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Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
Two sentiments governed the postwar world: fear and hope. These two feelings dominated the debates that gave birth to both the Charter of the United Nations and the Universal Declaration of Human Rights. The League of Nations had failed. Leaders had expressed the desire for a world grounded in human rights but could not agree on what that meant or whether individual rights trumped the sovereign rights of nations. The UN Charter reflected these concerns, recognizing human rights but leaving their scope undefined. No precedents existed to guide the work. A committee of eighteen nations, chaired by Eleanor Roosevelt, accepted the unprecedented assignment of defining basic rights for all people everywhere. After consulting with noted jurists, philosophers, and social justice organizations, the committee set out to draft a document that would recognize the horrors of war and engender a commitment to peace. They envisioned a world governed more by hope than by fear. It was hard work. The debate was punctuated by escalating Cold War politics. A legally binding document seemed out of reach. All efforts turned instead to securing a declaration of human rights, which ultimately paved the way for legally binding commitments and energized a budding human rights movement.
Pain is subjective. The level of pain a person experiences is affected not only by the painful stimulus but also by the person’s psychological interpretation of the pain and previous experiences. Medical procedures are inevitably associated with some level of discomfort but, by using analgesic and anaesthetic medications appropriately, we can minimise the pain experienced. In the outpatient setting, pain is the main driver of procedure acceptability. When appropriate techniques and equipment are used, and when analgesic use is tailored to the patient and the procedure, most women deem outpatient hysteroscopic procedures acceptable. Although performing hysteroscopic procedures under general anaesthetic means that perioperative pain is not an issue, it is still important to recognise the possibility of post-operative pain and provide adequate analgesia to manage it accordingly. The aim of this chapter is to cover techniques that can minimise pain and to discuss the use of analgesic and anaesthetic medication for hysteroscopic procedures.
Life course research embraces the complexity of health and disease development, tackling the extensive interactions between genetics and environment. This interdisciplinary blueprint, or theoretical framework, offers a structure for research ideas and specifies relationships between related factors. Traditionally, methodological approaches attempt to reduce the complexity of these dynamic interactions and decompose health into component parts, ignoring the complex reciprocal interaction of factors that shape health over time. New methods that match the epistemological foundation of the life course framework are needed to fully explore adaptive, multilevel, and reciprocal interactions between individuals and their environment. The focus of this article is to (1) delineate the differences between lifespan and life course research, (2) articulate the importance of complex systems science as a methodological framework in the life course research toolbox to guide our research questions, (3) raise key questions that can be asked within the clinical and translational science domain utilizing this framework, and (4) provide recommendations for life course research implementation, charting the way forward. Recent advances in computational analytics, computer science, and data collection could be used to approximate, measure, and analyze the intertwining and dynamic nature of genetic and environmental factors involved in health development.
To examine relationships between suicidal ideation, self-harm, and suicide attempts, including the timing of the phenomena.
Subjects and methods
The British National Psychiatric Morbidity Survey (NPMS) 2000, a randomised cross-sectional survey of the British population (n = 8,580), included detailed questions about suicidal phenomena.
Suicidal phenomena were common in the survey population: a fifth had experienced tedium vitae, and nearly one in six had had death wishes or considered suicide. 4.4% of the study population had attempted suicide at some time. The relationships between individual elements of suicidality, though not absolute, were strong. The relationships tended to be hierarchical. The results suggested that suicidal thinking represents a strong indicator of vulnerability to suicidal acts, less so to self-harm. Although suicidal phenomena were more common in women, the relationship of the different elements were not affected by gender.
Studies in non clinical populations allow full appreciation of the nature and burden of suicidality. The topic of suicide is sensitive, so there may have been under-reporting, although the level of missing data was around 0.1%. Nevertheless, the sample was large and closely representative of the whole British populace.
Suicidality is common in the British population. The strong relationships between elements of suicidality are clinically important.
