Right frontal anxiolytic-sensitive EEG ‘theta’ rhythm in the stop-signal task is a theory-based anxiety disorder biomarker

Psychiatric diagnoses currently rely on a patient’s presenting symptoms or signs, lacking much-needed theory-based biomarkers. Our neuropsychological theory of anxiety, recently supported by human imaging, is founded on a longstanding, reliable, rodent ‘theta’ brain rhythm model of human clinical anxiolytic drug action. We have now developed a human scalp EEG homolog—goal-conflict-specific rhythmicity (GCSR), i.e., EEG rhythmicity specific to a balanced conflict between goals (e.g., approach-avoidance). Critically, GCSR is consistently reduced by different classes of anxiolytic drug and correlates with clinically-relevant trait anxiety scores (STAI-T). Here we show elevated GCSR in student volunteers divided, after testing, on their STAI-T scores into low, medium, and high (typical of clinical anxiety) groups. We then tested anxiety disorder patients (meeting diagnostic criteria) and similar controls recruited separately from the community. The patient group had higher average GCSR than their controls—with a mixture of high and low GCSR that varied with, but cut across, conventional disorder diagnosis. Consequently, GCSR scores should provide the first theoretically-based biomarker that could help diagnose, and so redefine, a psychiatric disorder.

Cross-species anxiety tests in psychiatry: pitfalls and promises

Behavioural anxiety tests in non-human animals are used for anxiolytic drug discovery, and to investigate the neurobiology of threat avoidance. Over the past decade, several of them were translated to humans with three clinically relevant goals: to assess potential efficacy of candidate treatments in healthy humans; to develop diagnostic tests or biomarkers; and to elucidate the pathophysiology of anxiety disorders. In this review, we scrutinise these promises and compare seven anxiety tests that are validated across species: five approach-avoidance conflict tests, unpredictable shock anticipation, and the social intrusion test in children. Regarding the first goal, three tests appear suitable for anxiolytic drug screening in humans. However, they have not become part of the drug development pipeline and achieving this may require independent confirmation of predictive validity and cost-effectiveness. Secondly, two tests have shown potential to measure clinically relevant individual differences, but their psychometric properties, predictive value, and clinical applicability need to be clarified. Finally, cross-species research has not yet revealed new evidence that the physiology of healthy human behaviour in anxiety tests relates to the physiology of anxiety symptoms in patients. To summarise, cross-species anxiety tests could be rendered useful for drug screening and for development of diagnostic instruments. Using these tests for aetiology research in healthy humans or animals needs to be queried and may turn out to be unrealistic.

Assessing the Anti-Inflammatory Activity of the Anxiolytic Drug Buspirone Using CRISPR-Cas9 Gene Editing in LPS-Stimulated BV-2 Microglial Cells

Buspirone is an anxiolytic drug with robust serotonin receptor 1A (Htr1a) agonist activities. However, evidence has demonstrated that this drug also targets the dopamine D3 receptor (Drd3), where it acts as a potent antagonist. In vivo, Drd3 blockade is neuroprotective and reduces inflammation in models of Parkinson’s disease. To test if buspirone also elicited anti-inflammatory activities in vitro, we generated stable Drd3−/− and Htr1a−/− BV2 microglial cell lines using CRISPR-Cas9 technology and then tested the effects of buspirone after lipopolysaccharide (LPS) challenge. We found that LPS exposure had no effect on cell viability, except in Htr1a−/− cells, where viability was reduced (p < 0.001). Drug treatment reduced viability in Drd3−/− cells, but not in WT or Htr1a−/− cells. Buspirone counteracted LPS-induced NO release, NOS2, IL-1β and TNF-α gene expression in WT cells, whereas it exerted limited effects in Drd3−/− or Htr1a−/− microglia. In summary, our findings indicate that buspirone attenuates microglial polarization after LPS challenge. These results also highlight some major effects of Drd3 or Htr1a genetic ablation on microglial biology, raising important questions on the complex role of neurotransmitters in regulating microglia functions.

The Study of the Effect of Sodium Nitroprusside in Anxiety-Like Behavior in Mice in Comparison With Diazepam

Anxiety has become a highly paramount field of research attention in psychopharmacology today. Sundry studies have shown a nitric oxide role in the regulation of anxiety. The goal of the study was to investigate sodium nitroprusside ability to affect anxiety-like behavior in mice and to compare this effect with the standard anxiolytic drug, diazepam, using both plus maze test and light/dark box test. The results revealed that sodium nitroprusside at a dose of 1 mg/kg had a significant effect on the behavior in both of the elevated plus maze test and light/dark test. However, at higher dose (3 mg/kg), it has significantly increased the anxiogenic-like effect in the light/dark box test. Diazepam at a dose of 2 mg/kg increased the time spent in open arms in elevated plus maze test and that in light chambers of light/dark test. These outcomes suggest that a nitric oxide pathway seems to play an important role in anxiety. Furthermore, sodium nitroprusside at a dose of 1 mg/kg showed a nearly anxiolytic ability, when compared with diazepam.

