scholarly journals Imaging the serotonin 1A receptor using [ 11 C]WAY100635 in healthy controls and major depression

2013 ◽  
Vol 368 (1615) ◽  
pp. 20120004 ◽  
Author(s):  
Natalie Hesselgrave ◽  
Ramin V. Parsey
Keyword(s):  
Response Prediction ◽  
Promoter Polymorphism ◽  
Binding Potential ◽  
Healthy Controls ◽  
Major Depressive ◽  
Genetic Components ◽  
Positron Emission ◽  
Temporal Model ◽  
Potential Tool ◽  
Treatment Response Prediction

As a neurotransmitter, serotonin (5-HT) is widely used throughout the brain and known to play a role in many processes including emotion and brain development. Of the 15 subtypes of 5-HT receptors, the 1A receptor (5-HT 1A ) has been implicated in depression and suicide. Using the [carbonyl- 11 C]WAY100635 ([ 11 C]WAY) ligand and positron emission tomography, we have studied the 5-HT 1A receptor, first in a group of healthy controls, then in two separate groups of subjects with major depressive disorder (MDD) (antidepressant exposed and not recently medicated), and, lastly, in a group of subjects remitted from MDD. All MDD subjects were medication-free at the time of scan. We found higher 5-HT 1A binding potential (BP F ) in MDD subjects not recently exposed to an antidepressant compared with controls and recently medicated MDD subjects; and higher BP F in subjects with the C(-1019)G promoter polymorphism. We replicated these findings in a novel cohort and reconciled our discrepant findings with other groups using alternate quantification techniques. We also reported higher BP F in subjects remitted from a major depressive episode than in controls. From this work, we proposed a temporal model in which 5-HT 1A BP F may be a trait abnormality of MDD. To further explore the genetic components of MDD and utility of 5-HT 1A imaging as a potential tool for biomarker or treatment response prediction, these findings should be replicated in a larger cohort using the [ 11 C]CUMI-101 agonist tracer.

scholarly journals Molecular connectivity disruptions in males with major depressive disorder

2018 ◽  
Vol 39 (8) ◽  
pp. 1623-1634 ◽  
Author(s):  
Rajapillai LI Pillai ◽  
Mengru Zhang ◽  
Jie Yang ◽  
J John Mann ◽  
Maria A Oquendo ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
High Sensitivity ◽  
Binding Potential ◽  
Molecular Connectivity ◽  
Major Depressive ◽  
Positron Emission ◽  
Healthy Control ◽  
Synaptic Receptors ◽  
Molecular Brain

In most positron emission tomography (PET) molecular brain imaging studies, regions of interest have been defined anatomically and examined in isolation. However, by defining regions based on physiology and examining relationships between them, we may derive more sensitive measures of receptor abnormalities in conditions such as major depressive disorder (MDD). Using an average of 52 normalized binding potential maps, acquired using radiotracer [11C]-WAY100635 and full arterial input analysis, we identified two molecular volumes of interest (VOIs) with contiguously high serotonin 1A receptor (5-HT1A) binding sites: the olfactory sulcus (OLFS) and a band of tissue including piriform, olfactory, and entorhinal cortex (PRF). We applied these VOIs to a separate cohort of 25 healthy control males and 16 males with MDD who received [11C]-WAY100635 imaging. Patients with MDD had significantly higher binding than controls in both VOIs, ( p < 0.01). To identify potential homeostatic disruptions in MDD, we examined molecular connectivity, i.e. the correlation between binding of raphe nucleus (RN) 5-HT1A autoreceptors and post-synaptic receptors in molecular VOIs. Molecular connectivity was significant in healthy controls ( p < 0.01), but not in patients with MDD. This disruption in molecular connectivity allowed identification of MDD cases with high sensitivity (81%) and specificity (88%).

scholarly journals EEG Biomarkers for Treatment Response Prediction in Major Depressive Illness

2019 ◽  
Vol 176 (1) ◽  
pp. 82-82 ◽  
Author(s):  
Alik S. Widge ◽  
Carolyn I. Rodriguez ◽  
Linda L. Carpenter ◽  
Ned H. Kalin ◽  
William McDonald ◽  
...  
Keyword(s):  
Treatment Response ◽  
Response Prediction ◽  
Depressive Illness ◽  
Major Depressive ◽  
Treatment Response Prediction

scholarly journals Electroencephalographic Biomarkers for Treatment Response Prediction in Major Depressive Illness: A Meta-Analysis

