Modulating neuroinflammation in COVID-19 patients with obsessive-compulsive disorder.

Exacerbation of symptoms of obsessive-compulsive disorder (OCD) during COVID-19 or new onset of the OCD symptoms resulting from COVID-19 infection is an understudied area of research. It is possible that increased proinflammatory immune status is associated with the onset of obsessive-compulsive symptoms in patients with COVID-19 and that targeted anti-inflammatory treatments for COVID-19 infection can mitigate the new onset of Obsessive-Compulsive (OC) spectrum symptoms. In this review, we cover OCD pathogenesis as related to COVID-19, summarize the impact of cytokines on behavior, and suggest that anti-cytokine treatments can help mitigate post-COVID-19 and new onset of the OC symptoms.

Randomized crossover feasibility trial of helminthic Trichuris suis ova versus placebo for repetitive behaviors in adult autism spectrum disorder.

Objectives: Inflammatory mechanisms are implicated in the aetiology of autism spectrum disorder (ASD), and use of the immunomodulator Trichuris suis Ova (TSO) is a novel treatment approach. This pilot study determined the effect sizes for TSO versus placebo on repetitive behaviours, irritability and global functioning in adults with ASD.Methods: A 28-week double-blind, randomised two-period crossover study of TSO versus placebo in ten ASD adults, aged 17-35, was completed, with a 4-week washout between each 12-week period at Montefiore Medical Center, Albert Einstein College of Medicine. Subjects with ASD, history of seasonal, medication or food allergies, Y-BOCS ≥6 and IQ ≥70 received 2,500 TSO ova or matching placebo every 2 weeks of each 12-week period.Results: Large effect sizes for improvement in repetitive behaviours (d = 1.0), restricted interests (d = 0.82), rigidity (d = 0.79) and irritability (d = 0.78) were observed after 12 weeks of treatment. No changes were observed in the social-communication domain. Differences between treatment groups did not reach statistical significance. TSO had only minimal, non-serious side effects.Conclusions: This proof-of-concept study demonstrates the feasibility of TSO for the treatment of ASD, including a favourable safety profile, and moderate to large effect sizes for reducing repetitive behaviours and irritability.Clinicaltrials.gov: NCT01040221.

Behavioral phenotype in a child with Prader-Willi syndrome and comorbid 47, XYY.

We report a 12-year-old male with Prader-Willi syndrome (PWS) and 47, XYY syndrome. Genetic work up revealed 47, XYY karyotype. PWS diagnosis was made by polymerase chain reaction methylation and maternal uniparental disomy (mUPD) was determined to be the etiology. Review of distinct behavioral features, possible interplay between the two syndromes and considerations for diagnoses are presented. To our knowledge, this is the first report of behavioral features in PWS with comorbid 47, XYY.

Mesenchymal stem cells in autism spectrum and neurodevelopmental disorders: pitfalls and potential promises.

OBJECTIVES: In this conceptual review, the authors discuss the promises and pitfalls in the use of mesenchymal stem cells as a potential experimental therapeutic for autism spectrum and other neurodevelopmental disorders. METHODS: The relevant literature in autism spectrum disorders and other neurodevelopmental disorders regarding immune dysregulation and neuroinflammation and relevant therapeutics with mesenchymal stem cell infusion is reviewed. The relevant literature pertaining to mesenchymal stem cells and their clinical applications is also reviewed. RESULTS: It is proposed that immune dysregulation and neuroinflammation play a role in the aetiology of autism spectrum disorders. Mesenchymal stem cells have been shown to have immune-modulating capabilities and are neuroprotective. There are three international studies that have utilized mesenchymal stem cell infusions as a treatment for children with autism spectrum disorders, all of which demonstrated improvement in autism rating scale scores, although each study has limitations which are described. CONCLUSIONS: Mesenchymal stem cell transplantation for the treatment of autism spectrum disorders is a novel approach that deserves further investigation, however substantial methodological and theoretical challenges and pitfalls remain before this can be considered a viable therapeutic option.

Cholinergic modulation in the olfactory bulb influences spontaneous olfactory discrimination in adult rats.

Cholinergic neuromodulation in the olfactory bulb has been hypothesized to regulate mitral cell molecular receptive ranges and the behavioral discrimination of similar odorants. We tested the effects of cholinergic modulation in the olfactory bulb of cannulated rats by bilaterally infusing cholinergic agents into the olfactory bulbs and measuring the rats' performances on separate spontaneous and motivated odor-discrimination tasks. Specifically, 6 microL/bulb infusions of vehicle (0.9% saline), the muscarinic antagonist scopolamine (7.6 mM and 38 mM), the nicotinic antagonist mecamylamine hydrochloride (3.8 mM and 19 mM), a combination of both antagonists, or the acetylcholinesterase inhibitor neostigmine (8.7 mM) were made 20 min prior to testing on an olfactory cross-habituation task or a rewarded, forced-choice odor-discrimination task. Spontaneous discrimination between chemically related odorants was abolished when nicotinic receptors were blocked in the olfactory bulb, and enhanced when the efficacy of cholinergic inputs was increased with neostigmine. Blocking muscarinic receptors reduced but did not abolish odor discrimination. Interestingly, no behavioral effects of modulating either nicotinic or muscarinic receptors were observed when rats were trained on a reward-motivated odor-discrimination task. Computational modeling of glomerular circuitry demonstrates that known nicotinic cholinergic effects on bulbar neurons suffice to explain these results.