379 research outputs found
Effects of depressive symptoms and peripheral DAT methylation on neural reactivity to alcohol cues in alcoholism
In alcohol-dependent (AD) patients, alcohol cues induce strong activations in
brain areas associated with alcohol craving and relapse, such as the nucleus
accumbens (NAc) and amygdala. However, little is known about the influence of
depressive symptoms, which are common in AD patients, on the brain’s
reactivity to alcohol cues. The methylation state of the dopamine transporter
gene (DAT) has been associated with alcohol dependence, craving and
depression, but its influence on neural alcohol cue reactivity has not been
tested. Here, we compared brain reactivity to alcohol cues in 38 AD patients
and 17 healthy controls (HCs) using functional magnetic resonance imaging and
assessed the influence of depressive symptoms and peripheral DAT methylation
in these responses. We show that alcoholics with low Beck’s Depression
Inventory scores (n=29) had higher cue-induced reactivity in NAc and amygdala
than those with mild/moderate depression scores (n=9), though subjective
perception of craving was higher in those with mild/moderate depression
scores. We corroborated a higher DAT methylation in AD patients than HCs, and
showed higher DAT methylation in AD patients with mild/moderate than low
depression scores. Within the AD cohort, higher methylation predicted craving
and, at trend level (P=0.095), relapse 1 year after abstinence. Finally, we
show that amygdala cue reactivity correlated with craving and DAT methylation
only in AD patients with low depression scores. These findings suggest that
depressive symptoms and DAT methylation are associated with alcohol craving
and associated brain processes in alcohol dependence, which may have important
consequences for treatment. Moreover, peripheral DAT methylation may be a
clinically relevant biomarker in AD patients
How alcohol makes the epigenetic clock tick faster and the clock reversing effect of abstinence
Investigating the Behavior of Sedimentary Mercury (Hg) During Burial‐Related Thermal Maturation
Understanding the behavior of mercury (Hg) in organic‐rich sediments as they undergo thermal maturation is important, for example, because enrichment of Hg in sedimentary deposits has become a widely used proxy for volcanism from Large Igneous Provinces (LIPs). In this study, we evaluate the effects of such processes on sedimentary Hg concentrations by investigating a common stratigraphic interval in three drill cores with different levels of thermal maturity (immature, mature and post‐mature) in Toarcian sediments (Posidonienschiefer Formation) from the Lower Saxony Basin, Germany. We present Hg concentrations, bulk organic geochemistry, and total sulfur data. Mercury concentrations in the mature and post‐mature sediments are increased >2‐fold relative to the immature material, which is greater than any potential differences in original Hg concentrations in the studied successions prior to burial. Organic‐carbon and host‐rock mass loss during thermal maturation may have concentrated Hg in the mature sediments to some extent, provided Hg is considered effectively immobile. The increased Hg, TOC‐normalized Hg, and TS‐normalized Hg are most likely linked to the “closed system” behavior of Hg in sedimentary basins and the relatively low temperatures (70–260°C) during maturation that resulted in limited Hg mobility. More speculatively, a certain degree of redistribution of Hg within the mature sediments is suggested by its enrichment in distinct stratigraphic levels. Regardless of the exact mechanisms at play, the elevated Hg concentrations in mature sediments amplify both Hg/TOC and Hg/TS, implying that thermal effects must be considered when using normalized Hg as a proxy for far‐field volcanic activity
The Eurasian epicontinental sea was an important carbon sink during the Palaeocene-Eocene thermal maximum
The Palaeocene-Eocene Thermal Maximum (ca. 56 million years ago) offers a primary analogue for future global warming and carbon cycle recovery. Yet, where and how massive carbon emissions were mitigated during this climate warming event remains largely unknown. Here we show that organic carbon burial in the vast epicontinental seaways that extended over Eurasia provided a major carbon sink during the Palaeocene-Eocene Thermal Maximum. We coupled new and existing stratigraphic analyses to a detailed paleogeographic framework and using spatiotemporal interpolation calculated ca. 720–1300 Gt organic carbon excess burial, focused in the eastern parts of the Eurasian epicontinental seaways. A much larger amount (2160–3900 Gt C, and when accounting for the increase in inundated shelf area 7400–10300 Gt C) could have been sequestered in similar environments globally. With the disappearance of most epicontinental seas since the Oligocene-Miocene, an effective negative carbon cycle feedback also disappeared making the modern carbon cycle critically dependent on the slower silicate weathering feedback.</p
