Neuroscience Applied最新文献

Cognitive inflexibility is a transdiagnostic endophenotype that presents across a range of disorders, including autism spectrum disorder (ASD), which is maintained through adulthood, and encompasses both cognitive and behavioral rigidity. There is evidence for immune dysfunction in a subgroup of ASD, including systemic inflammation, cytokine dysregulation and anti-brain autoantibodies. Although immunome pathways are involved in ASD pathophysiology, there is little known about how they relate to symptom domains or symptom severity, and whether such biomarkers may be useful in optimizing future clinical trials. We correlated baseline clinical measures of cognitive inflexibility and resultant irritability with immunome biomarker levels in children with ASD, aged 5–18 years with ABC-I scores ≥18, CGI-S scores ≥4 and SRS-2 scores ≥66T, at Albert Einstein College of Medicine (AECOM). Non-parametric Spearman correlations and estimated multivariable regression analyses adjusting for potential confounders, including other clinical variables, race, sex, and age were completed. Strong positive correlations (r_s > .70) were found between the Montefiore Einstein Rigidity Scale – Revised (MERS-R) Total Score and the pro-inflammatory cytokines IL-6 (r_s=.80), granulocyte-colony stimulating factor (GCSF; r_s =.72), macrophage inflammatory protein-1 alpha (MIP-1a; r_s =.71). The MERS-R subscales also had moderate and strong correlations with the immunome biomarkers. The MERS-R Total Rigidity Subscale Score had a strong positive relationship with IL-6 (r_s = 0.7856). Using multivariable regression analyses significant relationships were found between the MERS-R Total Rigidity Subscale Score and proinflammatory cytokine IL-18 (p = 0.02), and a nonsignificant trend was found between it and IFN-alpha2 (β = −4.982, p = 0.058). The ABC-I was significantly correlated with pro-inflammatory cytokine IL-18 (p = .013), IFN-alpha2 (p = 0.039), the anti-inflammatory cytokine IL-10 (p = 0.02), and adaptive immunity cytokine IL-2 (p = 0.041). This preliminary data is the first to examine the relationship of clinical measures of cognitive inflexibility and immunome biomarkers in children with ASD, and may provide a framework for better understanding the relationship between immunome mechanisms, cognitive inflexibility, and ASD symptomatology. Clinicaltrials.gov: NCT03202303.

Mouse preclinical research is of great scientific interest to understand the mechanisms of human diseases and test potential therapeutic interventions. Researchers characterize biological and physiological traits, behaviors and disease symptoms using standardized phenotypic protocols in the context of in vivo mouse studies. However, the procedures applied do not always fully translate to reported outcomes in clinical trials. Quality of life (QoL) and wellbeing (WB) are particularly relevant outcomes in human medicine in general, and in neurology in particular, that are routinely measured by patient self-reports but rarely monitored in mouse research. In this novel scoping review, we have identified and described the instruments/tests and outcomes used to assess QoL and WB in recent mouse research (spanning 13 years). We found that WB was stated to be measured more frequently in murine studies (77 publications fulfilled our selection criteria) than QoL (only 13 articles). Instruments measuring WB were commonly used in neurology but less frequently in behavior and psychiatric research articles. Interestingly, we found a high variability of QoL and WB instruments/tests used as well as outcomes measured in the reviewed mouse studies. In addition, among similar parameters tested, we observed variable methodological procedures and mouse sample sizes. Thus, there is a lack of consensus on how to measure QoL and WB in the mouse research field. For ensuring a better translation from mouse to human, outcomes that are important in clinical trials (e.g., QoL and WB) should be measured in mouse studies. Finally, we would like to point out that a proper standardization of QoL and WB assessment protocols, for instance through a modified Delphi consultation survey, should be pursued by the mouse research community.

Review registration

The study was registered on the PROSPERO Database (registration number CRD42018103507)