Possible involvement of corticosterone and serotonin in antidepressant and antianxiety effects of chromium picolinate in chronic unpredictable mild stress induced depression and anxiety in rats

Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-d-aspartate receptor agonist, are increased. The enzyme amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Åsberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single-nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.

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“… 48 Rodent studies have indicated that PIC may protect against depressive- and anxiety-like behaviors. 49 , 50 , 51 …”

Section: Discussionmentioning

confidence: 99%

An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation

et al. 2016

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“…Several clinical studies have also discovered promising antidepressant effects of chromium picolinate complex in atypical depression (Davidson et al, 2003; Docherty et al, 2005) and potentiation of pharmacotherapy for dysthymic disorder (McLeod et al, 1999). Administration of chromium picolinate in an animal model of chronic unpredictable mild stress increases the concentration of cortical and cerebellar serotonin levels and decreases plasma corticosterone levels, which could be involved in some observed improvements in depression and anxiety symptoms (Dubey et al, 2015). The observed beneficial effects of chromium picolinate are commonly attributed to the presence of chromium in the complex, while PIC is generally considered to be the non-active ingredient used to solubilize bioactive chromium.…”

Section: Kynurenine Pathway Metabolites In Psychiatric Disorders Amentioning

confidence: 99%

Kynurenine pathway metabolites and suicidality

2017

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Suicide is a major global problem, claiming more than 800,000 lives annually. The neurobiological changes that underlie suicidal ideation and behavior are not fully understood. Suicidal patients have been shown to display elevated levels of inflammation both in the central nervous system and the peripheral blood. A growing body of evidence suggests that inflammation is associated with a dysregulation of the kynurenine pathway in suicidal patients, resulting in an imbalance of neuroactive metabolites. Specifically, an increase in the levels of the NMDA receptor agonist quinolinic acid and a simultaneous decrease in neuroprotective metabolites have been observed in suicidal patients, and may contribute to the development of suicidality via changes in glutamate neurotransmission and neuroinflammation. The cause of the dysregulation of kynurenine metabolites in suicidality is not known, but is likely due to differential activity of the involved enzymes in patients. As knowledge in these areas is rapidly growing, targeting the kynurenine pathway enzymes may provide novel therapeutic approaches for managing suicidal behavior.

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“…Oceniając wpływ suplementacji chromem na lęk i pamięć u szczurów oraz myszy, wykonano testy behawioralne -test labiryntu krzyżowego (elevated plus maze) i test spontanicznej zmienności zachowania (spontaneous alternation behavior). Wykazano, że Cr działa przeciwdepresyjnie i przeciwlękowo, a za jego działanie odpowiedzialne jest prawdopodobnie nasilenie neuroprzekaźnictwa serotoninergicznego [49][50][51].…”

Section: Chrom W Zaburzeniach Psychicznychunclassified

Biological significance of chromium III for the human organism

Piotrowska¹,

Pilch²,

Tota³

et al. 2017

Med Pr

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Currently, chromium is probably the most controversial transition metal. In recent publications it is clearly stated that it is not an essential micronutrient and should be considered to have a pharmacological effect. Conflicting scientific reports along with a huge amount of dietary supplements, as well as dietary and sports nutrients available on the market have prompted the authors to investigate the available information on the range of possible application, efficacy and safety of products containing salts or chelates of chromium III. The authors reviewed articles in electronic databases for the years 1959-2016, and selected works describing the biochemical, physiological and toxic properties of chromium salts and chelates and the range of possible applications in medicine, dietetics and sport. A critical analysis of reports dealing with the effect of chromium on the carbohydrate and lipid metabolism, body composition, lean body mass and sports performance was carried out. The authors indicated papers analyzing the mechanism of action of chromium in the cognitive and affective disorders. Much attention has been paid to the safety use of chromium III supplements. There are still some unsolved issues. In the field of toxicology, a limited number of reports about environmental exposure to trivalent chromium in the workplace draws our attention. In the field of biochemical research, there is still a need to clarify the mechanism of psychiatric and endocrinological activity, especially in conjunction with the immune system. Med Pr 2018;69(2):211-223.

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Possible involvement of corticosterone and serotonin in antidepressant and antianxiety effects of chromium picolinate in chronic unpredictable mild stress induced depression and anxiety in rats

Cited by 46 publications

References 22 publications

An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation

An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation

Kynurenine pathway metabolites and suicidality

Biological significance of chromium III for the human organism

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