Social anxiety disorder (SAD) is a strong risk factor for the development of depressive disorders (major depressive disorder or dysthymia).
Identification of blood-based molecular predictors of a subsequent depressive episode in SAD.
Objectives: To screen SAD patient serum for biomarkers which predict the onset of depressive disorders over a 2-year follow-up period.
Multiplexed-immunoassay data obtained from 143 SAD patients without co-morbid depressive disorders, recruited within the Netherlands Study of Depression and Anxiety (NESDA), were investigated. The serum screen included 165 mainly immunological, metabolical and hormonal analytes. Predictive performance of identified biomarkers and clinical variables (e.g. Beck Anxiety Inventory) was assessed using receiver operating characteristics curves (ROC) and represented by the area under the ROC curve (AUC). Stepwise logistic regression was used to select an optimal set of patient parameters, combining predictive serum analytes and clinical variables.
A set of four serum analytes and four associated clinical variables reached an AUC of 0.86 for the identification of SAD individuals, who developed a subsequent depressive episode. Throughout our analyses, biomarker panels yielded superior discriminative performance compared to clinical variables alone.
We report the discovery of a serum marker panel with good predictive performance to identify SAD individuals prone to develop depressive disorders in a naturalistic cohort design. Furthermore, we emphasise the importance to combine biological markers and clinical parameters for disease course predictions in psychiatry. Validated biomarkers could help to identify SAD patients at risk of a depressive episode, thus facilitating early treatment and improving clinical outcome.
Rodent models of schizophrenia (SCZ) are indispensable when screening for novel treatments, but quantifying their translational relevance with the underlying human pathophysiology has proved difficult. A novel systems methodology (shown in Figure 1) was developed integrating and comparing proteomic data of anterior prefrontal cortex tissue from SCZ post-mortem brains and matched controls with data obtained from four established glutamatergic rodent models, with the aim of evaluating which of these models represent SCZ most closely. Liquid chromatography coupled tandem mass spectrometry (LC-MSE) proteomic profiling was applied comparing healthy and “disease state” in human post-mortem samples and rodent brain tissue samples. Protein-protein interaction networks were constructed from significant abundance changes and enrichment analyses enabled the identification of pathophysiological characteristics of the disorder, which were represented across all four rodent models. Subsequently, these functional domains were used for cross-species comparisons. Five functional domains such as “development and differentiation” represented across all four rodent models, were identified. It was quantified that the chronic phencyclidine (cPCP) model represented SCZ brain changes most closely for four of these functional domains, by using machine-learning techniques. This is the first study aiming to quantify which rodent model recapitulates the neuropathological features of SCZ most closely. The methodology and findings presented here support recent efforts to overcome translational hurdles of preclinical psychiatric research by associating behavioural endophenotypes with distinct biological processes.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Health anxiety is an under-recognised but a frequent cause of distress. It is particularly common in general hospitals.
We carried out an 8-year follow-up of medical out-patients with health anxiety (hypochondriasis) enrolled in a randomised-controlled trial in five general hospitals in London, Middlesex and Nottinghamshire. Randomisation was to a mean of six sessions of cognitive behaviour therapy adapted for health anxiety (CBT-HA) or to standard care in the clinics. The primary outcome was a change in score on the Short Health Anxiety Inventory, with generalised anxiety and depression as secondary outcomes. Of 444 patients aged 16–75 years seen in cardiology, endocrinology, gastroenterology, neurology and respiratory medicine clinics, 306 (68.9%) were followed-up 8 years after randomisation, including 36 who had died. The study is registered with controlled-trials.com, ISRCTN14565822.
There was a significant difference in the HAI score in favour of CBT-HA over standard care after 8 years [1.83, 95% confidence interval (CI) 0.25–3.40, p = 0.023], between group differences in generalised anxiety were less (0.54, 95% CI −0.29 to 1.36), p = 0.20, ns), but those for depression were greater at 8 years (1.22, 95% CI 0.42–2.01, p < 0.003) in CBT-HA than in standard care, most in standard care satisfying the criteria for clinical depression. Those seen by nurse therapists and in cardiology and gastrointestinal clinics achieved the greatest gains with CBT-HA, with greater improvement in both symptoms and social function.
