Vortioxetine reduces BOLD signal during performance of the N-back working memory task:a randomised neuroimaging trial in remitted depressed patients and healthy controls

Cognitive dysfunction is common in depression during both acute episodes and remission. Vortioxetine is a novel multi-modal antidepressant that has improved cognitive function including executive function in depressed patients in randomised placebo controlled clinical trials. However, it is unclear whether vortioxetine is able to target directly the neural circuitry implicated in the cognitive deficits in depression. Remitted depressed (n=48) and healthy volunteers (n=48) were randomised to receive 14 days treatment with 20mg vortioxetine or placebo in a double blind design. The effects of treatment on functional Magnetic Resonance Imaging (fMRI) responses during an N-back working memory task were assessed at baseline and at the end of treatment. Neuropsychological measures of executive function, speed and information processing, attention and learning and memory were examined with the Trail Making Test (TMT), Rey Auditory Learning Test (RAVLT), and Digit Symbol Substitution Test (DSST) before and after treatment; subjective cognitive function was assessed using the perceived deficits questionnaire (PDQ). Compared to placebo, vortioxetine reduced activation in the right dorsolateral prefrontal cortex and left hippocampus during the N-Back task compared to placebo. Vortioxetine also increased TMT-A performance and self-reported cognitive function on the PDQ. These effects were seen across both subject groups. Vortioxetine modulates neural responses across a circuit subserving working memory in a direction opposite to the changes described in depression, when performance is maintained. This study provides evidence that vortioxetine has direct effects on the neural circuitry supporting cognitive function that can be dissociated from its effects on the mood symptoms of depression

Global Carbon Budget 2023

This is the final version. Available on open access from Copernicus Publications via the DOI in this recordData availability statement: This living-data update documents changes in methods and data sets applied to this most recent global carbon budget as well as evolving community understanding of the global carbon cycle. The data presented in this work are available at https://doi.org/10.18160/GCP-2023 (Friedlingstein et al., 2023). The data presented here are made available in the belief that their wide dissemination will lead to greater understanding of and new scientific insights into how the carbon cycle works, how humans are altering it, and how we can mitigate the resulting human-driven climate change. Full contact details and information on how to cite the data shown here are given at the top of each page in the accompanying database and are summarized in Table 2. The accompanying database includes three Excel files or ganized in the following spreadsheets. The file Global_Carbon_Budget_2023v1.0.xlsx includes the following: 1. a summary 2. the global carbon budget (1959–2022), 3. the historical global carbon budget (1750–2022), 4. global CO2 emissions from fossil fuels and cement pro duction by fuel type and the per capita emissions (1850– 2022), 5. CO2 emissions from land-use change from the individ ual bookkeeping models (1959–2022); 6. the ocean CO2 sink from the individual global ocean biogeochemistry models and f CO2 products (1959– 2022), 7. the terrestrial CO2 sink from the individual DGVMs (1959–2022), 8. the cement carbonation CO2 sink (1959–2022). The file National_Fossil_Carbon_Emissions_2023v1.0.xlsx includes the following: 1. a summary, 2. territorial country CO2 emissions from fossil fuels and cement production (1850–2022), 3. consumption country CO2 emissions from fossil fuels and cement production and emissions transfer from the international trade of goods and services (1990–2020) using CDIAC/UNFCCC data as reference, 4. emissions transfers (consumption minus territorial emissions, 1990–2020), 5. country definitions. The file National_LandUseChange_Carbon_Emissions_ 2023v1.0.xlsx includes the following: 1. a summary 2. territorial country CO2 emissions from land use change (1850–2022) from three bookkeeping models. All three spreadsheets are published by the Integrated Carbon Observation System (ICOS) Carbon Portal and are available at https://doi.org/10.18160/GCP-2023 (Friedlingstein et al., 2023). National emissions data are also available on Zenodo (Andrew and Peters, 2022, https://doi.org/10.5281/zenodo.7215364), from the Global Carbon Atlas (http://www.globalcarbonatlas.org/, last access: 9 November 2023, Global Carbon Project, 2023), and from Our World in Data (https://ourworldindata.org/co2-emissions, last access: 9 November 2023, Our World in Data, 2023).Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate is critical to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFOS) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on land-use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly, and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) is estimated with global ocean biogeochemistry models and observation-based fCO2 products. The terrestrial CO2 sink (SLAND) is estimated with dynamic global vegetation models. Additional lines of evidence on land and ocean sinks are provided by atmospheric inversions, atmospheric oxygen measurements, and Earth system models. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and incomplete understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the year 2022, EFOS increased by 0.9 % relative to 2021, with fossil emissions at 9.9±0.5 Gt C yr−1 (10.2±0.5 Gt C yr−1 when the cement carbonation sink is not included), and ELUC was 1.2±0.7 Gt C yr−1, for a total anthropogenic CO2 emission (including the cement carbonation sink) of 11.1±0.8 Gt C yr−1 (40.7±3.2 Gt CO2 yr−1). Also, for 2022, GATM was 4.6±0.2 Gt C yr−1 (2.18±0.1 ppm yr−1; ppm denotes parts per million), SOCEAN was 2.8±0.4 Gt C yr−1, and SLAND was 3.8±0.8 Gt C yr−1, with a BIM of −0.1 Gt C yr−1 (i.e. total estimated sources marginally too low or sinks marginally too high). The global atmospheric CO2 concentration averaged over 2022 reached 417.1±0.1 ppm. Preliminary data for 2023 suggest an increase in EFOS relative to 2022 of +1.1 % (0.0 % to 2.1 %) globally and atmospheric CO2 concentration reaching 419.3 ppm, 51 % above the pre-industrial level (around 278 ppm in 1750). Overall, the mean of and trend in the components of the global carbon budget are consistently estimated over the period 1959–2022, with a near-zero overall budget imbalance, although discrepancies of up to around 1 Gt C yr−1 persist for the representation of annual to semi-decadal variability in CO2 fluxes. Comparison of estimates from multiple approaches and observations shows the following: (1) a persistent large uncertainty in the estimate of land-use changes emissions, (2) a low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) a discrepancy between the different methods on the strength of the ocean sink over the last decade