e9096bec48624258f19e28c377edc63a pmc_33352710.pdf dd6352d2ce556475ff0825f9c380eac53609b749 pmc_33352710.pdf ca2df951df9e70fd65f45cb482500a4179780aee809f8caec90f76e6824a7982 pmc_33352710.pdf Title: The Tryptophan System in Cocaine-Induced Depression Subject: Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.039) and the Kyn/5-HT ratio (11 + 15 vs. 112 + 136; p = 0.012), whereas there were no differences between CUD-primary-MDD and MDD. Effect size coefficients show a gradient for all targeted markers (d range 0.72–1.67). Results suggest different pathogenesis for CUD-induced-MDD, with lower participation of the tryptophan system, probably more related to other neurotransmitter pathways and accordingly suggesting the need for a different pharmacological treatment approach. Keywords: primary/substance-induced depression; cocaine use disorder; tryptophan; serotonin; kynurenine Author: Francina Fonseca, Joan-Ignasi Mestre-Pintó, Àlex Gómez-Gómez, Diana Martinez-Sanvisens, Rocío Rodríguez-Minguela, Esther Papaseit, Clara Pérez-Mañá, Klaus Langohr, Olga Valverde, Óscar J. Pozo, Magí Farré, Marta Torrens and on behalf of NEURODEP GROUP Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Dec 22 07:55:35 2020 CET ModDate: Tue Dec 22 08:03:56 2020 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1424062 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CUAJJQ+Pxbsy Type 1 Builtin yes yes no 10 0 UEAHMI+VnURWPalladioL-Bold Type 1 Custom yes yes no 14 0 VGPJFX+Pxsy Type 1 Builtin yes yes no 19 0 YTCSAA+VnURWPalladioL Type 1 Custom yes yes no 23 0 TXOHBH+URWPalladioL-Ital Type 1 Custom yes yes no 27 0 CXLYPC+URWPalladioL-Bold Type 1 Custom yes yes no 32 0 PLKYIS+URWPalladioL-Roma Type 1 Custom yes yes no 36 0 OFLXAT+Rpxr Type 1 Builtin yes yes no 40 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 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Experimental Section Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Subjects Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Clinical Assessments Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Psychiatric Assessment Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Acute Tryptophan Depletion Test (ATD) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Selection of the Serotonin Kynurenine Pathway Biomarkers Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Children: Item: Title: Demographic and Clinical Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Acute Tryptophan Depletion Test (ATD) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Kynurenine Pathway Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: Controls vs. MDD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Cocaine Use Disorder Groups Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Overall Perspective Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Info: Title: The Tryptophan System in Cocaine-Induced Depression Author: Francina Fonseca, Joan-Ignasi Mestre-Pintó, Àlex Gómez-Gómez, Diana Martinez-Sanvisens, Rocío Rodríguez-Minguela, Esther Papaseit, Clara Pérez-Mañá, Klaus Langohr, Olga Valverde, Óscar J. Pozo, Magí Farré, Marta Torrens and on behalf of NEURODEP GROUP Subject: Major depression disorder (MDD) is the most prevalent psychiatric comorbid condition in cocaine use disorder (CUD). The comorbid MDD might be primary-MDD (CUD-primary-MDD) or cocaine-induced MDD (CUD-induced-MDD), and their accurate diagnoses and treatment is a challenge for improving prognoses. This study aimed to assess the tryptophan/serotonin (Trp/5-HT) system with the acute tryptophan depletion test (ATD), and the kynurenine pathway in subjects with CUD-primary-MDD, CUD-induced-MDD, MDD and healthy controls. The ATD was performed with a randomized, double-blind, crossover, and placebo-controlled design. Markers of enzymatic activity of indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase, kynurenine aminotransferase (KAT) and kynureninase were also established. Following ATD, we observed a decrease in Trp levels in all groups. Comparison between CUD-induced-MDD and MDD revealed significant differences in 5-HT plasma concentrations (512 + 332 ng/mL vs. 107 + 127 ng/mL, p = 0.039) and the Kyn/5-HT ratio (11 + 15 vs. 112 + 136; p = 0.012), whereas there were no differences between CUD-primary-MDD and MDD. Effect size coefficients show a gradient for all targeted markers (d range 0.72 1.67). Results suggest different pathogenesis for CUD-induced-MDD, with lower participation of the tryptophan system, probably more related to other neurotransmitter pathways and accordingly suggesting the need for a different pharmacological treatment approach. 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