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Concept: Agoraphobia

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Severe social withdrawal (called hikikomori, and defined as isolation lasting more than six months and not due to an apparent mental disorder) has drawn increasing public attention in Japan. It is unclear whether hikikomori is merely a symptom or syndrome of social withdrawal.

Concepts: Mental disorder, Anxiety disorder, Panic disorder, Fear, Social anxiety, Anxiety disorders, Social anxiety disorder, Agoraphobia

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Unexpected, recurrent panic attacks and anxious apprehension are two distinct emotional phenomena that constitute the core symptoms for diagnosing panic disorder. Taking a neuroscience perspective the current review paper presents both epidemiological and experimental psychophysiological evidence suggesting that panic attacks can be conceptualized as an unconditioned circa defense response pattern to intense internal threat stimuli, characterized by strong autonomic surge and escape behavior and abnormal plastic changes of the brain. Anxious apprehension develops after the experience of such severe panic attacks as conditioned responses to mild body symptoms. Theoretically these conditioned fear responses can be considered as post-encounter defense characterized by increased selective attention, increased threat appraisal and defensive freezing and startle potentiation evidencing altered brain circuits evoked by mild body symptoms. Agoraphobic avoidance starts very early during the defensive cascade and can be conceived as motivated behavior driven by the incentive to be in a safe context that is under control of the individual.

Concepts: Anxiety, Psychology, Anxiety disorder, Fear, Social anxiety disorder, Panic attack, Agoraphobia, Panic

26

Panic disorder with agoraphobia is characterized by panic attacks and anxiety in situations where escape might be difficult. However, neuroimaging studies specifically focusing on agoraphobia are rare. Here we used functional magnetic resonance imaging (fMRI) with disorder-specific stimuli to investigate the neural substrates of agoraphobia.

Concepts: Brain, Neuroscience, Magnetic resonance imaging, Anxiety disorder, Panic disorder, Social anxiety disorder, Panic attack, Agoraphobia

24

Many patients with social anxiety disorder (SAD) experience inadequate symptom relief from available treatments. Ketamine is a potent N-methyl-D-aspartate (NMDA) receptor antagonist with a potentially novel mechanism of action for the treatment of anxiety disorders. Therefore, we conducted a double-blind, randomized, placebo-controlled crossover trial in 18 adults with DSM-5 SAD and compared the effects between intravenous ketamine (0.5 mg/kg over 40 min) and placebo (normal saline) on social phobia symptoms. Ketamine and placebo infusions were administered in a random order with a 28-day washout period between infusions. Ratings of anxiety were assessed 3-hours post-infusion and followed for 14 days. We used linear mixed models to assess the impact of ketamine and placebo on anxiety symptoms. Outcomes were blinded ratings on the Liebowitz Social Anxiety Scale (LSAS) and self-reported anxiety on a visual analog scale (VAS-Anxiety). We also used the Wilcoxon signed-rank test to compare the proportion of treatment responders. Based on prior studies, we defined response as a greater than 35% LSAS reduction and 50% VAS-Anxiety reduction. We found ketamine resulted in a significantly greater reduction in anxiety relative to placebo on the LSAS (Time*Treatment: F9,115=2.6, p=0.01) but not the VAS-Anxiety (Time*Treatment: F10,141=0.4, p=0.95). Participants were significantly more likely to exhibit a treatment response after ketamine infusion relative to placebo in the first two weeks following infusion measured on the LSAS (33.33% response ketamine vs 0% response placebo, Wilcoxon signed-rank test z=2.24, p=0.025) and VAS (88.89% response ketamine vs 52.94% response placebo, Wilcoxon signed-rank test z=2.12, p=0.034). In conclusion, this proof-of-concept trial provides initial evidence that ketamine may be effective in reducing anxiety. ClinicalTrials.gov Identifier: NCT02083926Neuropsychopharmacology accepted article preview online, 29 August 2017. doi:10.1038/npp.2017.194.

