F174. Higher Baseline Plasma Serotonin, and a Greater Decrease in Serotonin Over Treatment, is Associated With Better SSRI Response in MDD

Holck, Amanda; Lindqvist, Daniel; Rossner, Rebecca; Mahan, Laura; Reus, Victor I.; Wolkowitz, Owen M.; Mellon, Synthia H.

doi:10.1016/j.biopsych.2018.02.788

Cited by 1 publication

(2 citation statements)

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“…Murine models have been used to show that the serotonin transporter (SERT) regulates ventral midbrain iron concentrations 39 , 50 . There are several factors increased in PD that could cause SERT dysfunction (⍺-synuclein pathology 41 , TNF-⍺ 42 , 51 52 , SSRI/SNRI use 53 ), and SERT dysfunction could, in turn, affect plasma serotonin levels; however, the effects of SERT dysfunction on plasma serotonin are nuanced 54 , 55 , and the mechanisms connecting SERT to iron remain unclear. An interesting possibility is that SERT is only one of multiple points of intersection between the serotonin system and iron regulation in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…In prior studies, low serotonin (or 5-HIAA) in both plasma and CSF has been demonstrated in PD patients either not taking SSRI or SNRI medications 28 , 35 , 36 or not taking any serotonergic agents 26 , 37 , 38 . However, two recent studies in the general population report that long-term SSRI treatment lowers plasma serotonin concentrations, and lower pretreatment plasma serotonin concentrations (and less change) predict poor treatment response 54 , 55 . Importantly, regardless of cause, the association of low plasma serotonin with higher nigral iron remained significant even after controlling for SSRI/SNRI use.…”

Section: Discussionmentioning

confidence: 99%

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Low plasma serotonin linked to higher nigral iron in Parkinson’s disease

Jellen

Lewis

et al. 2021

Sci Rep

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A growing body of evidence suggests nigral iron accumulation plays an important role in the pathophysiology of Parkinson’s disease (PD), contributing to dopaminergic neuron loss in the substantia nigra pars compacta (SNc). Converging evidence suggests this accumulation might be related to, or increased by, serotonergic dysfunction, a common, often early feature of the disease. We investigated whether lower plasma serotonin in PD is associated with higher nigral iron. We obtained plasma samples from 97 PD patients and 89 controls and MRI scans from a sub-cohort (62 PD, 70 controls). We measured serotonin concentrations using ultra-high performance liquid chromatography and regional iron content using MRI-based quantitative susceptibility mapping. PD patients had lower plasma serotonin (p < 0.0001) and higher nigral iron content (SNc: p < 0.001) overall. Exclusively in PD, lower plasma serotonin was correlated with higher nigral iron (SNc: r(58) = − 0.501, p < 0.001). This correlation was significant even in patients newly diagnosed (< 1 year) and stronger in the SNc than any other region examined. This study reveals an early, linear association between low serotonin and higher nigral iron in PD patients, which is absent in controls. This is consistent with a serotonin-iron relationship in the disease process, warranting further studies to determine its cause and directionality.

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