The relationship of self-esteem and self-efficacy to treatment outcomes of alcohol-dependent men and women

This study investigates whether self-esteem is associated with clinical and demographic characteristics, self-efficacy expectancies, and post-treatment drinking outcomes. Forty-one (40.6%) women and 60 (59.4%) men were recruited during inpatient alcohol dependence treatment. At baseline, lower self-esteem was significantly associated with current depression and other psychiatric disorders. Self-esteem was not related to gender, relapse, other one-year drinking outcomes, or self-efficacy. Age and psychiatric disorders were strong predictors of self-esteem at follow-up. This study suggests that different perceptions of the self have unique roles in recovery from alcohol use disorders.     

The Trauma Recovery Group: A Cognitive-Behavioral Program for Post-Traumatic Stress Disorder in Persons with Severe Mental Illness

To address the problem of post-traumatic stress disorder (PTSD) in severe mental illness, the Trauma Recovery Group, a mixed gender cognitive-behavioral program, was developed and piloted at a community mental health center. The 21-week program includes breathing retraining, education about PTSD, cognitive restructuring, coping with symptoms, and making a recovery plan. Eighty clients were assessed at baseline and 41 provided follow-up data. Retention in the group was good: 59%. Treatment completers improved significantly in PTSD symptoms and diagnosis, depression, and post-traumatic cognitions, but dropouts did not. The results support the feasibility of the program and suggest it produces clinical benefits. Kim T. Mueser and Elisa Bolton are affiliated with the Department of Psychiatry, Dartmouth Medical School, New Hampshire-Dartmouth Psychiatric Research Center, 105 Pleasant St., Concord, NH, 03301, USA. Patricia C. Carty, Michael J.Bradley, Kimberly F. Ahlgren, Diane R. DiStaso, Andrew Gilbride, Carol Liddell are affiliated with The Mental Health Center of Greater Manchester, Manchester, NH, USA     

Health-related quality of life and functioning in remitted bipolar I outpatients

The aim of this study was to characterize the health-related quality of life (HR-QOL) and functioning in 90 bipolar I remitted outpatients. According to Diagnostic and Statistical Manual of Mental Disorders IV remission specifiers, patients were categorized into 4 groups: group 1, fully remitted; group 2, less than 2 months remitted; group 3, with persisting manic symptoms; group 4, with persisting depressive symptoms. The severity of psychopathology was evaluated by using the Bech-Rafaelsen Mania-Melancholia Scale. The HR-QOL, functioning, and insight were assessed via the medical outcomes study 36-item short form, the global assessment of functioning scale, and the scale to assess unawareness of mental disorder, respectively. Fully remitted patients reported the highest scores in almost all domains of medical outcomes study 36-item short form, and had significantly higher scores on physical functioning, general health, social functioning, and mental health compared to patients with persisting depressive symptoms. Furthermore, patients with persisting manic symptoms reported significantly higher scores on general health, vitality and mental health than the group with persisting depressive symptoms. In contrast, the global assessment of functioning scale score differed among the 4 groups, with fully remitted patients reporting higher, although not statistically significant, scores than the other groups. Our data suggest that the persistence of depressive or manic symptoms seem to affect self-report measures of HR-QOL. An affectively biased cognition may explain the gap between patient's perception of functioning and estimated functional adjustment, as assessed by clinicians.     

Small-fiber involvement in spinobulbar muscular atrophy (Kennedy's disease)

We assessed the involvement of cutaneous innervation in two subjects with a molecularly confirmed diagnosis of spinobulbar muscular atrophy (SBMA) using antidromic nerve conduction studies, quantitative sensory testing, and sweat tests, as well as immunohistochemical techniques and confocal microscopy of glabrous and hairy skin biopsy. Both patients showed a marked reduction in amplitude of sensory action potentials and moderate or severe abnormalities of tactile thresholds and mechanical pain perception. A severe reduction of sweat drops on the Silastic imprint test and a widespread loss of small myelinated and unmyelinated fibers in hairy skin were also observed. Fiber loss involved either somatic or autonomic fibers and did not show any distal-proximal gradient. These results, together with loss of Meissner corpuscles and their large myelinated afferent fibers in glabrous skin, confirmed the extensive involvement of sensory neurons of large and small size and revealed an autonomic skin denervation in SBMA.     

Myelinated nerve endings in human skin

We used immunohistochemical techniques and confocal microscopy to study the morphometry of myelinated nerve endings in glabrous and hairy skin. A total of 30 healthy volunteers took part in this study designed to assess the possibility of obtaining reliable information on myelinated fibers using samples of hairy skin and to determine whether differences exist between myelinated terminations from different sites. We obtained consistent information on cutaneous myelinated terminations using hairy as well as glabrous skin samples. Myelinated endings from hairy and glabrous skin differ in density and distribution. However, from a comparison of our findings with data from nerve biopsy studies, we conclude that all cutaneous myelinated terminations are thinner terminal branches of large myelinated A beta fibers, whereas cutaneous terminations of small myelinated A delta fibers lose their myelin before entering the dermis and become indistinguishable from C-fiber terminations. The classic criteria, based on fiber size, used to distinguish myelinated fiber subgroups in sensory nerves are therefore not suitable for identifying myelinated terminations in the skin.     

