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- Tangen, A, et al.
(författare)
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Associations Between Cognition and Serotonin 1B Receptor Availability in Healthy Volunteers: A [11C]AZ10419369 Positron Emission Tomography Study
- 2023
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Ingår i: The international journal of neuropsychopharmacology. - : Oxford University Press (OUP). - 1469-5111 .- 1461-1457. ; 26:4, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe serotonin system has been implicated in several psychiatric disorders. All major psychiatric disorders are associated with cognitive impairment, but treatment improving cognitive deficits is lacking, partly due to limited understanding of the neurobiology of cognitive functioning. Several markers for the serotonin system have been associated with cognitive functions. Our research group previously has reported a positive correlation between serotonin (5-HT1B) receptor availability in the dorsal brainstem and visuospatial memory in a pilot study of healthy individuals. Here, we aim to replicate our previous finding in a larger group of healthy volunteers as well as to investigate putative associations between 5-HT1B receptor availability and other cognitive domains.MethodsForty-three healthy individuals were examined with positron emission tomography using the 5-HT1B receptor radioligand [11C]AZ10419369 and a visuospatial memory test to replicate our previous finding as well as tests of verbal fluency, cognitive flexibility, reaction time, and planning ability to explore other domains potentially associated with the serotonin system.ResultsReplication analysis revealed no statistically significant association between 5-HT1B receptor availability in the dorsal brainstem and visuospatial memory performance. Exploratory analyses showed age-adjusted correlations between 5-HT1B receptor availability in whole brain gray matter and specific brain regions, and number of commission errors, reaction time, and planning ability.ConclusionsHigher 5-HT1B receptor availability was associated with more false-positive responses and faster reaction time but lower performance in planning and problem-solving. These results corroborate previous research supporting an important role of the serotonin system in impulsive behavior and planning ability.
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- López, E, et al.
(författare)
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[Psychedelic psychiatry]
- 2024
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Ingår i: Lakartidningen. - 1652-7518. ; 121
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Tidskriftsartikel (refereegranskat)
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- Price, RB, et al.
(författare)
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International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators
- 2022
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 27:1112, s. 5096-5112
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Tidskriftsartikel (refereegranskat)abstract
- Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; β*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; β*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630
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- Svensson, JE, et al.
(författare)
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In vivo correlation of serotonin transporter and 1B receptor availability in the human brain: a PET study
- 2022
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X. ; 47:10, s. 1863-1868
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Tidskriftsartikel (refereegranskat)abstract
- Synaptic serotonin levels in the brain are regulated by active transport into the bouton by the serotonin transporter, and by autoreceptors, such as the inhibitory serotonin (5-HT) 1B receptor which, when activated, decreases serotonin release. Animal studies have shown a regulatory link between the two proteins. Evidence of such coupling could translate to an untapped therapeutic potential in augmenting the effect of selective serotonin reuptake inhibitors through pharmacological modulation of 5-HT1B receptors. Here we will for the first time in vivo examine the relationship between 5-HT1B receptors and serotonin transporters in the living human brain. Seventeen healthy individuals were examined with PET twice, using the radioligands [11C]AZ10419369 and [11C]MADAM for quantification of the 5-HT1B receptor and the 5-HT transporter, respectively. The binding potential was calculated for a set of brain regions, and the correlations between the binding estimates of the two radioligands were studied. [11C]AZ10419369 and [11C]MADAM binding was positively correlated in all examined brain regions. In most cortical regions the correlation was strong, e.g., frontal cortex, r(15) = 0.64, p = 0.01 and parietal cortex, r(15) = 0.8, p = 0.0002 while in most subcortical regions, negligible correlations was observed. Though the correlation estimates in cortex should be interpreted with caution due to poor signal to noise ratio of [11C]MADAM binding in these regions, it suggests a link between two key proteins involved in the regulation of synaptic serotonin levels. Our results indicate a need for further studies to address the functional importance of 5-HT1B receptors in treatment with drugs that inhibit serotonin reuptake.
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- Hsiao, Tiger Yu-Yang, et al.
(författare)
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JWST Reveals a Possible z similar to 11 Galaxy Merger in Triply Lensed MACS0647-JD
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 949:2
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Tidskriftsartikel (refereegranskat)abstract
- MACS0647-JD is a triply lensed z similar to 11 galaxy originally discovered with the Hubble Space Telescope. The three lensed images are magnified by factors of similar to 8, 5, and 2 to AB mag 25.1, 25.6, and 26.6 at 3.5 mu m. The brightest is over a magnitude brighter than other galaxies recently discovered at similar redshifts z > 10 with JWST. Here, we report new JWST imaging that clearly resolves MACS0647-JD as having two components that are either merging galaxies or stellar complexes within a single galaxy. The brighter larger component "A" is intrinsically very blue (ss similar to-2.6 +/- 0.1), likely due to very recent star formation and no dust, and is spatially extended with an effective radius similar to 70 +/- 24 pc. The smaller component "B" (r similar to 20-+ 58 pc) appears redder (ss similar to-2 +/- 0.2), likely because it is older (100-200 Myr) with mild dust extinction (AV similar to 0.1 mag). With an estimated stellar mass ratio of roughly 2:1 and physical projected separation similar to 400 pc, we may be witnessing a galaxy merger 430 million years after the Big Bang. We identify galaxies with similar colors in a high-redshift simulation, finding their star formation histories to be dissimilar, which is also suggested by the spectral energy distribution fitting, suggesting they formed further apart. We also identify a candidate companion galaxy "C" similar to 3 kpc away, likely destined to merge with A and B. Upcoming JWST Near Infrared Spectrograph observations planned for 2023 January will deliver spectroscopic redshifts and more physical properties for these tiny magnified distant galaxies observed in the early universe.
