Medical conditions and depressive, anxiety, and somatic symptoms in older adults with and without generalized anxiety disorder

OBJECTIVE: The objective of this study was to examine medical illness and anxiety, depressive, and somatic symptoms in older medical patients with generalized anxiety disorder (GAD). METHOD: A case-control study was designed and conducted in the University of California, San Diego (UCSD) Geriatrics Clinics. A total of fifty-four older medical patients with GAD and 54 matched controls participated. MEASUREMENTS: The measurements used for this study include: Brief Symptom Inventory-18, Mini International Neuropsychiatric Interview, and the Anxiety Disorders Interview Schedule. RESULTS: Older medical patients with GAD reported higher levels of somatic symptoms, anxiety, and depression than other older adults, as well as higher rates of diabetes and gastrointestinal conditions. In a multivariate model that included somatic symptoms, medical conditions, and depressive and anxiety symptoms, anxiety symptoms were the only significant predictors of GAD. CONCLUSION: These results suggest first, that older medical patients with GAD do not primarily express distress as somatic symptoms; second, that anxiety symptoms in geriatric patients should not be discounted as a byproduct of medical illness or depression; and third, that older adults with diabetes and gastrointestinal conditions may benefit from screening for anxiety.

Self-attentional processes in anxiety:an experimental study

Self-attention research has demonstrated a relationship between dispositional self-focus, anxiety proneness and fear arousal. In addition, the effect of self-focus manipulations on approach-avoidance tasks involving a feared stimulus are strikingly similar to the effects obtained from manipulation of other cognitive factors such as perceived self-efficacy. A number of experiments were designed to explore the relationship between self-focused attention and ffilxiety. Data from the experiments demonstrate that self-attention influences a variety of cognitive variables which have been considered as central factors in anxiety. Concomitants of self-focus are increased awareness of physiological arousal and overestimation of such arousal, the identification of self-discrepancies, cognitive failures and performance deficits and the activation of physical threat concepts in memory. These factors are conceptualised as central in the negative evaluation of physiological arousal and coping resources in anxiety. Clinically anxious individuals typically have high scores in dispositional self-consciousness and body-consciousness. In patients suffering from generalised anxiety or panic disorders maladaptive self-focusing tendencies can be related to specific life stressors which render aspects of the self salient. An analysis of the ideational component of anxiety revealed three subcomponents; negative social ideation (worry about other people's reaction to the self), negative somatic ideation (worry about physical symptoms and health) and obsessional ideation (the experience of uncontrollable and repetitive thoughts) which were differentially associated with measures of dispositional self-focus. The frequency and content of an.xious w-orry is associated with specific self-focusing tendencies. It is proposed that the 'attentional style' of the individual is an important determinant of the nature and intensity of their affective response in a threatening situation. A self-attentional model of anxiety is proposed and the complex interaction between self-focus and other cognitive factors in anxiety such as appraisal of arousal and coping resources and perceived levels of self-efficacy is discussed. The model presents new directions for research and therapeutic intervention in anxiety.

Psychophysiological responses to visceral and somatic pain in functional chest pain identify clinically relevant pain clusters

Background: Despite chronic pain being a feature of functional chest pain (FCP) its experience is variable. The factors responsible for this variability remain unresolved. We aimed to address these knowledge gaps, hypothesizing that the psychophysiological profiles of FCP patients will be distinct from healthy subjects. Methods: 20 Rome III defined FCP patients (nine males, mean age 38.7 years, range 28-59 years) and 20 healthy age-, sex-, and ethnicity-matched controls (nine males, mean 38.2 years, range 24-49) had anxiety, depression, and personality traits measured. Subjects had sympathetic and parasympathetic nervous system parameters measured at baseline and continuously thereafter. Subjects received standardized somatic (nail bed pressure) and visceral (esophageal balloon distension) stimuli to pain tolerance. Venous blood was sampled for cortisol at baseline, post somatic pain and post visceral pain. Key Results: Patients had higher neuroticism, state and trait anxiety, and depression scores but lower extroversion scores vs controls (all p < 0.005). Patients tolerated less somatic (p < 0.0001) and visceral stimulus (p = 0.009) and had a higher cortisol at baseline, and following pain (all p < 0.001). At baseline, patients had a higher sympathetic tone (p = 0.04), whereas in response to pain they increased their parasympathetic tone (p ≤ 0.008). The amalgamating the data, we identified two psychophysiologically distinct 'pain clusters'. Patients were overrepresented in the cluster characterized by high neuroticism, trait anxiety, baseline cortisol, pain hypersensitivity, and parasympathetic response to pain (all p < 0.03). Conclusions & Inferences: In future, such delineations in FCP populations may facilitate individualization of treatment based on psychophysiological profiling. © 2013 John Wiley & Sons Ltd.

