Allosteric Site Mediates Inhibition of Tonic NMDA Receptor Activity by Low Dose Ketamine.

Ketamine, a general anesthetic, has rapid and sustained antidepressant effects when administered at lower doses. At anesthetic doses, ketamine causes a drastic reduction in excitatory transmission by lodging in the centrally located hydrophilic pore of the NMDA receptor, where it blocks ionic flow. In contrast, the molecular and cellular targets responsible for the antidepressant effects of ketamine remain controversial. Here, we report functional and structural evidence that, at nanomolar concentrations, ketamine interacts with membrane-accessible hydrophobic sites where it stabilizes desensitized receptors to cause an incomplete, voltage- and pH-dependent reduction in NMDA receptor activity. This allosteric mechanism spares brief receptor activations and reduces preferentially currents from tonically active receptors. The hydrophobic site is a promising target for safe and effective therapies against acute and chronic neurodegeneration.

Evaluation and treatment of older-age bipolar disorder: a narrative review.

OBJECTIVES: This narrative review aims to synthesize information from the literature regarding older-age bipolar disorder (OABD) in order to provide up-to-date information on this important illness. METHODS: We searched Ovid (Medline, Embase and PsychInfo) on October 1, 2020, using the keywords "bipolar disorder", "older adults" and "elderly" to identify relevant articles on OABD. Additionally, the bibliography of identified articles was reviewed for pertinent studies. DISCUSSIONS: OABD is a term that is used to describe bipolar disorder (BD) occurring amongst individuals ≥50 years of age. Evidence indicates that OABD accounts for a quarter of all cases of BD. When compared to individuals with early-onset BD, individuals with OABD have a greater association with cerebrovascular disease and other neurological disorders, less family history of mood disorders, and utilize almost four times the total amount of mental health services. In addition, they are four times more likely to have psychiatric hospitalizations when compared to age-matched controls. Despite a dearth of controlled studies on the use of pharmacotherapy amongst individuals with OABD, available evidence from mixed-age studies indicates the efficacy of commonly used medications in individuals with early-onset BD. Additionally, psychosocial treatments have been found to be effective as adjunctive management strategies amongst individuals with OABD. Furthermore, electroconvulsive therapy may be effective in the treatment of refractory cases of OABD. CONCLUSIONS: There is a great need for an improved understanding of the phenomenology and neurobiology of OABD. Additionally, research into effective treatments for this serious psychiatric disorder will mitigate the suffering of individuals with OABD.

Vanishing Adrenal Mass in Pregnancy.

OBJECTIVES: The evaluation of an adrenal mass is challenging. We present the case of a 33-year-old pregnant woman who was found to have an adrenal incidentaloma. Four months after the initial imaging, the mass vanished. METHODS: We described the case of a pregnant woman with hypertension and an incidentally found right adrenal mass. RESULTS: A magnetic resonance imaging scan showed a right adrenal mass measuring 7.9 × 3.9 × 3.0 cm with a multilobulated appearance. Initial biochemical testing was concerning for a pheochromocytoma with positive metanephrines during hospitalization while being treated for an infection. Repeat outpatient adrenal hormone results, including metanephrines, were negative. Four months after her initial magnetic resonance imaging scan, the right adrenal mass was no longer present. CONCLUSION: A 33-year-old pregnant woman was found to have a right adrenal mass that later vanished as a result of the resolution of a unilateral adrenal hemorrhage. Predisposing factors to adrenal hemorrhage in the presented case include pregnancy, infection, and hypertension.

Antidepressants for anxiety disorders in late-life: A systematic review.

BACKGROUND: Anxiety in late-life is a frequently encountered condition. The aim of this review is to systematically examine the efficacy and tolerability of antidepressants for treating anxiety disorders among older adults. METHODS: Electronic searches of The Cochrane Central Register of Controlled Trials and the standard bibliographic databases PubMed, MEDLINE, EMBASE, and PsycINFO were performed in August 2018 and updated in October 2018 for randomized controlled trials (RCTs) evaluating antidepressants for late-life anxiety. The quality of each study was appraised using criteria developed by the Centre for Evidence-Based Medicine. RESULTS: Data from 12 papers describing 10 RCTs of antidepressants for late-life anxiety are included in this review. There were 2 studies each of sertraline, escitalopram, and duloxetine, and 1 study each of citalopram, paroxetine, venlafaxine, and imipramine. Across all trials, antidepressants were associated with a significant reduction in anxiety symptoms at the end of the study period. Limitations of the trials include a preponderance of generalized anxiety disorder and relatively less data on other anxiety disorders, and limited data on long-term use of antidepressants for anxiety. CONCLUSIONS: Antidepressants are beneficial for treating anxiety disorders in late life and are generally well tolerated.

Marijuana Use by Patients with Multiple Sclerosis.

BACKGROUND: With social attitudes about marijuana changing and patients sometimes seeking nonmainstream treatment options, the main goal of this study was to investigate the prevalence of, and factors associated with, marijuana use by patients with multiple sclerosis (MS). METHODS: Adult patients with MS (n = 521) and controls (n = 279) from a study of clinical, neuroimaging, genetic, and environmental factors in MS progression were included. Patients with MS stated whether they had ever used marijuana before MS diagnosis, after MS diagnosis, and in the preceding 3 months as part of an in-person questionnaire. The control group stated whether they had ever used marijuana and in the preceding 3 months. RESULTS: The percentage of patients with MS reporting ever use of marijuana was 39.9%, compared with 32.7% of controls. Marijuana use in the preceding 3 months was significantly more prevalent among patients with MS (9.4%) compared with controls (0.4%) (P < .001). Marijuana use was most prevalent in male patients with MS (P = .004) and in patients with MS who used complementary and alternative medicine (P = .045). Cigarette smoking was associated with marijuana use in patients with MS (P < .001) and controls (P = .001). Increasing age was associated with decreasing prevalence of marijuana use in the patients with MS (P < 0.001). CONCLUSIONS: Patients with MS are more likely to report recent marijuana use than are people without MS. Owing to potential adverse effects, marijuana use by patients with MS may warrant vigilance by MS caregivers, given shifting social attitudes and the trend towards legalization of marijuana in the United States.