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Common and disorder-specific cortical thickness alterations in internalizing, externalizing and thought disorders
Gechang Yu1, Zhaowen Liu1, Xinran Wu1
1From the Institute of Science and Technology for Brain Inspired Intelligence, Fudan University, Shanghai, China (Yu, Wu, Fan, Peng, Kuang, Kang, Dong, Zhao, Feng, Sahakian, Robbins, Zhang); the Key Laboratory of Computational Neuroscience and Brain Inspired Intelligence, Fudan University, Ministry of Education, China (Yu, Wu, Fan, Peng, Kuang, Feng, Zhang); the Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Mass., USA (Liu); the Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA (Liu); the Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Mass., USA (Liu); the Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China (Becker); the School of Computer Science and Technology, East China Normal University, Shanghai, China (Zhang); the Shanghai Center for Mathematical Sciences, Fudan University, Shanghai, China (Kang); the MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China (Dong, Zhao); the Zhangjiang Fudan International Innovation Center, Shanghai, China (Zhao); the PONS Centre Shanghai, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China (Schumann); the PONS Centre Berlin, Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charitéplatz 1, Berlin, Germany (Feng); the Shanghai Center for Mathematical Sciences, Shanghai, China (Feng); the Department of Computer Science, University of Warwick, Coventry, UK (Feng); the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Feng); the Fudan ISTBI-ZJNU Algorithm Centre for Brain-inspired Intelligence, Zhejiang Normal University, Jinhua, China (Feng); the Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK (Sahakian); the Department of Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK (Robbins); the Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Que., Canada (Palaniyappan); the Department of Psychiatry, Schulich School of Medicine and Dentistry, Western University, London, Ont., Canada (Palaniyappan); the Robarts Research Institute, Western University, London, Ont., Canada (Palaniyappan); the Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, Ont., Canada (Palaniyappan).
Background:
A growing body of neuroimaging studies has reported common neural abnormalities among mental disorders in adults. However, it is unclear whether the distinct disorder-specific mechanisms operate during adolescence despite the overlap among disorders.
Methods:
We studied a large cohort of more than 11 000 preadolescent (age 9-10 yr) children from the Adolescent Brain and Cognitive Development cohort. We adopted a regrouping approach to compare cortical thickness (CT) alterations and longitudinal changes between healthy controls (n = 4041) and externalizing (n = 1182), internalizing (n = 1959) and thought disorder (n = 347) groups. Genome-wide association study (GWAS) was performed on regional CT across 4468 unrelated European youth.
Results:
Youth with externalizing or internalizing disorders exhibited increased regional CT compared with controls. Externalizing (p = 8 × 10-4, Cohen d = 0.10) and internalizing disorders (p = 2 × 10-3, Cohen d = 0.08) shared thicker CT in the left pars opercularis. The somatosensory and the primary auditory cortex were uniquely affected in externalizing disorders, whereas the primary motor cortex and higher-order visual association areas were uniquely affected in internalizing disorders. Only youth with externalizing disorders showed decelerated cortical thinning from age 10-12 years. The GWAS found 59 genome-wide significant associated genetic variants across these regions. Cortical thickness in common regions was associated with glutamatergic neurons, while internalizing-specific regional CT was associated with astrocytes, oligodendrocyte progenitor cells and GABAergic neurons.
Limitations:
The sample size of the GWAS was relatively small.
Conclusion:
Our study provides strong evidence for the presence of specificity in CT, developmental trajectories and underlying genetic underpinnings among externalizing and internalizing disorders during early adolescence. Our results support the neurobiological validity of the regrouping approach that could supplement the use of a dimensional approach in future clinical practice.
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