Objective
The longitudinal course of neuropsychological functioning after the first manic episode in bipolar disorder is unknown. The present study evaluated cognitive change in bipolar disorder in ...the first 3 years after the initial manic episode.
Methods
Ninety‐one newly diagnosed patients with bipolar disorder and 61 demographically similar healthy participants received a neuropsychological evaluation assessing multiple cognitive domains at baseline, 1‐year, and 3‐year time points. Patients also received clinical assessments including mood ratings at all time points.
Results
Patients showed deficits in all domains at baseline, but similar longitudinal trajectories across time relative to healthy participants in most cognitive domains. For processing speed, patients showed more gains than controls from baseline to 1 year, but these gains stabilized thereafter. Patients with alcohol/substance abuse showed an initial delay but subsequent recovery in executive functioning. Patients who discontinued antipsychotic treatment showed better cognitive outcomes in verbal memory.
Conclusion
Appropriately treated patients with bipolar disorder showed favorable cognitive outcome in the first 3 years after experiencing an initial manic episode, arguing against cognitive neuroprogression at this stage of the illness. Discontinuation of antipsychotic treatment may be associated with better cognitive outcomes, but clarification of the role of antipsychotics on cognitive functioning requires further investigation.
IntroductionDespite replicated cross-sectional evidence of aberrant levels of peripheral inflammatory markers in individuals with major depressive disorder (MDD), there is limited literature on ...associations between inflammatory tone and response to sequential pharmacotherapies.ObjectivesTo assess associations between plasma levels of pro-inflammatory markers and treatment response to escitalopram and adjunctive aripiprazole in adults with MDD.MethodsIn a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10– 20 mg daily for 8 weeks. Responders continued on escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers – C-reactive protein, Interleukin (IL)-1β, IL-6, IL-17, Interferon gamma (IFN)-Γ, Tumour Necrosis Factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2) - measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyses to assess associations between inflammatory markers and treatment response.ResultsPre-treatment levels of IFN-Γ and CCL-2 were significantly higher in escitalopram non-responders compared to responders. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.ConclusionsPre-treatment levels of IFN-Γ and CCL-2 were predictive of response to escitalopram. Increasing levels of these pro-inflammatory markers may predict non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.Disclosure of InterestNone Declared
► Silver ions and silver nanoparticles affect neurotransmitters in rat brain. ► Silver ions and silver nanoparticles induce apoptosis in vitro by both death receptor and mitochondrial pathways. ► ...Silver ions and 14nm silver nanoparticles seem to have similar neurotoxic mechanisms.
We compared the neurotoxic effects of 14nm silver nanoparticles (AgNPs) and ionic silver, in the form of silver acetate (AgAc), in vivo and in vitro. In female rats, we found that AgNPs (4.5 and 9mg AgNP/kg bw/day) and ionic silver (9mg Ag/kg bw/day) increased the dopamine concentration in the brain following 28 days of oral administration. The concentration of 5-hydroxytryptamine (5-HT) in the brain was increased only by AgNP at a dose of 9mg Ag/kg bw/day. Only AgAc (9mg Ag/kg bw/day) was found to increase noradrenaline concentration in the brain. In contrast to the results obtained from a 28-day exposure, the dopamine concentration in the brain was decreased by AgNPs (2.25 and 4.5mg/kg bw/day) following a 14-day exposure. These data suggest that there are differential effects of silver on dopamine depending on the length of exposure. In vitro, AgNPs, AgAc and a 12kDa filtered sub-nano AgNP fraction were used to investigate cell death mechanisms in neuronal-like PC12 cells. AgNPs and the 12kDa filtered fraction decreased cell viability to a similar extent, whereas AgAc was relatively more potent. AgNPs did not induce necrosis. However, apoptosis was found to be equally increased in cells exposed to AgNPs and the 12kDa filtered fraction, with AgAc showing a greater potency. Both the mitochondrial and the death receptor pathways were found to be involved in AgNP- and AgAc-induced apoptosis. In conclusion, 14nm AgNPs and AgAc affected brain neurotransmitter concentrations. AgNP affected 5-HT, AgAc affected noradrenaline, whereas both silver formulations affected dopamine. Furthermore, apoptosis was observed in neuronal-like cells exposed to AgNPs, a 12kDa filtered fraction of AgNP, and AgAc. These findings suggest that ionic silver and a 14nm AgNP preparation have similar neurotoxic effects; a possible explanation for this could be the release and action of ionic silver from the surface of AgNPs.
