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Although neuroimaging studies suggest brain regional abnormalities in depressive disorders, it remains unclear whether abnormalities are present at illness onset or reflect disease progression.
We hypothesized that cerebral variations were present in adolescents with subthreshold depression known to be at high risk for later full-blown depression.
We examined brain structural and diffusion-weighted magnetic resonance images of adolescents with subthreshold depression.
The participants were extracted from the European IMAGEN study cohort of healthy adolescents recruited at age 14. Subthreshold depression was defined as a distinct period of abnormally depressed or irritable mood, or loss of interest, plus two or more depressive symptoms but without diagnosis of Major Depressive Episode. Comparisons were performed between adolescents meeting these criteria and control adolescents within the T1-weighted imaging modality (118 and 475 adolescents respectively) using voxel-based morphometry and the diffusion tensor imaging modality (89 ad 422 adolescents respectively) using tract-based spatial statistics. Whole brain analyses were performed with a statistical threshold set to p< 0.05 corrected for multiple comparisons.
Compared with controls, adolescents with subthreshold depression had smaller gray matter volume in caudate nuclei, medial frontal and cingulate cortices; smaller white matter volume in anterior limb of internal capsules, left forceps minor and right cingulum; and lower fractional anisotropy and higher radial diffusivity in the genu of corpus callosum.
The findings suggest that adolescents with subthreshold depression have volumetric and microstructural gray and white matter changes in the emotion regulation frontal-striatal-limbic network.
Gender representation is a pervasive problem in political science. We draw on evidence from the 2017 and 2018 American Political Science Association (APSA) Annual Meeting programs to discuss diversity and representation in large political science disciplinary conferences. APSA program divisions differ substantially in their gender representation: although some are representative of their organized-section membership, others are not, and some sections are particularly likely to feature “manels.” We present representation data by organized section, with discussions of what representation looks like and identifying different types of representation goals. We conclude by offering guidelines for increasing gender representation, for both future submitters and program chairs.
Exemplar models are a popular class of models used to describe language change. Here we study how limiting the memory capacity of an individual in these models affects the system's behaviour. In particular, we demonstrate the effect this change has on the extinction of categories. Previous work in exemplar dynamics has not addressed this question. In order to investigate this, we will inspect a simplified exemplar model. We will prove for the simplified model that all the sound categories but one will always become extinct, whether memory storage is limited or not. However, computer simulations show that changing the number of stored memories alters how fast categories become extinct.
The nature of glass transitions in chalcogenides and modified oxides depends on the network mean coordination number
. These display systematic trends when spanning across the three topological phases: flexible, intermediate, and stressed-rigid. Trends in the glass-transition temperature Tg(
) show a monotonic increase with
, but the nonreversing enthalpy of relaxation at Tg, ΔHnr(
), shows a deep- and square-well-like minimum with the walls representing the rigidity and stress transitions with increasing
, respectively. In the well, the ΔHnr(
) term remains minuscule (∼0) corresponding to the isostatically rigid intermediate phase (IP). The melt fragility index (m) shows rather low values, m(
) < 20 for IP compositions, but increases outside the IP. Glass compositions in the IP show absence of network stress, form compacted networks, possess thermally reversing glass transitions, and display high glass-forming tendency—functionalities that have attracted widespread interest in understanding the physics of glasses and applications of the new IP formed.
This paper addresses the levels of psychological distress experienced at age 42 years by men and women born in 1958 and 1970. Comparing these cohorts born 12 years apart, we ask whether psychological distress has increased, and, if so, whether this increase can be explained by differences in their childhood conditions.
Data were utilized from two well-known population-based birth cohorts, the National Child Development Study and the 1970 British Cohort Study. Latent variable models and causal mediation methods were employed.
After establishing the measurement equivalence of psychological distress in the two cohorts we found that men and women born in 1970 reported higher levels of psychological distress compared with those born in 1958. These differences were more pronounced in men (b = 0.314, 95% confidence interval 0.252–0.375), with the magnitude of the effect being twice as strong compared with women (b = 0.147, 95% confidence interval 0.076–0.218). The effect of all hypothesized early-life mediators in explaining these differences was modest.
Our findings have implications for public health policy, indicating a higher average level of psychological distress among a cohort born in 1970 compared with a generation born 12 years earlier. Due to increases in life expectancy, more recently born cohorts are expected to live longer, which implies – if such differences persist – that they are likely to spend more years with mental health-related morbidity compared with earlier-born cohorts.
