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Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities.
We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8–18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities.
While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample.
Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.
The present paper presents a fundamentally novel approach to model individual differences of persons with the same biologically heterogeneous mental disorder. Unlike prevalent case-control analyses, that assume a clear distinction between patient and control groups and thereby introducing the concept of an ‘average patient’, we describe each patient's biology individually, gaining insights into the different facets that characterize persistent attention-deficit/hyperactivity disorder (ADHD).
Using a normative modeling approach, we mapped inter-individual differences in reference to normative structural brain changes across the lifespan to examine the degree to which case-control analyses disguise differences between individuals.
At the level of the individual, deviations from the normative model were frequent in persistent ADHD. However, the overlap of more than 2% between participants with ADHD was only observed in few brain loci. On average, participants with ADHD showed significantly reduced gray matter in the cerebellum and hippocampus compared to healthy individuals. While the case-control differences were in line with the literature on ADHD, individuals with ADHD only marginally reflected these group differences.
Case-control comparisons, disguise inter-individual differences in brain biology in individuals with persistent ADHD. The present results show that the ‘average ADHD patient’ has limited informative value, providing the first evidence for the necessity to explore different biological facets of ADHD at the level of the individual and practical means to achieve this end.
Toxic anterior segment syndrome (TASS), a complication of cataract surgery, is a sterile inflammation of the anterior chamber of the eye. An outbreak of TASS was recognized at an outpatient surgical center and its affiliated hospital in December 2002.
Medical records of patients who underwent cataract surgery during the outbreak were reviewed, and surgical team members who participated in the operations were interviewed. Potential causes of TASS were identified and eliminated. Feedwater from autoclave steam generators and steam condensates were analyzed by use of spectroscopy and ion chromatography.
During the outbreak, 8 (38%) of 21 cataract operations were complicated by TASS, compared with 2 (0.07%) of 2,713 operations performed from January 1996 through November 2002. Results of an initial investigation suggested that cataract surgical equipment may have been contaminated by suboptimal equipment reprocessing or as a result of personnel changes. The frequency of TASS decreased (1 of 44 cataract operations) after reassignment of personnel and revision of equipment reprocessing procedures. Further investigation identified the presence of impurities (eg, sulfates, copper, zinc, nickel, and silica) in autoclave steam moisture, which was attributed to improper maintenance of the autoclave steam generator in the outpatient surgical center. When impurities in autoclave steam moisture were eliminated, no cases of TASS were observed after more than 1,000 cataract operations.
Suboptimal reprocessing of cataract surgical equipment may evolve over time in busy, multidisciplinary surgical centers. Clinically significant contamination of surgical equipment may result from inappropriate maintenance of steam sterilization systems. Standardization of protocols for reprocessing of cataract surgical equipment may prevent outbreaks of TASS and may be of assistance during outbreak investigations.
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