biostudies-literatureGumusoglu SBAmerican Heart AssociationNICHD NIH HHSNHLBI NIH HHSCarver College of Medicine and Iowa Neuroscience Institute Carver Trust Early-Stage Investigator awardUniversity of Iowa Summer Undergraduate Research FellowshipU.S. Department of Health & Human Services | National Institutes of HealthIowa Medical Student Research Program Summer Fellowship864-875https://www.ebi.ac.uk/biostudies/studies/S-EPMC10948883biostudies-literatureUnknown49(5)Psychiatric and obstetric diseases are growing threats to public health and share high rates of co-morbidity. G protein-coupled receptor signaling (e.g., vasopressin, serotonin) may be a convergent psycho-obstetric risk mechanism. Regulator of G Protein Signaling 2 (RGS2) mutations increase risk for both the gestational disease preeclampsia and for depression. We previously found preeclampsia-like, anti-angiogenic obstetric phenotypes with reduced placental Rgs2 expression in mice. Here, we extend this to test whether conserved cerebrovascular and serotonergic mechanisms are also associated with risk for neurobiological phenotypes in the Rgs2 KO mouse. Rgs2 KO exhibited anxiety-, depression-, and hedonic-like behaviors. Cortical vascular density and vessel length decreased in Rgs2 KO; cortNeuropsychopharmacology : official publication of the American College of NeuropsychopharmacologyAnti-angiogenic mechanisms and serotonergic dysfunction in the Rgs2 knockout model for the study of psycho-obstetric risk.PMC10948883R01 HD089940HD08994018SCG34350001P50HD10355601A119IPLOI34760288T32 HL00734422POST30908921HD0008495T32HL007121-453UL1TR002537RR024980Weaver KRCoulter KJKamal MSullivan HRGantz SCSchickling BMBlaine BMGumusoglu SBKiel MDZhang YSantillan DALauffer MCDevor EJGugel ASantillan MKfalseAnti-angiogenic mechanisms and serotonergic dysfunction in the Rgs2 knockout model for the study of psycho-obstetric risk.Psychiatric and obstetric diseases are growing threats to public health and share high rates of co-morbidity. G protein-coupled receptor signaling (e.g., vasopressin, serotonin) may be a convergent psycho-obstetric risk mechanism. Regulator of G Protein Signaling 2 (RGS2) mutations increase risk for both the gestational disease preeclampsia and for depression. We previously found preeclampsia-like, anti-angiogenic obstetric phenotypes with reduced placental Rgs2 expression in mice. Here, we extend this to test whether conserved cerebrovascular and serotonergic mechanisms are also associated with risk for neurobiological phenotypes in the Rgs2 KO mouse. Rgs2 KO exhibited anxiety-, depression-, and hedonic-like behaviors. Cortical vascular density and vessel length decreased in Rgs2 KO; cort2024-01-01T00:00:00Z2024 Apr2026-06-01T10:13:13.871Z2025-06-28T03:05:59.186ZS-EPMC109488833784873310.1038/s41386-023-01749-3