Decreased CCK(B) receptor binding in rat amygdala in animals demonstrating greater anxiety-like behavior.

Wunderlich GR, Raymond R, DeSousa NJ, Nobrega JN, Vaccarino FJ.

Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 3G3.

RATIONALE: The potentiation of the acoustic startle response (ASR) by stimuli associated with aversive events is mediated via the amygdala and is used as an index of "anxiety" and "fear". In laboratory animals, cholecystokinin(B) (CCK(B)) agonists increase anxiety and fear and activation of amygdala CCK(B) receptors potentiates ASR. Additionally, antagonism of CCK(B) receptors attenuates fear-potentiated ASR. OBJECTIVES: To investigate the putative role of CCK(B) receptors in individual differences in fear and anxiety, we examined individual differences in amygdala CCK(B) receptor binding for animals demonstrating low versus high baseline and fear-potentiated ASR. Additionally, we examined individual differences in CCK(B) binding for animals demonstrating low versus high anxiety-like behavior on the elevated plus-maze (EPM). METHODS: Male Wistar rats were tested in the ASR, fear-potentiated ASR, and EPM paradigms. Following testing, brain slices were mounted and incubated with 50 pM (125)I-CCK8 (non-sulfated), a selective CCK(B) receptor ligand, in the presence or absence of 1 micro M non-radioactively labeled CCK and then exposed on tritium-sensitive film for 2-3 days. RESULTS: Animals with high fear-potentiated ASR showed decreased CCK(B) receptor binding in both the basolateral and central amygdaloid nuclei. Animals with high anxiety-like responses on the EPM showed decreased CCK(B) binding in the basolateral, but not central, amygdala. There were no differences in amygdala CCK(B) binding in animals demonstrating low versus high baseline ASR. None of the groups showed differences in CCK(B) receptor binding in the nucleus accumbens. CONCLUSIONS: These results show that there is a down-regulation of amygdala CCK(B) receptor binding in animals demonstrating greater anxiety-like responding in the fear-potentiated ASR and EPM models of anxiety, possibly as a compensation for increased CCK activity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12404082&dopt=Abstract anxiety medicine




Cocaine-induced anxiety: alleviation by diazepam, but not buspirone, dimenhydrinate or diphenhydramine.

Paine TA, Jackman SL, Olmstead MC.

Department of Psychology, Queen's University, Kingston, Ontario, Canada.

Clinical reports and animal experiments indicate that both cocaine administration and cocaine withdrawal increase anxiety. We investigated the ability of a number of putative anxiolytic agents to alleviate these anxiety states using the elevated plus-maze. Rats in the cocaine condition received either saline or cocaine (20 mg/kg) 40 min prior to testing; those in the withdrawal condition were tested 48 h following a chronic treatment regime (saline or cocaine 20 mg/kg per day for 14 days). Prior to testing, animals received a benzodiazepine (1.0 or 2.0 mg/kg diazepam), a serotonergic agonist (0.5 or 1.0 mg/kg buspirone), an antihistamine (50 mg/kg dimenhydrinate or 27 mg/kg diphenhydramine) or a saline injection. All drugs were administered intraperitoneally. Cocaine administration and cocaine withdrawal reduced the percentage time spent on and the number of entries into the open arms. Diazepam dose-dependently alleviated cocaine withdrawal-induced anxiety and non-significantly attenuated cocaine-induced anxiety. Buspirone, dimenhydrinate and diphenhydramine did not consistently alleviate the anxiety caused by either cocaine pre-treatment regime; in the saline conditions, however, each of these treatments was anxiogenic. In summary, benzodiazepines alleviated cocaine-induced anxiety, while future research on the ability of serotonergic and antihistaminergic drugs to alleviate these anxiety states is warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12409990&dopt=Abstract anxiety medicine




Childhood adversity and anxiety versus dysthymia co-morbidity in major depression.

Harkness KL, Wildes JE.

Department of Psychology, University of Oregon, USA.

