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BH4 Deficiency and Treatment-Refractory Depression: Unraveling the Molecular Landscape and Exploring Therapeutic Strategies for Neurotransmitter Dysfunction

Scott, Jonathan (2024) BH4 Deficiency and Treatment-Refractory Depression: Unraveling the Molecular Landscape and Exploring Therapeutic Strategies for Neurotransmitter Dysfunction. Master Essay, University of Pittsburgh.

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Tetrahydrobiopterin (BH4) deficiency is a rare, yet significant metabolic disorder associated with various monoamine synthesis and psychiatric disorders. Recent advancements in BH4 deficiency research focusing on its potential correlation with treatment-refractory depression (TRD) alongside the comprehensive cerebrospinal fluid (CSF) analysis. This research has shown a potential for novel avenues of therapeutic interventions.
Analysis of CSF has emerged as a pivotal tool in deciding treatment plans for the individuals with TRD. These studies have found deficiencies in neurotransmitter metabolites within the CSF of some individuals with TRD. This could suggest that there is a disruption in the synthesis pathway of BH4. To treat the deficiency of BH4 a supplementation therapy of medication called sapropterin is used. To monitor the participants of the study they collected a baseline score for both suicidality and depression. The participants were then given treatment of sapropterin and scored again to find insight into the psychiatric burdens associated with the BH4 deficiency. The identification of the BH4 deficiency in participants with TRD has sparked major interests in exploring BH4 supplementation as a potential therapeutic option.
The complexities of BH4 metabolism and TRD necessitate further investigation to identify precise mechanisms of action in the potential correlation. The cohort studies identified many participants who showed a decrease in suicidality and depression through supplementation of BH4 and addressing any other symptoms from supplementation. Early identification of BH4 deficiency in individuals with TRD could create opportunities for personalized treatment approaches leading to better clinical outcomes and enhancing the quality of life of people with TRD.
The importance of expanding awareness within the medical community regarding BH4 deficiency and its psychiatric implications is not to be underestimated. BH4 deficiency research has unveiled a potential link with treatment-refractory depression, offering novel insights into the pathophysiology of mental illness. Future studies implementing animal models hold promise for elucidating the underlying mechanisms of BH4 deficiency and leading to targeted therapeutic interventions for individuals with BH4 deficiencies.


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Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Scott, Jonathanjds217@pitt.edujds2170009-0008-1565-525X
ContributionContributors NameEmailPitt UsernameORCID
Committee ChairPan, Lisalisapanmd@gmail.comUNSPECIFIEDUNSPECIFIED
Committee MemberFinegold, Daviddnf@pitt.edudnfUNSPECIFIED
Committee MemberHernandez, Wenndyweh119@pitt.eduweh119UNSPECIFIED
Committee MemberBuchanich, Jeaninejeanine@pitt.edujeanineUNSPECIFIED
Date: 21 May 2024
Date Type: Completion
Submission Date: 30 April 2024
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 49
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Human Genetics
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Uncontrolled Keywords: Tetrahydrobiopterin, BH4, Treatment-refractory Depression, Metabolism, Psychiatry
Date Deposited: 21 May 2024 14:29
Last Modified: 21 May 2024 14:29


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