CBT-HA is a highly long-term effective treatment for pathological health anxiety with long-term benefits. Standard care for health anxiety in medical clinics promotes depression. Nurse therapists are effective practitioners.
This study examined the association of spatial working memory and attenuated psychotic-like experiences and related symptoms with social and role functioning. Findings from this study suggest that symptom dimensions and working memory impairment were associated with diminished functioning across a variety of domains. Specifically, negative symptoms and working memory impairment were inversely associated with both social and role functioning, whereas positive and disorganized symptoms showed inverse associations with social functioning only. Symptom dimensions did not moderate cognitive and functional variables, although working memory and attenuated clinical symptoms had an additive effect on functioning. Post-hoc analyses examining symptom dimensions simultaneously showed negative symptoms to be the variable most strongly predictive of overall functioning. These findings suggest that even in a non-clinical sample, sub-threshold psychosis symptoms and cognition may influence people’s social and role functioning.
Beginning with loose aggregations of dust particles coated with heterogeneous ices under vacuum at Kuiper Belt temperatures, moving to Jupiter/Saturn distances and eventually to low-perihelion orbit, we consider the likely development of the gaseous phase within a cometary nucleus over the course of its lifetime. From the perspective of physical chemistry, we consider limits on the spatial and temporal distribution and composition of this gaseous phase. The implications of the gaseous phase for heat transfer and for the possible spatial and temporal development of liquid phases are calculated. We conclude that the likely temperatures, pressures, and compositions beneath the outer crust of typical cometary nuclei are such that fluidised phases can exist at significant depths and that these reservoirs give a coherent explanation for the high-intensity outbursts observed from cometary nuclei at large distances from perihelion.
Here we use polarimetric measurements from an Autonomous phase-sensitive Radio-Echo Sounder (ApRES) to investigate ice fabric within Whillans Ice Stream, West Antarctica. The survey traverse is bounded at one end by the suture zone with the Mercer Ice Stream and at the other end by a basal ‘sticky spot’. Our data analysis employs a phase-based polarimetric coherence method to estimate horizontal ice fabric properties: the fabric orientation and the magnitude of the horizontal fabric asymmetry. We infer an azimuthal rotation in the prevailing horizontal c-axis between the near-surface (z ≈ 10–50 m) and deeper ice (z ≈ 170–360 m), with the near-surface orientated closer to perpendicular to flow and deeper ice closer to parallel. In the near-surface, the fabric asymmetry increases toward the center of Whillans Ice Stream which is consistent with the surface compression direction. By contrast, the fabric orientation in deeper ice is not aligned with the surface compression direction but is consistent with englacial ice reacting to longitudinal compression associated with basal resistance from the nearby sticky spot.
We document a positive and strong correlation between speciation and extinction rates in the Paleozoic zooplankton graptoloid clade, between 481 and 419 Ma. This correlation has a magnitude of ~0.35–0.45 and manifests at a temporal resolution of <50 kyr and, for part of our data set, <25 kyr. It cannot be explained as an artifact of the method used to measure rates, sampling bias, bias resulting from construction of the time series, autocorrelation, underestimation of species durations, or undetected phyletic evolution. Correlations are approximately equal during the Ordovician and Silurian, despite the very different speciation and extinction regimes prevailing during these two periods, and correlation is strongest in the shortest-lived cohorts of species.
