Molecular Modeling and In Vitro Functional Analysis of the RGS12 PDZ Domain Variant Associated with High-Penetrance Familial Bipolar Disorder DOI Open Access
Percy Selasi Agogo-Mawuli, Josefina Méndez,

Emily A. Oestreich

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11431 - 11431

Published: Oct. 24, 2024

Bipolar disorder's etiology involves genetics, environmental factors, and gene-environment interactions, underlying its heterogeneous nature treatment complexity. In 2020, Forstner colleagues catalogued 378 sequence variants co-segregating with familial bipolar disorder. A notable candidate was an R59Q missense mutation in the PDZ (PSD-95/Dlg1/ZO-1) domain of RGS12. We previously demonstrated that RGS12 loss removes negative regulation on kappa opioid receptor, disrupting basal ganglia dopamine homeostasis dampening responses to dopamine-eliciting psychostimulants. Here, we investigated variation context potential functional alterations. first validated a new target for wildtype domain-the SAPAP3 C-terminus-by molecular docking, surface plasmon resonance (SPR), co-immunoprecipitation. While initial dynamics (MD) studies predicted negligible effects ligand binding, SPR showed significant reduction binding affinity three peptide targets tested. AlphaFold2-generated models modest protein-peptide which is consistent reduced observed by SPR, suggesting substituted glutamine side chain may weaken vivo targets, likely through allosteric changes. This difference adversely affect CNS signaling related dynorphin individuals this variation, potentially impacting disorder pathophysiology.

Language: Английский

The neuropathology of Self-Injurious Behavior: Studies using animal models DOI
Darragh P. Devine

Brain Research, Journal Year: 2024, Volume and Issue: 1844, P. 149172 - 149172

Published: Aug. 18, 2024

Language: Английский

Citations

3
Neurocognitive correlates of polygenic risk for bipolar disorder among youth with and without bipolar disorder DOI
Xinyue Jiang, Clement C. Zai, Megan Mio

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 369, P. 845 - 853

Published: Oct. 18, 2024

Language: Английский

Citations

1
Polygenic risk scores for mood disorders and actigraphy estimates of sleep and circadian rhythms: A preliminary study in bipolar disorders DOI Creative Commons

Vincent Hennion,

Jan Scott,

V. Martinot

et al.

Journal of Sleep Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Summary In bipolar disorders, abnormalities of sleep patterns and circadian rhythms activity are observed during mood episodes, but also persist euthymia. Shared vulnerabilities between disorders have been suggested. This exploratory study investigated the association polygenic risk scores for disorder major depressive disorder, actigraphy estimates patterns, in a sample 62 euthymic individuals with disorder. The score – were calculated three stringent thresholds significance. Data reduction was applied to aggregate measures into dimensions using principal component analysis. A higher associated more fragmented sleep, while later peak activity. These results remained significant after adjustment age, sex, subtype, body mass index, current symptoms, tobacco use, medications prescribed at inclusion, not correction multiple testing. conclusion, genetic depression might be different should replicated larger independent samples.

Language: Английский

Citations

0
Thyroid Dysfunction and Bipolar Disorder: A Literature Review Integrating Neurochemical, Endocrine, and Genetic Perspectives DOI Open Access

Sarah J Norman,

Ayzia C Carney,

Fernanda Algarin

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 11, 2024

Thyroid disorders are common in medicine, while bipolar (BDs), though less frequent, significant due to global prevalence, the economic burden on healthcare systems and long-term health implications, effects of psychiatric illness quality life. Clinical research has suggested thyroid hormone imbalances can cause symptoms similar clinical features observed BDs. Despite increased attention this area study, much remains unknown regarding how issues contribute development This review explores complex link between BDs, focusing neurochemical dynamics, changes hypothalamic-pituitary-thyroid (HPT) axis, genetic factors. Furthermore, literature examines importance understanding these factors linking both conditions emphasizes necessity for therapies targeting their shared underlying mechanisms.

Language: Английский

Citations

0
Molecular Modeling and In Vitro Functional Analysis of the RGS12 PDZ Domain Variant Associated with High-Penetrance Familial Bipolar Disorder DOI Open Access
Percy Selasi Agogo-Mawuli, Josefina Méndez,

Emily A. Oestreich

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11431 - 11431

Published: Oct. 24, 2024

Bipolar disorder's etiology involves genetics, environmental factors, and gene-environment interactions, underlying its heterogeneous nature treatment complexity. In 2020, Forstner colleagues catalogued 378 sequence variants co-segregating with familial bipolar disorder. A notable candidate was an R59Q missense mutation in the PDZ (PSD-95/Dlg1/ZO-1) domain of RGS12. We previously demonstrated that RGS12 loss removes negative regulation on kappa opioid receptor, disrupting basal ganglia dopamine homeostasis dampening responses to dopamine-eliciting psychostimulants. Here, we investigated variation context potential functional alterations. first validated a new target for wildtype domain-the SAPAP3 C-terminus-by molecular docking, surface plasmon resonance (SPR), co-immunoprecipitation. While initial dynamics (MD) studies predicted negligible effects ligand binding, SPR showed significant reduction binding affinity three peptide targets tested. AlphaFold2-generated models modest protein-peptide which is consistent reduced observed by SPR, suggesting substituted glutamine side chain may weaken vivo targets, likely through allosteric changes. This difference adversely affect CNS signaling related dynorphin individuals this variation, potentially impacting disorder pathophysiology.

Language: Английский

Citations

0