Loss of Sustained Activity in the Ventromedial Prefrontal Cortex in Response to Repeated Stress in Individuals with Early-Life Emotional Abuse: Implications for Depression Vulnerability

Repeated psychosocial stress in early-life has significant impact on both behavior and neural function which, together, increase vulnerability to depression. However, neural mechanisms related to repeated stress remain unclear. We hypothesize that early-life stress may result in a reduced capacity for cognitive control in response to a repeated stressor, particularly in individuals who developed maladaptive emotional processing strategies, namely trait rumination. Individuals who encountered early-life stress but have adaptive emotional processing, namely trait mindfulness, may demonstrate an opposite pattern. Using a mental arithmetic task to induce mild stress and a mindful breathing task to induce a mindful state, we tested this hypothesis by examining blood perfusion changes over time in healthy young men. We found that subjects with early-life stress, particularly emotional abuse, failed to sustain neural activation in the orbitofrontal and ventromedial prefrontal cortex (vmPFC) over time. Given that the vmPFC is known to regulate amygdala activity during emotional processing, we subsequently compared the perfusion in the vmPFC and the amygdala in depression-vulnerable (having early-life stress and high in rumination) and resilient (having early-life stress and high in mindfulness) subjects. We found that depression-vulnerable subjects had increased amygdala perfusion and reduced vmPFC perfusion during the later runs than that during the earlier stressful task runs. In contrast, depression-resilient individuals showed the reverse pattern. Our results indicate that the vmPFC of depression-vulnerable subjects may have a limited capacity to inhibit amygdala activation to repeated stress over time, whereas the vmPFC in resilient individuals may adapt to stress quickly. This pilot study warrants future investigation to clarify the stress-related neural activity pattern dynamically to identify depression vulnerability at an individual level

Loss of Sustained Activity in the Ventromedial Prefrontal Cortex in Response to Repeated Stress in Individuals with Early-Life Emotional Abuse: Implications for Depression Vulnerability

Repeated psychosocial stress in early-life has significant impact on both behavior and neural function which, together, increase vulnerability to depression. However, neural mechanisms related to repeated stress remain unclear. We hypothesize that early-life stress may result in a reduced capacity for cognitive control in response to a repeated stressor, particularly in individuals who developed maladaptive emotional processing strategies, namely trait rumination. Individuals who encountered early-life stress but have adaptive emotional processing, namely trait mindfulness, may demonstrate an opposite pattern. Using a mental arithmetic task to induce mild stress and a mindful breathing task to induce a mindful state, we tested this hypothesis by examining blood perfusion changes over time in healthy young men. We found that subjects with early-life stress, particularly emotional abuse, failed to sustain neural activation in the orbitofrontal and ventromedial prefrontal cortex (vmPFC) over time. Given that the vmPFC is known to regulate amygdala activity during emotional processing, we subsequently compared the perfusion in the vmPFC and the amygdala in depression-vulnerable (having early-life stress and high in rumination) and resilient (having early-life stress and high in mindfulness) subjects. We found that depression-vulnerable subjects had increased amygdala perfusion and reduced vmPFC perfusion during the later runs than that during the earlier stressful task runs. In contrast, depression-resilient individuals showed the reverse pattern. Our results indicate that the vmPFC of depression-vulnerable subjects may have a limited capacity to inhibit amygdala activation to repeated stress over time, whereas the vmPFC in resilient individuals may adapt to stress quickly. This pilot study warrants future investigation to clarify the stress-related neural activity pattern dynamically to identify depression vulnerability at an individual level

Psychological and neural mechanisms of trait mindfulness in reducing depression vulnerability

Mindfulness-based interventions are effective for reducing depressive symptoms. However, the psychological and neural mechanisms are unclear. This study examined which facets of trait mindfulness offer protection against negative bias and rumination, which are key risk factors for depression. Nineteen male volunteers completed a 2-day functional magnetic resonance imaging study. One day utilized a stress-induction task and the other day utilized a mindful breathing task. An emotional inhibition task was used to measure neural and behavioral changes related to state negative bias, defined by poorer performance in inhibiting negative relative to neutral stimuli. Associations among trait mindfulness [measured by the Five Facet Mindfulness Questionnaire (FFMQ)], trait rumination, and negative bias were examined. Non-reactivity scores on the FFMQ correlated negatively with rumination and negative bias following the stress induction. Non-reactivity was inversely correlated with insula activation during inhibition to negative stimuli after the mindful breathing task. Our results suggest non-reactivity to inner experience is the key facet of mindfulness that protects individuals from psychological risk for depression. Based on these results, mindfulness could reduce vulnerability to depression in at least two ways: (i) by buffering against trait rumination and negative bias and (ii) by reducing automatic emotional responding via the insula

What Attracts Women to the IT Field? The First Process of Occupational Socialization

