biostudies-literaturePan LANCATS NIH HHSNCRR NIH HHSNIMH NIH HHS42-50https://www.ebi.ac.uk/biostudies/studies/S-EPMC10171090biostudies-literatureUnknown174(1)<h4>Objective</h4>Treatment-refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. At least 15% of cases of major depressive disorder remain refractory to treatment. The authors previously identified a young adult with treatment-refractory depression and multiple suicide attempts with an associated severe deficiency of CSF tetrahydrobiopterin, a critical cofactor for monoamine neurotransmitter synthesis. Treatment with sapropterin, a tetrahydrobiopterin analogue, led to dramatic and long-lasting remission of depression. This sentinel case led the authors to hypothesize that the incidence of metabolic abnormalities contributing to treatment-refractory depression is underrecognized.<h4>Method</h4>The authors conducted a case-control, targetThe American journal of psychiatryNeurometabolic Disorders: Potentially Treatable Abnormalities in Patients With Treatment-Refractory Depression and Suicidal Behavior.PMC10171090UL1 TR000005UL1 RR024153K23 MH082884Baca CAFinegold DNRengasamy MDobrowolski SKVockley JNaviaux RKPerel JDiler RBrent DAHughes MSegreti AMSteinfeld RPan LAWalano NZimmer TMartin PKassiff SMcKain BWPasquino MHyland KPeters DGfalseNeurometabolic Disorders: Potentially Treatable Abnormalities in Patients With Treatment-Refractory Depression and Suicidal Behavior.<h4>Objective</h4>Treatment-refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. At least 15% of cases of major depressive disorder remain refractory to treatment. The authors previously identified a young adult with treatment-refractory depression and multiple suicide attempts with an associated severe deficiency of CSF tetrahydrobiopterin, a critical cofactor for monoamine neurotransmitter synthesis. Treatment with sapropterin, a tetrahydrobiopterin analogue, led to dramatic and long-lasting remission of depression. This sentinel case led the authors to hypothesize that the incidence of metabolic abnormalities contributing to treatment-refractory depression is underrecognized.<h4>Method</h4>The authors conducted a case-control, target2017-01-01T00:00:00Z2017 Jan2025-04-21T22:44:00.083Z2025-04-05T18:54:49.92ZS-EPMC101710902752349910.1176/appi.ajp.2016.15111500