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Glutamate imbalance in key structure of the default mode network in adults with attention-deficit/hyperactivity disorder

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Abstract

The default mode network (DMN) is atypically active in patients with ADHD, likely contributing to the inattention patterns observed in patients with the disorder. Nonetheless, magnetic resonance spectroscopy (MRS) studies have rarely targeted the posterior cingulate cortex, a key DMN region, and little is known about the biochemical setting within this network in patients with ADHD. We aimed to assess the differences in metabolite profiles of the posterior cingulate cortex—a key region of the DMN—between patients with ADHD and controls. Five brain metabolites—glutamate, inositol, N-acetyl aspartate, choline, and creatine—were measured through MRS in the posterior cingulate cortex of patients and controls in a 3.0 T scanner. Between-group comparison of neurometabolite concentrations in PCC was performed using multivariate analysis of covariance. A total of 88 patients and 44 controls were included in the analysis. Patients with ADHD showed lower levels of glutamate in the posterior cingulate cortex compared to controls (p = 0.003). Lower concentrations of glutamate in the posterior cingulate cortex suggest that a glutamatergic imbalance within the posterior cingulate cortex might play a role in the pathogenesis of ADHD. Further understanding of the causes and consequences of such glutamate decrease might help explain how some glutamate-related drug effects impact on ADHD symptomatology.

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Funding

The authors would like to acknowledge the patients assessed in ProDAH-A and all its members. This study was financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES, Finance Code 001) and FIPE-HCPA 160600, GPPG-HCPA 01–321. In addition to the financial support received from the Conselho Nacional de Desenvolvimento Científco e Tecnológico (Grants 466,722/2014–1, 424,041/2016–2, 426,905/2016–2, 140,853/2019–7), grant #2020/05652–0 São Paulo Research Foundation (FAPESP), and the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (Grants PqG-19/2551–0001731-6; PqG-19/2551–0001668-9). The funding agencies mentioned were not involved in study design, in the collection, analysis and interpretation of data, in the writing of the report or in the decision to submit the article for publication.

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Authors and Affiliations

  1. Adulthood ADHD Outpatient Program (ProDAH), Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Marcos Vinícius Vidor, Eduardo Schneider Vitola, Cibele Edom Bandeira, Maria Eduarda de Araujo Tavares, Renata Basso Cupertino, Alana Castro Panzenhagen, Bruna Santos da Silva, Isabel Ghirardi Falkenberg, Pedro Olavo Barreto, Stefania Pigatto Teche, Felipe Almeida Picon, Diego L. Rovaris, Claiton Henrique Dotto Bau & Eugenio Horacio Grevet

  2. Department of Physiology and Biophysics, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, São Paulo, Brazil

    Marcos Vinícius Vidor & Diego L. Rovaris

  3. Qualiphy Soluções Em Imaginologia E Radioproteção, Porto Alegre, Brazil

    Alexandre Ribeiro Martins

  4. Department of Psychiatry, University of Vermont, Burlington, USA

    Renata Basso Cupertino

  5. Department of Psychiatry and Behavioral Sciences, PPG Psiquiatria, Federal University of Rio Grande Do Sul (UFRGS), R. Ramiro Barcelos, 2400, 2º Andar, Porto Alegre, RS, Brazil

    Luis Augusto Rohde & Eugenio Horacio Grevet

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  1. Marcos Vinícius Vidor
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Correspondence to Eugenio Horacio Grevet.

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Conflict of interest

Dr. Vidor was the recipient of a PhD scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—PBE-DPM, Bolsa Especial para Doutorado em Pesquisa Médica). Luis Augusto Rohde has received honoraria, has been on the speakers’ bureau/advisory board, and/or has acted as a consultant for Medice, Novartis/Sandoz, and Shire/Takeda in the last two years, and receives authorship royalties from OxfordPress and ArtMed. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by him has received unrestricted educational and research support from the following pharmaceutical companies in the last three years: Janssen-Cilag, Novartis/Sandoz, and Shire/Takeda. Eugênio Horácio Grevet has served as a speakers’ bureau/advisory board for Shire Pharmaceuticals in the past 3 years and has received travel awards from Shire for taking part in psychiatric meetings. Dr. Vitola, MSc Bandeira, Mr. Martins, MSc Tavares, Dr. Cupertino, Ms. Panzehagen, Dr. da Silva, Ms. Falkenberg, Mr. Barreto, Dr. Teche, Dr. Picon, Dr. Rovaris, and Dr. Bau reported no biomedical financial interests or potential conflicts of interest.

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Vidor, M.V., Vitola, E.S., Bandeira, C.E. et al. Glutamate imbalance in key structure of the default mode network in adults with attention-deficit/hyperactivity disorder. Eur Arch Psychiatry Clin Neurosci (2024). https://doi.org/10.1007/s00406-024-01805-z

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