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Background: The mental health burden from fear of future terrorism has not been given much research attention compared to the immediate mental distress such as post-traumatic stress disorder (PTSD). Such neglected ongoing mental health morbidity associated with threats of terrorism had been described as pre-traumatic stress syndrome (PTSS)., Objective: The study highlighted this phenomenon (PTSS) in Nigeria by examining the catastrophic burden of the fear of future terrorism and associated psychiatric burden among adult population in Kaduna city., Method: Participants were students and staff of Kaduna State University (KASU), Kaduna Polytechnic, and students awaiting admission into Kaduna State University. They responded to the following instruments after obtaining their informed consents: a sociodemographic questionnaire, the Terrorism Catastrophising Scale (TCS), and the depression and Generalised Anxiety Disorder (GAD) portion of Mini International Neuropsychiatric Interview (MINI)., Results: The TCS showed that 78.8% of the participants had from moderate to severe clinical distress on fear of terrorism. The TCS has a Cronbach's alpha of 0.721 and also had significant moderate correlation with depression (r=0.278; p<0.01) and GAD (r=0.201; p<0.01) scales of MINI., Conclusion: The study illustrated that the mental health burden from the fear of terrorism was high and this was relatively related to depression and GAD. This highlighted the need for ongoing monitoring and called for their effective prevention from the identified underlying cognitive mechanisms., (Copyright © 2017. Published by Elsevier B.V.)

Objective: The determination of soft signs can be a conducive practice to understand the differential etiology between depression and anxiety. This study aims at examining malleolar hypoesthesia role in distinguishing between patients with generalised anxiety disorder (GAD) and major depression disorder (MDD). Methods: This study examines the presence of malleolar hypoesthesia in patients with GAD ( n  = 47) compared to patients with MDD ( n  = 48) and healthy individuals (controls; n  = 99). The Wartenberg wheel, a medical device for neurological use, was employed to determine the presence of hypoesthesia on both sides of the ankles. Results: The data revealed: i) MDD patients showed higher hypoesthesia than GAD patients ( p  = .008), ii) participants with hypoesthesia had higher anxiety and depression scores than participants without hypoesthesia (all p  < .001) and iii) logistic regression model indicated that hypoesthesia can be a predictor of MDD relative to GAD diagnosis (Odds Ratio: 17.43 (1.40-217.09; p  = .026)). Conclusions: Malleolar hypoesthesia was higher in MDD than GAD. The detection of hypoesthesia may help to investigate the differential etiology between MDD and GAD diagnosis.

Objective: the aim of this study was to examine the bidirectional association of vision loss (VL) and hearing loss (HL) with anxiety over a 12-year period., Design: this was a prospective population-based study., Setting: community-dwelling French adults., Participants: the study included 3,928 adults aged 65 and above from the Three-City study., Methods: the relationships of VL, as assessed by near visual acuity and self-reported HL to a diagnosis of generalised anxiety disorder (GAD) were assessed over 12 years. A further objective was to explore whether sensory loss has a differential relationship with GAD than with anxiety symptoms, assessed by the Spielberger's State-Trait Anxiety Inventory., Results: at baseline, HL [odds ratio (OR) = 1.41, 95% confidence interval (CI) 1.02-1.96, P = 0.04], but not mild or moderate to severe VL, was associated with self-reported anxiety symptoms (OR = 1.07 95% CI 0.63-1.83, P = 0.80; OR = 0.66 95% CI 0.12-2.22, P = 0.50, respectively). Neither vision nor HL was significantly associated with incident GAD. Baseline GAD was related to increased risk of incident HL (OR = 1.17, 95% CI 1.07-1.28, P < 0.001), but not mild or moderate to severe vision loss (OR = 1.01, 95% CI 0.96-1.06, P = 0.81; OR = 0.97, 95% CI 0.89-1.05, P = 0.45, respectively)., Conclusions: increased anxiety symptoms were observed in older adults with HL, whereas we found no evidence for an association between VL and anxiety. Anxiety was prospectively associated with increased risk of reporting HL. Improved detection of anxiety in older adults with HL may improve quality of life., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: In this maintenance treatment study, we sought to evaluate the effect on anxiety ratings, safety and tolerability of 3 months of weekly ketamine in 20 patients with treatment-refractory DSM IV generalised anxiety disorder (GAD) and/or social anxiety disorder (SAD), and subsequent assessment of remission post-treatment., Methods: This was an uncontrolled open-label study in 20 patients who had been responders in an ascending dose ketamine study. The study was undertaken in a university clinic. Patients received one or two weekly ketamine doses of 1 mg/kg injected subcutaneously for 3 months. Data were collected from December 2015-June 2017., Results: There were 10 women (50%) and 10 men (50%); 15 patients (75%) met criteria for GAD and 18 (90%) for SAD. One hour after dosing, Fear Questionnaire ratings decreased by ~50%, as did Hamilton Anxiety ratings. Clinician Administered Dissociative States Scale mean scores declined over time, from 20 points at week 1 to 8.8 points at week 14. Compared with pre-dose values, mean systolic and diastolic blood pressure increased by ~10 mm Hg at 30 min. The most common adverse events were nausea, dizziness and blurred vision. Of the 20 patients, 18 reported improved social functioning and/or work functioning during maintenance treatment., Conclusions: Weekly ketamine dosing was safe and well tolerated, and post-dose dissociative symptoms tended to reduce after repeated dosing. Patients reported marked improvements in functionality and in their personal lives. Maintenance ketamine may be a therapeutic alternative for patients with treatment refractory GAD/SAD., Trial Registration: http://www.anzctr.org.au/ACTRN12615000617561.

