Intolerance of uncertainty (IoU) is important in the development and maintenance of worry and generalized anxiety disorder (GAD; Dugas et al., 1997). However, it remains unclear why some people respond so negatively to uncertainty and have poor clinical outcomes. We adapted the IoU model to include the influence of developmental and/or attachment factors, and their possible importance to intolerability of uncertainty and associated hypothetical worries. Seven consecutive GAD referrals for CBT were naturalistically treated with the novel approach. All participants completed the 7-item Generalized Anxiety Disorder Scale (GAD-7; Spitzer et al., 2006), the Penn State Worry Questionnaire (PSWQ; Meyer et al., 1990), as well as a novel 10-item Premonition Bias Questionnaire (PBQ; C. Chigwedere et al., unpublished). From pre- to post-treatment, results for both GAD (p=.001) and worry (p=.005) improved significantly. Clinically significant change or a post-treatment score within the normal population range were observed for both the GAD-7 and PSWQ. The change in believability of worry, measured on the PBQ was also significant from pre- to post-treatment (p=.008). Overall, the novel approach may be an alternative approach to treating GAD, with some potential, both as an adjunctive or standalone treatment. However, this is a small case series and the presented novel approach requires empirical support and evaluation in larger experimental studies.

Group cognitive behavioural therapy (gCBT) is commonly used in Increasing Access to Psychological Therapies (IAPT) services. However, there is limited knowledge of the efficacy of gCBT as a delivery format for generalised anxiety disorder (GAD). To address gaps in literature, this study aims to explore the efficacy and attrition of individual and group CBT interventions, respectively, at Step 3 for GAD using data from a routine IAPT service over a 24-month period. Data were retrospectively derived from a routine serviceʼs IAPTus database, separating those eligible for comparison into group (n = 44) and individual (n = 55) CBT for GAD. Outcomes were differences in pre–post self-reported anxiety (GAD-7) and depression (PHQ-9) scores, clinical recovery and attrition for gCBT and individual CBT. Both gCBT and individual CBT yielded significant reductions in self-reported anxiety and depression scores over time. Results indicate that 53% of patients attending individual CBT achieved clinical recovery, with similar but less competitive rates of 41% in gCBT. Attrition rates were similar between gCBT (29.5%) and individual CBT (27.3%), respectively. Preliminary results suggest that both individual and gCBT are effective interventions for GAD patients in IAPT, offering symptom alleviation and comparable recovery and attrition rates post-intervention. This observational design offers credibility and insight into a pragmatic evaluative and explorative comparison. gCBT may offer an acceptable and potentially economical alternative.

Dysfunctions of glutamatergic and GABAergic neurotransmission are two important hypotheses for the pathogenesis of schizophrenia. Thus, genes in the pathway are candidates for schizophrenia susceptibility. Phosphate-activated glutaminase (GLS), glutamine synthetase (GLUL), glutamic acid decarboxylase (GAD), GABA transaminase (ABAT) and succinic semialdehyde dehydrogenase (ALDH5A1) are five primary enzymes in glutamate and GABA synthetic and degradative pathway. In order to investigate the possible involvement of these genes in the development of paranoid schizophrenia, we genotyped 80 paranoid schizophrenics from northern China and 108 matched controls by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP) methods or directly sequencing of PCR product. Seven SNPs were found to be polymorphic in the population investigated. No significant differences in the genotype distributions or allele frequencies between patients and controls were found. Therefore, we conclude the polymorphisms studied in the five genes do not play major roles in pathogenesis of paranoid schizophrenia in the population investigated.

Generalized anxiety disorder (GAD) is a common (lifetime prevalence: 5.1%), recurrent condition, which often heralds other psychiatric disorders, notably depression. As by definition it is a disorder progressing over months, treatment should be designed on a long term basis. And yet, few studies have been conducted beyond the classical 6–8 weeks characterizing the acute treatment phase. This is especially true of anxiolytics, but also of antidepressants, with the exception of paroxetine and venlafaxine, which are the only drugs approved in this indication in Western countries. The efficacy of psychotherapy, notably relaxation and cognitive-behavioral therapy, is established in the treatment of GAD, but its preferred indications and possible combination with antidepressants are still to be specified. Long term, not to say very long term studies of GAD, as well as depression, will still be required in the future to improve its management and specify therapeutic modalities (combination treatment, optimal duration, continuous or intermittent therapy, choice of psychotherapeutic techniques or agents, …). Early and adequately prolonged treatment should not only result in more numerous remission periods, but also in decreased frequency of co-morbidities whether depressive, addictive, or of another nature, and should also reduce the social impact of GAD.

