Biochemical Analyses of Cerebrospinal Fluid for the Diagnosis of Neurometabolic Conditions. What Can We Expect?

Batllori, Marta; Molero-Luís, Marta; Casado, Mercedes; Sierra, Cristina; Artuch, Rafael; Ormazábal, Aída

doi:10.1016/j.spen.2016.11.002

Cited by 10 publications

(7 citation statements)

References 55 publications

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“…Furthermore, given the characteristics of these compounds and their rostro-caudal distribution, the collection and transport of the CSF samples need to be performed following a careful and precise protocol. 2,6 Biogenic amine testing has been available in Greece since 2014, and the laboratory performing this test has followed the protocol of the laboratory of the neurometabolic unit, at Sant Joan de Deu hospital in Barcelona Spain. 13 Assuming geographical and interlaboratory variations for biogenic amine concentrations, the establishment of own reference intervals by the Greek laboratory was considered mandatory.…”

Section: Discussionmentioning

confidence: 99%

“…1 The availability of reliable biomarkers reflecting their metabolic homeostasis is essential for the diagnosis of these diseases, which in turn is essential for their prompt management. 2 Monoamine neurotransmitters, also called biogenic amines, are low-molecular-weight organic bases derived from aromatic amino acids. 3 They include serotonin and the catecholamines dopamine, norepinephrine, and epinephrine.…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid Concentrations of Neurotransmitters in a Greek Pediatric Reference Population

Vilanakis

Pons²,

Papakonstantinou³

et al. 2022

Neuropediatrics

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Biogenic amines and pterins analysis in cerebrospinal fluid (CSF) are reliable biomarkers for the diagnosis of inherited disorders of monoamine neurotransmitters. Objective: The objectives of this study were the establishment of reference values of CSF biogenic amine metabolites in a cohort of Greek children; the detection of primary defects of biogenic amine metabolism, and the assessment of biogenic amine metabolites in children with different neurological disorders. Methods: CSF biogenic amine metabolites and pterins (biopterin and neopterin) were analyzed using high-performance liquid chromatography with electrochemical and fluorescence detection. Three hundred sixty-three samples were analyzed: 60 infants and children with no history of neurological disorder, 6 with inherited disorders of monoamine neurotransmitters, and 297 with diverse neurological disorders. Results: Reference values were stratified in 6 age groups. Strong correlation of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) levels with age was detected (p<0.001). Two patients were diagnosed with a defect in the biogenic amine synthetic pathway and 3 with a defect of tetrahydrobiopterin (BH4) cofactor production. HVA and 5HIAA abnormalities were detected within different groups of neurological disorders, but none followed a specific pattern of HVA and 5HIAA abnormalities. Conclusions: In the current study Greek reference values of biogenic amines and pterins in CSF are presented. Five new patients with inherited monoamine neurotransmitter disorders are described. Nonspecific secondary biogenic amine disturbances can be seen in patients with different neurological disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Concentrations of Neurotransmitters in a Greek Pediatric Reference Population

Vilanakis

Pons²,

Papakonstantinou³

et al. 2022

Neuropediatrics

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“…5-HIAA and MHPG levels in plasma in SZ have been inversely and directly associated with depression/anxiety or excitement components of the PANSS scale, respectively [ 54 ], although some authors have alerted about the difficulty to correlate the levels of blood/urine monoamines with brain neurotransmission status, even in severe genetic conditions affecting DA and 5-HT metabolism [ 55 ]. However, the associations detected for these two metabolites with PANSS symptoms in our study are in the opposite direction.…”

Section: Discussionmentioning

confidence: 99%

Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology

Afia

Vila

MacDowell

et al. 2021

J Neuroinflammation

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Background The cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA). Methods This work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by high-performance liquid chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored. Results In the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzyme expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolite content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC. Conclusions Thus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.

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“…5-HIAA and MHPG levels in plasma in SZ have been inversely and directly associated with depression/anxiety or excitement components of PANSS scale, respectively [48], although some authors have alerted about the difficulty to correlate the levels of blood/urine monoamines with brain neurotransmission status, even in severe genetic conditions affecting DA and 5-HT metabolism [49]. However, the associations detected for these two metabolites with PANSS symptoms in our study are in the opposite direction.…”

Section: Discussionmentioning

confidence: 99%

Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology

Afia

Vila

MacDowell

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background: the cortico-cerebellar-thalamic-cortical circuit has been implicated in the emergence of psychotic symptoms in schizophrenia (SZ). The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA). Methods: this work describes alterations in KP in the post-mortem prefrontal cortex (PFC) and cerebellum (CB) of 15 chronic SZ patients and 14 control subjects in PFC and 13 control subjects in CB using immunoblot for protein levels and ELISA for interleukins and QA and KYNA determinations. Monoamine metabolites were analysed by High Performance Liquid Chromatography and SZ symptomatology was assessed by Positive and Negative Syndrome Scale (PANSS). The association of KP with inflammatory mediators, monoamine metabolism and SZ symptomatology was explored. Results: in the PFC, the presence of the anti-inflammatory cytokine IL-10 together with IDO2 and KATII enzymes decreased in SZ, while TDO and KMO enzymes expression increased. A network interaction analysis showed that in the PFC IL-10 was coupled to the QA branch of the kynurenine pathway (TDO-KMO-QA), whereas IL-10 associated with KMO in CB. KYNA in the CB inversely correlated with negative and general PANSS psychopathology. Although there were no changes in monoamine metabolites content in the PFC in SZ, a network interaction analysis showed associations between dopamine and methoxyhydroxyphenylglycol degradation metabolite. Direct correlations were found between general PANSS psychopathology and the serotonin degradation metabolite, 5-hydroxyindoleacetic acid. Interestingly, KYNA in the CB inversely correlated with 5-hydroxyindoleacetic acid in the PFC. Conclusions: thus, this work found alterations in KP in two brain areas belonging to the cortico-cerebellar-thalamic-cortical circuit associated with SZ symptomatology, with a possible impact across areas in 5-HT degradation.

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Biochemical Analyses of Cerebrospinal Fluid for the Diagnosis of Neurometabolic Conditions. What Can We Expect?

Cited by 10 publications

References 55 publications

Cerebrospinal Fluid Concentrations of Neurotransmitters in a Greek Pediatric Reference Population

Cerebrospinal Fluid Concentrations of Neurotransmitters in a Greek Pediatric Reference Population

Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology

Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology

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