The median raphe nucleus in anxiety revisited

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Intrahippocampal injection of brain-derived neurotrophic factor increases anxiety-related, but not panic-related defensive responses: involvement of serotonin

Changes in brain-derived neurotrophic factor (BDNF)mediated signaling in the hippocampus have been implicated in the etiology of depression and in the mode of action of antidepressant drugs. There is also evidence from animal studies to suggest that BDNF-induced changes in the hippocampus may play a role in another stress-related pathology: anxiety. However, it is still unknown whether this neurotrophin plays a differential role in defensive responses associated with distinguished subtypes of anxiety disorders found in the clinic, such as generalized anxiety and panic disorder. In the present study, we investigated the effect of an acute BDNF injection into the rat dorsal hippocampus (DH) on inhibitory avoidance acquisition and escape expression measured in the elevated T-maze (ETM). We also assessed whether serotonergic neurotransmission may account for such effects. Intra-DH BDNF injection (200 pg) facilitated inhibitory avoidance in ETM. BDNF was equally anxiogenic in the light/dark transition test. Preadministration of the 5-HT1A receptor antagonist WAY-100635 fully counteracted the anxiogenic effect of BDNF in both tests. Intra-DH midazolam administration (10 nmol) impaired avoidance acquisition in ETM, suggesting an anxiolytic effect. Therefore, in the DH, facilitation of BDNF signaling seems to enhance 5-HT1A receptor-mediated neurotransmission to exert an anxiogenic effect associated with generalized anxiety. Behavioural Pharmacology 23:80-88 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic-related, defensive responses in rats tested in the elevated T-maze

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.

A Functionalist Perspective on Social Anxiety and Avoidant Personality Disorder

A developmental-evolutionary perspective is used to synthesize basic research from the neurosciences, ethology, genetics, and developmental psychology into a unified framework for understanding the nature and origins of social anxiety and avoidant personality disorder. Evidence is presented that social anxiety disorder (social phobia) and avoidant personality disorder may be alternate conceptualizations of the same disorder because they have virtually the same symptoms and genetic basis, and respond to the same pharmacologic and psychotherapeutic interventions. A functionalist perspective on social anxiety is formulated to (a) explain the origins of normative states of anxiety, (b) outline developmental pathways in the transition from normative anxiety to social anxiety and avoidant personality disorders, and (c) account for the processes leading to gender-differentiated patterns of anxiety-related disorders after puberty.

Psychometric properties of the Spence Children's Anxiety Scale with young adolescents

The psychometric properties of the Spence Children's Anxiety Scale (SCAS) were examined with 875 adolescents aged 13 and 14 years. This self-report measure was designed to evaluate symptoms relating to separation anxiety, social phobia, obsessive-compulsive disorder, panic-agoraphobia, generalized anxiety, and fears of physical injury. Results of confirmatory and exploratory factor analyses supported six factors consistent with the hypothesized subtypes of anxiety. There was support also for a model in which the first-order factors loaded significantly on a single second-order factor of anxiety in general. The internal consistency of the total score and sub-scales was high, and 12-week test-retest reliability was satisfactory. The SCAS correlated strongly with a frequently used child self-report measure of anxiety and significantly, albeit at a lower level, with a measure of depression. (C) 2002 Elsevier Inc. All rights reserved.

A parent-report measure of children's anxiety: psychometric properties and comparison with child-report in a clinic and normal sample

This study examined the psychometric properties of the parent version of the Spence Children's Anxiety Scale (SCAS-P); 484 parents of anxiety disordered children and 261 parents in a normal control group participated in the study. Results of confirmatory factor analysis provided support for six intercorrelated factors, that corresponded with the child self-report as well as with the classification of anxiety disorders by DSM-IV (namely separation anxiety, generalized anxiety, social phobia, panic/agoraphobia, obsessive-compulsive disorder, and fear of physical injuries). A post-hoc model in which generalized anxiety functioned as the higher order factor for the other five factors described the data equally well. The reliability of the subscales was satisfactory to excellent. Evidence was found for both convergent and divergent validity: the measure correlated well with the parent report for internalizing symptoms, and lower with externalizing symptoms. Parent-child agreement ranged from 0.41 to 0.66 in the anxiety-disordered group, and from 0.23 to 0.60 in the control group. The measure differentiated significantly between anxiety-disordered children versus controls, and also between the different anxiety disorders except GAD. The SCAS-P is recommended as a screening instrument for normal children and as a diagnostic instrument in clinical settings. (C) 2003 Elsevier Ltd. All rights reserved.

The Kava Anxiety Depression Spectrum Study (KADSS): A randomized, placebo-controlled, cross-over trial using an aqueous extract of Piper methysticum.

