5-HT and 5-HIAA in cerebrospinal fluid in depression

Gjerris, Annette; Sørensen, Anders; Rafaelsen, Ole J.; Werdelin, L.; Alling, Crister; Linnoila, Markku

doi:10.1016/0165-0327(87)90056-5

Cited by 53 publications

(24 citation statements)

References 58 publications

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“…They also had high levels of both state (mean [SD] score, 57 [12]) and trait (mean [SD] score, 62 [7]) anxiety. Approximately half of the patients had a positive family history of depression.…”

Section: Resultsmentioning

confidence: 99%

“…Hence, in the brain, cerebral serotonin turnover may be estimated from the sum of differences in rates at which serotonin and its metabolites enter and leave the cerebral circulation. In CSF, 5-HIAA concentrations are approximately 200 times that of serotonin, 7 thereby rendering 5-HIAA levels an approximation of serotonin turnover. Given that 5-HIAA is effectively a terminal metabolite, the prime determinants of outward flux at steady state are the brain concentration and production rate.…”

Section: Commentmentioning

confidence: 99%

“…While our combined observations of elevated internal jugular venous 5-HIAA concentration in unmedicated patients and reduced serotonin turnover following SSRI therapy appear to run counter to this thesis, an elevated rate of serotonin metabolism could represent a process by which the availability of serotonin to be released neuronally is lowered. Interestingly, Gjerris et al 7 in their initial cerebrospinal fluid (CSF) study actually documented elevated Differences between groups were analyzed using analysis of variance. *P Ͻ .05. serotonin levels in lumbar CSF in patients with depression.…”

Section: Commentmentioning

confidence: 99%

“…No structured psychotherapy was provided to the patient either within or external to the study. Repeat research studies with blood sampling from the same internal jugular vein were performed after approximately 12 weeks of therapy (mean [SD] duration of therapy, 98 [7] days). Patients were examined weekly for the purposes of the study or more frequently if required on clinical grounds.…”

Section: Participantsmentioning

confidence: 99%

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Elevated Brain Serotonin Turnover in Patients With Depression

Barton¹,

Esler²,

Dawood³

et al. 2008

Arch Gen Psychiatry

192

107

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Context:The biological basis for the development of major depressive disorder (MDD) remains incompletely understood.Objective: To quantify brain serotonin (5-hydroxytryptamine ) turnover in patients with MDD.Design: Patients with depression were studied both untreated and during administration of a selective serotonin reuptake inhibitor (SSRI) in an unblinded study of sequential design. Healthy volunteers were examined on only 1 occasion. Direct internal jugular venous blood sampling was used to directly quantify brain serotonin turnover. The effect of serotonin transporter (5-HTT) genotype on brain serotonin turnover was evaluated and the influence of SSRI therapy on serotonin turnover was investigated.Setting: Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the research catheterization laboratory of a major training hospital and medical research institute. Conclusions: Brain serotonin turnover is elevated in unmedicated patients with MDD and is influenced by the 5-HTT genotype. The marked reduction in serotonin turnover following SSRI treatment and the accompanying improvement in symptoms suggest that high brain serotonin turnover may be a biological substrate of MDD. Psychiatry. 2008;65(1):38-46 T HE ETIOLOGY OF MAJOR DEpressive disorder (MDD) has been linked to brain monoaminergic neuronal dysfunction. Arch Gen1,2 Of particular interest is the role of brain serotonin (5-hydroxytryptamine [5-HT]) in MDD. The diversity of roles played by serotonin coupled with the lack of a demonstrated relationship between different clinical presentations and biochemical abnormalities has hampered the development of sensitive markers of the disease. Indeed, brain serotonin-releasing neurons subserve diverse although incompletely understood functions related to emotions and behavior, feeding and adiposity, 3 and light stimulation. 4 We have previously demonstrated influences of obesity and feeding 5 and season and sunlight 6 on brain serotonin turnover in humans. The principal means of intraneuronal metabolism of serotonin is via oxidative deamination by monoamine oxidase resulting in formation of 5-hydroxyindoleacetic acid (5-HIAA) (Figure 1). Deamination followed by reduction, conjugation with sulfate or glucuronide, and

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Section: Resultsmentioning

confidence: 99%

Section: Commentmentioning

confidence: 99%

Section: Commentmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

See 2 more Smart Citations

Elevated Brain Serotonin Turnover in Patients With Depression

Barton¹,

Esler²,

Dawood³

et al. 2008

Arch Gen Psychiatry

192

107

View full text Add to dashboard Cite

show abstract

“…Raised and not lowered brain levels have already been found in depressives [Gjerris et al, 1987]. It is again my firm belief that stressed, anxious, and depressed patients would be better treated with selective TPH activation inhibitors that decrease 5-HT rather than compounds having transmitter reuptake inhibitory activity that increases this monoamine.…”

Section: Tryptophan Hydroxylase Activation Blockadementioning

confidence: 94%

Toward a better understanding of depression and anxiety. The importance of tryptophan hydroxylase activation blockade: The origin of a unique anxiolytic antidepressant

Gittos¹

2010

Drug Development Research

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The serotonin (5-HT) deficiency theory of depression has misled medical science. Inhibitors of 5-HT reuptake were the basis of the hypothesis and display limited efficacy with a pronounced delay of onset in action coupled with a side-effect profile that includes increased anxiety. In the present commentary, a recommendation for the reinstatement of the prolongation of the d-amphetamine stereotypy test is made as a means to generate new molecules capable of blocking stress-induced tryptophan hydroxylase (TPH) activation and its elevation of 5-HT, now regarded as the cause of depression The selective TPH activation inhibitor, AGN 2979, is already known to exert powerful, rapid antidepressant and anxiolytic properties in the clinic with a notable lack of the side effects associated with monoamine reuptake inhibition. Drug Dev Res 71:331-334, 2010.

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Assessing the Assessment of Brain Serotonin Turnover

Anderson¹

2008

Arch Gen Psychiatry

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5-HT and 5-HIAA in cerebrospinal fluid in depression

Cited by 53 publications

References 58 publications

Elevated Brain Serotonin Turnover in Patients With Depression

Elevated Brain Serotonin Turnover in Patients With Depression

Toward a better understanding of depression and anxiety. The importance of tryptophan hydroxylase activation blockade: The origin of a unique anxiolytic antidepressant

Assessing the Assessment of Brain Serotonin Turnover

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