Objective: Generalized anxiety disorder (GAD) is a common anxiety disorder. Although lots of research done to reveal neurobiological basis of GAD, it is still unclear. Diagnosis of GAD depends on subjective complaints of patients, thus the need for a biological marker is constantly emerging. In this study, we aimed to investigate diagnostic value of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in GAD., Methods: We evaluated MDA, SOD, and CAT levels in peripheral blood of 46 patients and 45 controls. MDA was measured with Ohkawa's methods, SOD was measured with Fridovich method, and CAT was measured with Beutler's method., Results: MDA was significantly increased in patients than controls, medians 4.05 nmol/mg and 1.71 nmol/mg respectively, p ＜0.001; SOD and CAT activity was significantly decreased in patients than controls, medians of SOD were 159.07 U/mg and 301.87 U/mg, p ＜0.001 respectively, medians for CAT were 138.47 U/mg and 160.60 U/mg respectively. We found high correlation between Hamilton Anxiety Rating Scale and SOD, MDA r values were 0.723 and 0.715 respectively, p ＜0.001 for both. Receiver operator characteristic (ROC) curve analysis showed high diagnostic performance for MDA and SOD, low diagnostic performance for CAT, areas under curve were 1.0, 1.0, and 0.648 respectively., Conclusion: Our results reveal possible diagnostic value of MDA, less likely of SOD but not CAT. Future studies should investigate diagnostic value of oxidants and antioxidantn enzymes in larger samples and include diagnostic value of these parameters.

