Child and adolescent psychiatry and mental health · 2026
Understanding the developmental trajectory of behavioral problems and subcortical structure morphometry in healthy children at 6 years old and long-term impact of early nutrition: the COGNIS study.
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Catena-Verdejo Elvira, Nieto-Ruiz Ana, García-Santos José Antonio, Herrmann Florian, De-Castellar Roser, Pérez-Hernández Mª Teresa, Catena Andrés, Campoy Cristina
Аннотация
BACKGROUND: Early behavioral problems may influence adult psychopathology, and early-life nutrition plays a critical role in shaping behavioral outcomes during childhood.
OBJECTIVE: This study investigated whether subcortical brain volumetry at age six is associated with early behavioral trajectories and the potential influence of early nutrition on this relationship.
METHODS: Data from 82 children participants in the COGNIS study were included in the present analysis. During the first 2 months of life, fifty infants were randomized to one of two formula diets until 18 months of age: a standard formula (SF, n = 26) or an experimental formula (EF, n = 24) supplemented with bioactive compounds. A reference group of breastfed infants (BF, n = 32) was also included. Behavioral assessments were conducted using the Child Behavior Checklist (CBCL) at 18 months, 2.5 years, and 4 years. Structural magnetic resonance imaging (MRI) was performed at 6 years to assess volumes of bilateral subcortical nuclei, brainstem, cerebellum, and total intracranial volume. Complete behavioral and imaging data were available for 37 participants (SF = 19, EF = 18). Weights for linear, quadratic, and mixed linear/quadratic growth curves were computed for CBCL total, internalizing, externalizing, and DSM-oriented scales. Non-parametric correlations between CBCL growth curves and subcortical brain volumetry were computed after adjusting for relevant confounding factors. Generalized linear mixed model for repeated measures was performed.
RESULTS: No significant effects of early nutrition on behavioral trajectories were found; in fact, EF and BF groups exhibited similar patterns across internalizing, externalizing, total problems and DSM-oriented scales. CBCL domains followed distinct developmental trajectories, and interestingly, children's subcortical volumetry of specific brain area at 6 years old, were primarily associated with non-linear behavioral growth curves. Amygdala volume correlated with total problems scores and DSM-oriented scales, while hippocampal volume was linked to internalizing, oppositional defiant, and ADHD-related behaviors. Cerebellar cortex volume correlated with ADHD and externalizing problems, the latter also associating with putamen. Pallidum volume was correlated with internalizing and anxiety symptoms.
CONCLUSIONS: These findings suggest that non-linear behavioral growth models more effectively reflect brain-behavior associations. Futhermore, subcortical brain morphometry, particularly of the hippocampus, may be shaped by behavioral patterns during critical developmental windows-most notably around 2.5 years of age.
OBJECTIVE: This study investigated whether subcortical brain volumetry at age six is associated with early behavioral trajectories and the potential influence of early nutrition on this relationship.
METHODS: Data from 82 children participants in the COGNIS study were included in the present analysis. During the first 2 months of life, fifty infants were randomized to one of two formula diets until 18 months of age: a standard formula (SF, n = 26) or an experimental formula (EF, n = 24) supplemented with bioactive compounds. A reference group of breastfed infants (BF, n = 32) was also included. Behavioral assessments were conducted using the Child Behavior Checklist (CBCL) at 18 months, 2.5 years, and 4 years. Structural magnetic resonance imaging (MRI) was performed at 6 years to assess volumes of bilateral subcortical nuclei, brainstem, cerebellum, and total intracranial volume. Complete behavioral and imaging data were available for 37 participants (SF = 19, EF = 18). Weights for linear, quadratic, and mixed linear/quadratic growth curves were computed for CBCL total, internalizing, externalizing, and DSM-oriented scales. Non-parametric correlations between CBCL growth curves and subcortical brain volumetry were computed after adjusting for relevant confounding factors. Generalized linear mixed model for repeated measures was performed.
RESULTS: No significant effects of early nutrition on behavioral trajectories were found; in fact, EF and BF groups exhibited similar patterns across internalizing, externalizing, total problems and DSM-oriented scales. CBCL domains followed distinct developmental trajectories, and interestingly, children's subcortical volumetry of specific brain area at 6 years old, were primarily associated with non-linear behavioral growth curves. Amygdala volume correlated with total problems scores and DSM-oriented scales, while hippocampal volume was linked to internalizing, oppositional defiant, and ADHD-related behaviors. Cerebellar cortex volume correlated with ADHD and externalizing problems, the latter also associating with putamen. Pallidum volume was correlated with internalizing and anxiety symptoms.
CONCLUSIONS: These findings suggest that non-linear behavioral growth models more effectively reflect brain-behavior associations. Futhermore, subcortical brain morphometry, particularly of the hippocampus, may be shaped by behavioral patterns during critical developmental windows-most notably around 2.5 years of age.