Roles of genetic and environmental factors in psychiatric comorbidities among children with neurodevelopmental delays

Abstract

BACKGROUND

Neurodevelopmental delays encompass a wide range of conditions that impair cognitive, motor, and social functioning, often increasing the risk of psychiatric comorbidities. Children with these delays frequently present with disorders such as attention-deficit/hyperactivity disorder (ADHD), anxiety, and behavioral disturbances, which can significantly affect development and quality of life. While genetic predisposition has been linked to these comorbidities, growing evidence highlights the role of environmental factors, including prenatal and early-life stressors. However, the interaction between genetic susceptibility and environmental influences remains poorly understood. Identifying specific genetic variants, environmental risks, and their interactions is essential for early detection and targeted interventions.

AIM

To investigate the combined effects of genetic and environmental factors on psychiatric comorbidities in children with neurodevelopmental delays, elucidate underlying mechanisms, and inform clinical management strategies.

METHODS

This retrospective cohort study included 80 children with confirmed neurodevelopmental delays and 40 age- and sex-matched typically developing controls. Comprehensive clinical and psychiatric evaluations, genetic testing (chromosomal microarray analysis and targeted next-generation sequencing), and environmental exposure assessments were conducted. Statistical analyses explored associations between genetic variants and psychiatric comorbidities, environmental risk factors, and gene-environment interactions.

RESULTS

Children with neurodevelopmental delays exhibited significantly higher rates of psychiatric comorbidities (70.0%) compared to controls (15.0%), with ADHD (42.5%), anxiety disorders (28.8%), and behavioral disorders (23.8%) being the most common. Pathogenic genetic variants were identified in specific pathways associated with distinct psychiatric presentations: Glutamatergic signaling variants were linked to anxiety disorders (odds ratio = 3.8), dopaminergic system variants to ADHD (odds ratio = 4.2), and synaptic function variants to both behavioral and anxiety disorders. Environmental factors, particularly prenatal maternal stress, early childhood adversity, and family dysfunction were strong predictors of psychiatric outcomes (β = 0.42). Significant gene-environment interactions were identified, indicating that environmental exposure can moderate the effects of genetic risks on psychiatric outcomes.

CONCLUSION

Psychiatric comorbidities in children with neurodevelopmental delays are significantly influenced by both genetic and environmental factors, with complex interactions between the two. These findings underscore the need for integrated assessments and targeted interventions addressing both biological and environmental contributors to improve outcomes in this vulnerable population.

Keywords: Neurodevelopmental delay; Psychiatric comorbidity; Genetic factors; Environmental factors; Child development

Core Tip: This study highlights the significant roles of both genetic and environmental factors in the development of psychiatric comorbidities among children with neurodevelopmental delays. Key findings include the identification of specific genetic variants associated with disorders such as attention-deficit/hyperactivity disorder and anxiety, as well as the influence of environmental stressors, including prenatal maternal stress and early childhood adversity. The complex interactions between genes and the environment underscore the need for integrated assessment approaches and targeted interventions to improve outcomes in this vulnerable population.