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Evidence suggests that early trauma may have a negative effect on cognitive functioning in individuals with psychosis, yet the relationship between childhood trauma and cognition among those at clinical high risk (CHR) for psychosis remains unexplored. Our sample consisted of 626 CHR children and 279 healthy controls who were recruited as part of the North American Prodrome Longitudinal Study 2. Childhood trauma up to the age of 16 (psychological, physical, and sexual abuse, emotional neglect, and bullying) was assessed by using the Childhood Trauma and Abuse Scale. Multiple domains of cognition were measured at baseline and at the time of psychosis conversion, using standardized assessments. In the CHR group, there was a trend for better performance in individuals who reported a history of multiple types of childhood trauma compared with those with no/one type of trauma (Cohen d = 0.16). A history of multiple trauma types was not associated with greater cognitive change in CHR converters over time. Our findings tentatively suggest there may be different mechanisms that lead to CHR states. Individuals who are at clinical high risk who have experienced multiple types of childhood trauma may have more typically developing premorbid cognitive functioning than those who reported minimal trauma do. Further research is needed to unravel the complexity of factors underlying the development of at-risk states.
To identify and synthesise the literature on the cost of mental disorders.
Systematic literature searches were conducted in the databases PubMed, EMBASE, Web of Science, EconLit, NHS York Database and PsychInfo using key terms for cost and mental disorders. Searches were restricted to January 1980–May 2019. The inclusion criteria were: (1) cost-of-illness studies or cost-analyses; (2) diagnosis of at least one mental disorder; (3) study population based on the general population; (4) outcome in monetary units. The systematic review was preregistered on PROSPERO (ID: CRD42019127783).
In total, 13 579 potential titles and abstracts were screened and 439 full-text articles were evaluated by two independent reviewers. Of these, 112 articles were included from the systematic searches and 31 additional articles from snowball searching, resulting in 143 included articles. Data were available from 48 countries and categorised according to nine mental disorder groups. The quality of the studies varied widely and there was a lack of studies from low- and middle-income countries and for certain types of mental disorders (e.g. intellectual disabilities and eating disorders). Our study showed that certain groups of mental disorders are more costly than others and that these rankings are relatively stable between countries. An interactive data visualisation site can be found here: https://nbepi.com/econ.
This is the first study to provide a comprehensive overview of the cost of mental disorders worldwide.
Acute rheumatic fever (ARF), an auto-immune response to a group A Streptococcus infection and precursor to rheumatic heart disease (RHD), remains endemic in many socio-economically disadvantaged settings. A Global Resolution on ARF and RHD was recently adopted at the 71st World Health Assembly where governments committed to improving efforts to prevent and control ARF and RHD. To inform these efforts, the objectives of this study were to examine associations between childhood ARF in the UK between 1958 and 1969 and a range of environmental and social factors. Of 17 416 children from the nationally representative birth cohort of the National Child Development Study, ARF was reported in 23 children during early childhood (between birth and the 7-year follow-up) and in 29 additional children during middle childhood (between the 7- and 11-year follow-ups). Risk factors associated with ARF in both early and middle childhood were: a large family size; attendance at a private nursery or class; a history of nephritis, kidney or urinary tract infections; and a history of throat or ear infections. Risk factors for ARF in early childhood alone were families with fathers in a professional or semi-professional occupation and families who moved out of their local neighbourhood. Risk factors in late childhood alone included overcrowding and free school meals. These data suggest that prevention strategies in ARF endemic settings may be enhanced by targeting, for example, new members entering a community and children in environments of close contact, such as a nursery or shared bedrooms.
Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.
In NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.
There was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.
A detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.
The combination of sensitivity and large sky coverage of the ALFALFA HI survey has enabled the detection of difficult to observe low mass galaxies in large numbers, including dwarf galaxies overlooked in optical surveys. Three different, but connected, studies of dwarf galaxies from the ALFALFA survey are of particular interest: SHIELD (Survey of HI in Extremely Low-mass Dwarfs), candidate gas-rich ultra-faint dwarf galaxies, and the (Almost) Dark population. SHIELD is a systematic multiwavelength study of all dwarf galaxies from ALFALFA with MHI < 107.2M⊙ and clear optical counterparts. Candidate gas-rich ultra-faint dwarf galaxies extend the dwarf galaxy population to even lower masses. These galaxies are identified as isolated HI clouds with no discernible optical counterpart but subsequent observations reveal that some are extremely faint, gas-dominated galaxies. Leo P, discovered first as an HI detection, and then found to be an actively star-forming galaxy, bridges the gap between these candidate galaxies and the SHIELD sample. The (Almost) Dark sample consists of galaxies whose optical counterparts are overlooked in current optical surveys but which are clear detections in ALFALFA. This sample includes field gas-rich ultra-diffuse galaxies. Coma P, with a peak surface brightness of only ∼26.4 mag arcsec−2 in g’, demonstrates the sort of extreme low surface brightness galaxy that can be discovered in an HI survey.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
The developmental course of daily functioning prior to first psychosis-onset remains poorly understood. This study explored age-related periods of change in social and role functioning. The longitudinal study included youth (aged 12–23, mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis (converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy control group (n = 164). Mixed-model analyses were performed to determine age-related differences in social and role functioning. We limited our analyses to functioning before psychosis conversion; thus, data of CHR-C participants gathered after psychosis onset were excluded. In controls, social and role functioning improved over time. From at least age 12, functioning in CHR was poorer than in controls, and this lag persisted over time. Between ages 15 and 18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A similar period of stagnation was apparent for role functioning, but to a lesser extent (p = .007). The results remained consistent when we accounted for the time to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in social and role functioning in adolescence, followed by a period of further stagnation in adulthood.
