Normative modeling of brain morphometry in clinical high risk for psychosis

Importance The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. Design, Setting, and Participants This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)–derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < −1.96) or supranormal (z > 1.96) scores. Results Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. Individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal or supranormal values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms (β = −0.08; 95% CI, −0.13 to −0.02; P = .02 for false discovery rate) and IQ (β = 0.09; 95% CI, 0.02-0.15; P = .02 for false discovery rate). Conclusions and Relevance In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk

Psychophysics of sweet and fat perception in obesity: problems, solutions and new perspectives

Psychophysical comparisons seem to show that obese individuals experience normal sweet and fat sensations, they like sweetness the same or less, but like fat more than the non-obese do. These psychophysical comparisons have been made using scales (visual analogue or category) that assume intensity labels (e.g. extremely) which denote the same absolute perceived intensity to all. In reality, the perceived intensities denoted by labels vary because they depend on experiences with the substances to be judged. This variation makes comparisons invalid. Valid comparisons can be made by asking the subjects to rate their sensory/hedonic experiences in contexts that are not related to the specific experiences of interest. Using this methodology, we present the evidence that the sensory and hedonic properties of sweet and fat vary with body mass index. The obese live in different orosensory and orohedonic worlds than do the non-obese; the obese experience reduced sweetness, which probably intensifies fat sensations, and the obese like both sweet and fat more than the non-obese do. Genetic variation as well as taste pathology contribute to these results. These psychophysical advances will impact experimental as well as clinical studies of obesity and other eating disorders