Neurosteroids and Self-Reported Pain in Veterans Who Served in the U.S. Military after September 11, 2001

Nearly half of Operation Enduring Freedom / Operation Iraqi Freedom (OEF/OIF) veterans experience continued pain post-deployment. Several investigations report analgesic effects of allopregnanolone and other neurosteroids in animal models, but few data are currently available focusing on neurosteroids in clinical populations. Allopregnanolone positively modulates GABAA receptors and demonstrates pronounced analgesic and anxiolytic effects in rodents, yet studies examining the relationship between pain and allopregnanolone in humans are limited. We thus hypothesized that endogenous allopregnanolone and other neurosteroid levels may be negatively correlated with self-reported pain symptoms in humans

Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation

Muscular dystrophy and peripheral neuropathy have been linked to mutations in genes encoding nuclear envelope proteins; however, the molecular mechanisms underlying these disorders remain unresolved. Nuclear envelope protein p19A is a protein of unknown function encoded by a gene at chromosome 4q35. p19A levels are significantly reduced in human muscle as cells differentiate from myoblasts to myotubes; however, its levels are not similarly reduced in all differentiation systems tested. Because 4q35 has been linked to facioscapulohumeral muscular dystrophy (FSHD) and some adjacent genes are reportedly misregulated in the disorder, levels of p19A were analyzed in muscle samples from patients with FSHD. Although p19A was increased in most cases, an absolute correlation was not observed. Nonetheless, p19A downregulation in normal muscle differentiation suggests that in the cases where its gene is inappropriately reactivated it could affect muscle differentiation and contribute to disease pathology

Posttraumatic Stress Disorder Symptom Network Analysis in U.S. Military Veterans: Examining the Impact of Combat Exposure

Recent work inspired by graph theory has begun to conceptualize mental disorders as networks of interacting symptoms. Posttraumatic stress disorder (PTSD) symptom networks have been investigated in clinical samples meeting full diagnostic criteria, including military veterans, natural disaster survivors, civilian survivors of war, and child sexual abuse survivors. Despite reliable associations across reported networks, more work is needed to compare central symptoms across trauma types. Additionally, individuals without a diagnosis who still experience symptoms, also referred to as subthreshold cases, have not been explored with network analysis in veterans. A sample of 1,050 Iraq/Afghanistan-era U.S. military veterans (851 males, mean age = 36.3, SD = 9.53) meeting current full-criteria PTSD (n = 912) and subthreshold PTSD (n = 138) were assessed with the Structured Clinical Interview for DSM-IV Disorders (SCID). Combat Exposure Scale (CES) scores were used to group the sample meeting full-criteria into high (n = 639) and low (n = 273) combat exposure subgroups. Networks were estimated using regularized partial correlation models in the R-package qgraph, and robustness tests were performed with bootnet. Frequently co-occurring symptom pairs (strong network connections) emerged between two avoidance symptoms, hypervigilance and startle response, loss of interest and detachment, as well as, detachment and restricted affect. These associations replicate findings reported across PTSD trauma types. A symptom network analysis of PTSD in a veteran population found significantly greater overall connectivity in the full-criteria PTSD group as compared to the subthreshold PTSD group. Additionally, novel findings indicate that the association between intrusive thoughts and irritability is a feature of the symptom network of veterans with high levels of combat exposure. Mean node predictability is high for PTSD symptom networks, averaging 51.5% shared variance. With the tools described here and by others, researchers can help refine diagnostic criteria for PTSD, develop more accurate measures for assessing PTSD, and eventually inform therapies that target symptoms with strong network connections to interrupt interconnected symptom complexes and promote functional recovery

Hyperintense lesions on magnetic resonance images in bipolar disorder

Background: To examine the magnetic resonance (MR) images of bipolar patients across a wide age range for the presence of hyperintense lesions compared to age- and gender-matched control subjects. Methods: Consecutive admissions to a mood disorders unit over a 2-year period were evaluated retrospectively for the presence of bipolar disorder by DSM-III-R criteria and whether they received an MR scan. Bipolar patients (n = 70, mean age = 49.9 ± 19.7 years) were age- and gender-matched to control subjects (n = 70, mean age = 53.2 ± 18.1 years) and the MR scans were rated to assess for the presence of hyperintensites. Results: Compared to control subjects, the bipolar patients demonstrated hyperintense lesions in the subependymal region, subcortical gray nuclei, and the deep white matter. Conclusions: Hyperintense lesions in bipolar patients are found in both the subcortical white matter and gray nuclei and may play an important role in the etiology of bipolar illness

The brief social phobic scale - a psychometric evaluation.

The Brief Social Phobia Scale (BSPS) is an observer-rated scale designed to assess the characteristic symptoms of social phobia, using three subscales-fear, avoidance, and physiological arousal-which may be combined into a total score. Each of 18 BSPS items is anchored to a 5-point rating scale. Psychometric evaluation of the BSPS in a sample of 275 social-phobia patients yielded a high level of reliability and validity. Test-retest reliability was excellent, as was internal consistency. The fear and avoidance subscales demonstrated highly significant correlations with remaining item totals; however, the physiological subscale did not. The BSPS also demonstrated significant relationships with other established scales that assess anxiety and disability, and it proved sensitive to treatment effects in a trial of a 5-HT3 antagonist and placebo. Factor analysis yielded six meaningful factors. We conclude that the BSPS provides a reliable, valid, and sensitive measure for the evaluation of social phobia.http://journals.cambridge.org/abstract_S003329179600421

Hypercortisolemia and hippocampal changes in depression

Hypercortisolemia is a frequently observed abnormality in patients with major depression. It has been hypothesized that the hippocampus, as a major feedback site for glucocorticoids, is involved in the pathophysiology of hypercortisolemia. Some have in fact posited that the hippocampus is marked by diminished size in depressed patients with hypercortisolemia. We tested this hypothesis by examining the relationship between hippocampal volume, assessed with magnetic resonance imaging, and hypercortisolemia using the dexamethasone suppression test (DST) in a group of 19 depressed patients. No differences in hippocampal volume were observed between patients and control subjects ( n = 30). Within the patient group, DST suppressors did not differ from DST nonsuppressors in hippocampal volume. However, a relationship between dhippocampal volume and 11 p.m. cortisol concentration was observed after covariance adjustment for age and sex. Furthermore, significant negative correlations were onserved between hippocampal volume and both age of depressive onset and number of hospitalizations. The results of this study therefore provide limited support for the hypothesis regarding an essential role of the hippocampus in the neuroendocrine elevation of glucocorticoids in depression

Source memory for emotional pictures in Alzheimer patients

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