Increased Brainstem Serotonergic Transporter Availability in Adult Migraineurs: an [18F]FP-CIT PET Imaging Pilot Study

Park, Eun Kyung; Hwang, Yu Mi; Chu, Min Kyung; Jung, Ki-Young

doi:10.1007/s13139-015-0373-x

Cited by 9 publications

(5 citation statements)

References 18 publications

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“…Furthermore, although the sample size may seem small in clinical research, in molecular research, it is considered a moderate sample size. For example, PET imaging studies in human use comparable sample sizes [47–50]. Importantly, despite the small sample size, we were able to show a statistically significant effect for lead after a Bonferroni correction for multiple comparisons.…”

Section: Discussionmentioning

confidence: 80%

Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers

et al. 2016

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Background Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia. Methods We analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb2+), manganese (Mn2+), cadmium (Cd2+), copper (Cu2+), magnesium (Mg2+), and zinc (Zn2+), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry. Results We found higher early-life Pb2+ exposure among patients with schizophrenia than controls. The differences in log Mn2+ and log Cu2+ changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb2+ levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb2+ levels and adult IQ. Conclusions In our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis.

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Section: Discussionmentioning

confidence: 80%

Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers

et al. 2016

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“…[123I]β-CIT used most prominently in SPECT imaging of DAT has high affinity for the serotonin transporter (SERT) 77 and is based off a chemistry sensitive to selective serotonin reuptake inhibitor medications 78 , 79 . In fact, FP-CIT tracers have been used to image SERT 80 , 81 , which has reasonably high distribution in the striatum 82 , 83 . The previously observed positive relationship between [123I]FP-CIT BP ND and BIS-11 28 could thus result from differences in FP-CIT specificity for DAT relative to SERT versus the greater DAT specificity of the FE-PE2I tracer we used here 84 .…”

Section: Discussionmentioning

confidence: 99%

Ventral striatal dopamine transporter availability is associated with lower trait motor impulsivity in healthy adults

et al. 2018

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Impulsivity is a transdiagnostic feature of a range of externalizing psychiatric disorders. Preclinical work links reduced ventral striatal dopamine transporter (DAT) availability with heightened impulsivity and novelty seeking. However, there is a lack of human data investigating the relationship between DAT availability, particularly in subregions of the striatum, and the personality traits of impulsivity and novelty seeking. Here we collected PET measures of DAT availability (BPND) using the tracer 18F-FE-PE2I in 47 healthy adult subjects and examined relations between BPND in striatum, including its subregions: caudate, putamen, and ventral striatum (VS), and trait impulsivity (Barratt Impulsiveness Scale: BIS-11) and novelty seeking (Tridimensional Personality Questionnaire: TPQ-NS), controlling for age and sex. DAT BPND in each striatal subregion showed nominal negative associations with total BIS-11 but not TPQ-NS. At the subscale level, VS DAT BPND was significantly associated with BIS-11 motor impulsivity (e.g., taking actions without thinking) after correction for multiple comparisons. VS DAT BPND explained 13.2% of the variance in motor impulsivity. Our data demonstrate that DAT availability in VS is negatively related to impulsivity and suggest a particular influence of DAT regulation of dopamine signaling in VS on acting without deliberation (BIS motor impulsivity). While needing replication, these data converge with models of ventral striatal functions that emphasize its role as a key interface linking motivation to action.

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“…By using neuroimaging methods (SPECT-images coregistered with MRI-scans) (Schuh-Hofer et al, 2007) it was shown that there is an increased availability of 5-HTT in brainstem in migraine patients during the interictal period. The recent PET-study also confirms that the 5-HTT availability is crucial in the pathomechanisms of migraine (Park et al, 2016). The limitation of the complete comparison of our results with the clinical studies is that the human observations are examining migraine during the interictal period opposite the NTG model of migraine, which is the ictal model of migraine.…”

Section: Discussionmentioning

confidence: 62%

Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect

Nagy-Grócz

Bohár

Fejes-Szabó

et al. 2017

Journal of Chemical Neuroanatomy

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serotonin transporter expression in rat spinal cord but anandamide modulated this effect.Journal of Chemical Neuroanatomy http://dx.doi.org/10. 1016/j.jchemneu.2017.06.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Migraine is one of the most prevalent neurological diseases, which affects 16% of the total population. The exact pathomechanism of this disorder is still not well understood, but it seems that serotonin and its transporter has a crucial role in the pathogenesis.One of the animal models of migraine is the systemic administration of nitroglycerin (NTG), a nitric oxide (NO) donor. NO can initiate a central sensitization process in the trigeminal system, which is also present in migraineurs.Recent studies showed that the endocannabinoid system has a modulatory role on the trigeminal activation and sensitization.Our aim was to investigate the effect of an endogenous cannabinoid, anandamide (AEA) on the NTG-induced changes on serotonin transporter (5-HTT) expression in the upper cervical spinal cord (C1-C2) of the rat, where most of the trigeminal nociceptive afferents convey.The animals were divided into four groups. Rats in the first group, called placebo, received only the vehicle solution as treatment. In the second group, they were treated with an intraperitoneal (i.p.) injection of NTG (10mg/kg). Rats in the third and fourth groups received i.p. AEA (2x5mg/kg) half hour before and one hour after the placebo or NTG treatment. Four hours after placebo/NTG injection, the animals were perfused and the cervical spinal cords were removed for immunohistochemistry and Western blotting.Our results show that both NTG and AEA alone are able to increase 5-HTT expression in the C1-C2 segments. Combination of NTG and AEA has an opposing effect on this marker, nullifying the effects of non-combined administration, probably by negative feedback mechanisms.

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Increased Brainstem Serotonergic Transporter Availability in Adult Migraineurs: an [18F]FP-CIT PET Imaging Pilot Study

Cited by 9 publications

References 18 publications

Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers

Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers

Ventral striatal dopamine transporter availability is associated with lower trait motor impulsivity in healthy adults

Nitroglycerin increases serotonin transporter expression in rat spinal cord but anandamide modulated this effect

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