognitive deficits also contribute to social dysfunction. In this study, we examined the correlations between everyday social outcomes, a performance based measure of social competence, and performance on 8 different social cognition tests in 179 patients with schizophrenia. Social cognition, social competence, and motivation-related negative symptoms accounted for 32% of the variance in real-world social outcomes. In addition, two different social cognition tests, along with expression-related negative symptoms accounted for 32% of the variance in performance-based assessments of social competence. These data suggest that negative symptoms exert an important influence on social outcomes and social competence, but not social cognition, and that social cognition and social competence exert separable influences on real-world social outcomes. Improving social outcomes seems to require a multi-faceted approach which considers social cognition, social competence, and negative symptoms.

Awareness of illness is a major factor in schizophrenia and extends into unawareness of cognitive and functional deficits. This unawareness of functional limitations has been shown to be influenced by several different predictive factors, including greater impairment and less severe depression. As treatment efforts are aimed at reducing cognitive deficits, discovery of the most efficient assessment strategies for detection of cognitive and functional changes is critical. In this study, we collected systematic assessments from high contact clinicians focusing on their impressions of the cognitive deficits and everyday functioning in a sample of 169 community dwelling patients with schizophrenia. The patients provided self-report on those same rating scales, as well as self-reporting their depression and performing an assessment of cognitive performance and functional skills. There was essentially no correlation between patients' self reports of their cognitive performance and functional skills and either clinician ratings of these skills or the results of the performance-based assessments. In contrast, clinician reports of cognitive impairments and everyday functioning were correlated with objective performance data. Depression on the part of patients was associated with ratings of functioning that were both more impaired and more congruent with clinician impressions, while overall patients reported less impairment than clinicians. These results underscore the limitations of self reported cognitive functioning even with structured rating scales. Concurrently, clinicians provided ratings of cognitive performance that were related to scores on objective tests, even though they were unaware of the results of those assessments.

Successful medication management is an essential ingredient for effective treatment for HIV. Risk factors for poor medication adherence, including neurocognitive impairment and low health literacy, are common in HIV patients. To better understand the most salient risks for poor management of HIV medications, we tested the interrelation of neurocognitive functioning, reading literacy for health related information, and numeracy and their effect on self-management of a simulated HIV medication regimen. Cross-sectional data on 191 HIV-positive men and women recruited from HIV outpatient clinics in South Florida were collected. Exploratory factor analysis was conducted with literacy, numeracy, and neurocognitive scores and suggested that four factors were present representing executive skill, verbal memory, planning, and motor speed. Both the literacy and numeracy scores loaded on the executive factor. Adjusted analyses showed that executive and planning skills were significantly related to medication management. Findings suggest that patients must rely on higher order cognitive skills to successfully navigate medication self-management, and that efforts to simplify health information that merely lowers readability are likely to meet with limited success.

Although several reports have documented heightened systemic inflammation in posttraumatic stress disorder (PTSD), few studies have assessed whether inflammatory markers serve as prospective biomarkers for PTSD risk. The present study aimed to characterize whether peripheral immune factors measured in blood samples collected in an emergency department immediately after trauma exposure would predict later chronic development of PTSD.Methods: Participants (N=505) were recruited from a hospital emergency department and underwent a 1.5-hour assessment. Blood samples were drawn, on average, about 3 hours after trauma exposure. Follow-up assessments were conducted 1, 3, 6, and 12 months after trauma exposure. Latent growth mixture modeling was used to identify classes of PTSD symptom trajectories.Results: Three distinct classes of PTSD symptom trajectories were identified: chronic (N=28), resilient (N=160), and recovery (N=85). Multivariate analyses of covariance revealed a significant multivariate main effect of PTSD symptom trajectory class membership on proinflammatory cytokines. Univariate analyses showed a significant main effect of trajectory class membership on plasma concentrations of proinflammatory tumor necrosis factor a (TNFa) and interferon-g (IFNg). Concentrations of proinflammatory TNFa and IFNg were significantly lower in individuals in the chronic PTSD class compared with those in the recovery and resilient classes. There were no significant differences in interleukin (IL) 1b and IL-6 concentrations by PTSD symptom trajectory class. Anti-inflammatory and other cytokines, as well as chemokines and growth factor concentrations, were not associated with development of chronic PTSD.Conclusions: Overall, the study findings suggest that assessing the proinflammatory immune response to trauma exposure immediately after trauma exposure, in the emergency department, may help identify individuals most at risk for developing chronic PTSD in the aftermath of trauma.

Between 50–80% of patients with schizophrenia do not believe they have any illness and self assessment of cognitive impairments and functional abilities is also impaired compared to other information, including informant reports and scores on performance-based ability measures. The present paper explores self- assessment accuracy in reference to real world functioning as measured by milestone achievement such as employment and independent living. Our sample included 195 people with schizophrenia examined with a performance-based assessment of neurocognitive abilities and functional capacity. We compared patient self-assessments across achievement of milestones, using patient performance on cognitive and functional capacity measures as a reference point. Performance on measures of functional capacity and cognition was better in people who had achieved employment and residential milestones. Patients with current employment and independence in residence rated themselves as more capable than those who were currently unemployed or not independent. However, individuals who had never had a job rated themselves as at least as capable as those who had been previously employed. These data suggest that lifetime failure to achieve functional milestones is associated with overestimation of abilities. As many patients with schizophrenia never achieve milestones, their self-assessment may be overly optimistic as a result