Rationale: Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The WHO recently recommended research into “aqueous” extracts of Kava. Objective: The objective of this study was to conduct the first documented human clinical trial assessing the anxiolytic and antidepressant efficacy of an aqueous extract of Kava. Design and participants: The Kava Anxiety Depression Spectrum Study was a 3-week placebo-controlled, double-blind crossover trial that recruited 60 adult participants with 1 month or more of elevated generalized anxiety. Five Kava tablets per day were prescribed containing 250 mg of kavalactones/day. Results: The aqueous extract of Kava reduced participants' Hamilton Anxiety Scale score in the first controlled phase by −9.9 (CI = 7.1, 12.7) vs. −0.8 (CI = −2.7, 4.3) for placebo and in the second controlled phase by −10.3 (CI = 5.8, 14.7) vs. +3.3 (CI = −6.8, 0.2). The pooled effect of Kava vs. placebo across phases was highly significant (p < 0.0001), with a substantial effect size (d = 2.24, η² [sub]p[sub] = 0.428). Pooled analyses also revealed highly significant relative reductions in Beck Anxiety Inventory and Montgomery–Asberg Depression Rating Scale scores. The aqueous extract was found to be safe, with no serious adverse effects and no clinical hepatotoxicity. Conclusions: The aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety.

Diagnosing postpartum depression in mothers and fathers : Whatever happened to anxiety?

Although anxiety disorders are documented in the literature for new mothers (but less so for fathers), rates of postpartum caseness tend to include only those with depression when diagnostic interviews or self-report measures validated on such interviews are used. This methodology therefore underestimates the true percentage of women and men who experience significant psychological difficulties postpartum. This has implications for assessment, treatment and screening for postnatal mood disorders. Two studies were conducted on a total of 408 women and 356 men expecting their first child. They were recruited antenatally, and interviewed at 6 weeks postpartum using the Diagnostic Interview Schedule. DSM-IV criteria were applied to determine the presence since birth of depression (major or minor), panic disorder, acute adjustment disorder with anxiety (meeting the criteria for generalised anxiety disorder except for the duration criterion), and phobia. The inclusion of diagnostic assessment for panic disorder and acute adjustment disorder with anxiety increased the rates of caseness by between 57 and 100% for mothers, and 31-130% for fathers, over the rates for major or minor depression. Inclusion of assessment for phobia further increased the rates of disorder in both samples.

Anxiety and Aboriginal and Torres Strait Islander young people

This chapter outlines issues of excessive anxiety in Indigenous youth. It describes what an anxiety disorder is and its consequences and how Indigenous youth seem to be at risk for developing such disorders. Issues concerning the delivery of traditional prevention and intervention programs are discussed and possible interventions are provided.

Motivational Interviewing changes the treatment trajectory of group Cognitive-Behavioural Therapy for anxiety

Anxiety disorders have been viewed as manifestations of broad underlying predisposing personality constructs such as neuroticism combined with more specific individual differences of unhelpful information processing styles. Given the high prevalence of anxiety and the significant impairment that it causes, there is an important need to continue to explore successful treatments for this disorder. Research indicates that there is still room for significantly improving attrition rates and treatment adherence. Traditionally Motivational Interviewing (MI) has been used to facilitate health behaviour change. Recently MI has been applied to psychotherapy and has been shown to improve the outcome of CBT. However, these studies have been limited to only considering pre- and post-treatment measures and neglected to consider when changes occur along the course of therapy. This leaves the unanswered question of what is the impact of pre-treatment MI on the treatment trajectory of therapy. This study provides preliminary research into answering this question by tracking changes on a weekly basis along the course of group CBT. Prior to group CBT, 40 individuals with a principal anxiety disorder diagnosis were randomly assigned to receive either 3 individual sessions of MI or placed on a waitlist control group. All participants then received the same dosage of 10 weekly 2 hour sessions of group CBT. Tracking treatment outcome trajectory over the course of CBT, the pre-treatment MI group, compared to the control group, experienced a greater improvement early on in the course of therapy in their symptom distress, interpersonal relationships and quality of life. This early advantage over the control group was then maintained throughout therapy. These results not only demonstrate the value of adding MI to CBT, but also highlight the immediacy of MI effects. Further research is needed to determine the robustness of these effects to inform clinical implications of how to best apply MI to improve treatment adherence to CBT for anxiety disorders.

The relationship of meta-worry and intolerance of uncertainty with pathological worry, anxiety, and depression

This study explored how meta-worry and intolerance of uncertainty relate to pathological worry, generalised anxiety, obsessive compulsive disorder, social phobia, and depression. University students (n = 253) completed a questionnaire battery. A series of regression analyses were conducted. The results indicated that meta-worry was associated with GAD, social phobia, obsessive compulsive, and depressive symptoms. Intolerance of uncertainty was related to GAD, social phobia, and obsessive compulsive symptoms, but not depressive symptoms. The importance of meta-worry and intolerance of uncertainty as predictors of pathological worry, GAD, social phobia, obsessive compulsive and depressive symptoms was also examined. Even though both factors significantly predicted the aforementioned symptoms, meta-worry emerged as a stronger predictor of GAD and obsessive compulsive symptoms than did intolerance of uncertainty. Intolerance of uncertainty, compared with meta-worry, appeared as a stronger predictor of social phobia symptoms. Findings emphasise the importance of addressing meta-worry and/or intolerance of uncertainty not only for the assessment and treatment of generalised anxiety disorder (GAD), but also obsessive compulsive disorder, social phobia, and depression.