Socialization in an occupation differs in important ways from organizational socialization. Entering a defined occupation is apt to involve a lifelong commitment, yet it is one that individuals often drift into gradually. Entering occupations involves five different, but overlapping processes: attraction, access, adjustment, identification and commitment (Trice & Beyer, 1993). The first of these five processes refers to the specific features of the occupation that get individuals attention and attract them to the occupation. Such features include specific members of the occupation to whom newcomers get attracted such as successful heroes and mentors. It could also be the activities distinctive of the occupational culture or the kinds of extrinsic and intrinsic rewards that the occupation appears to offer. This research study focuses on the attraction process of occupational socialization to the information technology (Ahuja, 2002) field of female students in order to understand women’s experiences and initial perceptions of the IT occupation. This study gathers empirical evidence from current female students in IT-related majors based on a qualitative approach and the use of focus groups as the elicitation technique. The goal of our research study is to contribute to a better understanding of the initial process of occupational socialization of female students in IT majors. The findings of this study, we believe, can help in improving and customizing recruitment strategies for female students that would emphasize the most attractive features of the IT occupation as perceived by women. In this research in progress we present the findings of our study based on eight focus groups conducted with students of three IT related academic majors in two academic institutions in the United States

IGFBP2 Produces Rapid-Acting and Long-Lasting Effects in Rat Models of Posttraumatic Stress Disorder Via a Novel Mechanism Associated with Structural Plasticity

Background: Posttraumatic stress disorder is an anxiety disorder characterized by deficits in the extinction of aversive memories. Insulin-like growth factor 1 (IGF1) is the only growth factor that has shown anxiolytic and antidepressant properties in human clinical trials. In animal studies, insulin-like growth factor binding protein 2 (IGFBP2) shows both IGF1-dependent and IGF1-independent pharmacological effects, and IGFBP2 expression is upregulated by rough-and-tumble play that induces resilience to stress. Methods: IGFBP2 was evaluated in Porsolt, contextual fear conditioning, and chronic unpredictable stress models of posttraumatic stress disorder. The dependence of IGFBP2 effects on IGF1- and AMPA-receptor activation was tested using selective receptor antagonists. Dendritic spine morphology was measured in the dentate gyrus and the medial prefrontal cortex 24 hours after in vivo dosing. Results: IGFBP2 was 100 times more potent than IGF1 in the Porsolt test. Unlike IGF1, effects of IGFBP2 were not blocked by the IGF1-receptor antagonist JB1, or by the AMPA-receptor antagonist 2,3-Dioxo-6-nitro-1,2,3,4 tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX) in the Porsolt test. IGFBP2 (1 microg/kg) and IGF1 (100 microg/kg i.v.) each facilitated contextual fear extinction and consolidation. Using a chronic unpredictable stress paradigm, IGFBP2 reversed stress-induced effects in the Porsolt, novelty-induced hypophagia, sucrose preference, and ultrasonic vocalization assays. IGFBP2 also increased mature dendritic spine densities in the medial prefrontal cortex and hippocampus 24 hours postdosing. Conclusions: These data suggest that IGFBP2 has therapeutic-like effects in multiple rat models of posttraumatic stress disorder via a novel IGF1 receptor-independent mechanism. These data also suggest that the long-lasting effects of IGFBP2 may be due to facilitation of structural plasticity at the dendritic spine level. IGFBP2 and mimetics may have therapeutic potential for the treatment of posttraumatic stress disorder

The use of a ward's history in training psychiatric child care workers

The importance of the contribution of historical-cultural factors to an inpatient treatment setting's contemporaneous psycho-social climate has been given little attention in published discussions of ward staff problems and training. This report illustrates some ways in which such historical-cultural forces, embodied in social myths and entrenched traditions, operate. Examples are provided from a ward of disturbed adolescents, where young child care workers struggled as a group with the daily stresses of providing therapeutic milieu support to children ambivalently seeking and resisting external controls for their feelings and impulses. The process of incorporating the analysis of historical-cultural factors in an inservice training program is described.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44275/1/10566_2005_Article_BF01642066.pd

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Non-Neoplastic and Neoplastic Pleural Endpoints Following Fiber Exposure

Exposure to asbestos fibers is associated with non-neoplastic pleural diseases including plaques, fibrosis, and benign effusions, as well as with diffuse malignant pleural mesothelioma. Translocation and retention of fibers are fundamental processes in understanding the interactions between the dose and dimensions of fibers retained at this anatomic site and the subsequent pathological reactions. The initial interaction of fibers with target cells in the pleura has been studied in cellular models in vitro and in experimental studies in vivo. The proposed biological mechanisms responsible for non-neoplastic and neoplastic pleural diseases and the physical and chemical properties of asbestos fibers relevant to these mechanisms are critically reviewed. Understanding mechanisms of asbestos fiber toxicity may help us anticipate the problems from future exposures both to asbestos and to novel fibrous materials such as nanotubes. Gaps in our understanding have been outlined as guides for future research