P11 promoter methylation predicts the antidepressant effect of electroconvulsive therapy
Although electroconvulsive therapy (ECT) is among the most effective treatment options for pharmacoresistant major depressive disorder (MDD), some patients still remain refractory to standard ECT practise. Thus, there is a need for markers reliably predicting ECT non/response. In our study, we have taken a novel translational approach for discovering potential biomarkers for the prediction of ECT response. Our hypothesis was that the promoter methylation of p11, a multifunctional protein involved in both depressive-like states and antidepressant treatment responses, is differently regulated in ECT responders vs. nonresponders and thus be a putative biomarker of ECT response. The chronic mild stress model of MDD was adapted with the aim to obtain rats that are resistant to conventional antidepressant drugs (citalopram). Subsequently, electroconvulsive stimulation (ECS) was used to select responders and nonresponders, and compare p11 expression and promoter methylation. In the rat experiments we found that the gene promoter methylation and expression of p11 significantly correlate with the antidepressant effect of ECS. Next, we investigated the predictive properties of p11 promoter methylation in two clinical cohorts of patients with pharmacoresistant MDD. In a proof-of-concept clinical trial in 11 patients with refractory MDD, higher p11 promoter methylation was found in responders to ECT. This finding was replicated in an independent sample of 65 patients with pharmacoresistant MDD. This translational study successfully validated the first biomarker reliably predicting the responsiveness to ECT. Prescreening of this biomarker could help to identify patients eligible for first-line ECT treatment and also help to develop novel antidepressant treatment procedures for depressed patients resistant to all currently approved antidepressant treatments.Peer reviewe
Tracing North Atlantic volcanism and seaway connectivity across the Paleocene–Eocene Thermal Maximum (PETM)
Abstract. There is a temporal correlation between the peak activity of the North
Atlantic Igneous Province (NAIP) and the Paleocene–Eocene Thermal Maximum
(PETM), suggesting that the NAIP may have initiated and/or prolonged this
extreme warming event. However, corroborating a causal relationship is
hampered by a scarcity of expanded sedimentary records that contain both
climatic and volcanic proxies. One locality hosting such a record is the island of Fur in Denmark, where an expanded pre- to post-PETM succession containing
hundreds of NAIP ash layers is exceptionally well preserved. We compiled a
range of environmental proxies, including mercury (Hg) anomalies,
paleotemperature proxies, and lithium (Li) and osmium (Os) isotopes, to
trace NAIP activity, hydrological changes, weathering, and seawater
connectivity across this interval. Volcanic proxies suggest that NAIP
activity was elevated before the PETM and appears to have peaked during the
body of the δ13C excursion but decreased considerably during
the PETM recovery. This suggests that the acme in NAIP activity, dominated
by flood basalt volcanism and thermogenic degassing from contact
metamorphism, was likely confined to just ∼ 200 kyr (ca. 56.0–55.8 Ma). The hundreds of thick (> 1 cm) basaltic ashes in the post-PETM strata
likely represent a change from effusive to explosive activity, rather than
an increase in NAIP activity. Detrital δ7Li values and clay
abundances suggest that volcanic ash production increased the basaltic reactive
surface area, likely enhancing silicate weathering and atmospheric carbon
sequestration in the early Eocene. Signals in lipid biomarkers and Os
isotopes, traditionally used to trace paleotemperature and weathering
changes, are used here to track seaway connectivity. These proxies indicate
that the North Sea was rapidly cut off from the North Atlantic in under 12 kyr during the PETM recovery due to NAIP thermal uplift. Our findings
reinforce the hypothesis that the emplacement of the NAIP had a profound and
complex impact on Paleocene–Eocene climate, both directly through volcanic
and thermogenic degassing and indirectly by driving regional uplift and
changing seaway connectivity
Effects of redox variability and early diagenesis on marine sedimentary Hg records