We infer that this correlation reflects approximately synchronous coupling of speciation and extinction in the graptoloids on timescales of a few tens of thousands of years. Almost half of graptoloid species in our data set have durations of <0.5 Myr, and previous studies have demonstrated that, during times of background extinction, short-lived species were selectively targeted by extinction. These observations may be consistent with the model of ephemeral speciation, whereby new species are inferred to form constantly and at high rate, but most of them disappear rapidly through extinction or reabsorption into the ancestral lineage. Diversity dependence with a lag of ~1 Myr, also documented elsewhere, may reflect a subsequent and relatively slow, competitive dynamic that governed those species that dispersed beyond their originating water mass and escaped the ephemeral species filter.
Fast ice flow on the Antarctic continent constitutes much of the mass loss from the ice sheet. However, geophysical methods struggle to constrain ice flow history at depth, or separate the signatures of topography, ice dynamics and basal conditions on layer structure. We develop and demonstrate a methodology to compare layer signatures in multiple airborne radar transects in order to characterize ice flow at depth, or improve coverage of existing radar surveys. We apply this technique to generate synthetic, along-flow radargrams and compare different deformation regimes to observed radargram structure. Specifically, we investigate flow around the central sticky spot of Whillans Ice Stream, West Antarctica. Our study suggests that present-day velocity flowlines are insufficient to characterize flow at depth as expressed in layer geometry, and streaklines provide a better characterization of flow around a basal sticky spot. For Whillans Ice Stream, this suggests that ice flow wraps around the central sticky spot, supported by idealized flow simulations. While tracking isochrone translation and rotation across survey lines is complex, we demonstrate that our approach to combine radargram interpretation and modeling can reveal critical details of past ice flow.
The foetal programming hypothesis posits that optimising early life factors e.g. maternal diets can help avert the burden of adverse childhood outcomes e.g. childhood obesity. To improve applicability to public health messaging, we investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity in a large consortium.
We harmonized and pooled individual participant data from up to 8,769 mother-child pairs in 7 European mother-offspring cohorts. Maternal early-, late-, and whole-pregnancy dietary quality and inflammatory potential were assessed with Dietary Approaches to Stop Hypertension (DASH) and energy-adjusted Dietary Inflammatory Index (E-DII), respectively. Primary outcome was childhood overweight and obesity (OWOB), defined as age- and sex-specific body-mass-index-z score (BMIz) > 85th percentile based on WHO growth standard. Secondary outcomes were sum-of-skinfold-thickness (SST), fat-mass-index (FMI) and fat-free-mass-index (FFMI) in available cohorts. Outcomes were assessed in early- [mean (SD) age: 2.8 (0.3) y], mid- [6.2 (0.6) y], and late-childhood [10.6 (1.2) y]. We used multivariable regression analyses to assess the associations of maternal E-DII and DASH with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Analyses were adjusted for maternal age, pre-pregnancy BMI, parity, lifestyle factors, energy intake, educational attainment, offspring age and sex.
A more pro-inflammatory maternal diet, indicated by higher E-DII, was associated with a higher risk of offspring late-childhood OWOB [pooled-OR (95% CI) comparing highest vs. lowest E-DII quartiles: 1.22 (1.01,1.47) for whole-pregnancy and 1.38 (1.05,1.83) for early-pregnancy; both P < 0.05]. Moreover, higher late-pregnancy E-DII was associated with higher mid-childhood FMI [pooled-β (95% CI): 0.11 (0.003,0.22) kg/m2; P < 0.05]; trending association was observed for whole-pregnancy E-DII [0.12 (-0.01,0.25) kg/m2; P = 0.07]. A higher maternal dietary quality, indicated by higher DASH score, showed a trending inverse association with late-childhood OWOB (pooled-OR (95% CI) comparing highest vs. lowest DASH quartiles: 0.58 (0.32,1.02; P = 0.06). Higher early-pregnancy DASH was associated with lower late-childhood SST [pooled-β (95% CI): -1.9 (-3.6,-0.1) cm; P < 0.05] and tended to be associated with lower late-childhood FMI [-0.34 (-0.71,0.04) kg/m2; P = 0.08]. Higher whole-pregnancy DASH tended to associate with lower early-childhood SST [-0.33 (-0.72,0.06) cm; P = 0.10]. Results were similar when modelling DASH and E-DII continuously.
