Anxiety Disorders: Wang L

Wang L, Simpson HB, Dulawa SC. · Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, Illinois, USA. · Behav Pharmacol. · Pubmed #19339874 No free full text.

Abstract: Obsessive-compulsive disorder (OCD) is a disorder characterized by unwanted and intrusive thoughts, images, or impulses and/or repetitive behavior. OCD is a major cause of disability; however, the genetic factors and pathophysiological mechanisms underlying this complex, heterogeneous disorder remain largely unknown. During the past decade, a number of putative mouse genetic models of OCD have been developed for the purpose of studying the neural mechanisms underlying this disorder and developing novel treatments. This review presents and evaluates these experimental preparations to date. Models using knockout or transgenic approaches, as well as those examining variation in genetically diverse populations, are evaluated and discussed.

Taché Y, Martinez V, Wang L, Million M. · CURE/Digestive Diseases Research Center, and Center for Neurovisceral Sciences and Woman's Health, West Los Angeles VA Medical Center, University of California-Los Angeles, 1130 Wilshire Boulevard, Los Angeles, CA 90073, U.S.A. ytaché@ucla.edu · Br J Pharmacol. · Pubmed #15100165 links to  free full text

Abstract: 1. The characterization of corticotropin releasing factor (CRF) and, more recently, the discovery of additional CRF-related ligands, urocortin 1, urocortin 2 and urocortin 3, the cloning of two distinct CRF receptor subtypes, 1 (CRF(1)) and 2 (CRF(2)), and the development of selective CRF receptor antagonists provided new insight to unravel the mechanisms of stress. Activation of brain CRF(1) receptor signaling pathways is implicated in stress-related endocrine response and the development of anxiety-like behaviors. 2. Compelling evidence in rodents showed also that both central and peripheral injection of CRF and urocortin 1 mimic acute stress-induced colonic response (stimulation of motility, transit, defecation, mucus and watery secretion, increased ionic permeability and occurrence of diarrhea) in rodents. Central CRF enhances colorectal distention-induced visceral pain in rats. Peripheral CRF reduced pain threshold to colonic distention and increased colonic motility in humans. 3. Nonselective CRF(1)/CRF(2) antagonists and selective CRF(1) antagonists inhibit exogenous (central or peripheral) CRF- and acute stress-induced activation of colonic myenteric neurons, stimulation of colonic motor function and visceral hyperalgesia while selective CRF(2) antagonists have no effect. None of the CRF antagonists influence basal or postprandial colonic function in nonstressed animals. 4. These findings implicate CRF(1) receptors in stress-related stimulation of colonic function and hypersensitivity to colorectal distention. Targeting CRF(1)-dependent pathways may have potential benefit against stress or anxiety-/depression-related functional bowel disorders.

Bouilleret V, Hogan RE, Velakoulis D, Salzberg MR, Wang L, Egan GF, O'Brien TJ, Jones NC. · Department of Medicine-Royal Melbourne Hospital, University of Melbourne, Royal Parade, Parkville, Victoria 3052, Australia. · Neuroimage. · Pubmed #19167503 No free full text.

Abstract: BACKGROUND: Imaging studies of epilepsy patients with comorbid affective disturbance demonstrate morphometric changes in limbic brain regions implicated in psychiatric disease. Genetic Absence Epilepsy Rats from Strasbourg (GAERS), specifically bred for their epilepsy phenotype, also exhibit elevated anxiety-like behaviors suggesting a common causality. Here we examined whether relevant cerebral morphological alterations exist in this rat strain using volumetric measurements and large deformation high dimensional mapping (HDM-LD), a tool recently validated to produce accurate three-dimensional surface representations of the hippocampus. METHODS: Volumetric MRI and the Open Field test of anxiety were performed in adult female GAERS (n=12) and Non-Epileptic Controls (NEC; n=11). The volumes of selected brain regions, including cortex, hippocampus, amygdala, thalamus, hypothalamus and lateral ventricles, were measured using Region-Of-Interest analysis from the MRI data and total volumes compared between the two strains. RESULTS: GAERS had increased amygdala (right: p=0.003; left p<0.001), cortices (right: p=0.006; left p=0.012) and ventricular volumes (p=0.002) when compared with NEC rats. Further, HDM-LD showed GAERS to have hippocampal volume loss in two regions: the medial hippocampal surface immediately caudal to the hippocampal commissure, and the lateral hippocampal surface over the mid-portion of the septotemporal axis. GAERS exhibited increased anxiety in the Open Field compared with NEC rats: reduced distance traveled (p<0.001) and reduced time in the centre area (p=0.042). CONCLUSIONS: Morphometric brain changes in GAERS could be relevant to their hyperanxious and epileptic phenotypes. This model may be useful in illuminating the pathogenesis of affective disorders generally, as well as modeling psychiatric comorbidities of epilepsy.

Wei TM, Wang L. · Lishui City Central Hospital, China. · Int J Psychiatry Med. · Pubmed #17236698 No free full text.

