Escitalopram Enhances the Association of Serotonin-1A Autoreceptors to Heteroreceptors in Anxiety Disorders

Hahn, Andreas; Lanzenberger, Rupert; Wadsak, Wolfgang; Spindelegger, Christoph; Moser, U.; Mien, Leonhard‐Key; Mitterhauser, Markus; Kasper, Siegfried

doi:10.1523/jneurosci.2409-10.2010

Cited by 46 publications

(52 citation statements)

References 77 publications

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“…Twenty-eight healthy subjects participated in this study (mean age ± SD = 26.5 ± 6.8 y, 17 female), who in part also served as control subjects in previous studies (57,(70)(71)(72)(73) (SI Materials and Methods). This project was approved by the Ethics Committee of the Medical University of Vienna and the General Hospital of Vienna.…”

Section: Methodsmentioning

confidence: 99%

“…PET measurements were carried out at the Department of Nuclear Medicine, Medical University of Vienna, and are essentially described elsewhere (57, 71) (SI Materials and Methods). Radiochemical variables for [carbonyl- Serotonin-1A (5-HT 1A ) autoreceptor binding of the dorsal raphe nucleus was obtained as described previously (57). A spherical region of interest of 4-mm diameter was defined manually within two slices of the original summed PET image (57,71,75,76).…”

Section: Methodsmentioning

confidence: 99%

“…Radiochemical variables for [carbonyl- Serotonin-1A (5-HT 1A ) autoreceptor binding of the dorsal raphe nucleus was obtained as described previously (57). A spherical region of interest of 4-mm diameter was defined manually within two slices of the original summed PET image (57,71,75,76). This yields a representative estimate of autoreceptor binding because in the human raphe nuclei, the majority (80-100%) of 5-HT 1A receptors is expressed on cell bodies of serotonergic neurons (77).…”

Section: Methodsmentioning

confidence: 99%

“…Because 5-HT 1A BP ND of the dorsal raphe nucleus is highly correlated with postsynaptic receptor binding (57,(86)(87)(88), we aimed to disentangle local from autoinhibitory effects. Using the BPM toolbox, this was realized by adjusting for regional 5-HT 1A binding when interpreting 5-HT 1A autoinhibition, and vice versa.…”

Section: Methodsmentioning

confidence: 99%

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Differential modulation of the default mode network via serotonin-1A receptors

Hahn

Wadsak

Windischberger

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

114

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Reflecting one's mental self is a fundamental process for evaluating the personal relevance of life events and for moral decision making and future envisioning. Although the corresponding network has been receiving growing attention, the driving neurochemical mechanisms of the default mode network (DMN) remain unknown. Here we combined positron emission tomography and functional magnetic resonance imaging to investigate modulations of the DMN via serotonin-1A receptors (5-HT 1A ), separated for 5-HT autoinhibition (dorsal raphe nucleus) and local inhibition (heteroreceptors in projection areas). Using two independent approaches, regional 5-HT 1A binding consistently predicted DMN activity in the retrosplenial cortex for resting-state functional magnetic resonance imaging and the Tower of London task. On the other hand, both local and autoinhibitory 5-HT 1A binding inversely modulated the posterior cingulate cortex, the strongest hub in the resting human brain. In the frontal part of the DMN, a negative association was found between the dorsal medial prefrontal cortex and local 5-HT 1A inhibition. Our results indicate a modulation of key areas involved in self-referential processing by serotonergic neurotransmission, whereas variations in 5-HT 1A binding explained a considerable amount of the individual variability in the DMN. Moreover, the brain regions associated with distinct introspective functions seem to be specifically regulated by the different 5-HT 1A binding sites. Together with previously reported modulations of dopamine and GABA, this regional specialization suggests complex interactions of several neurotransmitters driving the default mode network.functional connectivity | resting-state networks | neurotransmitter modulation

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Differential modulation of the default mode network via serotonin-1A receptors

Hahn

Wadsak

Windischberger

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

114

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“…Interestingly, increased 5-HT 1A autoreceptor binding is associated with reduced response to antidepressants [102,140], which could reflect greater autoreceptor-mediated inhibition of 5-HT. Treatment of anxiety disorder patients with antidepressants appears to normalize the imbalance between increased 5-HT 1A autoreceptor levels and decreased 5-HT 1A heteroreceptors [141]. In addition, the level of 5-HT 1A autoreceptors is altered by additional factors.…”

Section: Association Of Rs6295 With Altered 5-ht 1a Receptor Expressimentioning

confidence: 99%

Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness

Albert

2012

Phil. Trans. R. Soc. B

118

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The serotonin-1A (5-HT 1A ) receptor is an abundant post-synaptic 5-HT receptor (heteroreceptor) implicated in regulation of mood, emotion and stress responses and is the major somatodendritic autoreceptor that negatively regulates 5-HT neuronal activity. Based on animal models, an integrated model for opposing roles of pre-and post-synaptic 5-HT 1A receptors in anxiety and depression phenotypes and response to antidepressants is proposed. Understanding differential transcriptional regulation of pre-versus post-synaptic 5-HT 1A receptors could provide better tools for their selective regulation. This review examines the transcription factors that regulate brain region-specific basal and stress-induced expression of the 5-HT 1A receptor gene (Htr1a). A functional polymorphism, rs6295 in the Htr1a promoter region, blocks the function of specific repressors Hes1, Hes5 and Deaf1, resulting in increased 5-HT 1A autoreceptor expression in animal models and humans. Its association with altered 5-HT 1A expression, depression, anxiety and antidepressant response are related to genotype frequency in different populations, sample homogeneity, disease outcome measures and severity. Preliminary evidence from gene Â environment studies suggests the potential for synergistic interaction of stress-mediated repression of 5-HT 1A heteroreceptors, and rs6295-induced upregulation of 5-HT 1A autoreceptors. Targeted therapeutics to inhibit 5-HT 1A autoreceptor expression and induce 5-HT 1A heteroreceptor expression may ameliorate treatment of anxiety and major depression.

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Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

et al. 2018

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Escitalopram Enhances the Association of Serotonin-1A Autoreceptors to Heteroreceptors in Anxiety Disorders

Cited by 46 publications

References 77 publications

Differential modulation of the default mode network via serotonin-1A receptors

Differential modulation of the default mode network via serotonin-1A receptors

Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness

Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

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Escitalopram Enhances the Association of Serotonin-1A Autoreceptors to Heteroreceptors in Anxiety Disorders

Cited by 46 publications

References 77 publications

Differential modulation of the default mode network via serotonin-1A receptors

Differential modulation of the default mode network via serotonin-1A receptors

Transcriptional regulation of the 5-HT1Areceptor: implications for mental illness

Will imaging individual raphe nuclei in males with major depressive disorder enhance diagnostic sensitivity and specificity?

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Product

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Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness