Sex-related differences in adult attention-deficit hyperactivity disorder patients – An analysis of external globus pallidus functional connectivity in resting-state functional MRI
Open accessAbstract
In the last two decades, there has been a growing body of research that identified sex-related differences in attention-deficit hyperactivity disorder (ADHD). Our objective was to quantify whether these sex differences are based on altered functional brain connectivity profiles. In addition, we investigated whether the presence of comorbid disorders, including depression, substance use disorder (SUD) and overweight, influenced these sex differences. A seed-based connectivity analysis of the external globus pallidus (GPe), an important inhibitory relay hub of the fronto-thalamo-striatal-loop, was performed. In a first step, we searched for sex-related differences in ADHD patients (N = 137) and separately in healthy controls (HC) (N = 45), after that, we compared an equal group of HC and ADHD patients to compare sex-related differences in ADHD patients and HC. In a second step, we studied whether the neural basis of comorbidity patterns is different between male and female patients. We observed that male ADHD patients demonstrated a decrease in functional connectivity (FC) from the GPe to the left middle temporal gyrus compared to female ADHD patients. Moreover, within the full ADHD group (N = 137), there was a lower FC in male patients from GPe to the right frontal pole/middle frontal gyrus compared to female patients. Male ADHD patients with depression demonstrated decreased FC from the GPe to parts of the occipital cortex compared to female ADHD patients with depression. No such effect was demonstrated for overweight or SUD. The current study reveals different FC profiles in males and females with ADHD, which are centered around altered connectivity with the GPe. An improved understanding of sex-differences in ADHD, and the role of comorbid disorders, therein can result in improved diagnostic and therapeutic opportunities for ADHD patients.
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Women with ADHD demonstrate more variable patterns, with relatively preserved fronto-striatal volume but more frequent alterations in limbic and parietal circuitry linked to emotional and attentional regulation.
“Women demonstrate more variable patterns, with relatively preserved fronto-striatal volume but more frequent alterations in limbic and parietal circuitry linked to emotional and attentional regulation [134].”
From ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives (2025) · cites this paper as [134]
The Discussion reports stronger external globus pallidus–prefrontal functional connectivity in women with ADHD than in men, and cites another study finding sex differences in regions including the superior parietal lobule. It does not report relatively preserved fronto-striatal volume or establish that limbic and parietal alterations are more frequent in women. The cited findings concern functional connectivity, not the structural-volume pattern claimed. (LLM, conf=0.86)
Experimental — accuracy not yet measuredResting-state studies reveal parallel patterns in network connectivity, with women showing more alterations in emotion-related circuits and men in motor-executive pathways.
“Resting-state studies reveal parallel patterns in network connectivity, with women showing more alterations in emotion-related circuits and men in motor–executive pathways [134].”
From ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives (2025) · cites this paper as [134]
The Discussion (page unavailable) reports sex-related differences in resting-state connectivity and links the region with higher connectivity in women with ADHD—the prefrontal cortex—to emotion control. The Conclusion (page unavailable) reports lower connectivity in men in frontal and temporal regions, and in occipital regions for men with comorbid depression; it does not establish the claimed contrast of women’s emotion-related alterations versus men’s motor–executive alterations. (LLM, conf=0.86)
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ADHD in Adulthood: Clinical Presentation, Comorbidities, and Treatment Perspectives
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“Women demonstrate more variable patterns, with relatively preserved fronto-striatal volume but more frequent alterations in limbic and parietal circuitry linked to emotional and attentional regulation [134].”
- Authors
- Dupont, G., van Rooij, D., Buitelaar, J. K., Reif, A., & Grimm, O.
- Affiliations
- Goethe University Frankfurt (DE)
- Radboud University Medical Center (NL)
- Corresponding author
- Dupont, Gabriele
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2022-09-02
- Volume
- 13
- Pages
- 962911-962911
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC9478108
- OpenAlex
- W4294176800
- Cited by
- 12
- References
- 47
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 4
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Horizon 2020 Framework Programme
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, sex differences, globus pallidus externus, functional connectivity, resting-state fMRI, comorbid depression, substance use disorders, overweight, middle temporal gyrus, frontal pole, occipital cortex
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