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Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence.
Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder.
Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers.
No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.
Few personalised medicine investigations have been conducted for mental health. We aimed to generate and validate a risk tool that predicts adult attention-deficit/hyperactivity disorder (ADHD).
Using logistic regression models, we generated a risk tool in a representative population cohort (ALSPAC – UK, 5113 participants, followed from birth to age 17) using childhood clinical and sociodemographic data with internal validation. Predictors included sex, socioeconomic status, single-parent family, ADHD symptoms, comorbid disruptive disorders, childhood maltreatment, ADHD symptoms, depressive symptoms, mother's depression and intelligence quotient. The outcome was defined as a categorical diagnosis of ADHD in young adulthood without requiring age at onset criteria. We also tested Machine Learning approaches for developing the risk models: Random Forest, Stochastic Gradient Boosting and Artificial Neural Network. The risk tool was externally validated in the E-Risk cohort (UK, 2040 participants, birth to age 18), the 1993 Pelotas Birth Cohort (Brazil, 3911 participants, birth to age 18) and the MTA clinical sample (USA, 476 children with ADHD and 241 controls followed for 16 years from a minimum of 8 and a maximum of 26 years old).
The overall prevalence of adult ADHD ranged from 8.1 to 12% in the population-based samples, and was 28.6% in the clinical sample. The internal performance of the model in the generating sample was good, with an area under the curve (AUC) for predicting adult ADHD of 0.82 (95% confidence interval (CI) 0.79–0.83). Calibration plots showed good agreement between predicted and observed event frequencies from 0 to 60% probability. In the UK birth cohort test sample, the AUC was 0.75 (95% CI 0.71–0.78). In the Brazilian birth cohort test sample, the AUC was significantly lower –0.57 (95% CI 0.54–0.60). In the clinical trial test sample, the AUC was 0.76 (95% CI 0.73–0.80). The risk model did not predict adult anxiety or major depressive disorder. Machine Learning approaches did not outperform logistic regression models. An open-source and free risk calculator was generated for clinical use and is available online at https://ufrgs.br/prodah/adhd-calculator/.
The risk tool based on childhood characteristics specifically predicts adult ADHD in European and North-American population-based and clinical samples with comparable discrimination to commonly used clinical tools in internal medicine and higher than most previous attempts for mental and neurological disorders. However, its use in middle-income settings requires caution.
ADHD diagnosis requires the presence of symptoms before the age of twelve. In clinical assessment of adults, the most frequent strategy to check this criterion is investigating self-report recall of symptoms, despite little evidence on the validity of this approach. We aim to evaluate the recall accuracy and factors associated with its reliability in a large population-based sample of adults.
Individuals from the 1993 Pelotas Birth Cohort were followed-up from childhood to adulthood. At the age of 22, 3810 individuals were assessed through structured interviews by trained psychologists regarding mental health outcomes, including ADHD diagnosis and ADHD symptoms in childhood. The retrospective recall was compared with available information on ADHD childhood symptoms at the age of eleven. We also assessed factors related to recall accuracy through multiple regression analyses.
Self-reported recall of childhood symptoms at 22 years of age had an accuracy of only 55.4%, with sensitivity of 32.8% and positive predictive value of 40.7%. Current inattention symptoms were associated with lower risk and social phobia with higher risk for false-positive endorsement, while higher levels of schooling correlated with lower risk and male gender with higher risk for false-negative endorsement.
Clinicians treating male patients with social phobia and ADHD symptoms should assess even more carefully retrospective recall of ADHD childhood symptoms. Moreover, characteristics associated with recall improvement do not impact accuracy robustly. In this context, the recall of childhood ADHD symptoms seems an unreliable method to characterize the neurodevelopmental trajectory in adults with currently-impairing ADHD symptomatology.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Attention deficit hyperactivity disorder (ADHD) is frequently associated with poorer reading ability; however, the specific neuropsychological domains linking this co-occurrence remain unclear. This study evaluates information-processing characteristics as possible neuropsychological links between ADHD symptoms and RA in a community-based sample of children and early adolescents with normal IQ (⩾70).
