Human 5-HT Transporter Availability Predicts Amygdala Reactivity<i>In Vivo</i>

Rhodes, Rebecca; Murthy, Naga Venkatesha; Dresner, M. Alex; Selvaraj, Sudhakar; Stavrakakis, N; Babar, Sayed; Cowen, Philip J.; Grasby, Paul M.

doi:10.1523/jneurosci.1175-07.2007

Cited by 86 publications

(79 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data are consistent with both preclinical animal findings (Burghardt et al, 2004(Burghardt et al, , 2007Forster et al, 2006) and indirect indices of 5-HT effects on human amygdala function (Hariri et al, 2002;Heinz et al, 2005;Fisher et al, 2006;Rhodes et al, 2007). The current pattern of 5-HTmediated amygdala reactivity, which can drive behavioral and physiologic arousal, may represent an important pathway through which SSRIs achieve an antidepressant effect.…”

Section: Discussionsupporting

confidence: 81%

“…Available data from animal studies indicate that relative increases in amygdala 5-HT result in potentiation of amygdala activation and associated behavioral phenomenon, such as fear conditioning (Burghardt et al, 2004(Burghardt et al, , 2007Forster et al, 2006). In humans, recent in vivo neuroimaging studies have revealed that decreased capacity for either 5-HT reuptake (Rhodes et al, 2007) or negative feedback autoregulation (Fisher et al, 2006) result in relatively increased amygdala reactivity. In addition, human functional genetic polymorphisms resulting in relatively increased 5-HT signaling are similarly associated with increased amygdala reactivity (Hariri et al, 2002;Heinz et al, 2005;Meyer-Lindenberg et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity

Bigos

Pollock

Aizenstein

et al. 2008

Neuropsychopharmacol

141

120

View full text Add to dashboard Cite

Variability in serotonin (5-HT) function is associated with individual differences in normal mood and temperament, as well as psychiatric illnesses, all of which are influenced by amygdala function. This study evaluated the acute effects of 5-HT reuptake blockade on amygdala function using pharmacological functional MRI. Eight healthy men completed a double-blind balanced crossover study with the selective 5-HT reuptake inhibitor, citalopram (20 mg infused over 30 min), and normal saline. Amygdala reactivity in response to novel facial expressions was assessed on three successive scans, once before drug/placebo infusion, once early in the infusion, and once at the end of infusion. Acute citalopram administration resulted in concentration-dependent increases in human amygdala reactivity to salient stimuli. The current pattern of 5-HT-mediated amygdala reactivity may represent an important pathway through which SSRIs achieve an antidepressant effect. Intriguingly, our data may also reveal a mechanism contributing to clinical observations of extreme agitation, restlessness, and suicidal ideation in some individuals during acute SSRI treatment. Developing a comprehensive model of how 5-HT modulates human amygdala reactivity supporting behavioral and physiological arousal will be instrumental for our understanding of basic neurobehavioral processes, their dysfunction in psychiatric illnesses, and their contribution to mechanism of treatment response.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity

Bigos

Pollock

Aizenstein

et al. 2008

Neuropsychopharmacol

141

120

View full text Add to dashboard Cite

show abstract

“…However, coregistration was limited since it required multiple investigations in different laboratories. Real-time simultaneous studies will be of particular interest for the interpretation of activation patterns (intravascular versus tissue signals) obtained with fMRI and H 2 15 O (or FDG) PET [31,32] and will be useful for the analysis of the effect of specific tasks on transmitter release and receptor binding, such as the determination of DOPA, raclopride and 5-hydroxytryptamine transporter by combining fMRI with PET [33][34][35]. A similar approach (fMRI and PET of receptor ligands) might be useful to elucidate the effects of drugs and their withdrawal (e.g.…”

Section: Real-time Imaging Of Complementary Informationmentioning

confidence: 99%

The potential of PET/MR for brain imaging

Heiss

2008

Eur J Nucl Med Mol Imaging

131

100

View full text Add to dashboard Cite

Introduction The completion of an integrated PET/MR prototype system for brain imaging is the latest step in the evolution of positron emission tomography. Early images with this new imaging system demonstrate that highresolution multiparametric studies can be combined without significant loss of performance of either imaging modality. Objective This new technology will make fusion of morphological and biological information much easier, yield real-time assessment of complementary variables and will provide dynamic information for kinetic model- IntroductionSince the first prototypes [1, 2] and the first commercial system [3], positron emission tomography (PET) has developed to multiring systems permitting high resolution and three-dimensional imaging of various physiological, functional and molecular targets. The first applications of PET were in brain research, and despite the many other diagnostic indications, particularly in oncology and cardiology, brain imaging remains a stronghold of PET.Therefore, this discussion of perspectives of an integrated PET/MR system is focused on research applications in neuroscience to which the combination of PET and MRI may add further impetus. This perspective is in parts speculative and it does not include a discussion of the technical or methodological challenges of combined PET/ MR imaging. These aspects are reviewed elsewhere in the articles of this supplement to EJNMMI. Development of PET for brain imagingThe progress in image quality may be followed by metabolic images of glucose consumption in one volunteer acquired on several generation PET systems over the years. The first transaxial image (Fig. 1a) was acquired on a single hexagonal array, the ECAT PET, which covered only the cortical rim. Early PET images suffered from limited spatial resolution (approximately 15 mm), low sensitivity and insufficient attenuation and scatter correction [3,4]. PET image quality improved with the four-ring PC-384 (Scanditronix) [5], which yielded seven simultaneous, partly overlapping transaxial images and that provided a spatial resolution of 8.4 mm FWHM across 12-mm slices (Fig. 1b) [6] and limited axial reconstruction (Fig. 2). Further improvements came with the Eur

show abstract

“…In a multi-modal neuroimaging study using the same threat-related faces matching BOLD fMRI paradigm as was used in our 5-HT 1A autoreceptor study, Rhodes et al [61] evaluated the association between 5-HTT binding in the amygdala, assessed with [ 11 C]DASB PET, and threat-related amygdala reactivity. The authors rstb.royalsocietypublishing.org Phil Trans R Soc B 368: 20120192…”

Section: (B) Serotonin Transportermentioning

confidence: 99%

Identifying serotonergic mechanisms underlying the corticolimbic response to threat in humans

Fisher

Hariri

2013

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

A corticolimbic circuit including the amygdala and medial prefrontal cortex (mPFC) plays an important role in regulating sensitivity to threat, which is heightened in mood and anxiety disorders. Serotonin is a potent neuromodulator of this circuit; however, specific serotonergic mechanisms mediating these effects are not fully understood. Recent studies have evaluated molecular mechanisms mediating the effects of serotonin signalling on corticolimbic circuit function using a multi-modal neuroimaging strategy incorporating positron emission tomography and blood oxygen level-dependent functional magnetic resonance imaging. This multi-modal neuroimaging strategy can be integrated with additional techniques including imaging genetics and pharmacological challenge paradigms to more clearly understand how serotonin signalling modulates neural pathways underlying sensitivity to threat. Integrating these methodological approaches offers novel opportunities to identify mechanisms through which serotonin signalling contributes to differences in brain function and behaviour, which in turn can illuminate factors that confer risk for illness and inform the development of more effective treatment strategies.

show abstract

Human 5-HT Transporter Availability Predicts Amygdala ReactivityIn Vivo

Cited by 86 publications

References 29 publications

Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity

Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity

The potential of PET/MR for brain imaging

Identifying serotonergic mechanisms underlying the corticolimbic response to threat in humans

Contact Info

Product

Resources

About