We examined the performance of human Schlemm's canal (SC) imaging using different OCT devices: CIRRUS 5000 (840 nm, spectral-domain (SD)-OCT), PLEX Elite 9000 (1060 nm, swept-source (SS)-OCT) and ...CASIA SS-1000 (1310 nm, SS-OCT), and analyzed potential impact factors on visualization and the quantitative assessment of SC morphology in a pilot study. Ten healthy subjects were imaged using three OCT devices by a single experienced operator on the same day. Each eye underwent two cubic scans by each device, one on nasal and the other on temporal quadrant. The B-scan showing the largest SC was manually selected for processing. Four quantitative metrics, including one morphological metric as cross-sectional area (CSA), and three performance metrics as contrast, continuity, and coverage, were derived from the datasets. Repeated-measures ANOVA was used to investigate the difference between these parameters from the three devices (P < 0.05). We found the CSA measured from CIRRUS was significantly larger than PLEX, followed by CASIA. The contrast was highest in CIRRUS, followed by PLEX and CASIA. The coverage was also higher in CIRRUS as compared to PLEX and CASIA. No significant difference was seen in the continuity from the three devices. In summary, we showed the measurements from the three devices were not interchangeable.
It remains unclear if diminished high frequency heart rate variability (HF-HRV) can be found across anxiety disorders. HF-HRV and heart rate (HR) were examined in panic (PD), generalized anxiety ...(GAD), social anxiety (SAD), and obsessive–compulsive disorder (OCD) relative to healthy controls at baseline and during anxiety stressors. All disorders evidenced diminished baseline HF-HRV relative to controls. Baseline HRV differences were maintained throughout relaxation. For hyperventilation, PD and GAD demonstrated greater HR than controls. Psychotropic medication did not account for HF-HRV differences except in OCD. Age and sex evidenced multiple main effects. Findings suggest that low baseline HF-HRV represents a common index for inhibitory deficits across PD, GAD, and SAD, which is consistent with the notion of autonomic inflexibility in anxiety disorders. Elevated HR responses to hyperventilation, however, are specific to PD and GAD.
► Patients with panic, obsessive–compulsive, generalized, and social anxiety disorder. ► Heart rate (HR) and HR variability (HRV) at rest, hyperventilation, and relaxation. ► Lower HRV in all four anxiety disorders at rest compared to healthy controls. ► Lower HRV maintained, but not increased during relaxation. ► Elevated HR to hyperventilation only in panic and generalized anxiety patients.
Although cognitive deficits in bipolar disorder have been associated with diminished functional outcome, this relationship has been studied primarily through cross-sectional designs, and has not been ...studied in patients early in the course of illness. The purpose of this study was to evaluate the impact of cognitive functioning on longitudinal 6-month functional and clinical outcome in recently diagnosed clinically stable patients with bipolar disorder.
A total of 53 recently diagnosed patients with DSM-IV bipolar disorder type I were assessed within 3 months of their first manic episode using a neuropsychological battery measuring verbal/pre-morbid intellectual functioning, learning/memory, spatial/non-verbal reasoning, attention/processing speed and executive function. Functional outcome was assessed at baseline and 6 months using the Multidimensional Scale of Independent Functioning (MSIF) and DSM-IV Global Assessment of Functioning Scale (GAF). Clinical outcome was assessed with symptom ratings and by monitoring onset of new mood episodes.
Memory, particularly verbal learning/memory, was robustly associated with 6-month functional outcome on the MSIF, even after partialling out the influence of mood symptoms and substance abuse co-morbidity. Depression ratings at 6 months, but not cognitive variables, were associated with 6-month GAF scores. Cognitive functioning was not associated with 6-month clinical outcome.
Memory was associated with 6-month longitudinal functional but not clinical outcome in recently diagnosed patients with bipolar disorder. These data further support the distinction between clinical and functional outcome, and emphasize the need for identification of, and development of treatments for, cognitive impairments early in the course of bipolar disorder.