Regulation of endothelial progenitor cell homing after arterial injury

Adult bone marrow and peripheral blood contain sub-populations of vascular precursor cells, which can differentiate into mature endothelial cells and have therefore been commonly termed endothelial progenitor cells (EPCs). Although EPCs encompass rather heterogeneous cell sub-populations of multiple origins and localization, these cells were basically characterized by expression of progenitor markers and by the development of colony-forming units and late endothelial outgrowth with terminal differentiation into mature endothelial cells. Notably, functional studies in vivo have implied the contribution of EPCs to therapeutic reendothelialization and inhibition of neointimal growth following endothelial injury. In the context of this regenerative arterial remodeling, an adequate homing of EPCs plays a central role. This multi-step process of EPC mobilization, recruitment and firm adhesion is regulated by key angiogenic chemokines (CCL2, CXCL1, CXCL7, CXCL12) and their respective receptors (CCR2, CXCR2, CXCR4). Furthermore, the recruitment of circulating EPCs to sites of arterial injury is synchronized by activated platelets and adhesion molecules of the selectin and integrin family. Thus, translating this molecular knowledge to interventional cardiovascular medicine, such a detailed understanding in the complex regulation of EPC homing may be helpful for more effectively preventing "in-stent" stenosis by facilitating stent endothelialization.     

Interaction between serine phosphorylated IRS-1 and beta1-integrin affects the stability of neuronal processes

Tumor necrosis factor-alpha (TNFalpha) released in the brain by HIV-activated macrophages/microglia is suspected to compromise neuronal survival. Previously, we have demonstrated that activated receptor for insulin-like growth factor I (IGF-IR) protects neurons from TNFalpha-induced neuronal damage (Wang et al. [ 2006] J. Neurosci. Res. 83:7-18). Because TNFalpha triggers phosphorylation of insulin receptor substrate 1 (IRS-1) on serine residues (pS-IRS-1; Rui et al. [ 2001] J. Clin. Invest. 107:181-189), and pS-IRS-1 binds integrins (Reiss et al. [ 2001] Oncogene 20:490-500), we asked how these events affect neuronal processes. We show that beta1-integrin and pS-IRS-1 colocalize in PC12 cells and in primary cortical neurons. TNFalpha treatment elevated membrane-associated pS-IRS-1, enhanced pS-IRS-1 interaction with beta1-integrin, and attenuated cell attachment to collagen IV. In contrast, IGF-I inhibited pS-IRS-1-beta1-integrin complexes and improved cell attachment. The domain of IRS-1 involved in beta1-integrin binding mapped between amino acids 426 and 740, and the expression of 426-740/IRS-1 mutant attenuated neuronal outgrowth. Our results indicate that TNFalpha facilitates the interaction of pS-IRS-1 and beta1-integrin and destabilizes neuronal processes. IGF-I counteracts TNFalpha-mediated accumulation of pS-IRS-1-beta1-integrin complexes supporting the stability of neuronal processes.     

Neocortical hyperexcitability in a human case of tuberous sclerosis complex and mice lacking neuronal expression of TSC1

OBJECTIVE: To identify brain regions, cell types, or both that generate abnormal electrical discharge in tuberous sclerosis complex (TSC). Here we examined excitatory and inhibitory synaptic currents in human tissue samples obtained from a TSC patient with no discernible cortical tubers and acute neocortical brain slices from a mouse featuring synapsin-driven conditional deletion of a TSC1 gene. These studies were designed to assess whether TSC gene inactivation alters excitability. METHODS: We used visualized patch-clamp (human and mouse) and extracellular field (mouse) recordings. Additional mice were processed for immunohistochemistry or Western blot analysis. RESULTS: Detailed anatomic studies in brain tissue sections from synapsin-TSC1 conditional knock-out mice failed to uncover gross anatomic defects, loss of lamination, or frank tuber formation. However, regions of abnormal and potentially activated neocortex were shown using antibodies to nonphosphorylated neurofilaments (SMI-311) and immediate early genes (c-Fos). Extracellular recordings from neocortical slices, examining synaptic activity in these regions, demonstrated clear differences in excitability between conditional knock-out and age-matched control mice. Whole-cell patch-clamp recordings demonstrated excitatory synaptic currents with strikingly long duration and epileptiform discharge patterns, similar to waveforms observed in our human tissue samples. These events were 1-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor mediated and were most prominent in neocortex. Normal-appearing inhibitory postsynaptic currents (human) and intrinsic neuronal firing patterns (mouse) were also recorded. INTERPRETATION: This combination of human and mouse tissue studies suggests, for the first time, that synaptic excitation is altered in a direction that favors seizure generation in TSC brain tissue regardless of cortical tubers.