Soil salinity is one of the major abiotic stresses affecting seed germination, crop growth and productivity. In this study, seeds of three wheat (Triticum aestiveum L.) and three barley (Hordeum vulgare L.) cultivars were treated with different concentrations of NaCl to investigate the effect of salt on seed germination physiology and metabolism through the characterization of seed germination pattern, gamma-aminobutyric acid (GABA) shunt metabolite accumulation [GABA, glutamate (Glu) and alanine (Ala)] and glutamate decarboxylase (GAD) expression using RT-PCR. A trend of decreasing germination percentage with increasing NaCl concentrations was observed. Under all salt stress treatments, data showed significant increase with positive correlation (r = 0.50–0.99) between abundance of GABA shunt metabolites and salt concentration in all wheat and barley cultivars for 5 days. Increased GABA content was associated with a small but significant increase in Ala and Glu content in all cultivars. In all NaCl treatments, the transcription of GAD in terms of RNA abundance showed a significant increase in all cultivars with positive correlation (r = 0.50–0.98). Data showed significant association between GAD RNA transcription and the response of germinating seeds to salt stress in terms of GABA shunt metabolite accumulation. The elevated expression of GAD under salinity suggests the need for elevated activity of the GAD-mediated conversion of Glu to GABA during seed germination, which provides alternative metabolic routes to the respiratory machinery, balancing carbon and nitrogen metabolism and osmolyte synthesis in germinating seeds of wheat and barley under salt stress.

Anxiety disorders are among the most prevalent psychiatric conditions. Despite many proven pharmacological and non-pharmacological treatments available, high rates of partial response and low rates of long-term remission remain. Ketamine has been receiving increasing attention as an interventional treatment modality in psychiatry, especially among refractory conditions, including major depressive disorder. There is limited yet growing evidence to support the use of ketamine in anxiety disorders. In this review of the literature, we present case reports, case series, and controlled trials demonstrating proof-of-concept for its potential role in the treatment of anxiety and anxiety spectrum disorders. Its unique mechanism of action, rapid onset, and high rate of response have driven its use in clinical practice. Ketamine is generally well tolerated by patients and has a limited side effect profile; however, the effects of long-term use are unknown. While there is a growing body of research and increasing clinical experience to suggest ketamine may have clinical applications in the treatment of refractory anxiety disorders, further research to determine long-term safety and tolerability is indicated.

Background: Cognitive exposure, a treatment of choice for hypothetical fears, involves listening repeatedly to a recorded scenario of one's worst hypothetical fear. A major limitation, however, is that the script cannot be easily modified. Aims: The current study assessed the feasibility of a brief guided internet-based written exposure therapy (iWET) for hypothetical fears, Mind at Peace. Method: Fifty-three adults presenting clinical levels of anxiety (GAD-7 ≥ 8) and worry (PSWQ ≥ 45) were recruited. A single group pre-test/post-test design including a 3-month follow-up was used. Mind at Peace is a 6-week iWET consisting of psychoeducation and five 30-minute weekly writing exposure sessions. Feasibility outcome measures included treatment adherence, attrition, treatment acceptability and preliminary efficacy. Primary outcome measures were the Generalized Anxiety Disorder-7 (GAD-7) and the Penn State Worry Questionnaire (PSWQ). Results: Attrition was higher (57%) and adherence lower (28%) than expected. Intent-to-treat repeated measures ANOVAs revealed significant and large improvements on the GAD-7 (ƞp2 = 0.36) and the PSWQ (ƞp2 = 0.23) with similar findings among study completers. Remission rates were higher on the GAD-7 than on the PSWQ, suggesting that Mind at Peace may primarily target general symptoms of generalized anxiety. Rates of acceptability varied, but nearly all study completers reported that they would recommend this treatment to a friend. Conclusions: This study provided valuable information on Mind at Peace. Methodological changes are proposed to improve its feasibility. A more definitive trial incorporating suggested methodological improvements is recommended.

The study examined the relative efficacy of group acceptance and commitment therapy (ACT) for generalised anxiety disorder (GAD) compared to group cognitive-behavioural therapy (CBT). Fifty-one individuals with GAD were randomly allocated to a 6-week intervention, either ACT or CBT. Participants were assessed at pre-treatment, post-treatment, and 3-month follow-up on symptom measures, quality of life, and process measures. Data from 38 participants (19 in each group) were available at post-assessment, indicating significant improvements on all measures for both treatment conditions. Treatment gains were maintained at follow-up, with significant further improvements in anxiety, depression and stress symptoms for both groups. While no between-group differences were found at treatment completion, a significant interaction indicating steeper reduction in worrying symptoms (d = .79) from pre- to post-assessment was found for the ACT group compared to the CBT group. Furthermore, in relation to worrying, at treatment completion 78.9% of participants in the ACT group achieved reliable change compared to 47.4% of participants in the CBT group. However, both groups showed equivalent reliable change rates of 60% at the follow-up assessment. The results suggest that group ACT was as efficacious as group CBT. While participants in the ACT group maintained treatment gains at follow-up, participants in the CBT group continued to improve between post-assessment and follow-up.