BACKGROUND: Childhood adversity places individuals with major depression at risk for anxiety and dysthymia co-morbidity. The goal of the present paper is to broaden this area of research by examining specificity between the type of adversity (e.g. abuse versus neglect/indifference) and the resulting co-morbid disorder (e.g. anxiety versus dysthymia co-morbidity). METHOD: The volunteer sample consisted of 76 women meeting Diagnostic and Statistical Manual (DSM-IV) criteria for major depression. Of these, 28 were diagnosed with a co-morbid anxiety disorder and 21 were diagnosed with co-morbid dysthymia. Childhood physical abuse, sexual abuse, psychological abuse, antipathy and indifference were assessed using a contextual interview and rating system. RESULTS: Severe sexual abuse and psychological abuse were significantly and preferentially associated with co-morbid anxiety, while severe physical abuse was significantly and preferentially associated with co-morbid dysthymia. Indifference and antipathy were significantly associated with both co-morbid anxiety and dysthymia. Multivariate analyses revealed that severe sexual abuse was the adverse childhood experience most strongly associated with co-morbid anxiety. CONCLUSIONS: These results suggest that particular adverse experiences in childhood do set up specific vulnerabilities to the expression of anxiety versus dysthymia co-morbidity in adulthood major depression. Cognitive mediators of these associations are discussed as avenues of future research.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12420893&dopt=Abstract anxiety medicine




Conditioned anxiety to nicotine.

File SE, Cheeta S, Irvine EE, Tucci S, Akthar M.

Psychopharmacology Research Unit, Centre for Neuroscience, GKT School of Biomedical Sciences, King's College London, Hodgkin Building, Guy's Campus, London SE1 1UL, UK.

RATIONALE: Despite its reinforcing properties nicotine has also been reported to produce anxiety in humans and anxiogenic effects in animal tests of anxiety. OBJECTIVE: The aims of this study were three-fold: (a) to investigate whether anxiety can be conditioned to cues associated with an acute anxiogenic dose of nicotine, (b) to investigate whether the conditioned anxiety is specific to a particular test of anxiety, and (c) to investigate whether nicotine pre-exposure influences the development of a conditioned anxiogenic effect. METHODS: An anxiogenic dose of nicotine was administered to rats either before or after experience with the social interaction (SI) test. The retention of a conditioned anxiogenic response was examined when the rats were re-tested undrugged in the SI test 24 h later. To test whether conditioned anxiety was test specific, rats that had been tested in the elevated plus-maze with an anxiogenic dose of nicotine were retested undrugged in the SI test 24 h later, and vice versa. We then examined the effects of 4 days or 4 weeks pre-exposure to nicotine on the development of a conditioned anxiogenic response in the SI test. RESULTS: Rats injected with nicotine (0.45 mg/kg s.c.) 5 min before the social interaction test spent significantly less time in SI, indicating an unconditioned anxiogenic effect than did vehicle-injected controls or rats injected with nicotine after the test. After 24 h when all groups were tested undrugged only those previously tested in SI after nicotine injection showed a significant conditioned anxiogenic effect. This conditioned anxiety was test specific. Rats injected with nicotine before the SI test did not show an anxiogenic response when tested 24 h later undrugged in the plus-maze, and vice versa. Furthermore, although 4 days exposure to nicotine (0.45 mg/kg s.c.) did not prevent the development of a conditioned anxiogenic response, 4 weeks self-administration of nicotine (total dose, 0.45 mg/kg i.v) in an operant chamber did not affect the acute anxiogenic response to nicotine in the SI test, but it did prevent the development of conditioned anxiety. CONCLUSIONS: The present findings suggest that anxiety can be conditioned following exposure to an anxiogenic dose of nicotine, and that this anxiety is specific to the contextual cues associated with the SI test.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12424555&dopt=Abstract anxiety medicine




Effect of intraperitoneal mRNA antisense-oligodeoxynucleotides to cholecystokinin on anxiety-like and learning behaviors in rats: association with pre-experimental stress.

