# Associations of serotonin-related brain morphology in early adolescence with behavioral and emotional problems

## TL;DR

This study found that specific brain regions related to serotonin are linked to behavioral and emotional problems in early adolescence.

## Contribution

The study identifies region-specific associations between serotonin-related brain morphology and behavioral problems in children.

## Key findings

- Smaller cortical surface area in certain serotonin-related regions was linked to higher behavioral problem scores.
- Thicker cortex in serotonin transporter-enriched regions was associated with higher problem scores.
- An independent adult sample confirmed a negative association between serotonin transporter availability and cortical thickness.

## Abstract

•We investigated serotonin-related brain regions and behavioral problems in early adolescence.•Widespread cortical surface area reductions were associated with higher problem scores.•Thicker cortex in serotonin transporter-enriched regions linked to higher problem scores.

We investigated serotonin-related brain regions and behavioral problems in early adolescence.

Widespread cortical surface area reductions were associated with higher problem scores.

Thicker cortex in serotonin transporter-enriched regions linked to higher problem scores.

We aimed to investigate the association of brain morphology with behavioral and emotional problems in early adolescence using a brain atlas of the serotonin system. This pre-registered study used data from the Generation R Study, a large birth cohort in Rotterdam, the Netherlands. A total of 2492 children were included at age 10 years, with neuroimaging data and self-reported behavioral and emotional problems. Cortical surface area and thickness were measured in ten serotonin-coupled brain regions. Our primary analysis revealed that higher total, attention, and externalizing problem scores were associated with smaller cortical surface area in Regions 8, 9, and 10 (covering cingulate, orbitofrontal, temporal, and parietal areas) after adjusting for intracranial volume, highlighting region-specific effects less confounded by overall head size. Among these regions, only Region 9 showed relative enrichment for 5-HT1A receptors, suggesting potential serotonergic involvement in externalizing problems. Secondary analyses showed that greater cortical thickness in Region 2, enriched with serotonin transporters (5-HTT) and involving parts of the temporal cortex and insula, was associated with higher total, attention, and internalizing problem scores (β = 0.07, PFDR = 0.003). A follow-up analysis in an independent adult sample (n = 100), with the same-subject structural MRI and molecular 5-HTT imaging, revealed a specific negative association between 5-HTT availability and cortical thickness in Region 2 (β = −0.22, P = 0.02). These findings suggest selective serotonergic contributions to cortical morphology related to behavioral problems.