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•Grazing incidence geometry yields scattering from only the laser excited regions of the substrate.•Fragmentation in the ablation plume is seen to occur on a timescale of 20 ps after ...laser ablation.•Small angle scattering can be used as a tool to characterize the evolution of nanostructures in the ablation plume.
Controlling the morphology of laser-derived nanomaterials is dependent on developing a better understanding of the particle nucleation dynamics in the ablation plume. Here, we utilize the femtosecond-length pulses from an x-ray free electron laser to perform time-resolved grazing incidence x-ray scattering measurements on a laser-produced silicon plasma plume. At 20 ps we observe a dramatic increase in the scattering amplitude at small scattering vectors, which we attribute to incipient formation of liquid silicon droplets. These results demonstrate the utility of XFELs as a tool for characterizing the formation dynamics of nanomaterials in laser-produced plasma plumes on ultrafast timescales.
Mg-1Ca/HA composites were produced by blending magnesium-calcium (1wt%) (Mg-1Ca) alloys with 5, 10 and 15wt% of hydroxyapatite (HA). Morphology, elemental and phase composition of Mg-1Ca/HA ...composites were examined. Biocompatibility assessments were also performed using an indirect contact method by culturing human adipose mesenchymal stem cells (hASCs) in the extracts of Mg-1Ca alloy, Mg-1Ca/HA composites and Dulbecco's modified eagle's medium. Mg-1Ca/HA composites could promote cell proliferation and at the same time, enhanced collagen type I (COL I) and osteocalcin (OCN) expressions of hASCs. Among the Mg-1Ca/HA composites, 10wt% of HA is the optimum amount to be added into Mg-1Ca alloy for enhanced bioactivity, thus emerging as a potential biomaterial for orthopedic fixation.
•Mg-1Ca/HA composites containing 5, 10 and 15wt% of HA were formed.•Apatite and α-Mg phases were detected in the Mg-1Ca/HA composites.•Mg-1Ca/10HA composite showed better enhancement in bone differentiation markers.
Planktic foraminifera are commonly used for first-order age control in deep-sea sediments from low-latitude regions based on a robust tropical–subtropical zonation scheme. Although multiple Neogene ...planktic foraminiferal biostratigraphic zonations for mid-latitude regions exist, quantification of diachroneity for the species used as datums to test paleobiogeographic patterns of origination and dispersal is lacking. Here, we update the age models for seven southwest-Pacific deep-sea sites using calcareous nannofossil and bolboform biostratigraphy and magnetostratigraphy, and use 11 sites between 37.9° N and 40.6° S in the western Pacific to correlate existing planktic foraminiferal biozonations and quantify the diachroneity of species used as datums. For the first time, northwest and southwest Pacific biozones are correlated and compared to the global tropical planktic foraminiferal biozonation. We find a high degree of diachroneity in the western Pacific, within and between the northwest and southwest regions, and between the western Pacific and the tropical zonation. Importantly, some datums that are found to be diachronous between regions have reduced diachroneity within regions. Much work remains to refine regional planktic foraminiferal biozonations and more fully understand diachroneity between the tropics and mid-latitudes. This study indicates that diachroneity is the rule for Late Neogene planktic foraminifera, rather than the exception, in mid-latitude regions.
Full understanding of diversity dynamics during the Great Ordovician Biodiversification Event (GOBE) requires analyses that investigate regional and species-level data and patterns. In this study, we ...combine bedding-plane scale data on brachiopod species counts and shell size collected from the Simpson Group of Oklahoma, USA, with species-level phylogenetic bio-geography for three articulated brachiopod lineages that occurred throughout Laurentia. From these data, we ascertain that the primary influences of brachiopod shell size and diversity in the Simpson Group reflect global drivers, notably temporal position and paleotemperature. Similarly, the primary speciation pattern observed within Hesperorthis, Mimella, and Oepikina is the oscillation in speciation mode between dispersal and vicariance, which reflect the connection and disconnection of geographic areas, respectively. Processes that facilitate cyclical connectivity are global to regional in scale such as oceanographic changes, glacial cycles, or tectonic pulses. Therefore, both regional and continental scale analyses reinforce the importance of global factors in driving diversification during the GOBE. Keywords: Ordovician, vicariance, dispersal, body size, North America, Oklahoma
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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