Open-Label Uridine for Treatment of Depressed Adolescents with Bipolar Disorder

Kondo, Douglas G.; Sung, Young Hoon; Hellem, Tracy L.; Delmastro, Kristen K.; Jeong, Eun Kee; Kim, Namkug; Shi, Xianfeng; Renshaw, Perry F.

doi:10.1089/cap.2010.0054

Cited by 20 publications

(20 citation statements)

References 34 publications

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“…Pyrimidine nucleosides, which include cytidine and uridine, constitute a class of molecules within the brain capable of impacting both energy metabolism and excitatory glutamatergic transmission, in addition to their role in the salvage pathway of pyrimidine nucleotide synthesis (Kondo et al, 2011). Cytidine and uridine have demonstrated antidepressant-like effects in studies conducted on rats completing the forced swim test (Carlezon et al, 2002(Carlezon et al, , 2005, as well as in patients with BD (Kondo et al, 2011;Yoon et al, 2009). It has been suggested that cytidine may exert neuroprotective effects by increasing cerebral high-energy phosphate levels and by reversing excess Glu neurotransmission (Hurtado et al, 2005;Radad, Gille, Xiaojing, Durany, & Rausch, 2007;Yoon et al, 2009).…”

Section: Pathway Analysismentioning

confidence: 99%

Biomarkers for major depressive and bipolar disorders using metabolomics: A systematic review

MacDonald¹,

Krishnan²,

Cervenka³

et al. 2018

American J of Med Genetics Pt B

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Major depressive disorder (MDD) and bipolar disorder (BD) lack robust biomarkers useful for screening purposes in a clinical setting. A systematic review of the literature was conducted on metabolomic studies of patients with MDD or BD through the use of analytical platforms such as in vivo brain imaging, mass spectrometry, and nuclear magnetic resonance. Our search identified a total of 7,590 articles, of which 266 articles remained for full-text revision. Overall, 249 metabolites were found to be dysregulated with 122 of these metabolites being reported in two or more of the studies included. A list of biomarkers for MDD and BD established from metabolites found to be abnormal, along with the number of studies supporting each metabolite and a comparison of which biological fluids they were reported in, is provided. Metabolic pathways that may be important in the pathophysiology of MDD and BD were identified and predominantly center on glutamatergic metabolism, energy metabolism, and neurotransmission.Using online drug registries, we also illustrate how metabolomics can facilitate the discovery of novel candidate drug targets. K E Y W O R D Sbiochemical, biomarker panel, mood disorders, omics

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Section: Pathway Analysismentioning

confidence: 99%

Biomarkers for major depressive and bipolar disorders using metabolomics: A systematic review

MacDonald¹,

Krishnan²,

Cervenka³

et al. 2018

American J of Med Genetics Pt B

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“…metabolically recycled). Uridine supplementation has long been established as safe as long-term therapy of UMP synthase deficiency (13), but more recently it has been trialled in the treatment of adolescents with bipolar disorders (14).…”

Section: Uridine Therapymentioning

confidence: 99%

Elevated plasma dihydroorotate in Miller syndrome: Biochemical, diagnostic and clinical implications, and treatment with uridine

Duley

Henman

Carpenter

et al. 2016

Molecular Genetics and Metabolism

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Background: Miller syndrome (post-axial acrofacial dystosis) arises from gene mutations for the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH).Nonetheless, despite demonstrated loss of enzyme activity dihydroorotate (DHO) has not been shown to accumulate, but paradoxically urine orotate has been reported to be raised, confusing the metabolic diagnosis. Methods:We analysed plasma and urine from a 4-year-old male Miller syndrome patient. DHODH mutations were determined by PCR and Sanger sequencing.Analysis of DHO and orotic acid (OA) in urine, plasma and blood-spot cards was performed using liquid chromatography-tandem mass spectrometry. In vitro stability of DHO in distilled water and control urine was assessed for up to 60 hours. The patient received a 3-month trial of oral uridine for behavioural problems. Results:The patient had early liver complications that are atypical of Miller syndrome. DHODH genotyping demonstrated compound-heterozygosity for frameshift and missense mutations. DHO was grossly raised in urine and plasma, and was detectable in dried spots of blood and plasma. OA was raised in urine but undetectable in plasma. DHO did not spontaneously degrade to OA. Uridine therapy did not appear to resolve behavioural problems during treatment, but it lowered plasma DHO. Conclusion:This case with grossly raised plasma DHO represents the first biochemical confirmation of functional DHODH deficiency. DHO was also easily detectable in dried plasma and blood spots. We concluded that DHO oxidation to OA must occur enzymatically during renal secretion. This case resolved the biochemical conundrum in previous reports of Miller syndrome patients, and opened the possibility of rapid biochemical screening.

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“…Uridine further provides a substrate in phosphatidylcholine (PC) synthesis [20][21][22]. It is understood that the mechanism of uridine in treating depression is via the cytidine 5 0 -diphosphocholine pathway which provides a critical substrate for phospholipid synthesis [23]. Primary research associated with uridine has demonstrated encouraging results as a possible antidepressant agent in analogue models with mice and also in improving symptoms of bipolar (depressive cycle) in children [21].…”

Section: Introductionmentioning

confidence: 99%

“…Primary research associated with uridine has demonstrated encouraging results as a possible antidepressant agent in analogue models with mice and also in improving symptoms of bipolar (depressive cycle) in children [21]. Uridine has also been shown to improve hippocampal metabolism and possibly raise dopamine levels [21,23]. While considered safe, uridine is both a complex and an expensive molecule for use in research.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

S-adenosylmethionine (SAMe) and Magnesium Orotate as adjunctives to SSRIs in sub-optimal treatment response of depression in adults: A pilot study

Bambling

Parham

Coulson³

et al. 2015

Advances in Integrative Medicine

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Open-Label Uridine for Treatment of Depressed Adolescents with Bipolar Disorder

Cited by 20 publications

References 34 publications

Biomarkers for major depressive and bipolar disorders using metabolomics: A systematic review

Biomarkers for major depressive and bipolar disorders using metabolomics: A systematic review

Elevated plasma dihydroorotate in Miller syndrome: Biochemical, diagnostic and clinical implications, and treatment with uridine

S-adenosylmethionine (SAMe) and Magnesium Orotate as adjunctives to SSRIs in sub-optimal treatment response of depression in adults: A pilot study

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