Abstract: OBJECTIVES: To investigate incidence and severity of anxiety symptoms in patients with hypertension. METHODS: A cross-sectional survey in 891 (432 females) hypertensive patients was conducted in a regional community. All patients were interviewed and detailed physical examination was performed. Zung self-rating anxiety scale (SAS) was used to evaluate the severity of anxiety symptoms. RESULTS: Anxiety was diagnosed on clinical grounds in 103 patients (11.6%) who also had a raw SAS score of more than 40. In all subjects surveyed, the average SAS score in females was higher than males (32.9+/- 7.1 vs 31.2+/-6.4, p < 0.001). The average SAS score was also higher in patients with hypertension of more than 3 years (32.4+/-7.0 vs 31.2+/-6.1, p = 0.01), in patients with severe hypertension (39.8+/-6.9 vs 29.6 4+/-4.5, p < 0.001), and in patients with a history of hospitalization for cardiovascular disorders (35.7+/-7.7 vs 31.7+/-6.6, p < 0.001). Multivariate regression analysis showed that female gender, duration of hypertension, and hospitalization history were independent predictors of anxiety symptoms (p < 0.05). CONCLUSIONS: Almost 12% of hypertensive patients have anxiety symptoms. Female gender, the duration of hypertension, and the history of hospitalization are associated with the occurrence and severity of anxiety symptoms in patients with hypertension.

Wang L, Maher TJ, Wurtman RJ. · Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. · FASEB J. · Pubmed #17218538 links to  free full text

Abstract: We explored the possibility that circulating glutamine affects gamma-aminobutyric acid (GABA) levels in rat striatal tissue and GABA concentrations in striatal extracellular fluid (ECF). Striatal microdialysates, each collected over a 20 min interval, were obtained after no treatment, oral L-glutamine (0.5 g/kg), or glutamine followed by NMDA (administered via the microdialysis probe). GABA concentrations were measured by HPLC using a stable OPA/sulfite precolumn derivatization and an electrochemical detection method. L-Glutamine administration significantly increased ECF GABA concentrations by 30%, and enhanced the response evoked by NMDA alone (70%) to 120% over baseline (all P<0.05). Striatal GABA levels increased significantly 2.5 h after oral L-glutamine (e.g., from 1.76 +/- 0.04 micromol/g in vehicle-treated rats to 2.00 +/- 0.15 micromol/g in those receiving 2.0 g/kg of glutamine). Striatal glutamine levels also increased significantly, but not those of glutamate. These data suggest that GABA synthesis in, and release from, rat striatum may be regulated in part by circulating glutamine. Hence, glutamine administration may provide a useful adjunct for treating disorders (e.g., anxiety, seizures) when enhanced GABAergic transmission is desired. Moreover, the elevation in plasma and brain glutamine associated with hepatic failure may, by increasing brain GABA release, produce some of the manifestations of hepatic encephalopathy.

Fullerton CS, Ursano RJ, Wang L. · Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814-4799, USA. · Am J Psychiatry. · Pubmed #15285961 links to  free full text

Abstract: OBJECTIVE: The events of Sept. 11, 2001, highlighted the importance of understanding the effects of trauma on disaster workers. To better plan for the health care of disaster workers, this study examined acute stress disorder, posttraumatic stress disorder (PTSD), early dissociative symptoms, depression, and health care utilization in disaster workers. METHOD: Exposed disaster workers (N=207) and unexposed comparison subjects (N=421) were examined at 2, 7, and 13 months after an airplane crash. RESULTS: Exposed disaster workers had significantly higher rates of acute stress disorder, PTSD at 13 months, depression at 7 months, and depression at 13 months than comparison subjects. Those who were younger and single were more likely to develop acute stress disorder. Exposed disaster workers with acute stress disorder were 3.93 times more likely to be depressed at 7 months. Those with high exposure and previous disaster experience or who had acute stress disorder were more likely to develop PTSD. Similarly, those who were depressed at 7 months were 9.5 times more likely to have PTSD. Those who were depressed at 13 months were 7.96 times more likely to also meet PTSD criteria. More exposed disaster workers than comparison subjects obtained medical care for emotional problems at 2, 7, and 13 months. Overall, 40.5% of exposed disaster workers versus 20.4% of comparison subjects had acute stress disorder, depression at 13 months, or PTSD. CONCLUSIONS: Exposed disaster workers are at increased risk of acute stress disorder, depression, or PTSD and seek care for emotional problems at an increased rate.

Fullerton CS, Ursano RJ, Vance K, Wang L. · Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA. · Psychiatr Q. · Pubmed #10934749 No free full text.

Abstract: In this paper we address three areas. First we review the literature on clinical intervention using debriefing, second we examine who attends debriefings by looking at a study of the 1989 plane crash at Ramstein, Germany and lastly we examine the effect of natural debriefing, i.e., talking to family and friends on psychiatric outcome in disaster workers by looking at a study of the Sioux City, Iowa United plane crash, 1989. Our data suggest that those with high exposure and females were more likely to attend a debriefing. People most likely to talk about the disaster with spouse/significant other, coworker and/or another person were: those with acute PTSD, higher total and intrusive Impact of Event symptoms, older, married, those with higher levels of education and higher levels of disaster exposure. Better understanding of who attends formal debriefings will help identify potential high-risk groups. Similarly, whether talking about the disaster is associated with fewer or greater psychological symptoms is important to understanding the outcome, mechanisms, and risks of debriefing.