Increased Resting-State Functional Connectivity in Patients With Autoimmune Addison Disease

Author:

van’t Westeinde Annelies1ORCID,Padilla Nelly2ORCID,Fletcher-Sandersjöö Sara3,Kämpe Olle4ORCID,Bensing Sophie3ORCID,Lajic Svetlana15ORCID

Affiliation:

1. Department of Women's and Children's Health, Karolinska Institutet, Pediatric Endocrinology Unit, Karolinska University Hospital , SE-171 76 Stockholm , Sweden

2. Department of Women's and Children's Health, Karolinska Institutet, Unit for Neonatology, Karolinska University Hospital , SE-171 76 Stockholm , Sweden

3. Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Endocrinology, Karolinska University Hospital , SE-171 76 Stockholm , Sweden

4. Department of Medicine (Solna), Center for Molecular Medicine, Karolinska Institutet, Sweden and Department of Endocrinology, Karolinska University Hospital , SE-171 76 Stockholm , Sweden

5. Department of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Pediatric Endocrinology Unit, Sahlgrenska University Hospital , SE-416 50 Gothenburg , Sweden

Abstract

Abstract Context Individuals with autoimmune Addison disease (AAD) take replacement medication for the lack of adrenal-derived glucocorticoid (GC) and mineralocorticoid hormones from diagnosis. The brain is highly sensitive to these hormones, but the consequence of having AAD for brain health has not been widely addressed. Objective The present study compared resting-state functional connectivity (rs-fc) of the brain between individuals with AAD and healthy controls. Methods Fifty-seven patients with AAD (33 female) and 69 healthy controls (39 female), aged 19 to 43 years were scanned with 3-T magnetic resonance imaging (MRI). Results Independent component and subsequent dual regression analyses revealed that individuals with AAD had stronger rs-fc compared to controls in 3 networks: the bilateral orbitofrontal cortex (OFC), the left medial visual and left posterior default mode network. A higher GC replacement dose was associated with stronger rs-fc in a small part of the left OFC in patients. We did not find any clear associations between rs-fc and executive functions or mental fatigue. Conclusion Our results suggest that having AAD affects the baseline functional organization of the brain and that current treatment strategies of AAD may be one risk factor.

Funder

Marianne and Marcus Wallenberg Foundation

Knut and Alice Wallenberg Foundation

International Fund raising for Congenital Adrenal Hyperplasia

European Society for Pediatric Endocrinology

Stockholm County Council

Swedish Research Council

Region Stockholm

Foundations of Lisa and Johan Grönberg

Stiftelsen Frimurare Barnhuset i Stockholm

Wera Ekströms stiftelse för Pediatrikforskning

Research and Education in Pediatric Endocrinology

Novo Nordisk Foundation

Torsten and Ragnar Söderberg

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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