2019 ◽  
Vol 176 (1) ◽  
pp. 44-56 ◽  
Author(s):  
Alik S. Widge ◽  
M. Taha Bilge ◽  
Rebecca Montana ◽  
Weilynn Chang ◽  
Carolyn I. Rodriguez ◽  
...  
Keyword(s):  
Treatment Response ◽  
Meta Analysis ◽  
Response Prediction ◽  
Depressive Illness ◽  
Major Depressive ◽  
Treatment Response Prediction

scholarly journals Evidence for a serotonergic subtype of major depressive disorder: A NeuroPharm-1 study.

2021 ◽  
Author(s):  
Kristin Kohler-Forsberg ◽  
Brice Ozenne ◽  
Elizabeth B Landman ◽  
Soren V Larsen ◽  
Asbjorn S Poulsen ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Emission Tomography ◽  
Healthy Controls ◽  
First Line ◽  
Major Depressive ◽  
Positron Emission ◽  
Ssri Treatment

Selective serotonin reuptake inhibitors (SSRIs) are the first line pharmacological treatment of Major Depressive Disorder (MDD), but only about half of patients benefit from it. Cerebral serotonin 4 receptor (5-HT4R) binding measured with positron emission tomography (PET) is inversely related to serotonin levels and can serve as a proxy for brain serotonin levels. We here determine if 5-HT4R differs between healthy and MDD individuals and if it is associated with successful outcomes of serotonergic treatment of MDD. We [11C]-SB207145 PET-scanned 100 (71 F) untreated patients with moderate to severe MDD and 91 (55 F) healthy controls; 40 patients were re-scanned after 8 weeks treatment. All patients started treatment with the SSRI escitalopram and were followed clinically after 1, 2, 4, 8 and 12 weeks. Treatment response was measured as change from baseline. Before treatment, patients with MDD had 8% lower global 5-HT4R binding than controls (95%CI[-13.1%;-2.5%], p<0.001). Non-responders did not differ from controls, whereas remitters had 9% lower binding than controls ([-16.1%;-2.7%], p=0.004). Independent of treatment outcomes, patients reduced their neostriatal 5-HT4R binding (-9%, [-12.8%;-5.0%], p<0.001) after serotonergic intervention. Overall, patients with MDD have lower cerebral 5-HT4R binding than controls, suggesting that 5-HT4R is a biomarker for MDD. The observation that SSRI treatment leads to reduced neostriatal 5-HT4R binding supports that the treatment does indeed increase brain 5-HT levels. Patients who remit to SSRIs have lower cerebral 5-HT4R prior to treatment than controls whereas non-responders do not differ. We propose that non-responders to SSRI's constitute a subgroup with non-serotonergic depression.

scholarly journals Gender-specific abnormalities in the serotonin transporter system in panic disorder

2013 ◽  
Vol 16 (4) ◽  
pp. 733-743 ◽  
Author(s):  
Dara M. Cannon ◽  
Jacqueline M. Klaver ◽  
Summer A. Klug ◽  
Paul J. Carlson ◽  
David A. Luckenbaugh ◽  
...  
Keyword(s):  
Panic Disorder ◽  
Serotonin Transporter ◽  
Anterior Cingulate ◽  
Serotonergic System ◽  
Binding Potential ◽  
Healthy Controls ◽  
Positron Emission ◽  
Serotonin Turnover ◽  
Inhibitor Treatment

