Evidence Base Update on the Assessment of Irritability, Anger, and Aggression in Youth

Irritability, anger, and aggression have garnered significant attention from youth mental health researchers and clinicians; however, fundamental challenges of conceptualization and measurement persist. This article reviews the evidence base for assessing these transdiagnostic constructs in children and adolescents.We conducted a preregistered systematic review of the evidence behind instruments used to measure irritability, anger, aggression, and related problems in youth. Searches were conducted in PsycINFO and PubMed, identifying 4,664 unique articles. Eligibility criteria focused on self- and proxy-report measures with peer-reviewed psychometric evidence from studies in English with youths ages 3-18. Additional measures were found through ancillary search strategies (e.g. book chapters, review articles, test publishers). Measures were screened and coded by multiple raters with acceptable reliability.Overall, 68 instruments met criteria for inclusion, with scales covering irritability (= 15), anger (= 19), aggression (= 45), and/or general overt externalizing problems (= 27). Regarding overall psychometric support, 6 measures (8.8%) were classified as Excellent, 46 (67.6%) were Good, and 16 (23.5%) were Adequate. Descriptive information (e.g. informants, scales, availability, translations) and psychometric properties (e.g. reliability, validity, norms) are summarized.Numerous instruments for youth irritability, anger, and aggression exist with varying degrees of empirical support for specific applications. Although some measures were especially strong, none had uniformly excellent properties across all dimensions, signaling the need for further research in particular areas. Findings promote conceptual clarity while also producing a well-characterized toolkit for researchers and clinicians addressing transdiagnostic problems affecting youth

FMS-like tyrosine kinase 3 ligand treatment of mice aggravates acute lung injury in response to Streptococcus pneumoniae: Role of pneumolysin

FMS-like tyrosine kinase-3 ligand (Flt3L) is a dendritic cell (DC) growth and differentiation factor with potential in antitumor therapies and antibacterial immunization strategies. However, the effect of systemic Flt3L treatment on lung-protective immunity against bacterial infection is incompletely defined. Here, we examined the impact of deficient (in Flt3L knockout [KO] mice), normal (in wild-type [WT] mice), or increased Flt3L availability (in WT mice pretreated with Flt3L for 3, 5, or 7 days) on lung DC subset profiles and lung-protective immunity against the major lung-tropic pathogen, Streptococcus pneumoniae. Although in Flt3L-deficient mice the numbers of DCs positive for CD11b (CD11b(pos) DCs) and for CD103 (CD103(pos) DCs) were diminished, lung permeability, a marker of injury, was unaltered in response to S. pneumoniae. In contrast, WT mice pretreated with Flt3L particularly responded with increased numbers of CD11b(pos) DCs and with less pronounced numbers of CD103(pos) DCs and impaired bacterial clearance and with increased lung permeability following S. pneumoniae challenge. Notably, infection of Flt3L-pretreated mice with S. pneumoniae lacking the pore-forming toxin, pneumolysin (PLY), resulted in substantially less lung CD11b(pos) DCs activation and reduced lung permeability. Collectively, this study establishes that Flt3L treatment enhances the accumulation of proinflammatory activated lung CD11b(pos) DCs which contribute to acute lung injury in response to PLY released by S. pneumoniae.Christina Brumshagen, Regina Maus, Andrea Bischof, Bianca Ueberberg, Jennifer Bohling, John J. Osterholzer, Abiodun D. Ogunniyi, James C. Paton, Tobias Welte, and Ulrich A. Mau