The participants (n = 1857, aged 6–15 years, 47% female) were evaluated for reading ability (reading single words aloud) and information processing [stimulus discriminability in the two-choice reaction-time task estimated using diffusion models]. ADHD symptoms were ascertained through informant (parent) report using the Development and Well-Being Assessment (DAWBA). Verbal working memory (VWM; digit span backwards), visuospatial working memory (VSWM, Corsi Blocks backwards), sex, socioeconomic status, and IQ were included as covariates.
In a moderated mediation model, stimulus discriminability mediated the effect of ADHD on reading ability. This indirect effect was moderated by age such that a larger effect was seen among younger children.
The findings support the hypothesis that ADHD and reading ability are linked among young children via a neuropsychological deficit related to stimulus discriminability. Early interventions targeting stimulus discriminability might improve symptoms of inattention/hyperactivity and reading ability.
Heated or cooled fluids at supercritical pressure show large variations in thermophysical properties, such as the density, dynamic viscosity and molecular Prandtl number, which strongly influence turbulence characteristics. To investigate this, direct numerical simulations were performed of a turbulent flow at supercritical pressure (CO
at 8 MPa) in an annulus with a hot inner wall and a cold outer wall. The pseudo-critical temperature lies close to the inner wall, which results in strong thermophysical property variations in that region. The turbulent shear stress and the turbulent intensities significantly decrease near the hot inner wall, but increase near the cold outer wall, which can be partially attributed to the mean dynamic viscosity and density stratification. This leads to decreased production of turbulent kinetic energy near the inner wall and vice versa near the outer wall. However, by analysing a transport equation for the coherent streak flank strength, it was found that thermophysical property fluctuations significantly affect streak evolution. Near the hot wall, thermal expansion and buoyancy tend to decrease streak coherence, while the viscosity gradient that exists across the streaks interacts with mean shear to act as either a source or a sink in the evolution equation for the coherent streak flank strength. The formation of streamwise vortices on the other hand is hindered by the torque that is the result of the kinetic energy and density gradients. Near the cold wall, the results are reversed, i.e. the coherent streak flank strength and the streamwise vortices are enhanced due to the variable density and dynamic viscosity. The results show that not only the mean stratification but also the large instantaneous thermophysical property variations that occur in heated or cooled fluids at supercritical pressure have a significant effect on turbulent structures that are responsible for the self-regeneration process in near-wall turbulence. Thus, instantaneous density and dynamic viscosity fluctuations are responsible for decreased (or increased) turbulent motions in heated (or cooled) fluids at supercritical pressure.
The control of Johne's disease requires the identification of Mycobacterium avium ssp. paratuberculosis (MAP)-positive herds. Boot swabs and liquid manure samples have been suggested as an easy-to-use alternative to sampling individual animals in order to diagnose subclinical Johne's disease at the herd level, but there is a need to evaluate performance of this approach in the field. Using a logistic regression model, this study aimed to calculate the threshold level of the apparent within-herd prevalence as determined by individual faecal culture, thus allowing the detection of whether a herd is MAP positive. A total of 77 boot swabs and 75 liquid manure samples were taken from 19 certified negative and 58 positive dairy herds. Faecal culture, three different polymerase chain reaction (PCR) methods and the combination of faecal culture with PCR were applied in order to detect MAP. For 50% probability of detection, a within-herd prevalence threshold of 1·5% was calculated for testing both matrices simultaneously by faecal culture and PCR, with the threshold increased to 4·0% for 90% probability of detection. The results encourage the use of boot swabs or liquid manure samples, or a combination both, for identifying MAP-positive herds and, to a certain extent, for monitoring certified Johne's disease-negative cattle herds.
