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Objectives: Low educational attainment is a risk factor for more rapid cognitive aging, but there is substantial variability in cognitive trajectories within educational groups. The aim of this study was to determine the factors that confer resilience to memory decline within educational strata. Methods: We selected 2573 initially nondemented White, African American, and Hispanic participants from the longitudinal community-based Washington Heights/Inwood Columbia Aging Project who had at least two visits. We estimated initial memory (intercept) and the rate of memory decline (slope) using up to five occasions of measurement. We classified groups according to the educational attainment groups as low (≤5 years), medium (6–11 years), and high (≥12 years). We used a multiple-group latent growth model to identify the baseline predictors of initial memory performance and rate of memory decline across groups. The model specification considered the influence of demographic, socioeconomic, biomedical, and cognitive variables on the intercept and the slope of memory trajectory. Results: Our results indicated that the three educational groups do not benefit from the same factors. When allowed to differ across groups, the predictors were related to cognitive outcomes in the highly educated group, but we found no unique predictor of cognition for the low educated older adults. Conclusions: These findings highlight that memory-protective factors may differ across older adults with distinct educational backgrounds, and the need to evaluate a broader range of potential resilience factors for older adults with few years of school.
During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.
Although cognitive-behavioural therapy (CBT) is an effective treatment for depression, less than half of patients achieve satisfactory symptom reduction during treatment. Targeting known psychopathological processes such as rumination may increase treatment efficacy. The aim of this study was to test whether adding group rumination-focused CBT (RFCBT) that explicitly targets rumination to routine medical management is superior to adding group CBT to routine medical management in treating major depression.
A total of 131 outpatients with major depression were randomly allocated to 12 sessions group RFCBT v. group CBT, each in addition to routine medical management. The primary outcome was observer-rated symptoms of depression at the end of treatment measured on the Hamilton Rating Scale for Depression. Secondary outcomes were rumination at post-treatment and depressive symptoms at 6 months follow-up (Trial registered: NCT02278224).
RFCBT significantly improved observer-rated depressive symptoms (Cohen's d 0.38; 95% CI 0.03–0.73) relative to group CBT at post-treatment on the primary outcome. No post-treatment differences were found in rumination or in depressive symptoms at 6 months follow-up, although these secondary analyses may have been underpowered.
This is the first randomized controlled trial providing evidence of benefits of RFCBT in major depression compared with CBT. Group RFCBT may be a beneficial alternative to group CBT for major depression.
Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.
To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.
We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.
Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.
Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.
Declaration of interest
D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.
The seventh-century AD switch from gold to silver currencies transformed the socio-economic landscape of North-west Europe. The source of silver, however, has proven elusive. Recent research, integrating ice-core data from the Colle Gnifetti drill site in the Swiss Alps, geoarchaeological records and numismatic and historical data, has provided new evidence for this transformation. Annual ice-core resolution data are combined with lead pollution analysis to demonstrate that significant new silver mining facilitated the change to silver coinage, and dates the introduction of such coinage to c. AD 660. Archaeological evidence and atmospheric modelling of lead pollution locates the probable source of the silver to mines at Melle, in France.
To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer’s disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests.
4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and individual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates.
All aMCI groups (n = 760) had a greater risk-AD than NC (n = 4,011; HR range = 3.66 – 9.25). The risk-AD was not different between visual (n = 208, 17 converters) and verbal aMCI (n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI (n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs. NC.
Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI.