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| 21. |
- Jiang, HT, et al.
(författare)
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Plasma Levels of Brain-Derived Neurotrophic Factor and S100B in Relation to Antidepressant Response to Ketamine
- 2021
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Ingår i: Frontiers in neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 15, s. 698633-
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Tidskriftsartikel (refereegranskat)abstract
- Evidence demonstrates that brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B) have a pivotal role in the pathogenesis of major depressive disorder (MDD) and they are proposed as predictors of antidepressant response. Ketamine produces rapid antidepressant effects in MDD and pre-clinical studies suggest the necessity of increased BDNF levels for the antidepressant action of ketamine. However, studies observing the change of blood BDNF levels after ketamine intervention are inconsistent and studies about the role of plasma S100B in ketamine administration in MDD patients are lacking.MethodWe evaluated mature BDNF (mBDNF), S100B levels in plasma and their associations with depression severity in 30 Selective Serotonin Reuptake Inhibitor (SSRI)-resistant MDD patients enrolled in a randomized controlled trial of ketamine compared (n= 20) to a placebo (n= 10) control (saline). Severity of depression was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS).ResultsPlasma mBDNF and S100B were not significantly changed after 1–2 days of single ketamine compared to placebo. Plasma mBDNF and S100B levels did not significantly differ in responders compared to non-responders of ketamine treatment. The change of plasma mBDNF levels was positively correlated with the improvement of MADRS score after 1–2 weeks of open-label ketamine treatment (rho = 0.495,p= 0.031), though this change did not survive correction for multiple comparisons.ConclusionThese findings do not support the hypothesis that ketamine treatment increases BDNF plasma levels in MDD patients. No effect of ketamine treatment on S100B plasma levels was seen.
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| 23. |
- Meena, Ashish Kumar, et al.
(författare)
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Two Lensed Star Candidates at z similar or equal to 4.8 behind the Galaxy Cluster MACS J0647.7+7015
- 2023
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Ingår i: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8205 .- 2041-8213. ; 944:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of two extremely magnified lensed star candidates behind the galaxy cluster MACS J0647.7+015 using recent multiband James Webb Space Telescope (JWST) NIRCam observations. The star candidates are seen in a previously known, z (phot) similar or equal to 4.8 dropout giant arc that straddles the critical curve. The candidates lie near the expected critical curve position, but lack clear counter-images on the other side of it, suggesting these are possibly stars undergoing caustic crossings. We present revised lensing models for the cluster, including multiply imaged galaxies newly identified in the JWST data, and use them to estimate background macro-magnifications of at least greater than or similar to 90 and greater than or similar to 50 at the positions of the two candidates, respectively. With these values, we expect effective, caustic-crossing magnifications of similar to[10(3)-10(5)] for the two star candidates. The spectral energy distributions of the two candidates match well the spectra of B-type stars with best-fit surface temperatures of similar to 10,000 K, and similar to 12,000 K, respectively, and we show that such stars with masses greater than or similar to 20 M (circle dot) and greater than or similar to 50 M (circle dot), respectively, can become sufficiently magnified to be observable. We briefly discuss other alternative explanations and conclude that these objects are likely lensed stars, but also acknowledge that the less-magnified candidate may alternatively reside in a star cluster. These star candidates constitute the second highest-redshift examples to date after Earendel at z (phot) similar or equal to 6.2, establishing further the potential of studying extremely magnified stars at high redshifts with JWST. Planned future observations, including with NIRSpec, will enable a more detailed view of these candidates in the near future.
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| 24. |
- Meena, Ashish Kumar, et al.
(författare)
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Two Lensed Star Candidates at z ≃ 4.8 behind the Galaxy Cluster MACS J0647.7+7015
- 2023
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of two extremely magnified lensed star candidates behind the galaxy cluster MACS J0647.7+015 using recent multiband James Webb Space Telescope (JWST) NIRCam observations. The star candidates are seen in a previously known, zphot ≃ 4.8 dropout giant arc that straddles the critical curve. The candidates lie near the expected critical curve position, but lack clear counter-images on the other side of it, suggesting these are possibly stars undergoing caustic crossings. We present revised lensing models for the cluster, including multiply imaged galaxies newly identified in the JWST data, and use them to estimate background macro-magnifications of at least ≳90 and ≳50 at the positions of the two candidates, respectively. With these values, we expect effective, caustic-crossing magnifications of ∼[103–105] for the two star candidates. The spectral energy distributions of the two candidates match well the spectra of B-type stars with best-fit surface temperatures of ∼10,000 K, and ∼12,000 K, respectively, and we show that such stars with masses ≳20 M⊙ and ≳50 M⊙, respectively, can become sufficiently magnified to be observable. We briefly discuss other alternative explanations and conclude that these objects are likely lensed stars, but also acknowledge that the less-magnified candidate may alternatively reside in a star cluster. These star candidates constitute the second highest-redshift examples to date after Earendel at zphot ≃ 6.2, establishing further the potential of studying extremely magnified stars at high redshifts with JWST. Planned future observations, including with NIRSpec, will enable a more detailed view of these candidates in the near future.
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