Course and predictors of persistence of attention deficit hyperactivity disorder (ADHD) in adults are still largely unknown. Neurobiological and clinical differences between child and adult ADHD raise the need for follow-up studies of patients diagnosed during adulthood. This study investigates predictors of ADHD persistence and the possibility of full remission 7 years after baseline assessment.
A 7-year follow-up study of adults with ADHD (n = 344, mean age 34.1 years, 49.9% males) was conducted. Variables from different domains (social demographics, co-morbidities, temperament, medication status, ADHD measures) were explored with the aim of finding potential predictors of ADHD persistence.
Retention rate was 66% (n = 227). Approximately a third of the sample (n = 70, 30.2%) did not maintain ADHD criteria and 28 (12.4%) presented full remission (<4 symptoms), independently of changes in co-morbidity or cognitive demand profiles. Baseline predictors of diagnostic persistence were higher number of inattention symptoms [odds ratio (OR) 8.05, 95% confidence interval (CI) 2.54–25.45, p < 0.001], number of hyperactivity/impulsivity symptoms (OR 1.18, 95% CI 1.04–1.34, p = 0.01), oppositional defiant disorder (OR 3.12, 95% CI 1.20–8.11, p = 0.02), and social phobia (OR 3.59, 95% CI 1.12–11.47, p = 0.03).
Despite the stage of brain maturation in adults suggests stability, approximately one third of the sample did not keep full DSM-IV diagnosis at follow-up, regardless if at early, middle or older adulthood. Although full remission is less common than in childhood, it should be considered as a possible outcome among adults.
Despite its importance as a public health concern, relatively little is known about the natural course of cannabis use disorders (CUDs). The primary objective of this research was to provide descriptive data on the onset, recovery and recurrence functions of CUDs during the high-risk periods of adolescence, emerging adulthood and young adulthood based on data from a large prospective community sample.
Probands (n = 816) from the Oregon Adolescent Depression Project (OADP) participated in four diagnostic assessments (T1–T4) between the ages of 16 and 30 years, during which current and past CUDs were assessed.
The weighted lifetime prevalence of CUDs was 19.1% with an average onset age of 18.6 years. Although gender was not significantly related to the age of initial CUD onset, men were more likely to be diagnosed with a lifetime CUD. Of those diagnosed with a CUD episode, 81.8% eventually achieved recovery during the study period. Women achieved recovery significantly more quickly than men. The recurrence rate (27.7%) was relatively modest, and most likely to occur within the first 36 months following the offset of the first CUD episode. CUD recurrence was uncommon after 72 months of remission and recovery.
CUDs are relatively common, affecting about one out of five persons in the OADP sample prior to the age of 30 years. Eventual recovery from index CUD episodes is the norm, although about 30% of those with a CUD exhibit a generally persistent pattern of problematic use extending 7 years or longer.
Q fever is a notifiable disease in Germany. The majority of the reported cases are related to outbreaks. The objective of our study was to evaluate the general role of Q fever in community-acquired pneumonia (CAP). We investigated respiratory samples and sera from 255 patients with CAP, who were enrolled into a CAPNETZ cohort in summer 2005. Altogether, our data showed a significant prevalence of Q fever as CAP (3·5%). If a patient's condition leads to a diagnostic test for Chlamydophila sp., Mycoplasma sp. or Legionella sp., then a Q fever diagnostic test should also be included. In particular, ELISA as a first diagnostic step is easy to perform. PCR should be performed at an early stage of the disease if no antibodies are detectable. Because of our highly promising findings we suggest performing PCR in respiratory samples.
Attention-deficit/hyperactivity disorder (ADHD) in adult life is a prevalent condition. We systematically reviewed the literature available by searching for meta-analyses assessing pharmacological and psychosocial interventions for adults with ADHD.
Using wide-ranging search terms, we retrieved 191 titles from the PubMed and Cochrane databases. Two independent evaluators judged all abstracts. Only meta-analyses about the treatment of adults with ADHD were included. Information from meta-analyses found was systematically extracted by 3 independent evaluators.