Objectives: A rich body of literature has established the role of body image distortion and dissatisfaction in the development and maintenance of eating disorders. However, many of the currently used techniques require explicit comparison of the person’s body to an external stimulus. As the body schema is a largely unconscious construct, explicit comparison tasks may reflect a proxy, rather than the body schema itself. Methods: Here we use an implicit mental motor imagery (MMI) task to interrogate the body schema in healthy control participants (N=40) and participants at a residential eating disorder treatment center (N=42). By comparing the time it takes to imagine making a movement along a part of the body to the time it takes to actually make the same movement, we were able to assess participants’ mental image of their body (i.e., body schema). Results: We found that participants with eating disorders, but not healthy controls, exhibited distortions of the body schema such that they believed their abdomen, buttocks, and thighs to be larger than they really are. Additionally, the MMI task used here provided information above and beyond traditional self-report measures (i.e., Body Shape Questionnaire). Together the MMI task and traditional measures provide the most information. Conclusions: Findings using the novel MMI task are in line with the literature; participants with eating disorders consider themselves to be larger than they truly are. Taken together, results of this study suggest that MMI tasks provide complementary information to traditional self-report measures. (JINS, 2018, 22, 000–000)
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).
Background: Congenital Myasthenic Syndromes (CMS) are heterogeneous disorders caused by genetically determined structural or functional differences in proteins involved with the neuromuscular junctions. Clinical and molecular genetics studies of CMS patients have revealed significant locus heterogeneity; there are 21 known genes related to CMS, but other genes may mimic the phenotype, justifying the use of a multi-gene panel for genetic testing Methods: Our group developed custom sequence capture probes designed to flank 27 different genes associated with CMS, including enrichment for all coding exons as well the flanking intronic regions. We enrolled 20 patients from the paediatric and adult neuromuscular clinic with a clinical phenotype of CMS. Using custom analytical, we -assessed the sequence variants and exon-level CNVs for each patient. Results: Thirteen male and seven female patients with median age of 12.25 years (range 1.5-39y) were assessed. We identified missense and CNVs in 17 patients, including established pathogenic mutations confirming the diagnosis in 5 patients Conclusions: The use of Next Generation Sequence with CNV for CMS can help determine the underlying causes of most CMS disorders and allow appropriate medical treatment, refined genetic counseling, and improved understanding of prognosis, justifying the implementation in the standard clinical screening of CMS.
Crib–biting is a stereotypic behaviour performed by approximately 5% of captive domestic horses. Dietary factors have been strongly associated with the development of oral stereotypies and risk factors for crib–biting, identified in recent epidemiological studies, include feeding high concentrate and/or low forage diets (Waters et al., 2002). Experimental work has shown that such diets are likely to result in increased gastric acidity (Murray and Eichorn, 1996; Nadeau et al., 2000). We therefore propose that young horses initiate crib–biting in an attempt to produce alkaline saliva to buffer their stomachs when alternative opportunities for mastication are limited. The aim of this study was to determine whether there was an association between crib–biting behaviour and stomach condition in foals.
Foals that had recently started to perform crib–biting were recruited into the study and compared with non–stereotypic foals. The stomachs of 15 crib-biting foals and 9 normal foals were examined using a video endoscope.
The re-emergence of debates on the decolonisation of knowledge has revived interest in the National Question, which began over a century ago and remains unresolved. Tensions that were suppressed and hidden in the past are now being openly debated. Despite this, the goal of one united nation living prosperously under a constitutional democracy remains elusive. This edited volume examines the way in which various strands of left thought have addressed the National Question, especially during the apartheid years, and goes on to discuss its relevance for South Africa today and in the future. Instead of imposing a particular understanding of the National Question, the editors identified a number of political traditions and allowed contributors the freedom to define the question as they believed appropriate – in other words, to explain what they thought was the Unresolved National Question. This has resulted in a rich tapestry of interweaving perceptions. The volume is structured in two parts. The first examines four foundational traditions: Marxism-Leninism (the Colonialism of a Special Type thesis); the Congress tradition; the Trotskyist tradition; and Africanism. The second part explores the various shifts in the debate from the 1960s onwards, and includes chapters on Afrikaner nationalism, ethnic issues, black consciousness, feminism, workerism and constitutionalism. The editors hope that by revisiting the debates not popularly known among the scholarly mainstream, this volume will become a catalyst for an enriched debate on our identity and our future.