N2 O abuse represents a significant problem because of the difficulty involved with identification and the toxicity related to chronic abuse including possible death. Health professionals should be aware of the toxic effects of N2 O and be able to identify potential N2 O abuse. (Am J Addict 2016;25:358-369).

Drugs acting at metabotropic glutamate receptors (mGluRs) are among the most promising agents under development for the treatment of psychiatric disorders. The research in this area is at a relatively early stage, as there are no drugs acting at mGluRs that have been approved for the treatment of any psychiatric disorder. However, in the areas of schizophrenia, anxiety disorders and mood disorders, research conducted in animal models appears to translate well into efficacy in human laboratory-based models of psychopathology and in preliminary clinical trials. Further, the genes coding for mGluRs are implicated in the risk for a growing number of psychiatric disorders. This review highlights the best studied mGluR strategies for psychiatry, based on human molecular genetics, studies in animal models and preliminary clinical trials. It describes the potential value of mGluR2 and mGluR5 agonists and positive allosteric modulators for the treatment of schizophrenia. It also reviews evidence that group II mGluR agonists and positive allosteric modulators as well as group I mGluR antagonists might also treat anxiety disorders and some forms of depression, while mGluR2 and group I mGluR antagonists (particularly mGluR5 antagonists) might have antidepressant properties. This review also links growing insights into the role of glutamate in the pathophysiology of these disorders to hypothesized mGluR-related treatment mechanisms.

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Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.

Irritable bowel syndrome (IBS), a functional gastrointestinal disorder, is present in 10% to 20% of the U.S. adult population. The syndrome is best defined as chronic abdominal discomfort with changes in stool frequency, consistency, and passage, with associated symptoms such as abdominal bloating or presence of mucus in stools. Several studies have shown that up to 70% to 90% of patients with IBS who seek treatment have psychiatric comorbidity, most notably mood and anxiety disorders. Recent studies have shown a high prevalence of IBS in psychiatric patients who seek treatment, with a prevalence of 19% in schizophrenia, 29% in major depression, and 46% in panic disorder among other disorders. Our article reviews the comorbidity of IBS in psychiatric patients and discusses implications for treatment.

Despite the small sample size, given the challenges in obtaining CSF from patients with depression these data are of interest in confirming some aspects of the inflammatory hypothesis of depression.

Backgrounds The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death. Methods Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements. Results We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up. Conclusion Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.

These findings demonstrate a consistently higher or deregulated autonomic arousal in PD patients at rest and during orthostatic challenge compared with HC. These data also reveal a possible association between the level of anxiety illness severity and sympathovagal balance, which may imply greater cardiac risk.