Concepts: Anxiety disorder, Panic disorder, Alprazolam, Fear, Social anxiety, Anxiety disorders, Social anxiety disorder, Agoraphobia

18

Research shows that people tend to consider believable conclusions as valid and unbelievable conclusions as invalid (belief bias). When applied to anxiogenic beliefs, this belief bias could well hinder the correction of dysfunctional convictions. Previous work has shown that high socially anxious students indeed display such fear-confirming, belief biased, reasoning. A critical next question is whether these findings translate to a clinical population of people with social anxiety disorder (SAD). We test whether (i) patients with SAD show belief bias with regard to SAD-relevant themes, (ii) this belief bias is specific for SAD patients or can also be found in panic disorder (PD) patients, (iii) differential belief bias effects in SAD are restricted to social anxiety concerns or are also evident in the context of reasoning with neutral themes.

Concepts: Critical thinking, Anxiety disorder, Panic disorder, Fear, Social anxiety, Social anxiety disorder, Panic attack, Agoraphobia

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Purpose: The association between striking life events, an important stress and acute anxiety disorder, and the occurrence of primary breast cancer is unclear. The current meta-analysis was designed to assess the relationship between striking life events and primary breast cancer incidence in women.

Concepts: Anxiety, Epidemiology, Cancer, Breast cancer, Metastasis, Estrogen, Panic disorder, Agoraphobia

6

Background: Placebo-controlled trials showed that both benzodiazepines (BDZ) and antidepressant drugs (AD) are effective in treating anxiety disorders. However, in the last years a progressive shift in the prescribing pattern from BDZ to newer AD has taken place. The aim of this systematic review and meta-analysis is to analyze whether controlled comparisons support such a shift. Methods: CINHAL, the Cochrane Library, MEDLINE, PubMed and Web of Science were searched from inception up to December 2012. A total of 22 studies met the criteria for inclusion. They were mostly concerned with tricyclic antidepressants (TCA; 18/22) and involved different anxiety disorders. In order to reduce clinical heterogeneity, only the 10 investigations that dealt with the comparison between TCA and BDZ in panic disorder were submitted to meta-analysis, whereas the remaining papers were individually summarized and critically examined. Results: According to the systematic review, no consistent evidence emerged supporting the advantage of using TCA over BDZ in treating generalized anxiety disorder (GAD), complex phobias and mixed anxiety-depressive disorders. Indeed, BDZ showed fewer treatment withdrawals and adverse events than AD. In panic disorder with and without agoraphobia our meta-analysis found BDZ treatments more effective in reducing the number of panic attacks than TCA (risk ratio, RR = 1.13; 95% CI = 1.01-1.27). Furthermore, BDZ medications were significantly better tolerated than TCA drugs, causing less discontinuation (RR = 0.40; 95% CI = 0.20-0.57) and side effects (RR = 0.41; 95% CI = 0.34-0.50). As to newer AD, BDZ trials resulted in comparable or greater improvements and fewer adverse events in patients suffering from GAD or panic disorder. Conclusions: The change in the prescribing pattern favoring newer AD over BDZ in the treatment of anxiety disorders has occurred without supporting evidence. Indeed, the role and usefulness of BDZ need to be reappraised. © 2013 S. Karger AG, Basel.

Concepts: Antidepressant, Selective serotonin reuptake inhibitor, Anxiety disorder, Generalized anxiety disorder, Panic disorder, Tricyclic antidepressant, Social anxiety disorder, Agoraphobia

4

Thigmotaxis refers to a specific behavior of animals (i.e., to stay close to walls when exploring an open space). Such behavior can be assessed with the open field test (OFT), which is a well-established indicator of animal fear. The detection of similar open field behavior in humans may verify the translational validity of this paradigm. Enhanced thigmotaxis related to anxiety may suggest the relevance of such behavior for anxiety disorders, especially agoraphobia.

Concepts: Anxiety disorder, Panic disorder, Social anxiety, Social anxiety disorder, Agoraphobia

4

Within maintenance models of social anxiety disorder (SAD), a number of cognitive and behavioural factors that drive the persistence of SAD have been proposed. However, these maintenance models do not address how SAD develops, or the origins of the proposed maintaining factors. There are also models of the development of SAD that have been proposed independently from maintenance models. These models highlight multiple factors that contribute risk to the onset of SAD, but do not address how these aetiological factors may lead to the development of the maintaining factors associated with SAD.

Concepts: Psychology, Anxiety disorder, Panic disorder, Alprazolam, Fear, Social anxiety, Social anxiety disorder, Agoraphobia