This paper investigates the association between perinatal health and all-cause mortality for specific age intervals, assessing the contribution of maternal socioeconomic characteristics and the presence of maternal-level confounding. Our study is based on a cohort of 12,564 singletons born between 1915 and 1929 at the Uppsala University Hospital. We fitted Cox regression models to estimate age-varying hazard ratios of all-cause mortality for absolute and relative birth weight and for gestational age. We found that associations with mortality vary by age and according to the measure under scrutiny, with effects being concentrated in infancy, childhood or early adult life. For example, the effect of low birth weight was greatest in the first year of life and then continued up to 44 years of age (HR between 2.82 and 1.51). These associations were confirmed in within-family analyses, which provided no evidence of residual confounding by maternal characteristics. Our findings support the interpretation that policies oriented towards improving population health should invest in birth outcomes and hence in maternal health.
Low income is a widely studied risk factor for child and adolescent
behavioural difficulties. Previous research on this relationship has
produced mixed findings.
To investigate the level, shape and homogeneity of income gradients in
different types of antisocial behaviour.
A representative sample of 7977 British children and adolescents, aged
5–16 years, was analysed. Hypotheses concerning the shapes and
homogeneity of the relationships between family socioeconomic status and
multiple antisocial behaviour outcomes, including clinical diagnoses of
oppositional-defiant disorder, conduct disorder and symptom subscales,
such as irritability and hurtfulness, were tested by structural equation
Consistent income gradients were demonstrated across all antisocial
behaviours studied. Disorder prevalence and mean symptom counts decreased
across income quintiles in a non-linear fashion.
Our findings emphasise that income gradients are similar across different
forms of antisocial behaviour and indicate that income may lead to
greater behavioural differences in the mid-income range and less
variation at low- and high-income extremes.
Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression.
We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery–Asberg Depression Rating Scale – Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point.
The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period.
The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.
Helicobacter pylori infection is a major cause of peptic ulcer and is also associated with chronic gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and adenocarcinoma of the stomach. Guidelines have been developed in the United States and Europe (areas with low prevalence) for the diagnosis and management of this infection, including the recommendation to ‘test and treat’ those with dyspepsia. A group of international experts performed a targeted literature review and formulated an expert opinion for evidenced-based benefits and harms for screening and treatment of H. pylori in high-prevalence countries. They concluded that in Arctic countries where H. pylori prevalence exceeds 60%, treatment of persons with H. pylori infection should be limited only to instances where there is strong evidence of direct benefit in reduction of morbidity and mortality, associated peptic ulcer disease and MALT lymphoma and that the test-and-treat strategy may not be beneficial for those with dyspepsia.
Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents.
Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography.
Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups.
High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.
We have criticized medical writers, but praise is due to those who write well, and there are many who do. It is not so easy to find their writing because there are not the indicators to good writing that there are to bad. We started our dissection of style with Watson and Crick’s description of DNA (see p. 25), but their article is now 60 years old. With kind permission of the author and of the publishers, we reproduce here a Viewpoint from the Lancet from 2013 that is a model of clarity. We are not asking you to read some deep theory about an arcane disease interesting only to a handful of sub-specialists. It is an essay about type 2 diabetes, a condition so common and important that it will interest almost all medical writers. Now, of course, most research projects are of only limited interest, but the writers’ messages would come across better by reflecting the succinctness and flow of this essay rather than the polysyllables and discursion of too many research articles.
The essay is reproduced here in full, after which we make comments. But a preliminary comment is that the essay does not start by telling us that type 2 diabetes is a disease of epidemic proportions: the author wastes no words telling us what we already know; he tells us right away what he wants to say. And a general comment is to note, as you read through, how few of the words and constructions that appear in our index appear in the essay.
People who write obscurely are either unskilled in writing or up to some mischief.
(Sir Peter Medawar, 1915–1987, British biologist. The threat and the glory, D. Pyke, ed., Oxford, Oxford University Press, 1990.)
Literary devices and figures of speech are not prominent in routine research papers, but are more likely in editorials and opinion pieces. Used properly, they enliven writing, which is why columnists – both in newspapers and magazines and in their medical equivalents – use them.
Metaphor is the most important and widespread figure of speech, and is (COD) the application of name or descriptive term to an object or action to which it is imaginatively but not literally applicable. It suggests a shared property. It is metaphorical when we write that a drug ‘locks onto’ a receptor, suggesting that drugs and receptors are like keys and locks. In previous chapters we have mentioned drawback (its original meaning now less well-known than its metaphorical one), elevated from bishop to archbishop, falling into groups, hormones having a role, a graveyard full of failed treatments, focusing a service, examining cars in depth, and a cocktail of drugs.
There are two reasons to be wary of metaphors: first, readers may misinterpret them, especially EAL readers, who may not understand them at all; and second, metaphors have a tendency to descend pretty quickly to cliché. Metaphors are intended to enliven writing; clichés, because they are overused, deaden it. There is no strict definition of cliché; nor is there a list in which to check whether a chosen metaphor has degenerated to cliché. As The Economist’s guide (see reference books) points out, ‘clichés weren’t always clichéd. The first person to use window of opportunity . . . was justly pleased with himself. [It] is a strong, vivid expression – or was. The trouble is that such expressions have been copied so often that they have lost their vividness.