Altered levels of interleukins and neurotrophic growth factors in mood disorders and suicidality: an analysis from periphery to central nervous system

Gadad, Bharathi S.; Vargas-Medrano, Javier; Ramos, Enrique; Najera, Katherine; Fagan, Matthew J.; Forero, Angelica; Thompson, Peter M.

doi:10.1038/s41398-021-01452-1

Cited by 24 publications

(19 citation statements)

References 39 publications

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“…Arguments about the roles of tryptophan catabolites and cytokines in the CNS often center around the relationship between their systemic and central concentrations. Several studies of blood and CSF cytokine concentrations have shown parallel qualitative and quantitative changes, including those on TGF-β ( Liu et al, 2022 ) with one report of IL-6 levels in blood correlating highly with mood ( Gadad et al, 2021 ). The CSF: serum ratio of IL-6 levels was sufficiently consistent to act as a potential biomarker of intracranial aneurysms ( Kaminska et al, 2021 ), while increased levels of IL-6 in rat brain parenchyma occurred in parallel with plasma and CSF values and with the severity of traumatic brain injury ( Chatzipanteli et al, 2012 ).…”

Section: Limitations and Uncertainties: Concentrations And Correlationsmentioning

confidence: 97%

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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Two of the molecular families closely associated with mediating communication between the brain and immune system are cytokines and the kynurenine metabolites of tryptophan. Both groups regulate neuron and glial activity in the central nervous system (CNS) and leukocyte function in the immune system, although neither group alone completely explains neuroimmune function, disease occurrence or severity. This essay suggests that the two families perform complementary functions generating an integrated network. The kynurenine pathway determines overall neuronal excitability and plasticity by modulating glutamate receptors and GPR35 activity across the CNS, and regulates general features of immune cell status, surveillance and tolerance which often involves the Aryl Hydrocarbon Receptor (AHR). Equally, cytokines and chemokines define and regulate specific populations of neurons, glia or immune system leukocytes, generating more specific responses within restricted CNS regions or leukocyte populations. In addition, as there is a much larger variety of these compounds, their homing properties enable the superimposition of dynamic variations of cell activity upon local, spatially limited, cell populations. This would in principle allow the targeting of potential treatments to restricted regions of the CNS. The proposed synergistic interface of ‘tonic’ kynurenine pathway affecting baseline activity and the superimposed ‘phasic’ cytokine system would constitute an integrated network explaining some features of neuroimmune communication. The concept would broaden the scope for the development of new treatments for disorders involving both the CNS and immune systems, with safer and more effective agents targeted to specific CNS regions.

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Section: Limitations and Uncertainties: Concentrations And Correlationsmentioning

confidence: 97%

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

et al. 2022

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“…Another one found a weak hippocampus-serum correlation for pro-BDNF but not for BDNF or the other two brain areas [ 48 ]. The third one also did not find a correlation for BDNF, but found a trend for GDNF [ 6 ].…”

Section: Resultsmentioning

confidence: 99%

“…Large compounds, such as brain-specific proteins, do not usually cross the BBB; for some of them, the permeability is still unknown. For example, in humans, it is not consensual yet whether brain-derived neurotrophic factor (BDNF) easily permeates the BBB (see references in [ 6 ]), and, therefore, whether blood BDNF may reflect central BDNF.…”

Section: Introductionmentioning

confidence: 99%

Neurospecific Molecules Measured in Periphery in Humans: How Do They Correlate with the Brain Levels? A Systematic Review

Tikhonova¹,

Zhanaeva²,

Shvaikovskaya³

et al. 2022

IJMS

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Human brain state is usually estimated by brain-specific substances in peripheral tissues, but, for most analytes, a concordance between their content in the brain and periphery is unclear. In this systematic review, we summarized the investigated correlations in humans. PubMed was searched up to June 2022. We included studies measuring the same endogenous neurospecific analytes in the central nervous system and periphery in the same subjects. Not eligible were studies of cerebrospinal fluid, with significant blood–brain barrier disruption, of molecules with well-established blood-periphery concordance or measured in brain tumors. Seventeen studies were eligible. Four studies did not report on correlation and four revealed no significant correlation. Four molecules were examined twice. For BDNF, there was no correlation in both studies. For phenylalanine, glutamine, and glutamate, results were contradictory. Strong correlations were found for free tryptophan (r = 0.97) and translocator protein (r = 0.90). Thus, only for three molecules was there some certainty. BDNF in plasma or serum does not reflect brain content, whereas free tryptophan (in plasma) and translocator protein (in blood cells) can serve as peripheral biomarkers. We expect a breakthrough in the field with advanced in vivo metabolomic analyses, neuroimaging techniques, and blood assays for exosomes of brain origin.

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“…BDNF is able to cross the blood-brain barrier and its plasma levels reflect the central nervous system levels ( 52 ). In addition, studies suggest that the mature form of BDNF and its precursor pro-BDNF could have opposite functions on neural plasticity: while mature BDNF promotes neuronal survival and growth, pro-BDNF induces neuron apoptosis ( 53 ).…”

Section: Discussionmentioning

confidence: 99%

Investigating Predictive Factors of Suicidal Re-attempts in Adolescents and Young Adults After a First Suicide Attempt, a Prospective Cohort Study. Study Protocol of the SURAYA Project

et al. 2022

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IntroductionSuicide is the fourth leading cause of death in youth. Previous suicide attempts are among the strongest predictors of future suicide re-attempt. However, the lack of data and understanding of suicidal re-attempt behaviors in this population makes suicide risk assessment complex and challenging in clinical practice. The primary objective of this study is to determine the rate of suicide re-attempts in youth admitted to the emergency department after a first suicide attempt. The secondary objectives are to explore the clinical, socio-demographic, and biological risk factors that may be associated with re-attempted suicide in adolescents and young adults.MethodsWe have developed a single-center prospective and naturalistic study that will follow a cohort of 200 young people aged 16 to 25 years admitted for a first suicide attempt to the emergency department of Lyon, France. The primary outcome measure will be the incidence rate of new suicide attempts during 3 months of follow-up. Secondary outcomes to investigate predictors of suicide attempts will include several socio-demographic, clinical and biological assessments: blood and hair cortisol levels, plasma pro- and mature Brain-Derived Neurotrophic Factor (BDNF) isoforms proportion, previous infection with toxoplasma gondii, and C-Reactive Protein (CRP), orosomucoid, fibrinogen, interleukin (IL)-6 inflammatory markers.DiscussionTo our knowledge, the present study is the first prospective study specifically designed to assess the risk of re-attempting suicide and to investigate the multidimensional predictive factors associated with re-attempting suicide in youth after a first suicide attempt. The results of this study will provide a unique opportunity to better understand whether youth are an at-risk group for suicide re-attempts, and will help us identify predictive factors of suicide re-attempt risk that could be translated into clinical settings to improve psychiatric care in this population.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03538197, first registered on 05/29/2018. The first patient was enrolled 05/22/2018.

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Altered levels of interleukins and neurotrophic growth factors in mood disorders and suicidality: an analysis from periphery to central nervous system

Cited by 24 publications

References 39 publications

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

An integrated cytokine and kynurenine network as the basis of neuroimmune communication

Neurospecific Molecules Measured in Periphery in Humans: How Do They Correlate with the Brain Levels? A Systematic Review

Investigating Predictive Factors of Suicidal Re-attempts in Adolescents and Young Adults After a First Suicide Attempt, a Prospective Cohort Study. Study Protocol of the SURAYA Project

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