A facial expression for anxiety

Anxiety and fear are often confounded in discussions of human emotions. However, studies of rodent defensive reactions under naturalistic conditions suggest anxiety is functionally distinct from fear. Unambiguous threats, such as predators, elicit flight from rodents (if an escape-route is available), whereas ambiguous threats (e.g., the odor of a predator) elicit risk assessment behavior, which is associated with anxiety as it is preferentially modulated by anti-anxiety drugs. However, without human evidence, it would be premature to assume that rodent-based psychological models are valid for humans. We tested the human validity of the risk assessment explanation for anxiety by presenting 8 volunteers with emotive scenarios and asking them to pose facial expressions. Photographs and videos of these expressions were shown to 40 participants who matched them to the scenarios and labeled each expression. Scenarios describing ambiguous threats were preferentially matched to the facial expression posed in response to the same scenario type. This expression consisted of two plausible environmental-scanning behaviors (eye darts and head swivels) and was labeled as anxiety, not fear. The facial expression elicited by unambiguous threat scenarios was labeled as fear. The emotion labels generated were then presented to another 18 participants who matched them back to photographs of the facial expressions. This back-matching of labels to faces also linked anxiety to the environmental-scanning face rather than fear face. Results therefore suggest that anxiety produces a distinct facial expression and that it has adaptive value in situations that are ambiguously threatening, supporting a functional, risk-assessing explanation for human anxiety.

Patient anxiety and experiences associated with an outpatient "one-stop" "see and treat" hysteroscopy clinic

BACKGROUND: "One-stop" outpatient hysteroscopy clinics have become well established for the investigation and treatment of women with abnormal uterine bleeding. However, the advantages of these clinics may be offset by patient factors such as anxiety, pain, and dissatisfaction. This study aimed to establish patients' views and experiences of outpatient service delivery in the context of a one-stop diagnostic and therapeutic hysteroscopy clinic, to determine the amount of anxiety experienced by these women and compare this with other settings, and to determine any predictors for patient preferences. METHODS: The 20-item State-Trait Anxiety Inventory was given to 240 women attending a one-stop hysteroscopy clinic: to 73 consecutive women before their appointment in a general gynecology clinic and to 36 consecutive women attending a chronic pelvic pain clinic. The results were compared with published data for the normal female population, for women awaiting major surgery, and for women awaiting a colposcopy clinic appointment. In addition, a questionnaire designed to ascertain patients' views and experiences was used. Logistic regression analysis was used to delineate the predictive values of diagnostic or therapeutic hysteroscopy, and to determine their effect on the preference of patients to have the procedure performed under general anesthesia in the future. RESULTS: Women attending the hysteroscopy clinic in this study reported significantly higher levels of anxiety than those attending the general gynecology clinic (median, 45 vs 39; p = 0.004), but the levels of anxiety were comparable with those of women attending the chronic pelvic pain clinic (median, 45 vs 46; p = 0.8). As compared with the data from the normal female population (mean, 35.7) and those reported for women awaiting major surgery (mean, 41.2), the levels of anxiety experienced before outpatient hysteroscopy clinic treatment were found to be higher (mean, 45.7). Only women awaiting colposcopy (6-item mean score, 51.1 +/- 13.3) experienced significantly higher anxiety scores than the women awaiting outpatient hysteroscopy (6-item mean score, 47.3 +/- 13.9; p = 0.002). Despite their anxiety, most women are satisfied with the outpatient hysteroscopy "see and treat" service. High levels of anxiety, particularly concerning pain but not operative intervention, were significant predictors of patients desiring a future procedure to be performed under general anesthesia. CONCLUSIONS: Outpatient hysteroscopy is associated with significant anxiety, which increases the likelihood of intolerance for the outpatient procedure. However, among those undergoing operative therapeutic procedures, dissatisfaction was not associated with the outpatient setting.