Cohen H, Matar MA, Buriakovsky I, Zeev K, Kotler M, Bourin M.

Ministry of Health Mental Health Center, Faculty of Health Sciences, Anxiety and Stress Research Unit, Ben Gurion University of the Negev, Beer-Sheva, Israel. hagitc bgumail.bgu.ac.il

RATIONALE: Cholecystokinin and its analogs generate anxiety in humans and measurable anxiety-like behaviors in rats. Cholecystokinin receptor blockers have been reported to have variable effects in the treatment of anxiety disorders. We demonstrated that intracerebroventricular administration of Cholecystokinin-antisense oligodeoxynucleotides (ASODN) for 3 days significantly diminished anxiety-like behavior in rats. OBJECTIVE: This study was designed to examine the effects of peripheral (intraperitoneal) administration of Cholecystokinin-ASODN on anxiety-like and learning behaviors in rats, in general and in a pre-experiment stress paradigm. METHODS: In the first study Cholecystokinin-ASODN was injected intraperitoneally to rats five times at 24-h intervals. Control groups received injections of either a scrambled oligodeoxynucleotide (ScrODN) or vehicle. On the sixth day, the rats were assessed in the elevated plus-maze paradigm and in the Morris water maze. In the second study, rats were pre-exposed to a cat for 10 min as a model for psychological stress, and then treated with intraperitoneal Cholecystokinin-ASODN and tested in both paradigms. RESULTS: The results show that for intact rats, intraperitoneal Cholecystokinin-ASODN significantly increased anxiety-like behavior and impaired retention performance in the Morris water maze, compared to both control groups. In stressed rats, Cholecystokinin-ASODN reduced anxiety-like behaviors in the plus-maze and improved performance in the water maze compared with controls. CONCLUSIONS: These results indicate that the anxiolytic effect of intraperitoneal Cholecystokinin-ASODN may be dependent on the baseline endogenous level of stress (i.e., on the Cholecystokinin levels). Basal endogenous levels of Cholecystokinin, as well as exogenous dosage of Cholecystokinin agonists and/or anxiolytic agents, appear to play an important role in the expression and/or control of anxiety-related behaviors in rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12450740&dopt=Abstract anxiety medicine




Anxiety but not depression determines health care-seeking behaviour in Chinese patients with dyspepsia and irritable bowel syndrome: a population-based study.

Hu WH, Wong WM, Lam CL, Lam KF, Hui WM, Lai KC, Xia HX, Lam SK, Wong BC.

Department of Medicine, University of Hong Kong, China.

AIMS: To study the prevalence of dyspepsia and irritable bowel syndrome and the effects of co-existing anxiety and depression on health care utilization by a population survey in Chinese. METHODS: Ethnic Chinese households were invited to participate in a telephone survey using a validated bowel symptom questionnaire and the hospital anxiety and depression scale. Gastrointestinal symptoms were classified as dyspepsia and irritable bowel syndrome according to the Rome I criteria and gastro-oesophageal reflux disease by the presence of weekly heartburn or acid regurgitation. The anxiety and depression scores were compared between patients who sought medical attention and those who did not, using multiple logistic regression analysis. RESULTS: One thousand, six hundred and forty-nine subjects completed the interview (response rate, 62%). The population prevalences of dyspepsia, irritable bowel syndrome and gastro-oesophageal reflux disease were 18.4%, 4.1% and 4.8%, respectively. Dyspepsia and irritable bowel syndrome were associated with anxiety, depression, medical consultation, sick leave and adverse effects on social life. The degree of anxiety was an independent factor associated with health care-seeking behaviour in both dyspeptics (P = 0.003) and irritable bowel syndrome patients (P = 0.036). CONCLUSIONS: Irritable bowel syndrome and dyspepsia are associated with anxiety, depression, significant social morbidity, health care utilization and days off work. Anxiety is an independent factor in determining health care utilization in patients with dyspepsia and irritable bowel syndrome.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12452941&dopt=Abstract anxiety medicine




Comorbidity of anxiety disorder among patients with bipolar I disorder in remission.