Teachers' recognition and referral of anxiety disorders in primary school children

This study investigated the ability of primary school teachers to recognise and refer children with anxiety symptoms. Two hundred and ninety-nine primary school teachers completed a questionnaire exploring their recognition and referral responses to five hypothetical vignettes that described boys and girls with varying severity of anxiety symptoms. Results revealed that teachers were generally able to recognise and make the decision to refer children with severe levels of anxiety. However, they had difficulty distinguishing between children with moderate anxiety symptoms and a severe anxiety disorder. Female teachers were more likely to refer children than were male teachers. The implications and future research are discussed.

Predicting depressive and anxiety disorders with the YASR internalising scales (empirical and DSM-oriented)

Background The Achenbach problem behaviour scales (CBCL/YSR) are widely used. The DSM-oriented anxiety and depression scales have been created to improve concordance between Achenbach’s internalising scales and DSM-IV depression and anxiety. To date no study has examined the concurrent utility of the young adult (YASR) internalising scales, either the empirical or newly developed DSM-oriented depressive or anxiety scales. Methods A sample of 2,551 young adults, aged 18–23 years, from an Australian cohort study. The association between the empirical and DSM-oriented anxiety and depression scales were individually assessed against DSMIV depression and anxiety diagnoses derived from structured interview. Odds ratios, ROC analyses and diagnostic efficiency tests (sensitivity, specificity, positive and negative predictive values) were used to report findings. Results YASR empirical internalising scale predicted DSM-IV mood disorders (depression OR = 6.9, 95% CI 5.0–9.5; anxiety OR = 5.1, 95% CI 3.8–6.7) in the previous 12 months. DSM-oriented depressive or anxiety scales did not appear to improve the concordance with DSM-IV diagnosed depression or anxiety. The internalising scales were much more effective at identifying those with comorbid depression and anxiety, with Ors between 10.1 and 21.7 depending on the internalising scale used. Conclusion DSM-oriented scales perform no better than the standard internalising in identifying young adults with DSM-IV mood or anxiety disorder.

Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear

Although the endocannabinoid system (ECS) has been implicated in brain development and various psychiatric disorders, precise mechanisms of the ECS on mood and anxiety disorders remain unclear. Here, we have investigated developmental and disease-related expression pattern of the cannabinoid receptor 1 (CB1) and the cannabinoid receptor 2 (CB2) genes in the dorsolateral prefrontal cortex (PFC) of humans. Using mice selectively bred for high and low fear, we further investigated potential association between fear memory and the cannabinoid receptor expression in the brain. The CB1, not the CB2, mRNA levels in the PFC gradually decrease during postnatal development ranging in age from birth to 50 years (r 2 > 0.6 & adj. p < 0.05). The CB1 levels in the PFC of major depression patients were higher when compared to the age-matched controls (adj. p < 0.05). In mice, the CB1, not the CB2, levels in the PFC were positively correlated with freezing behavior in classical fear conditioning (p < 0.05). These results suggest that the CB1 in the PFC may play a significant role in regulating mood and anxiety symptoms. Our study demonstrates the advantage of utilizing data from postmortem brain tissue and a mouse model of fear to enhance our understanding of the role of the cannabinoid receptors in mood and anxiety disorders

Challenging the myth of an "epidemic" of common mental disorders : trends in the global prevalence of anxiety and depression between 1990 and 2010

Background Anxiety disorders and major depressive disorder (MDD) are common and disabling mental disorders. This paper aims to test the hypothesis that common mental disorders have become more prevalent over the past two decades. Methods We conducted a systematic review of prevalence, remission, duration, and excess mortality studies for anxiety disorders and MDD and then used a Bayesian meta-regression approach to estimate point prevalence for 1990, 2005, and 2010. We also conducted a post-hoc search for studies that used the General Health Questionnaire (GHQ) as a measure of psychological distress and tested for trends to present a qualitative comparison of study findings. Results This study found no evidence for an increased prevalence of anxiety disorders or MDD. While the crude number of cases increased by 36%, this was explained by population growth and changing age structures. Point prevalence of anxiety disorders was estimated at 3.8% (3.6-4.1%) in 1990 and 4.0% (3.7-4.2%) in 2010. The prevalence of MDD was unchanged at 4.4% in 1990 (4.2-4.7%) and 2010 (4.1-4.7%). However, 8 of the 11 GHQ studies found a significant increase in psychological distress over time. Conclusions The perceived "epidemic" of common mental disorders is most likely explained by the increasing numbers of affected patients driven by increasing population sizes. Additional factors that may explain this perception include the higher rates of psychological distress as measured using symptom checklists, greater public awareness, and the use of terms such as anxiety and depression in a context where they do not represent clinical disorders.