It was essential to move past case-control studies and instead capture individual differences and interpret them in the context of a normal spectrum of biological systems in order to advance precision psychiatry. For a study, researchers sought to determine if subcortical volume baseline deviations from a normal reference range were a more accurate indicator of an antipsychotic treatment’s effectiveness than raw volume in individuals with first-episode psychosis (FEP) who had never taken an antipsychotic drug.

Patients with first-episode psychosis who were referred from various clinical settings at the University of Alabama in Birmingham (emergency department, inpatient units, and outpatient clinics) were included in the prospective longitudinal research. There were 286 patients in all who underwent screening; 114 gave their permission, 104 were recruited in the therapy study, and 85 finished it. 16 weeks were spent watching the patients. Age and sex were used to match the controls. Data were gathered between June 2016 and July 2021, and from August 2021 to June 2022, data were examined. The main goal of the study was to assess the relationship between baseline raw volumes and volume deviations in subcortical brain areas and response to antipsychotic medication in individuals with FEP who had never taken antipsychotic medication before. Raw brain volumes or changes in volume deviation following therapy weren’t looked at.

The mean (SD) age of the 190 individuals that were included was 23.7 (5.5) years, with 111 (58.4%) of them being male. Volumes and variations were measured in 98 FEP patients, and data from 92 controls were utilized as a benchmark for case-control comparisons and the calibration of reference curves. In case-control comparisons, FEP patients exhibited smaller volumes of the raw thalamus (P =.002, F = 9.63, df = 1), hippocampus (P =.009, F = 17.23, df = 1), amygdala (P =.01, F = 6.55, df = 1), ventral diencephalon (P =.03, F = 4.84, df = 1), and brainstem volumes (P = .004; F = 8.39; df = 1). 36 FEP patients (36%) out of 98 patients showed severe abnormalities. In the caudate (z = -2.17; P =.03) and putamen (z = -2.15; P =.03), raw volume and deviation measurements showed statistically different associations with treatment response.

Normative modeling may capture the interindividual variation of regional brain volumes in FEP patients and identify structural disease in a therapeutically pertinent manner, according to these results. In the field of psychiatry, where group-level studies have been unable to produce accurate maps of structural pathology, this holds promise for advancement in precision medicine.