Tamam L, Ozpoyraz N.

Department of Psychiatry, Faculty of Medicine, Cukurova University, Adana, Turkey. Ltamam mail.cu.edu.tr

The aim of this study was to assess the comorbidity of lifetime and current prevalences of anxiety disorders among 70 patients with bipolar I disorder in remission using structured diagnostic interviews and to examine the association between comorbidity and several demographic and clinical variables. Forty-three (61.4%) bipolar I patients also met DSM-IV criteria for at least one lifetime comorbid anxiety disorder. Obsessive-compulsive disorder (39%) was the most common comorbid lifetime anxiety disorder, followed by simple phobia (26%) and social phobia (20%). First episode and male sex were found to have lower rates of comorbid current anxiety disorders. The presence of anxiety disorders was related to significantly higher scores on both anxiety and general psychopathology scales. The results of the present study support previous findings of a high comorbidity rate of anxiety disorders in bipolar I disorder cases and indicate that the presence of an anxiety disorder leads to more severe psychopathology levels in bipolar I patients. Copyright 2002 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12239436&dopt=Abstract anxiety medicine




Rationale and principles for early intervention with young children at risk for anxiety disorders.

Hirshfeld-Becker DR, Biederman J.

Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, 02138, USA. dhirshfeld partners.org

Anxiety disorders are one of the most prevalent categories of disorder among adults and children. Children of parents with anxiety disorders are known to be at higher risk for anxiety disorders themselves, with manifestations of this risk often appearing in toddlerhood or early childhood. Yet because affected parents are often unskilled in anxiety management, they often have difficulty in helping their young children learn to manage anxiety. Literature on the course of anxiety disorders through childhood and on effective cognitive-behavioral interventions suggests that preventive interventions even with very young children could potentially be of benefit in mitigating the course of these often debilitating disorders. This paper outlines the rationale for offering early or preventive interventions to preschool-age children at risk and their parents and discusses means of identifying children to target for intervention and the importance of parental involvement. Drawing upon the literature on parental factors in childhood anxiety disorders as well as on effective intervention strategies with preschool-age children, it delineates principles for intervention with parents and effective components of intervention with youngsters in this age range.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12240705&dopt=Abstract anxiety medicine




The Comorbidity of Major Depression and Anxiety Disorders: Recognition and Management in Primary Care.

Hirschfeld RM.

Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston.

BACKGROUND: Depressive and anxiety disorders commonly occur together in patients presenting in the primary care setting. Although recognition of individual depressive and anxiety disorders has increased substantially in the past decade, recognition of comorbidity still lags. The current report reviews the epidemiology, clinical implications, and management of comorbidity in the primary care setting. METHOD: Literature was reviewed by 2 methods: (1) a MEDLINE search (1980-2001) using the key words depression, depressivedisorders, and anxietydisorders; comorbidity was also searched with individual anxiety diagnoses; and (2) direct search of psychiatry, primary care, and internal medicine journals over the past 5 years. RESULTS: Between 10% and 20% of adults in any given 12-month period will visit their primary care physician during an anxiety or depressive disorder episode (although typically for a nonpsychiatric complaint); more than 50% of these patients suffer from a comorbid second depressive or anxiety disorder. The presence of depressive/anxiety comorbidity substantially increases medical utilization and is associated with greater chronicity, slower recovery, increased rates of recurrence, and greater psychosocial disability. Typically, long-term treatment is indicated, although far less research is available to guide treatment decisions. Selective serotonin reuptake inhibitor antidepressants are the preferred treatment based on efficacy, safety, and tolerability criteria. Knowledge of their differential clinical and pharmacokinetic profiles can assist in optimizing treatment. CONCLUSION: Increased recognition of the high prevalence and negative psychosocial impact of depression and anxiety disorder comorbidity will lead to more effective treatment. While it is hoped that early and effective intervention will yield long-term benefits, research is needed to confirm this.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15014592&dopt=Abstract anxiety medicine