Our knowledge of the universe comes from recording the photon and particle fluxes incident on the Earth from space. We thus require sensitive measurement across the entire energy spectrum, using large telescopes with efficient instrumentation located on superb sites. Technological advances and engineering constraints are nearing the point where we are recording as many photons arriving at a site as is possible. Major advances in the future will come from improving the quality of the site. The ultimate site is, of course, beyond the Earth’s atmosphere, such as on the Moon, but economic limitations prevent our exploiting this avenue to the degree that the scientific community desires. Here we describe an alternative, which offers many of the advantages of space for a fraction of the cost: the Antarctic Plateau.
Effects of soil tillage systems and nitrogen (N) fertilizer management on spring wheat yield components, grain yield and N-use efficiency (NUE) were evaluated in contrasting weather of 2013 and 2014 on a clay soil at the Royal Agricultural University's Harnhill Manor Farm, Cirencester, UK. Three tillage systems – conventional plough tillage (CT), high intensity non-inversion tillage (HINiT) and low intensity non-inversion tillage (LINiT) for seedbed preparation – were compared at four rates of N fertilizer (0, 70, 140 and 210 kg N/ha). Responses to the effects of the management practices were strongly influenced by weather conditions and varied across seasons. Grain yields were similar between LINiT and CT in 2013, while CT produced higher yields in 2014. Nitrogen fertilization effects also varied across the years with no significant effects observed on grain yield in 2013, while in 2014 applications up to 140 kg N/ha increased yield. Grain protein ranged from 10·1 to 14·5% and increased with N rate in both years. Nitrogen-use efficiency ranged from 12·6 to 49·1 kg grain per kg N fertilizer and decreased as N fertilization rate increased in both years. There was no tillage effect on NUE in 2013, while in 2014 NUE under CT was similar to LINiT and higher than HINiT. The effect of tillage and N fertilization on soil moisture and soil mineral N (SMN) fluctuated across years. In 2013, LINiT showed significantly higher soil moisture than CT, while soil moisture did not differ between tillage systems in 2014. Conventional tillage had significantly higher SMN at harvest time in 2014, while no significant differences on SMN were observed between tillage systems in 2013. These results indicate that LINiT can be used to produce similar spring wheat yield to CT on this particular soil type, if a dry cropping season is expected. Crop response to N fertilization is limited when soil residual N is higher, while in conditions of lower residual SMN, a higher N supply is needed to increase yield and improve grain protein content.
Background: Schema Theory proposes that the development of maladaptive schemas are based on a combination of memories, emotions and cognitions regarding oneself and one's relationship to others. A cognitive model of psychosis suggests that schemas are crucial to the development and persistence of psychosis. Little is known about the impact that schemas may have on those considered to be at clinical high risk (CHR) of developing psychosis. Aims: To investigate schemas over time in a large sample of CHR individuals and healthy controls. Method: Sample included 765 CHR participants and 280 healthy controls. Schemas were assessed at baseline, 6 and 12 months using the Brief Core Schema Scale (BCSS). Baseline schemas were compared to 2-year clinical outcome. Results: CHR participants evidenced stable and more maladaptive schemas over time compared to controls. Schemas at initial contact did not vary amongst the different clinical outcome groups at 2 years although all CHR outcome groups evidenced significantly worse schemas than healthy controls. Although there were no differences on baseline schemas between those who later transitioned to psychosis compared to those who did not, those who transitioned to psychosis had more maladaptive negative self-schemas at the time of transition. Associations between negative schemas were positively correlated with earlier abuse and bullying. Conclusions: These findings demonstrate a need for interventions that aim to improve maladaptive schemas among the CHR population. Therapies targeting self-esteem, as well as schema therapy may be important work for future studies.
A series of research reports has indicated that the use of substances such as cannabis, alcohol and tobacco are higher in youth at clinical high risk (CHR) of developing psychosis than in controls. Little is known about the longitudinal trajectory of substance use, and findings on the relationship between substance use and later transition to psychosis in CHR individuals are mixed.
At baseline and 6- and 12-month follow-ups, 735 CHR and 278 control participants completed the Alcohol and Drug Use Scale and a cannabis use questionnaire. The longitudinal trajectory of substance use was evaluated with linear mixed models.
