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Background <p>Early behavioral problems may influence adult psychopathology, and early-life nutrition plays a critical role in shaping behavioral outcomes during childhood.</p> Objective <p>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.</p> Methods <p>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, <i>n</i> = 26) or an experimental formula (EF, <i>n</i> = 24) supplemented with bioactive compounds. A reference group of breastfed infants (BF, <i>n</i> = 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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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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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  • 发表日期：

    2026年2月19日

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  • Elvira Catena-Verdejo,
  • Ana Nieto-Ruiz,
  • José Antonio García-Santos,
  • Florian Herrmann,
  • Roser De-Castellar,
  • Mª Teresa Pérez-Hernández,
  • Andrés Catena,
  • Cristina Campoy

摘要

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.