AbstractThe central serotonergic system has been implicated in the pathophysiology of panic disorder (PD) by evidence of abnormally elevated serotonin-turnover, reduced pre- and post-synaptic 5-HT1A−receptor sensitivity and binding and clinical improvement during administration of agents that enhance serotonergic transmission. Polymorphisms in genes that putatively influence serotonergic neurotransmission increase the vulnerability for developing PD specifically in males. We tested the hypotheses that serotonin transporter (5-HTT) binding is elevated in PD subjects vs. healthy controls in regions where in vivo evidence exists for both elevated 5-HTT and 5-HT1A receptor levels in PD and investigated whether the extent of this difference depends upon gender. Volunteers were out-patients with current PD (n=24) and healthy controls (n=24). The non-displaceable component of 5-HTT binding-potential (BPND) was measured using positron emission tomography and the 5-HTT selective radioligand, [11C]DASB. PD severity was assessed using the PD Severity Scale. The 5-HTT-BPND was increased in males with PD relative to male controls in the anterior cingulate cortex (F=8.96, pFDR=0.01) and midbrain (F=5.09, pFDR=0.03). In contrast, BPND did not differ between females with PD and female controls in any region examined. The finding that 5-HTT-binding is elevated in males but not in females with PD converges with other evidence suggesting that dysfunction within the central serotonergic system exists in PD, and also indicates that such abnormalities are influenced by gender. These findings conceivably may reflect a sexual dimorphism that underlies the greater efficacy of serotonin reuptake inhibitor treatment in females vs. males with PD.

Liquid Biopsies in the Management of Bladder Cancer: Next-Generation Biomarkers for Diagnosis, Surveillance, and Treatment-Response Prediction

2017 ◽  
Vol 22 (5-6) ◽  
pp. 389-401 ◽  
Author(s):  
Yu Yang ◽  
Catherine R. Miller ◽  
Antonio Lopez-Beltran ◽  
Rodolfo Montironi ◽  
Monica Cheng ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Treatment Response ◽  
Response Prediction ◽  
Next Generation ◽  
Liquid Biopsies ◽  
Treatment Response Prediction

Occurrence of Interleukin-2 (330 G/T) Promoter Polymorphism in ARV associated hepatotoxicity

2019 ◽  
Vol 19 (3) ◽  
pp. 206-215
Author(s):  
HariOm Singh ◽  
Nayana Nambiar ◽  
Dharmesh Samani ◽  
Raman R. Gangakhedkar
Keyword(s):  
Hepatic Injury ◽  
Interleukin 2 ◽  
Promoter Polymorphism ◽  
Healthy Controls ◽  
Hiv Replication ◽  
Hiv Patients ◽  
Pcr Rflp

Background: IL-2 cytokine is involved in HIV replication and is also known to cause hepatic injury. Polymorphisms in the IL-2 gene are associated with altered interleukin-2 production. Methods: Hence, we assessed the prevalence of IL-2-303G/T polymorphism in 165 HIV patients (34 with and 131without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method. Results: In patients with hepatotoxicity, IL-2-303GT, -303GT+TT genotypes were less prevalent as compared to without hepatotoxicity and healthy controls (29.4% vs. 42.7%, 58.8% vs. 69.5%; 29.4% vs. 40.6%, 58.8% vs. 66.5%, respectively). In patients with hepatotoxicity using tobacco and alcohol, IL-2-303GT,-303TT genotypes were distributed higher as compared to non-users (42.9% vs. 25.9%, OR=8.52, 42.9% vs. 25.9%, OR=9.09, and 28.6% vs. 29.6%, OR=1.63, 42.9% vs. 25.9%, OR=2.93), while IL-2-303TT genotype occurred more often in HIV patients consuming alcohol (34.1% vs. 23.0%). Nevirapine users with hepatotoxicity overrepresented the IL-2-303GT,-303TT genotypes as compared to efavirenz (34.8% vs. 18.2%, OR=4.64, 34.8% vs. 18.2%, OR=3.88). Among nevirapine users, IL-2-303GT genotype was associated with susceptibility to the acquisition of hepatotoxicity with borderline significance (OR=4.24, P=0.06). HIV patients using nevirapine majorly represented the IL-2-303TT genotype (26.9% vs. 25.0%, OR=2.35) while HIV patients with nevirapine + alcohol usage presented the IL-2 -330TT genotype at a higher frequency (34.2% vs. 23.5%, OR=1.51). In patients with hepatotoxicity using nevirapine + alcohol, the genotype IL-2 - 330TT was predominant (60.0% vs. 27.8%, OR=3.16). Conclusion: Thus, IL-2-303G/T polymorphism did not confer the susceptibility to ARV associated hepatotoxicity. However, IL-2-303G/T polymorphism with nevirapine usage may facilitate the risk for acquisition of ARV associated hepatotoxicity.

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