Analysis of pooled data suggests that pro-inflammatory, low-quality maternal antenatal diets may influence offspring body composition and obesity risk, especially during mid- or late-childhood. Due to variation of data availability at each timepoint, our results should be interpreted with caution. Because most associations were observed at mid-childhood or later, future studies will benefit from a longer follow-up.
Pelagic seabirds often nest on islands that are far from productive foraging areas. The Procellariiformes (petrels, shearwaters and albatrosses) are among the longest-ranging seabirds; they have several adaptations that permit them to efficiently utilize distant foraging areas and fast for long periods during incubation (Phillips & Hamer 1999). Giant petrels (Macronectes spp.) are large surface-nesting procellariiforms. They feed both by direct predation and by scavenging carrion, and they are the largest avian predator-scavengers in the Southern Ocean. Among procellariiform seabirds, one partner forages while their mate remains on the nest to incubate their single egg (Warham 1990). Northern giant petrels (Macronectes halli) have incubation shifts lasting up to 17 days (Cooper et al. 2001). In general, incubating procellariiform seabirds do not feed during their shift (Warham 1990). We report the first case to our knowledge of a procellariiform seabird, a northern giant petrel, actively feeding at its nest whilst incubating.
We present a broad study of linear, clustered, noble gas puffs irradiated with the frequency doubled (527 nm) Titan laser at Lawrence Livermore National Laboratory. Pure Ar, Kr, and Xe clustered gas puffs, as well as two mixed-gas puffs consisting of KrAr and XeKrAr gases, make up the targets. Characterization experiments to determine gas-puff density show that varying the experimental parameter gas-delay timing (the delay between gas puff initialization and laser-gas-puff interaction) provides a simple control over the gas-puff density. X-ray emission (>1.4 keV) is studied as a function of gas composition, density, and delay timing. Xe gas puffs produce the strongest peak radiation in the several keV spectral region. The emitted radiation was found to be anisotropic, with smaller X-ray flux observed in the direction perpendicular to both laser beam propagation and polarization directions. The degree of anisotropy is independent of gas target type but increases with photon energy. X-ray spectroscopic measurements estimate plasma parameters and highlight their difference with previous studies. Electron beams with energy in excess of 72 keV are present in the noble gas-puff plasmas and results indicate that Ar plays a key role in their production. A drastic increase in harder X-ray emissions (X-ray flash effect) and multi-MeV electron-beam generation from Xe gas-puff plasma occurred when the laser beam was focused on the front edge of the linear gas puff.
The Developmental Origins of Disease hypothesis has spurred increased interest in how prenatal exposures affect lifelong health, while mechanisms such as epigenetics may explain the multigenerational influences on health. Such factors are not well captured within conventional epidemiologic study designs. We explored the feasibility of collecting information on the offspring and grand-offspring of participants in a long-running study.
The Bogalusa Heart Study is a study, begun in 1973, of life-course cardiovascular health in a semirural population (65% white and 35% black).
Female participants who had previously provided information on their pregnancies were contacted to obtain contact information for their daughters aged 12 and older. Daughters were then contacted to obtain reproductive histories, and invited for a clinic or lab visit to measure cardiovascular risk factors.
Two hundred seventy-four daughters of 208 mothers were recruited; 81% (223) had a full clinic visit and 19% (51) a phone interview only. Forty-five percent of the daughters were black, and 55% white. Mean and median age at interview was 27, with 15% under the age of 18. The strongest predictors of participation were black race, recent maternal participation in the parent study, and living in or near Bogalusa. Simple correlations for cardiovascular risk factors across generations were between r = 0.19 (systolic blood pressure) and r = 0.39 (BMI, LDL).
It is feasible to contact the children of study participants even when participants are adults, and initial information on the grandchildren can also be determined in this manner.