DBS shows promise in treating OCD patients with comorbidities

A study published March 24, 2021, in Frontiers in Psychiatry found that patients with obsessive compulsive disorder (OCD) as well as other psychiatric comorbidities may respond well to deep brain stimulation (DBS). Although the effectiveness of DBS for OCD has been well-documented, the interplay with comorbid disorders has not been as thoroughly studied. The latest research retrospectively examined five patients seeking DBS for OCD between 2015 and 2019. Patients exhibited comorbidities including substance use disorder, eating disorder, autism spectrum disorder, major depression, attention deficit hyperactivity disorder, and tic disorder. Overall, these patients experienced significant improvement in OCD and mood symptoms. In this study, patients averaged a 44% reduction on the Yale-Brown Obsessive-Compulsive Scale (YBOCS). A 35% reduction on the YBOCS is a good clinical response. Four of the patients experienced full response – with the fifth having a partial response with approximately 25% reduction in OCD symptoms. Patients also reported an average of 53% reduction in depression symptoms.

COVID-19-associated seizures linked to higher risk of death

A new study led by investigators at Massachusetts General Hospital and Beth Israel Deaconess Medical Center indicates that some hospitalized patients with COVID-19 experience non-convulsive seizures, which may put them at a higher risk of dying. The findings were published March 11, 2021, in the Annals of Neurology. The research team analyzed medical information for 197 hospitalized patients with COVID-19 who underwent electroencephalogram (EEG) monitoring for various reasons at nine institutions in North America and Europe. The EEG tests detected nonconvulsive seizures in 9.6% of patients, some of whom had no prior neurological problems. Patients who had seizures needed to be hospitalized for a longer time, and they were four times more likely to die while in the hospital than patients without seizures, suggesting that neurological complications may be an important contributor to the morbidity and mortality associated with COVID-19. “Our results suggest that patients with COVID-19 should be monitored closely for nonconvulsive seizures. Treatments are available and warranted in patients at high risk; however, further research is needed to clarify how aggressively to treat seizures in COVID-19,” said co-senior author Mouhsin Shafi.

Antibodies could make things worse in neurodegeneration

Scientists at The Scripps Research Institute have shown that misfolded α-synuclein could trigger inflammatory signaling in microglia – and that an anti α-synuclein antibody made the effect worse. The authors tested the effects of α-synuclein antibodies on human induced pluripotent stem cell-derived microglia to test whether previous work in mice, which suggested that α-synuclein aggregates led to inflammation by activating microglia and causing the release of proinflammatory cytokines, would translate to humans. They found that α-synuclein did cause the release of cytokines, in particular interleukin-1β. Surprisingly, however, the addition of anti-synuclein antibodies increased IL-1β levels. Amyloid-β aggregates, though they are thought of as a hallmark of Alzheimer’s disease (AD), and the addition of amyloid-β antibodies further exacerbated inflammation. “These findings may have important implications for antibody therapies aimed at depleting misfolded/aggregated proteins from the human brain, as they may paradoxically trigger neuroinflammation in human microglia,” the authors wrote. They reported their results in the March 29, 2021, online issue of the Proceedings of the National Academy of Sciences.

Ultrarare variants give insights into schizophrenia

Scientists at Columbia University have identified a new schizophrenia-linked variant by studying the Ashkenazi Jewish population, which is descended from a group of roughly 300 individuals alive roughly 750 years ago. Today, the Ashkenazi Jewish population numbers more than 10 million individuals, but due to the recent genetic bottleneck, several rare variants are strongly overrepresented in this population, which has been instrumental to identifying other risk genes for common, complex disorders, which have been hard to identify via GWAS approaches. The team hypothesized that ultrarare variants related to schizophrenia would be overrepresented in the Ashkenazi Jewish population as well and set out to search for them. Comparing the exomes from almost 800 schizophrenia cases with roughly 460 controls, the team was able to identify about 140 missense or loss-of-function variants that occurred in at least three cases, but no controls. Functionally, the variants implicated pathways related to the cell adhesion molecule cadherin. The team concluded that “deleterious [ultrarare variants] are greatly overrepresented in the Ashkenazi population, yielding enhanced power for association studies. Identification of the cadherin/protocadherin family as risk genes helps specify the synaptic abnormalities central to schizophrenia.” They published their results in the March 22, 2021, issue of Neuron.