Stephen Murata , Monica Feliz R. Castillo , Michael Murphy , Markus Schwarz , Natalie Moll , Brendan Martin , Elif Weidinger , Bianka Leitner , Norbert Mueller , Angelos Halaris
{"title":"治疗难治性双相抑郁症中炎症调节对色氨酸和犬尿氨酸通路调节的影响","authors":"Stephen Murata , Monica Feliz R. Castillo , Michael Murphy , Markus Schwarz , Natalie Moll , Brendan Martin , Elif Weidinger , Bianka Leitner , Norbert Mueller , Angelos Halaris","doi":"10.1016/j.npbr.2019.07.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Adjunctive immune-modulation can be safe and effective for treatment-resistant bipolar depression (TRBDD), but molecular work is needed to further characterize the safety and efficacy involved in treatment response and the reversal of treatment resistance. Here we profiled the kynurenine pathway (KP) for biomarkers associated with TRBDD and treatment response to celecoxib (CBX)-augmentation.</p></div><div><h3>Methods</h3><p>47 TRBDD patients with moderately severe HAMD-17 scores were randomized to receive either escitalopram (ESC) (10 mg twice daily) + CBX (200 mg twice daily), or ESC (10 mg twice daily) + placebo (PBO) (twice daily). Plasma kynurenine pathway (KP) metabolite levels were measured at baseline, week 4, and week 8, and in a healthy control (HC) group of subjects (N = 35) once.</p></div><div><h3>Results</h3><p>Patients receiving ESC + CBX had 4.278 greater odds of responding (<em>p</em> = 0.021) with NNT=3, and 15.300 greater odds of remitting (<em>p</em> < 0.001) with NNT=2, compared with ESC + PBO patients. Study patients exhibited elevated baseline tryptophan (<em>p</em> < 0.001), low kynurenine/tryptophan (<em>p</em> < 0.001), elevated 3-hydryoxykynurenine/kynurenine (adj-<em>p*</em><0.001), low kynurenic acid/3-hydroxykynurenine, and low picolinic acid/quinolinic acid (<em>p</em> < 0.001) compared to healthy controls. Treatment responders exhibited tryptophan depletion (<em>p</em> = 0.020) without a concomitant change in kynurenine/tryptophan ratio by week 8 (<em>p</em> = 0.163).</p></div><div><h3>Conclusion</h3><p>Clinical response to CBX augmentation is not associated with altered neurotoxic or neuroprotective indices within the time frame of this study. TRBDD revealed alterations in neuroprotective and neurotoxic indices, in the context of low kynurenine/tryptophan and high tryptophan. Treatment responders revealed a depletion in tryptophan by week 8, without concomitant kynurenine pathway (KP) activation.</p></div>","PeriodicalId":49756,"journal":{"name":"Neurology Psychiatry and Brain Research","volume":"33 ","pages":"Pages 65-72"},"PeriodicalIF":0.0000,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.npbr.2019.07.001","citationCount":"6","resultStr":"{\"title\":\"Effects of inflammation modulation on tryptophan and kynurenine pathway regulation in treatment resistant bipolar depression\",\"authors\":\"Stephen Murata , Monica Feliz R. Castillo , Michael Murphy , Markus Schwarz , Natalie Moll , Brendan Martin , Elif Weidinger , Bianka Leitner , Norbert Mueller , Angelos Halaris\",\"doi\":\"10.1016/j.npbr.2019.07.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Adjunctive immune-modulation can be safe and effective for treatment-resistant bipolar depression (TRBDD), but molecular work is needed to further characterize the safety and efficacy involved in treatment response and the reversal of treatment resistance. Here we profiled the kynurenine pathway (KP) for biomarkers associated with TRBDD and treatment response to celecoxib (CBX)-augmentation.</p></div><div><h3>Methods</h3><p>47 TRBDD patients with moderately severe HAMD-17 scores were randomized to receive either escitalopram (ESC) (10 mg twice daily) + CBX (200 mg twice daily), or ESC (10 mg twice daily) + placebo (PBO) (twice daily). Plasma kynurenine pathway (KP) metabolite levels were measured at baseline, week 4, and week 8, and in a healthy control (HC) group of subjects (N = 35) once.