Somatic cell gene therapy for diabetes mellitus: engineering a surrogate B-cell

Improved methods of insulin delivery are required for the treatment of insulin-dependent diabetes mellitus (IDDM) to achieve a more physiological profile of glucose homeostasis. Somatic cell gene therapy offers the prospect that insulin could be delivered by an autologous cell implant, engineered to secrete insulin in response to glucose. This study explores the feasibility of manipulating somatic cells to behave as a surrogate insulin-secreting β-cells. Initial studies were conducted using mouse pituitary AtT20 cells as a model, since these cells possess an endogenous complement of enzymes capable of processing proinsulin to mature insulin. Glucose sensitive insulin secretion was conferred to these cells by transfection with plasmids containing the human preproinsulin gene (hppI-1) and the GLUT2 gene for the glucose transporter isoform 2. Insulin secretion was responsive to changes in the glucose concentration up to about 50μM. Further studies to up-rate this glucose sensitivity into the mM range will require manipulation of the hexokinase and glucokinase enzymes. Intraperitoneal implantation of the manipulated AtT20 cells into athymic nude mice with streptozotocin-induced diabetes resulted in decreased plasma glucose concentrations. The cells formed vascularised tumours in vivo which were shown to contain insulin-secreting cells. To achieve proinsulin processing in non-endocrine cells, co-transfection with a suitable enzyme, or mutagenesis of the proinsulin itself are necessary. The mutation of the human preproinsulin gene to the consensus sequence for cleavage by the subtilisin-like serine protease, furin, was carried out. Co-transfection of human fibroblasts with wild-type proinsulin and furin resulted in 58% conversion to mature insulin by these cells. Intraperitoneal implantation of the mature-insulin secreting human fibroblasts into the diabetic nude mouse animal model gave less encouraging results than the AtT20 cells, apparently due to poor vascularisation. Cell aggregations removed from the mice at autopsy were shown to contain insulin secreting cells only at the periphery. This thesis provides evidence that it is possible to construct, by cellular engineering, a glucose-sensitive insulin-secreting surrogate β-cell. Therefore, somatic cell gene therapy offers a feasible alternative for insulin delivery in IDDM patients.

Drug action on anxiety models with special reference to serotonergic mechanisms

A study has been made of drugs acting at 5-HT receptors on animal models of anxiety. An elevated X-maze was used as a model of anxiety for rats and the actions of various ligands for the 5-HT receptor, and its subtypes, were examined in this model. 5-HT agonists, with varying affinities for the 5-HT receptor subtypes, were demonstrated to have anxiogenic-like activity. The 5-HT2 receptor antagonists ritanserin and ketanserin exhibited an anxiolytic-like profile. The new putatuve anxiolytics ipsapirone and buspirone, which are believed to be selective for 5-HT1 receptors, were also examined. The former had an anxiolytic profile whilst the latter was without effect. Antagonism studies showed the anxiogenic response to 8-hydroxy-2-(Di-n-propylamino)tetralin (8-OH-DPAT) to be antagonised by ipsapirone, pindolol, alprenolol and para-chlorophenylalanine, but not by diazepam, ritanserin, metoprolol, ICI118,551 or buspirone. To confirm some of the results obtained in the elevated X-maze the Social Interaction Test of anxiety was used. Results in this test mirrored the effects seen with the 5-HT agonists, ipsapirone and pindolol, whilst the 5-HT2 receptor antagonists were without effect. Studies using operant conflict models of anxiety produced marginal and varying results which appear to be in agreement with recent criticisms of such models. Finally, lesions of the dorsal raphe nucleus (DRN) were performed in order to investigate the mechanisms involved in the production of the anxiogenic response to 8-OH-DPAT. Overall the results lend support to the involvement of 5-HT, and more precisely 5-HT1, receptors in the manifestation of anxiety in such animal models.

Effects of some 5-hydroxytryptamine and related ligands in anxiety models

Drugs acting at 5-HT receptors were evaluated on three animal models of anxiety. On the elevated X-maze test the majority of 5-HT1 agonists were found to be anxiogenic. However, ipsapirone was anxiolytic and buspirone and gepirone were inactive. The 5-HT2 agonist DOI and the 5-HT2 antagonist ritanserin were anxiolytic while ICI 169,369, a 5-HT2 antagonist was inactive. All 5-HT3 antagonists tested were inactive in this test, while the indirect serotomimetics zimeldine and fenfluramine were anxiogenic. Neither beta-adrenoceptor agonists nor antagonists had reproducible effects on anxiety in this model. Combined beta-1/beta-2 adrenoceptor antagonists reversed the anxiogenic effects of 8-OH-DPAT while selective beta-1 or beta-2 antagonists did not. On the social interaction model the 5-HT1 agonists 8-OH-DPAT, RU 24969 and 5-MeODMT were anxiogenic and ipsapirone was anxiolytic. The 5-HT2 agonist DOI and the beta-adrenoceptor- and 5-HT- antagonist pindolol were anxiolytic, while the 5-HT2 and 5-HT3 antagonists were inactive. In the marble burying test, the 5-HT upake inhibitors zimeldine, fluvoxamine, indalpine and citalopram, the 5-HT1B/5-HT1C agonists mCPP and TFMPP and the 5-HT2/5-HT1C agonist DOI reduced marble burying without affecting locomotor activity. 5-HT1A agonists and the 5-HT2 and 5-HT3 antagonists were without effect. Lesions of the dorsal raphe nucleus reversed the anxiogenic effects of 8-OH-DPAT in the X-maze model. The implication of these results for the understanding of the pharmacology of 5-HT in anxiety is discussed.