In silico evaluation of the role of lisdexamfetamine on attention-deficit/hyperactivity disorder common psychiatric comorbidities: mechanistic insights on binge eating disorder and depression

Frontiers in Neuroscience

Neuroscience

Mireia Coma¹  Cristina Segú-Vergés²  Carmen Montoto³  Tamara Pozo-Rubio³  Juncal Sabate Chueca³  Javier Quintero⁴  José Ramón Gutiérrez-Casares⁵ 

[1] Anaxomics Biotech, Barcelona, Spain;Anaxomics Biotech, Barcelona, Spain;Research Programme on Biomedical Informatics (GRIB), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain;Department of Medical, Takeda Farmacéutica España, Madrid, Spain;Servicio de Psiquiatría, Hospital Universitario Infanta Leonor, Departamento de Medicina Legal, Patología y Psiquiatría, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain;Unidad Ambulatoria de Psiquiatría y Salud Mental de la Infancia, Niñez y Adolescencia, Hospital Perpetuo Socorro, Badajoz, Spain;

关键词: attention-deficit/hyperactivity disorder;    lisdexamfetamine;    mathematical modeling;    binge eating disorder;    depression;   

DOI  :  10.3389/fnins.2023.1118253

 received in 2022-12-07, accepted in 2023-06-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition well recognized in the pediatric population that can persist into adulthood. The vast majority of patients with ADHD present psychiatric comorbidities that have been suggested to share, to some extent, the pathophysiological mechanism of ADHD. Lisdexamfetamine (LDX) is a stimulant prodrug approved for treating ADHD and, in the US, also for binge eating disorder (BED). Herein, we evaluated, through a systems biology-based in silico method, the efficacy of a virtual model of LDX (vLDX) as ADHD treatment to improve five common ADHD psychiatric comorbidities in adults and children, and we explored the molecular mechanisms behind LDX’s predicted efficacy. After the molecular characterization of vLDX and the comorbidities (anxiety, BED, bipolar disorder, depression, and tics disorder), we created a protein-protein interaction human network to which we applied artificial neural networks (ANN) algorithms. We also generated virtual populations of adults and children-adolescents totaling 2,600 individuals and obtained the predicted protein activity from Therapeutic Performance Mapping System models. The latter showed that ADHD molecular description shared 53% of its protein effectors with at least one studied psychiatric comorbidity. According to the ANN analysis, proteins targeted by vLDX are predicted to have a high probability of being related to BED and depression. In BED, vLDX was modeled to act upon neurotransmission and neuroplasticity regulators, and, in depression, vLDX regulated the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, and glutamatergic excitotoxicity. In conclusion, our modeling results, despite their limitations and although requiring in vitro or in vivo validation, could supplement the design of preclinical and potentially clinical studies that investigate treatment for patients with ADHD with psychiatric comorbidities, especially from a molecular point of view.

【 授权许可】

Unknown   
Copyright © 2023 Gutiérrez-Casares, Segú-Vergés, Sabate Chueca, Pozo-Rubio, Coma, Montoto and Quintero.