Metabolomic disorders: confirmed presence of potentially treatable abnormalities in patients with treatment refractory depression and suicidal behavior.
Cerebral folate deficiency
metabolomics
suicide
tetrahydrobiopterin
treatment refractory depression
Journal
Psychological medicine
ISSN: 1469-8978
Titre abrégé: Psychol Med
Pays: England
ID NLM: 1254142
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
medline:
26
9
2023
pubmed:
5
11
2022
entrez:
4
11
2022
Statut:
ppublish
Résumé
Refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. Approximately 15% of patients with major depressive disorder are refractory to currently available treatments. We hypothesized metabolic abnormalities contributing to treatment refractory depression are associated with distinct findings identifiable in the cerebrospinal fluid (CSF). Our hypothesis was confirmed by a previous small case-controlled study. Here we present a second, larger replication study. We conducted a case-controlled, targeted, metabolomic evaluation of 141 adolescent and adult patients with well-characterized history of depression refractory to three maximum-dose, adequate-duration medication treatments, and 36 healthy controls. Plasma, urine, and CSF metabolic profiling were performed by coupled gas chromatography/mass spectrometry, and high-performance liquid chromatography, electrospray ionization, tandem mass spectrometry. Abnormalities were identified in 67 of 141 treatment refractory depression participants. The CSF abnormalities included: low cerebral folate ( Examination of metabolic disorders in treatment refractory depression identified an unexpectedly large proportion of patients with potentially treatable abnormalities. The etiology of these abnormalities and their potential roles in pathogenesis remain to be determined.
Sections du résumé
BACKGROUND
Refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. Approximately 15% of patients with major depressive disorder are refractory to currently available treatments. We hypothesized metabolic abnormalities contributing to treatment refractory depression are associated with distinct findings identifiable in the cerebrospinal fluid (CSF). Our hypothesis was confirmed by a previous small case-controlled study. Here we present a second, larger replication study.
METHODS
We conducted a case-controlled, targeted, metabolomic evaluation of 141 adolescent and adult patients with well-characterized history of depression refractory to three maximum-dose, adequate-duration medication treatments, and 36 healthy controls. Plasma, urine, and CSF metabolic profiling were performed by coupled gas chromatography/mass spectrometry, and high-performance liquid chromatography, electrospray ionization, tandem mass spectrometry.
RESULTS
Abnormalities were identified in 67 of 141 treatment refractory depression participants. The CSF abnormalities included: low cerebral folate (
CONCLUSIONS
Examination of metabolic disorders in treatment refractory depression identified an unexpectedly large proportion of patients with potentially treatable abnormalities. The etiology of these abnormalities and their potential roles in pathogenesis remain to be determined.
Identifiants
pubmed: 36330595
doi: 10.1017/S0033291722003233
pii: S0033291722003233
pmc: PMC10520591
doi:
Substances chimiques
Folic Acid
935E97BOY8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6046-6054Références
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