Eight meta-analyses were identified. Results from those meta-analyses suggest that stimulants are effective in decreasing ADHD symptoms on a short-term basis with a medium to large effect size (ES). Short-acting stimulants might be superior to long-acting stimulants, but no data on difference in adherence are available for the comparison of these two types of formulation. Bupropion is superior to placebo but less effective than stimulants. No conclusions about the impact of psychosocial interventions can be drawn based on meta-analyses so far.
The efficacy of stimulants in reducing ADHD symptoms for adults is well documented in meta-analyses, but there is a concerning lack of meta-analysis about other treatment interventions.
The available meta-analytic literature does not cover questions of essential clinical relevance for adults with ADHD.
Both inhibitory-based executive functioning (IB-EF) and basic information processing (BIP) deficits are found in clinic-referred attention deficit hyperactivity disorder (ADHD) samples. However, it remains to be determined whether: (1) such deficits occur in non-referred samples of ADHD; (2) they are specific to ADHD; (3) the co-morbidity between ADHD and oppositional defiant disorder/conduct disorder (ODD/CD) has additive or interactive effects; and (4) IB-EF deficits are primary in ADHD or are due to BIP deficits.
We assessed 704 subjects (age 6–12 years) from a non-referred sample using the Development and Well-Being Assessment (DAWBA) and classified them into five groups: typical developing controls (TDC; n = 378), Fear disorders (n = 90), Distress disorders (n = 57), ADHD (n = 100), ODD/CD (n = 40) and ADHD+ODD/CD (n = 39). We evaluated neurocognitive performance with a Two-Choice Reaction Time Task (2C-RT), a Conflict Control Task (CCT) and a Go/No-Go (GNG) task. We used a diffusion model (DM) to decompose BIP into processing efficiency, speed–accuracy trade-off and encoding/motor function along with variability parameters.
Poorer processing efficiency was found to be specific to ADHD. Faster encoding/motor function differentiated ADHD from TDC and from fear/distress whereas a more cautious (not impulsive) response style differentiated ADHD from both TDC and ODD/CD. The co-morbidity between ADHD and ODD/CD reflected only additive effects. All ADHD-related IB-EF classical effects were fully moderated by deficits in BIP.
Our findings challenge the IB-EF hypothesis for ADHD and underscore the importance of processing efficiency as the key specific mechanism for ADHD pathophysiology.
Preliminary research implicates threat-related attention biases in paediatric anxiety disorders. However, major questions exist concerning diagnostic specificity, effects of symptom-severity levels, and threat-stimulus exposure durations in attention paradigms. This study examines these issues in a large, community school-based sample.
A total of 2046 children (ages 6–12 years) were assessed using the Development and Well Being Assessment (DAWBA), Childhood Behavior Checklist (CBCL) and dot-probe tasks. Children were classified based on presence or absence of ‘fear-related’ disorders, ‘distress-related’ disorders, and behavioural disorders. Two dot-probe tasks, which differed in stimulus exposure, assessed attention biases for happy-face and threat-face cues. The main analysis included 1774 children.
For attention bias scores, a three-way interaction emerged among face-cue emotional valence, diagnostic group, and internalizing symptom severity (F = 2.87, p < 0.05). This interaction reflected different associations between internalizing symptom severity and threat-related attention bias across diagnostic groups. In children with no diagnosis (n = 1411, mean difference = 11.03, s.e. = 3.47, df = 1, p < 0.001) and those with distress-related disorders (n = 66, mean difference = 10.63, s.e. = 5.24, df = 1, p < 0.05), high internalizing symptoms predicted vigilance towards threat. However, in children with fear-related disorders (n = 86, mean difference = −11.90, s.e. = 5.94, df = 1, p < 0.05), high internalizing symptoms predicted an opposite tendency, manifesting as greater bias away from threat. These associations did not emerge in the behaviour-disorder group (n = 211).
The association between internalizing symptoms and biased orienting varies with the nature of developmental psychopathology. Both the form and severity of psychopathology moderates threat-related attention biases in children.