Association between peripheral hsa-miR-4456 expression and plasma oxytocin in men with hypersexual disorder and healthy controls: a secondary cross-sectional analysis
8 affiliations
- 1Center for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet
- 2Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital
- 3Department of Clinical Sciences/Psychiatry, Umeå University
- 4Medical School, University of Cyprus
- 5Department of Clinical Neuroscience/Psychology, Karolinska Institutet
- 6Center for Clinical Research Dalarna, Uppsala University
- 7Department of Medicine, Karolinska Institutet, Karolinska University Hospital
- 8Department of Laboratory Medicine, Clinical Physiology, Karolinska Institutet
Abstract
Introduction: MicroRNAs are candidate regulators and biomarkers of molecular processes relevant to behavior, but their relationships with neuroendocrine signaling in humans remain poorly characterized. Earlier studies in overlapping cohorts identified hypermethylation-associated downregulation of peripheral blood-derived hsa-miR-4456 in men with hypersexual disorder and implicated oxytocin-related pathways through in-silico target prediction; a subsequent study found higher plasma oxytocin in the same clinical context. Whether miR-4456 expression and oxytocin covary within the same individuals had not been examined.
Methods: We performed a secondary cross-sectional analysis of baseline, pretreatment measurements from clinically characterized men with hypersexual disorder and healthy male controls. miR-4456 was measured by RT-qPCR in EDTA blood-derived material and plasma oxytocin by radioimmunoassay. The submitted pooled robust regression included 74 paired measurements; revised group-adjusted and interaction models included 73 complete cases (51 hypersexual disorder and 22 controls). miR-4456, but not oxytocin, was rank-based inverse-normal transformed using Blom's method.
Results: In the submitted pooled model, higher miR-4456 was associated with lower plasma oxytocin (β = −4.039 pmol/L, 95% CI −6.149 to −1.930; p < 0.001). After adjustment for diagnostic group, the estimate remained negative but was attenuated (β = −1.522, 95% CI −3.376 to 0.333; p = 0.106). The control-specific estimate was −0.613 (95% CI −3.693 to 2.467; p = 0.696), the hypersexual-disorder estimate was −2.223 (95% CI −4.514 to 0.069; p = 0.057), and the interaction was not significant ( p = 0.414). Post hoc sensitivity analyses were directionally consistent but imprecise.
Conclusions: To our knowledge, this is the first human study to directly examine paired peripheral miR-4456 and plasma oxytocin measurements. Although diagnostic-group differences explained part of the pooled association, the paired observation connects previously separate epigenetic, expression, pathway-prediction, and neuroendocrine findings and identifies a focused hypothesis for independent replication. The cross-sectional peripheral measurements do not establish directionality, causation, or central nervous system regulation. Experimental studies are needed to determine whether miR-4456 has any functional influence on oxytocin-related biology.
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BibTeX
@article{bostrom2026association,
title = {{Association between peripheral hsa-miR-4456 expression and plasma oxytocin in men with hypersexual disorder and healthy controls: a secondary cross-sectional analysis}},
author = {Adrian E. Desai Boström and Andreas Chatzittofis and Peter Andersson and Josephine Savard and Katarina Görts Öberg and Stefan Arver and John N. Flanagan and Jussi Jokinen},
journal = {Frontiers in Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnins.2026.1946302},
url = {https://www.frontiersin.org/articles/10.3389/fnins.2026.1946302/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association between peripheral hsa-miR-4456 expression and plasma oxytocin in men with hypersexual disorder and healthy controls: a secondary cross-sectional analysis
AU - Adrian E. Desai Boström
AU - Andreas Chatzittofis
AU - Peter Andersson
AU - Josephine Savard
AU - Katarina Görts Öberg
AU - Stefan Arver
AU - John N. Flanagan
AU - Jussi Jokinen
PY - 2026
DA - 2026/10/14
JO - Frontiers in Neuroscience
DO - 10.3389/fnins.2026.1946302
UR - https://www.frontiersin.org/articles/10.3389/fnins.2026.1946302/full
AB - Introduction: MicroRNAs are candidate regulators and biomarkers of molecular processes relevant to behavior, but their relationships with neuroendocrine signaling in humans remain poorly characterized. Earlier studies in overlapping cohorts identified hypermethylation-associated downregulation of peripheral blood-derived hsa-miR-4456 in men with hypersexual disorder and implicated oxytocin-related pathways through in-silico target prediction; a subsequent study found higher plasma oxytocin in the same clinical context. Whether miR-4456 expression and oxytocin covary within the same individuals had not been examined. Methods: We performed a secondary cross-sectional analysis of baseline, pretreatment measurements from clinically characterized men with hypersexual disorder and healthy male controls. miR-4456 was measured by RT-qPCR in EDTA blood-derived material and plasma oxytocin by radioimmunoassay. The submitted pooled robust regression included 74 paired measurements; revised group-adjusted and interaction models included 73 complete cases (51 hypersexual disorder and 22 controls). miR-4456, but not oxytocin, was rank-based inverse-normal transformed using Blom's method. Results: In the submitted pooled model, higher miR-4456 was associated with lower plasma oxytocin (β = −4.039 pmol/L, 95% CI −6.149 to −1.930; p < 0.001). After adjustment for diagnostic group, the estimate remained negative but was attenuated (β = −1.522, 95% CI −3.376 to 0.333; p = 0.106). The control-specific estimate was −0.613 (95% CI −3.693 to 2.467; p = 0.696), the hypersexual-disorder estimate was −2.223 (95% CI −4.514 to 0.069; p = 0.057), and the interaction was not significant ( p = 0.414). Post hoc sensitivity analyses were directionally consistent but imprecise. Conclusions: To our knowledge, this is the first human study to directly examine paired peripheral miR-4456 and plasma oxytocin measurements. Although diagnostic-group differences explained part of the pooled association, the paired observation connects previously separate epigenetic, expression, pathway-prediction, and neuroendocrine findings and identifies a focused hypothesis for independent replication. The cross-sectional peripheral measurements do not establish directionality, causation, or central nervous system regulation. Experimental studies are needed to determine whether miR-4456 has any functional influence on oxytocin-related biology.
SN - 1662-453X
SN - 1662-4548
ER -