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Decoding anxiety–impulsivity subtypes in preadolescent internalising disorders: findings from the Adolescent Brain Cognitive Development study

Published online by Cambridge University Press:  21 September 2023

Huaxin Fan
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China
Zhaowen Liu
Affiliation:
School of Computer Science, Northwestern Polytechnical University, China
Xinran Wu
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China
Gechang Yu
Affiliation:
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China
Xinrui Gu
Affiliation:
Sino-European School of Technology, Shanghai University, China
Nanyu Kuang
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China
Kai Zhang
Affiliation:
School of Computer Science and Technology, East China Normal University, Shanghai, China
Yu Liu
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China
Tianye Jia
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China
Barbara J. Sahakian
Affiliation:
Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK and Department of Psychiatry, University of Cambridge School of Clinical Medicine, UK
Trevor W. Robbins
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China; Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK and Department of Psychology, University of Cambridge, UK
Gunter Schumann
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China and PONS-Center, Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité Universitätsmedizin Berlin, Germany
Wei Cheng
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China; Fudan ISTBI—ZJNU Algorithm Centre for Brain-inspired Intelligence, Zhejiang Normal University, China and Shanghai Medical College and Zhongshan Hospital Immunotherapy Technology Transfer Center, China
Jianfeng Feng
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China
Benjamin Becker
Affiliation:
State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China; Department of Psychology, The University of Hong Kong, Hong Kong, China
Jie Zhang*
Affiliation:
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, China and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, China
*
Correspondence: Jie Zhang. Email: jzhang080@gmail.com

Abstract

Background

Internalising disorders are highly prevalent emotional dysregulations during preadolescence but clinical decision-making is hampered by high heterogeneity. During this period impulsivity represents a major risk factor for psychopathological trajectories and may act on this heterogeneity given the controversial anxiety–impulsivity relationships. However, how impulsivity contributes to the heterogeneous symptomatology, neurobiology, neurocognition and clinical trajectories in preadolescent internalising disorders remains unclear.

Aims

The aim was to determine impulsivity-dependent subtypes in preadolescent internalising disorders that demonstrate distinct anxiety–impulsivity relationships, neurobiological, genetic, cognitive and clinical trajectory signatures.

Method

We applied a data-driven strategy to determine impulsivity-related subtypes in 2430 preadolescents with internalising disorders from the Adolescent Brain Cognitive Development study. Cross-sectional and longitudinal analyses were employed to examine subtype-specific signatures of the anxiety–impulsivity relationship, brain morphology, cognition and clinical trajectory from age 10 to 12 years.

Results

We identified two distinct subtypes of patients who internalise with comparably high anxiety yet distinguishable levels of impulsivity, i.e. enhanced (subtype 1) or decreased (subtype 2) compared with control participants. The two subtypes exhibited opposing anxiety–impulsivity relationships: higher anxiety at baseline was associated with higher lack of perseverance in subtype 1 but lower sensation seeking in subtype 2 at baseline/follow-up. Subtype 1 demonstrated thicker prefrontal and temporal cortices, and genes enriched in immune-related diseases and glutamatergic and GABAergic neurons. Subtype 1 exhibited cognitive deficits and a detrimental trajectory characterised by increasing emotional/behavioural dysregulations and suicide risks during follow-up.

Conclusions

Our results indicate impulsivity-dependent subtypes in preadolescent internalising disorders and unify past controversies about the anxiety–impulsivity interaction. Clinically, individuals with a high-impulsivity subtype exhibit a detrimental trajectory, thus early interventions are warranted.

Type
Original Article
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists

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Footnotes

*

These authors contributed equally to this work.

#

These authors contributed equally as senior authors.

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