Mapping phenotypic and genetic relationships among irritability, depression and ADHD in adolescence using network...

Area of Science:

• Child and Adolescent Psychiatry
• Developmental Psychology
• Behavioral Genetics

Background:

• Irritability is a frequent reason for child and adolescent mental health referrals.
• Current understanding debates whether irritability is a mood disorder feature, oppositional defiant disorder (ODD) symptom, or core to attention-deficit/hyperactivity disorder (ADHD).

Purpose of the Study:

• To investigate the network relationships between adolescent irritability, ODD, ADHD, and depression.
• To examine the influence of polygenic scores (PGS) for depression and ADHD on these relationships.

Main Methods:

• Network analyses were conducted on data from the Avon Longitudinal Study of Parents and Children (ALSPAC) at ages 13 and 15.
• Phenotypes were assessed using the Development and Well-Being Assessment (DAWBA), Short Mood and Feelings Questionnaire (SMFQ), and Strengths and Difficulties Questionnaire (SDQ).
• Confirmatory network analysis was used in the Millennium Cohort Study (MCS) to test replicability.

Main Results:

• Irritability showed the strongest association with headstrong/hurtful ODD items, followed by ADHD and depression.
• An association was found between irritability and depression polygenic scores, but not ADHD polygenic scores.
• Irritability acted as a primary pathway connecting ADHD and ODD symptoms to depression.

Conclusions:

• While irritability is transdiagnostic, it phenotypically aligns most closely with ODD and behavioral problems, supporting its classification as an ODD specifier in ICD-11.
• Irritability serves as a critical link between ADHD and behavioral issues with depression, necessitating monitoring and treatment in affected youth.