Volcanism is a dominant natural source of mercury (Hg) to the atmosphere, biosphere, ocean and sediments. In recent years, sedimentary Hg contents have emerged as a tool to reconstruct volcanic activity, and particularly activity of (subaerially emplaced) large igneous provinces in geological deep time. More specifically, Hg has shown potential as a useful proxy to illuminate the previously elusive impact of such large-scale volcanism on marine and terrestrial paleo-environments. While Hg is now widely applied as volcanism tracer, non-volcanic factors controlling sedimentary Hg content are generally not well constrained. Part of this uncertainty stems from our inability to directly observe a natural unperturbed “steady-state” environment as a baseline, as the modern Hg cycle is heavily influenced by anthropogenic activity. Here we focus on the effects of ambient redox conditions in the water column and shallow sediments (early diagenesis), quantify their influence on the geological Hg record and thereby contribute to constraining their potential impact on the use of Hg as a proxy for deep-time volcanic activity. Constraining these factors is of critical importance for the application of Hg as such a proxy. Many periods in the geological past for which records have been generated, such as the Mesozoic Oceanic Anoxic Events, are marked by a variety of high-amplitude environmental perturbations, including widespread deoxygenation and deposition of organic-rich sediments. We estimate the impact of redox changes and early diagenesis on the geological Hg record using a suite of (sub)recent–Pleistocene and Upper Cretaceous sediments representing oxic to euxinic marine conditions. Our sample set includes a transect through an oxygen minimum zone and cores that record transient shifts in oxygenation state, as well as post-depositional effects – all unrelated to volcanism, to the best of our knowledge. We find substantial alterations to the Hg record and the total organic carbon and total sulfur content, which are typically assumed to be the most common carrier phases of Hg in marine sediments. Moreover, these biases can lead to signal alteration on a par with those interpreted to result from volcanic activity. Geochemical modifications are ubiquitous and their potential magnitude implies that the factors leading to biases in the geological record warrant careful consideration before interpretation. Factors of particular concern to proxy application are (1) the disproportionate loss of organic carbon and sulfur relative to Hg during oxidation that strongly modulates normalized Hg records, (2) the evasion of Hg in anoxic and mildly euxinic sediments and (3) sharp focusing of Hg during post-depositional oxidation of organic matter. We suggest that paired analyses of additional redox-sensitive trace elements such as molybdenum, and organic-matter characteristics, particularly the type of organic matter, could provide first-order constraints on the role that redox and diagenetic changes played in shaping the Hg record as part of checking the attribution of enrichments to volcanic activity
Mercury records covering the past 90 000 years from lakes Prespa and Ohrid, SE Europe
The element mercury (Hg) is a key pollutant, and much insight has been gained by studying the present-day Hg cycle. However, many important processes within this cycle operate on timescales responsive to centennial- to millennial-scale environmental variability, highlighting the importance of also investigating the longer-term Hg records in sedimentary archives. To this end, we here explore the timing, magnitude, and expression of Hg signals retained in sediments over the past ∼ 90 kyr from two lakes, linked by a subterranean karst system: Lake Prespa (Greece, North Macedonia, and Albania) and Lake Ohrid (North Macedonia and Albania). Results suggest that Hg fluctuations are largely independent of variability in common host phases in each lake, and the recorded sedimentary Hg signals show distinct differences first during the Late Pleistocene (Marine Isotope Stages 2–5). The Hg signals in Lake Prespa sediments highlight an abrupt, short-lived peak in Hg accumulation coinciding with local deglaciation. In contrast, Lake Ohrid shows a broader interval with enhanced Hg accumulation and, superimposed, a series of low-amplitude oscillations in Hg concentration peaking during the Last Glacial Maximum, which may result from elevated clastic inputs. Divergent Hg signals are also recorded during the Early and Middle Holocene (Marine Isotope Stage 1). Here, Lake Prespa sediments show a series of large Hg peaks, while Lake Ohrid sediments show a progression to lower Hg values. Since ∼ 3 ka, anthropogenic influences overwhelm local fluxes in both lakes. The lack of coherence in Hg accumulation between the two lakes suggests that, in the absence of an exceptional perturbation, local differences in sediment composition, lake structure, Hg sources, and water balance all influence the local Hg cycle and determine the extent to which Hg signals reflect local- or global-scale environmental changes
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