Platelet serotonin transporter function after short-term paroxetine treatment in patients with panic disorder

Kang, Eun-Ho; Shim, Hyun-Bo; Kim, Kyung-Jeong; Park, Joo-Eon; Lee, In-Soo; Yu, Bum-Hee

doi:10.1016/j.psychres.2008.12.007

Cited by 7 publications

(5 citation statements)

References 32 publications

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“…Mice lacking SERT display elevated anxiety-like behaviors and impaired fear extinction retention (Wellman et al, 2007). Decreased expression of SERT has been reported in individuals with anxiety disorders (Kang et al, 2010), which may contribute to impaired fear extinction learning reported in these disorders (Graham and Milad, 2011). Similarly, alterations in the serotonergic circuitry is seen in individuals with AN, a disorder characterized by CR (Kaye et al, , 2009).…”

Section: Discussionmentioning

confidence: 99%

Caloric Restriction Enhances Fear Extinction Learning in Mice

Riddle

McKenna

Yoon

et al. 2013

Neuropsychopharmacol

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Fear extinction learning, the ability to reassess a learned cue of danger as safe when it no longer predicts aversive events, is often dysregulated in anxiety disorders. Selective serotonin reuptake inhibitors (SSRI's) enhance neural plasticity and their ability to enhance fear extinction learning may explain their anxiolytic properties. Caloric restriction (CR) has SSRI-like effects on neural plasticity and anxiety-related behavior. We implemented CR in mice to determine its effects on conditioned-fear responses. Wild type and serotonin transporter (SERT) knockout mice underwent CR for 7 days leading to significant weight loss. Mice were then tested for cued fear learning and anxiety-related behavior. CR markedly enhanced fear extinction learning and its retention in adolescent female mice, and adults of both sexes. These effects of CR were absent in SERT knockout mice. Moreover, CR phenocopied behavioral and molecular effects of chronic fluoxetine, but there was no additive effect of CR in fluoxetine-treated mice. These results demonstrate that CR enhances fear extinction learning through a SERT-dependent mechanism. These results may have implications for eating disorders such as anorexia nervosa (AN), in which there is a high prevalence of anxiety before the onset of dietary restriction and support proposals that in AN, CR is a motivated effort to control dysregulated fear responses and elevated anxiety.

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Section: Discussionmentioning

confidence: 99%

Caloric Restriction Enhances Fear Extinction Learning in Mice

Riddle

McKenna

Yoon

et al. 2013

Neuropsychopharmacol

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“… 11 , 12 Several serotonin transporter (5-HTT) abnormalities have been detected in panic disorder (PD), although results concerning the synaptic serotonin state are still inconsistent. 13 , 14 It has been reported that a hyperserotonergic state resulting from impaired 5-HTT function can cause an anxiety or fear response by stimulating the amygdala. 15 Conversely, serotonergic agents are known to relieve panic symptoms.…”

Section: Introductionmentioning

confidence: 99%

Increased mean platelet volume in patients with panic disorder

Kokaçya¹,

Çöpoğlu²,

Kıvrak³

et al. 2015

NDT

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ObjectiveThe relationship between platelet activation and psychiatric disorders has been shown in previous work. Mean platelet volume (MPV) is a measure of platelet size and a good indicator of platelet activity, which increases in cardiovascular diseases (CVDs). It is known that anxiety is a considerable factor in the etiology of mortality in CVDs. The aim of the present study was to investigate any probable difference in the MPV of patients with panic disorder (PD).MethodsSixty-one drug-free patients, aged 18–65 years and diagnosed with PD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were included in the study, along with 63 healthy age- and sex-matched volunteers. The body mass index (BMI) was calculated and MPV measured for each subject.ResultsThe MPV was found to be higher in the PD group compared to the control group (P=0.004). There were no significant differences between the two groups in terms of platelet count or BMI.ConclusionAlterations in platelet activity may be a reflection of abnormal 5-hydroxytryptamine (5-HT) 1A receptor function in the central nervous system of subjects with a diagnosis of PD. These findings may elucidate the relationship between CVDs and PD. The findings of the present study suggest that MPV is increased in PD patients.

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“…CYP2D6 exhibits large inter-individual differences in paroxetine metabolism resulting in variation in the steady state plasma concentrations of the drug. This behaviour of CYP2D6 towards paroxetine is related to the dose-response profile of depression patients and has serious clinical implications such as suicide [16,17]. Determination of antidepressants is of practical importance in the medical field since it reduces unnecessary fatality cases among highly depressed patients resulting from hepatotoxicity and other drug related issues.…”

Section: Introductionmentioning

confidence: 99%

An Amperometric Cytochrome P450-2D6 Biosensor System for the Detection of the Selective Serotonin Reuptake Inhibitors (SSRIs) Paroxetine and Fluvoxamine

Ajayi

Nxusani

Douman

et al. 2016

JNanoR

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Paroxetine is the second most prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant drug, characterized by extensive inter-individual variation in steady state plasma concentrations resulting in drug toxicity amongst patinets. A nanopolymeric biosensor for studying the biotransformation of paroxetine is presented. The bioelectrode system consists of cytochrome P450-2D6 enzyme encapsulated in nanotubular poly (8-anilino-1-napthalene sulphonic acid) electrochemically deposited on gold. The biosensing procedure involved the determination of the extent of modulation of fluvoxamine responses to the P450-2D6 enzyme electrode after incubation in paroxetine standard solutions. Paroxetine inhibited the activity of cytochrome P450-2D6 (CYP2D6) resulting in a decrease in the fluvoxamine signal of the biosensor. The biosensor gave a linear analytical response for the paroxetine in the interval 0.005 and 0.05 μM, with a detection limit of 0.002 μM and a response time of 30 s. Electrochemical Michaelis–Menten kinetics of the reversible competitive inhibition of the fluvoxamine responses of the biosensor by 0, 0.05 and 0.1 μM paroxetine gave apparent Michaelis–Menten constant (KMapp) values of 1.00 μM, 1.11 μM and 1.25 μM, respectively. The corresponding value for the maximum response, IMAX was 0.02 A. The dissociation constant, KI, value evaluated from Dixon analysis of the paroxetine modulation data was estimated to be-0.02 μM while Cornish-Bowden analysis confirmed the competitive inhibitory characteristics of the enzyme.

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Platelet serotonin transporter function after short-term paroxetine treatment in patients with panic disorder

Cited by 7 publications

References 32 publications

Caloric Restriction Enhances Fear Extinction Learning in Mice

Caloric Restriction Enhances Fear Extinction Learning in Mice

Increased mean platelet volume in patients with panic disorder

An Amperometric Cytochrome P450-2D6 Biosensor System for the Detection of the Selective Serotonin Reuptake Inhibitors (SSRIs) Paroxetine and Fluvoxamine

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