</p></div><div><h3>Results</h3><p>Patients receiving ESC + CBX had 4.278 greater odds of responding (<em>p</em> = 0.021) with NNT=3, and 15.300 greater odds of remitting (<em>p</em> < 0.001) with NNT=2, compared with ESC + PBO patients. Study patients exhibited elevated baseline tryptophan (<em>p</em> < 0.001), low kynurenine/tryptophan (<em>p</em> < 0.001), elevated 3-hydryoxykynurenine/kynurenine (adj-<em>p*</em><0.001), low kynurenic acid/3-hydroxykynurenine, and low picolinic acid/quinolinic acid (<em>p</em> < 0.001) compared to healthy controls. Treatment responders exhibited tryptophan depletion (<em>p</em> = 0.020) without a concomitant change in kynurenine/tryptophan ratio by week 8 (<em>p</em> = 0.163).</p></div><div><h3>Conclusion</h3><p>Clinical response to CBX augmentation is not associated with altered neurotoxic or neuroprotective indices within the time frame of this study. TRBDD revealed alterations in neuroprotective and neurotoxic indices, in the context of low kynurenine/tryptophan and high tryptophan. 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Effects of inflammation modulation on tryptophan and kynurenine pathway regulation in treatment resistant bipolar depression
Background
Adjunctive immune-modulation can be safe and effective for treatment-resistant bipolar depression (TRBDD), but molecular work is needed to further characterize the safety and efficacy involved in treatment response and the reversal of treatment resistance. Here we profiled the kynurenine pathway (KP) for biomarkers associated with TRBDD and treatment response to celecoxib (CBX)-augmentation.
Methods
47 TRBDD patients with moderately severe HAMD-17 scores were randomized to receive either escitalopram (ESC) (10 mg twice daily) + CBX (200 mg twice daily), or ESC (10 mg twice daily) + placebo (PBO) (twice daily). Plasma kynurenine pathway (KP) metabolite levels were measured at baseline, week 4, and week 8, and in a healthy control (HC) group of subjects (N = 35) once.
Results
Patients receiving ESC + CBX had 4.278 greater odds of responding (p = 0.021) with NNT=3, and 15.300 greater odds of remitting (p < 0.001) with NNT=2, compared with ESC + PBO patients. Study patients exhibited elevated baseline tryptophan (p < 0.001), low kynurenine/tryptophan (p < 0.001), elevated 3-hydryoxykynurenine/kynurenine (adj-p*<0.001), low kynurenic acid/3-hydroxykynurenine, and low picolinic acid/quinolinic acid (p < 0.001) compared to healthy controls. Treatment responders exhibited tryptophan depletion (p = 0.020) without a concomitant change in kynurenine/tryptophan ratio by week 8 (p = 0.163).
Conclusion
Clinical response to CBX augmentation is not associated with altered neurotoxic or neuroprotective indices within the time frame of this study. TRBDD revealed alterations in neuroprotective and neurotoxic indices, in the context of low kynurenine/tryptophan and high tryptophan. Treatment responders revealed a depletion in tryptophan by week 8, without concomitant kynurenine pathway (KP) activation.
期刊介绍：
Neurology, Psychiatry & Brain Research publishes original papers and reviews in
biological psychiatry,
brain research,
neurology,
neuropsychiatry,
neuropsychoimmunology,
psychopathology,
psychotherapy.
The journal has a focus on international and interdisciplinary basic research with clinical relevance. Translational research is particularly appreciated. Authors are allowed to submit their manuscript in their native language as supplemental data to the English version.
Neurology, Psychiatry & Brain Research is related to the oldest German speaking journal in this field, the Centralblatt fur Nervenheilkunde, Psychiatrie und gerichtliche Psychopathologie, founded in 1878. The tradition and idea of previous famous editors (Alois Alzheimer and Kurt Schneider among others) was continued in modernized form with Neurology, Psychiatry & Brain Research. Centralblatt was a journal of broad scope and relevance, now Neurology, Psychiatry & Brain Research represents a journal with translational and interdisciplinary perspective, focusing on clinically oriented research in psychiatry, neurology and neighboring fields of neurosciences and psychology/psychotherapy with a preference for biologically oriented research including basic research. Preference is given for papers from newly emerging fields, like clinical psychoimmunology/neuroimmunology, and ideas.
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