Background: Worry exposure is a cognitive–behaviour therapy (CBT) technique frequently used to treat GAD, yet there are only a few studies on its effectiveness. Aim: To compare two worry exposure protocols developed for GAD to make a preliminary determination about the most effective way in which to present the feared stimuli to participants. Method: Nine university students suffering from GAD were administered four 1-hour treatment sessions. Exposure was conducted by either directly imagining (DI) or via audio-recording/playback (AR) exposure to their feared event. General worry and intolerance of uncertainty (IOU) were the primary dependent variables. Results: All participants in the DI and half of the AR condition reported subclinical GAD at post-treatment, with results being maintained at 3-month follow-up and the treatment responders also reported decreased depression, anxiety and stress. Conclusions: The DI protocol was more effective than the AR methodology in this sample, and may be an appropriate standard for worry exposure research and clinical practice.

Background: Internet-delivered cognitive behaviour therapy (iCBT) has been found to be an effective way to disseminate psychological treatment, and support given by a therapist seems to be important in order to achieve good outcomes. Little is known about what the therapists actually do when they provide support in iCBT and whether their behaviour influences treatment outcome. Aims: This study addressed the content of therapist e-mails in guided iCBT for generalized anxiety disorder. Method: We examined 490 e-mails from three therapists providing support to 44 patients who participated in a controlled trial on iCBT for generalized anxiety disorder. Results: Through content analysis of the written correspondence, eight distinguishable therapist behaviours were derived: deadline flexibility, task reinforcement, alliance bolstering, task prompting, psychoeducation, self-disclosure, self-efficacy shaping, and empathetic utterances. We found that task reinforcement, task prompting, self-efficacy shaping and empathetic utterances correlated with module completion. Deadline flexibility was negatively associated with outcome and task reinforcement positively correlated with changes on the Penn State Worry Questionnaire. Conclusions: Different types of therapist behaviours can be identified in iCBT, and though many of these behaviours are correlated to each other, different behaviours have an impact on change in symptoms and module completion.

This study explored whether intolerance of uncertainty and/or meta-worry discriminate between non-clinical individuals and those diagnosed with generalised anxiety disorder (GAD group). The participants were 107 GAD clients and 91 university students. The students were divided into two groups (high and low GAD symptom groups). A multivariate analysis of covariance (MANCOVA) adjusting for age indicated that intolerance of uncertainty distinguished between the low GAD symptom group and the high GAD symptom group, and between the low GAD symptom group and the GAD group. Meta-worry distinguished all three groups. A discriminant function including intolerance of uncertainty and meta-worry classified 94.4% of the GAD group and 97.9% of the low GAD symptom group. Only 6.8% of the high GAD symptom group was classified correctly, 77.3% of the high GAD symptom group was classified as GAD. Findings indicated that intolerance of uncertainty and meta-worry may assist with the diagnosis and treatment of GAD.

The presence of inhibitory bipolar cells in salamander retina was investigated by a comparative analysis of the distribution of glutamate- and GABA-immunoreactivities (GLU-IR; GABA-IR) using a postembedding immunocytochemical method. GLU-IR was found in virtually all photoreceptors, bipolar cells and ganglion cells, neuronal elements that transfer information vertically through the retina. GLU-IR also was found in numerous amacrine cells in the mid and proximal inner nuclear layer as well as in the cytoplasm of horizontal cells, while the nucleus of horizontal cells was either lightly labeled or not labeled at all. GLU-IR was found in the outer plexiform layer and intensely in the inner plexiform layer, in which there was no apparent sublamination. Forty-seven percent of Type IB bipolar cells in the distal inner nuclear layer and 13% of the displaced bipolar cells were GABA-IR. All bipolar cells were also GLU-IR, indicating that GABA-IR bipolar cells were a subset of GLU-IR bipolar cells rather than a separate population. About 12% of the Type IB bipolar cells were moderately GABA-IR and likely comprised a GABAergic subtype. GLU-IR levels in the presumed GABAergic bipolar cells were higher than in other purely GLU-IR bipolar cells suggesting that these GABA-IR bipolar cells are glutamatergic as well. All of the displaced bipolar cells were only lightly GABA-IR, indicating that displaced bipolar cells comprise a more homogeneous class of glutamatergic cell than orthotopic bipolar cells. GAD-IR co-localized with GABA-IR in orthotopic but not displaced bipolar cells, further supporting the idea that some orthotopic bipolar cells are GABAergic. A small proportion of bipolar cells in salamander retina contain relatively high levels of both GABA and glutamate. Co-release of these substances by bipolar cells could contribute to the “push-pull” modulation of ganglion cell responses.