CHR participants endorsed significantly higher cannabis and tobacco use severity, and lower alcohol use severity, at baseline and over a 1-year period compared with controls. CHR youth had higher lifetime prevalence and frequency of cannabis, and were significantly younger upon first use, and were more likely to use alone and during the day. Baseline substance use did not differentiate participants who later transitioned to psychosis (n = 90) from those who did not transition (n = 272). Controls had lower tobacco use than CHR participants with a prodromal progression clinical outcome and lower cannabis use than those with a psychotic clinical outcome at the 2-year assessment.
In CHR individuals cannabis and tobacco use is higher than in controls and this pattern persists across 1 year. Evaluation of clinical outcome may provide additional information on the longitudinal impact of substance use that cannot be detected through evaluation of transition/non-transition to psychosis alone.
Forecasting the maize yield of China's Jilin province from 1962 to 2004, with climate conditions and fertilizer as predictors, was investigated using multiple linear regression (MLR) and non-linear artificial neural network (ANN) models. Yield was set to be a function of precipitation from July to August, precipitation in September and the amount of fertilizer used. Fertilizer emerged as the dominant predictor and was non-linearly related to yield in the ANN model. Given the difficulty of acquiring fertilizer data for maize, the current study was also tested using the previous year's yield in the place of fertilizer data. Forecast skill scores computed under both cross-validation and retroactive validation showed ANN models to significantly outperform MLR and persistence (i.e. forecast yield is identical to last year's observed yield). As the data were non-stationary, cross-validation was found to be less reliable than retroactive validation in assessing the forecast skill.
White matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD.
Diffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract.
We detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients.
WM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.
Deterioration in premorbid functioning is a common feature of schizophrenia, but sensitivity to psychosis conversion among clinical high-risk samples has not been examined. This study evaluates premorbid functioning as a predictor of psychosis conversion among a clinical high-risk sample, controlling for effects of prior developmental periods. Participants were 270 clinical high-risk individuals in the North American Prodrome Longitudinal Study—I, 78 of whom converted to psychosis over the next 2.5 years. Social, academic, and total maladjustment in childhood, early adolescence, and late adolescence were rated using the Cannon–Spoor Premorbid Adjustment Scale. Early adolescent social dysfunction significantly predicted conversion to psychosis (hazard ratio = 1.30, p = .014), independently of childhood social maladjustment and independently of severity of most baseline positive and negative prodromal symptoms. Baseline prodromal symptoms of disorganized communication, social anhedonia, suspiciousness, and diminished ideational richness mediated this association. Early adolescent social maladjustment and baseline suspiciousness together demonstrated moderate positive predictive power (59%) and high specificity (92.1%) in predicting conversion. Deterioration of academic and total functioning, although observed, did not predict conversion to psychosis. Results indicate early adolescent social dysfunction to be an important early predictor of conversion. As such, it may be a good candidate for inclusion in prediction algorithms and could represent an advantageous target for early intervention.
Recent community-based research has suggested that psychotic experiences act as markers of severity of psychopathology. There has, however, been a lack of clinic-based research. We wished to investigate, in a clinical sample of adolescents referred to a state-funded mental health service, the prevalence of (attenuated or frank) psychotic experiences and the relationship with (i) affective, anxiety and behavioural disorders, (ii) multimorbid psychopathology, (iii) global functioning, and (iv) suicidal behaviour.
The investigation was a clinical case–clinical control study using semi-structured research diagnostic psychiatric assessments in 108 patients newly referred to state adolescent mental health services.
Psychotic experiences were prevalent in a wide range of (non-psychotic) disorders but were strong markers of risk in particular for multimorbid psychopathology (Z = 3.44, p = 0.001). Young people with psychopathology who reported psychotic experiences demonstrated significantly poorer socio-occupational functioning than young people with psychopathology who did not report psychotic experiences, which was not explained by multimorbidity. Psychotic experiences were strong markers of risk for suicidal behaviour. Stratified analyses showed that there was a greatly increased odds of suicide attempts in patients with a major depressive disorder [odds ratio (OR) 8.89, 95% confidence interval (CI) 1.59–49.83], anxiety disorder (OR 15.4, 95% CI 1.85–127.94) or behavioural disorder (OR 3.13, 95% CI 1.11–8.79) who also had psychotic experiences compared with patients who did not report psychotic experiences.
Psychotic experiences (attenuated or frank) are an important but under-recognized marker of risk for severe psychopathology, including multimorbidity, poor functioning and suicidal behaviour in young people who present to mental health services.
Twenty-two consecutive VLBI images of supernova 1993J in the galaxy M81 taken over 7 years show, in unprecedented detail, the dynamic evolution of the expanding radio shell of an exploded star. High precision astrometry using phase-referencing shows that the supernova expands isotropically, and that its geometric center has a formal proper motion of 190±110 km s−1 w.r.t. the core of M81. Systematic changes in the images most likely reflect a pattern of inhomogeneities in the medium left over from the progenitor star, or possibly instabilities in the expanding shell. As the shockfront sweeps up the medium, it is progressively decelerated, and after 7 years it has slowed to less than 1/2 its original expansion velocity. SN1993J is likely now entering the early stages of the adiabatic phase common in much older supernova remnants.