Background: Vortioxetine is a multimodal antidepressant that has been developed for the treatment of major depressive and anxiety disorders. The aim of this review is to quantitatively synthesize all data of the efficacy, safety and tolerability of Vortioxetine in treating anxiety disorder., Method: Terms of "Vortioxetine" OR "LuAA21004" AND "anxiety" OR "fear" OR "panic" OR "phobia" were searched. A total of two phase II and five phase III clinical trials were found., Results: Vortioxetine was overall superior to placebo in terms of the mean change from baseline in HAM-A total score at week 8 with the pool effect size of -2.95, 95% CIs, -4.37 to -1.53, p<0.01. The patients who received 5 mg of Vortioxetine had higher response rate when compared to placebo (pooled odds ratio=1.4, 95% CI = 1.08 to 1.82, p=0.01). However, the pooled odds ratio of the HAMA remission rate was not statistically significant for both Vortioxetine and placebo (pooled odds ratio= 1.06, 95% CI = 0.86 to 1.30, p=0.62). Although the discontinuation due to adverse effects was higher in Vortioxetine than placebo group (pooled OR= 1.55, 95% CI = 1.04 to 2.31, P= 0.037), the lack of efficacy (pooled OR= 0.39, 95% CI = 0.27 to 0.57, P<0.01) was higher in placebo than Vortioxetine group. Most of the adverse effects were mild and moderate. Overall, Vortioxetine displayed a good safety and tolerability profile., Conclusion: This review supports the use of Vortioxetine for anxiety disorder. However, further longterm placebo-control observational study or a post market survey would help in strengthening the evidence for this treatment modality., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Inflammatory responses and inflammatory cytokines have been implicated in the pathogenesis of affective disorders, particularly major depression. Given the limited evidence relating to the potential role of proinflammatory cytokines in generalised anxiety disorder (GAD), we aimed to examine peripheral proinflammatory cytokines in Chinese patients with GAD., Methods: A case-controlled cross-sectional study design, with recruitment of 48 patients with first episode GAD and 48 matched healthy controls. All participants completed measures of anxiety using well-established questionnaires, and serum levels of pro-inflammatory cytokines were measured using multiplex technology., Results: Serum levels of CRP, IL-1α, IL-2, IL-6, IL-8, IL-12, IFN-γ, and GM-CSF were significantly higher in the GAD group in comparison to the control group (p < 0.05). Pearson correlation revealed significant positive correlations between anxiety measures and serum levels of CRP, IL-1α, IL-6, IL-8, IFN-γ, and GM-CSF (p < 0.05)., Limitations: The cross-sectional study design does not permit definite conclusions on causal directions between inflammation and GAD. The study was limited to a panel of 8 cytokines and does not exclude the possibility of other important cytokines being involved., Conclusions: These findings indicate an elevated peripheral proinflammatory response, and provide further support for low grade inflammation in GAD. Further research may identify an 'inflammatory signature' for diagnosis and treatment response, and guide the search for novel pharmacological interventions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Generalised anxiety disorder (GAD) is a common psychiatric illness characterised by selective morpho-functional brain alterations. The breath of neuroimaging studies investigating the neural basis of GAD is extensive; however, its pathophysiology is still largely unknown. Specifically for proton Magnetic Resonance Spectroscopy (¹H MRS) investigations, which have the aim of identifying differences in metabolite levels between conditions in key brain areas, often showed contrasting results. Indeed, there are selected ¹H MRS studies reporting deficits of key metabolites in GAD patients; however, collectively the literature remains mixed with respect to consistency of major findings. In this review, we evaluate published ¹H MRS studies on GAD with the final aim of providing a comprehensive overview of the extent of neurometabolic dysfunctions associated with GAD. Interestingly, the majority of the studies reviewed showed altered metabolite levels in the dorsolateral prefrontal cortex and hippocampus suggesting regional specificity. These results also provide evidence of the utility of ¹H MRS not only for elucidating the pathophysiology of neuropsychiatric diseases, but also for the identification of more beneficial and targeted pharmacological interventions. Additionally, future studies are warranted to overcome methodological differences observed across the studies.

Patients receiving ketamine for refractory depression and anxiety report dissociative symptoms in the first 60 min post-dose. The most commonly used instrument to assess this is the Clinician-Administered Dissociative States Scale (CADSS), developed based on the assessment of patients with dissociative symptoms. Its psychometric properties for ketamine-induced dissociation have not been reported. We evaluated these from a study using 0.25-1 mg/kg ketamine and midazolam (as an active control) in 18 patients with treatment-resistant anxiety. Dissociation ratings were increased by ketamine in a dose-dependent manner. In contrast, midazolam showed no effect on ratings of dissociation. For individual CADSS items, the magnitude of change and the ketamine dose at which changes were observed were not homogenous. The Cronbach alpha for the total scale was high (0.937), with acceptable item-rest correlations for almost all individual items. Purposefully removing items to maximise alpha did not lead to meaningful improvements. Acceptable internal consistency was still observed after removing items which lacked evidence of responsiveness at lower doses. The high Cronbach alpha values identified in this study suggests that the CADSS is an internally consistent instrument for evaluating ketamine-induced dissociation in clinical trials in anxiety, although it does not capture symptoms such as thought disorder.

Introduction: Previous investigations have demonstrated that major depression is associated with particular patterns of cytokine signalling. The primary aim of this study was to examine peripheral pro-inflammatory and anti-inflammatory cytokines and immune balance in Generalised Anxiety Disorder (GAD)., Methods: A case-controlled cross-sectional study design was employed: 54 patients with GAD and 64 healthy controls were recruited. Participants completed self-report measures of anxiety and depression. Two pro-inflammatory and two anti-inflammatory cytokines were measured using multiplex technology., Results: Case-control logistic regression analyses revealed significant differences in serum levels of IL-10, TNF-α, and IFN-γ between GAD and control groups after adjusting for age, gender, body mass index, smoking and alcohol consumption: these group differences were independent of the presence or degree of depression. Comparison of pro-inflammatory to anti-inflammatory cytokine ratios indicated that there were significantly higher ratios of TNF-α/IL10, TNF-α/IL4, IFN-γ/IL10, and IFN-γ/IL4 in the GAD group compared to the control group., Conclusions: This study is the first to investigate both pro- and anti-inflammatory cytokines and their balance in patients with GAD in comparison to healthy controls. The findings indicate a relatively increased pro-inflammatory response and decreased anti-inflammatory response and provide the first demonstration of an altered cytokine balance in GAD. Serum cytokine levels in GAD were independent of the presence of depression., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)