Anxiety in gynecology: three clinical cases

Tofisopam is an anxiolytic drug, available for prescription by gynecologist. This paper discusses three typical case vignettes, where woman’s anxiety interfered with her somatic condition and responded on tofisopam. There is also a discussion of combination of tofisopam with hormonal therapy and it’s efficacy and safety.

Monitoring Adverse Psychosocial Outcomes One and Two Years After the Lac-Mégantic Train Derailment Tragedy (Eastern Townships, Quebec, Canada)

Introduction:In July 2013, a train carrying 72 cars of crude oil derailed in the town of Lac-Mégantic (Eastern Townships, Quebec, Canada). This disaster provoked a major conflagration, explosions, 47 deaths, the destruction of 44 buildings, the evacuation of one-third of the local population, and an unparalleled oil spill. Notwithstanding the environmental impact, many citizens of this town and in surrounding areas have suffered and continue to suffer substantial losses as a direct consequence of this catastrophe.Problem:To tailor public health interventions and to meet the psychosocial needs of the community, the Public Health Department of Eastern Townships has undertaken repeated surveys to monitor health and well-being over time. This study focuses on negative psychosocial outcomes one and two years after the tragedy.Methods:Two cross-sectional surveys (2014 and 2015) were conducted among large random samples of adults in Lac-Mégantic and surrounding areas (2014: n = 811; 2015: n = 800), and elsewhere in the region (2014: n = 7,926; 2015: n = 800). A wide range of psychosocial outcomes was assessed (ie, daily stress, main source of stress, sense of insecurity, psychological distress, excessive drinking, anxiety or mood disorders, psychosocial services use, anxiolytic drug use, gambling habits, and posttraumatic stress symptoms [PSS]). Exposure to the tragedy was assessed using residential location (ie, six-digit postal code) and intensity of exposure (ie, intense, moderate, or low exposure; from nine items capturing human, material, or subjective losses). Relationships between such exposures and adverse psychosocial outcomes were examined using chi-squares and t-tests. Distribution of outcomes was also examined over time.Results:One year after the disaster, an important proportion of participants reported human, material, and subjective losses (64%, 23%, and 54%, respectively), whereas 17% of people experienced intense exposure. Participants from Lac-Mégantic, particularly those intensely exposed, were much more likely to report psychological distress, depressive episode, anxiety disorders, and anxiolytic drug use, relative to less-exposed ones. In 2015, 67% of the Lac-Mégantic participants (76% of intensely exposed) reported moderate to severe PSS. Surprisingly, the use of psychosocial services in Lac-Mégantic declined by 41% from 2014 to 2015.Conclusion:The psychosocial burden in the aftermath of the Lac-Mégantic tragedy is substantial and persistent. Public health organizations responding to large-scaling disasters should monitor long-term psychosocial consequences and advocate for community-based psychosocial support in order to help citizens in their recovery process.

The 5-HT1A Agonist Buspirone Decreases Liver Oxidative Stress and Exerts Protective Effect Against CCl4– Toxicity

We aimed to study the effect of buspirone, an anxiolytic drug and 5-HT1A agonist on liver injury induced by carbon tetrachloride (CCl4) in rats. Rats were orally treated with CCl4 (2.8 mL/kg in olive oil) along with buspirone at 10, 20 or 30 mg/kg once daily starting with CCl4 and for one week thereafter. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities were determined in the serum. Markers of oxidative stress: lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels were measured in the liver. Moreover, paraoxonase 1 activity was determined in the liver and serum. The administration of CCl4 led to significant increases in serum ALT, AST, and ALP activities. Results showed that there were significantly increased hepatic MDA, nitrite and decreased GSH levels. PON1 activity decreased both in the liver and serum, respectively. The immunohistochemical investigations using anti-caspase-3 antibody revealed that CCl4 caused apoptosis to many hepatocytes. DNA studies showed that CCl4 caused hypoploidy in hepatocytes. Rats treated with 20-30 mg/kg buspirone showed significant decrease in serum ALT and AST by 19.5-34.3% and 24.2-31.4%, respectively. Serum ALP decreased by 21.7% after 30 mg/kg buspirone. In the liver, the higher dose of the drug resulted in decreased MDA (by 15.8%), decreased nitric oxide (17.4%) and increased GSH (by 20.1%). Significantly increased serum PON1 activity by 43.9-53.5% was observed after treatment with 20-30 mg/kg buspirone. On histopathologic examination of liver sections, there was mild protective effect for the drug at 30 mg/kg. Sections stained with anti- caspase- 3 confirmed the results obtained from histopathological examination. Moreover, buspirone given at 30 mg/kg resulted in an increase in % of cells containing normal values of DNA. These results indicate that buspirone decreases liver oxidative stress and exerts protective effect against CCl4- toxicity. The study thus indicates more beneficial effects of buspirone as an anxiolytic drug and that the drug could be used safely in patients with liver disease.