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Whereas accuracy is used as an indicator of cognitive flexibility in preschool‐age children, reaction time (RT), or a combination of accuracy and RT, provide better indices of performance as children transition to school. Theoretical models and cross‐sectional studies suggest that a speed‐accuracy tradeoff may be operating across this transition, but the lack of longitudinal studies makes this transition difficult to understand. The current study explored the longitudinal and bidirectional associations between accuracy and RT on the DCCS (mixed block) at 5, 6, and 7 years of age using cross‐lagged panel analyses. The study also examined the roles of working memory and language, as potential longitudinal mediators between RT at Time X and accuracy at Time X + 1, and explored the role of inhibitory control. The sample consisted of 425 children from the Quebec Longitudinal Study of Child Development. Results show lagged associations from slower RT to greater improvements in accuracy between 5 and 6 years and between 6 and 7 years. Further, higher accuracy at 6 years predicted faster RT at 7 years. Only working memory acted as a partial mediator between RT at 5 years and accuracy at 6 years. These results provide needed longitudinal evidence to support theoretical claims that slower RT precedes improved accuracy in the development of cognitive flexibility, that working memory may be involved in the early stage of this process, and that accuracy and reaction time become more efficient in later stages of this process. [ABSTRACT FROM AUTHOR]

This article reviews the literature on the association between cannabis use (CU) and psychosocial functioning, operationalized here as academic achievement, economic prospects, social relationships and quality of life. So far, study results have been inconsistent. To clarify whether CU has an impact on psychosocial functioning, this article mainly reviewed prospective and longitudinal studies published since 2000 and examined whether studies controlled for confounding factors (e.g. socio-demographics, other substance use, psychopathology, social environment). The review suggested that when confounding variables are controlled for, the association between CU and psychosocial outcomes is generally small or non-significant. When significant associations remain, they are for chronic, dependent or early onset CU specifically, suggesting that the frequency of use and age of onset may be necessary elements to detect persistent, however small, psychosocial consequences. These results illustrate the importance of controlling for intra- and inter-individual differences to examine the link between CU and later psychosocial functioning. Results also suggest that policy and prevention efforts should consider targeting the individual and environmental factors (e.g. early academic and cognitive functioning, social disadvantage, family functioning, personality, smoking) that account for much of the association between CU and later psychosocial problems, rather than, or in addition to, CU itself. [ABSTRACT FROM AUTHOR]

Objective: Only a minority of drug and alcohol users develops a substance use disorder. Previous studies suggest that this differential vulnerability commonly reflects a developmental trajectory characterized by diverse externalizing behaviors. In this study, we examined the relation between child and adolescent externalizing behaviors and adolescent substance use in a prospectively followed Canadian birth cohort, accounting for the temporal sequence of a wide variety of contributing factors. Methods: Two hundred and forty-two adolescents followed since birth (date range: 1996 to 2012) were assessed on externalizing behavior (age 17 months to 16 years), alcohol and cannabis use at age 16, age of alcohol use onset, family history of substance use problems, family functioning (age 11 to 15), sensation seeking (age 16), prenatal substance exposure, socioeconomic status (age 1 to 9), and sex. Results: Age of alcohol use onset was predicted by a family history of substance use problems, externalizing traits from ages 6 to 10 and 11 to 16, sensation seeking at age 16, prenatal alcohol and tobacco exposure and family functioning at ages 11 to 15. High frequencies of alcohol and cannabis use at age 16 were both predicted by externalizing traits from ages 11 to 16, a family history of substance use problems and sensation seeking after controlling for other individual, environmental and familial variables. The association between familial substance use problems and substance use during adolescence was partially mediated by externalizing traits from age 11 to 16. Conclusions: The present findings provide prospective evidence for a developmental risk pathway for adolescent substance use, potentially identifying those who could benefit from early interventions. [ABSTRACT FROM AUTHOR]

EF skills play a central role in the etiology and maintenance of anxiety, but it is unclear whether they act as moderators or mediators in the relation between early behavioral inhibition (BI) and later anxiety. The current study tested two models by examining whether two executive functions (EF) skills (cognitive flexibility and working memory) assessed at age 6 acted as moderators or mediators in the relation between BI at 5 years and anxiety symptoms at 7 years. The sample consisted of 422 children from the Quebec Longitudinal Study of Child Development. We tested the moderation model, main and interaction effects using hierarchical multiple regression analyses and the mediation model with the product of coefficients test. Results showed that higher BI at 5 years predicted high anxiety at 7 years only at low levels of cognitive flexibility or working memory at 6 years. This suggests that high levels of cognitive flexibility or working memory at 6 years may act as protective factors. In contrast, neither cognitive flexibility nor working memory at age 6 acted as mediators in the association between BI at 5 years and anxiety at 7 years. Results support the hypothesis that goal-driven cognitive control processes act as moderators and promote adaptive functioning by dampening the effect of early BI on later anxiety. [ABSTRACT FROM AUTHOR]

This study examined (1) longitudinal invariance of executive function (EF) factors across early childhood, (2) EF development, and (3) its association with later cognitive functions and academic performance. We measured cognitive flexibility, working memory, inhibitory control, and complex EF in 465 children (72% white) at 3.5, 5, 6, and 7 years. Confirmatory factor analyses supported a one-factor EF model at each age. Across time, factor loadings were invariant, and intercepts were invariant for measures of cognitive flexibility only. In latent growth analyses, EF increased more rapidly between 3.5 and 6 than 6–7 years. EF at 3.5 years and its growth (slope from 3.5 to 7 years) predicted later executive and non-executive function in hypothesized ways, indicating that the factor captured EF rather than other general cognitive abilities. Moreover, EF at 3.5 years and its growth predicted academic performance at 9 and 17 years, suggesting that interventions to improve EF could have the potential to improve academic performance across elementary and secondary education. The data that support the findings of this study are available from the corresponding author, NCR, upon reasonable request, but are subject to institutional, federal and provincial privacy regulations. • A one-factor model of cool executive function (EF) across early childhood (3.5 - 7 years) was supported. • EF factors exhibited partial strong longitudinal invariance with only cognitive flexibility being strongly invariant. • Latent EF ability improved significantly across childhood, more so between 3.5 - 6 years than 6 - 7 years. • Latent EF factors predicted later performance in EF related tasks, but not short-term memory or vocabulary. [ABSTRACT FROM AUTHOR]

Among children exposed to elevated maternal depression symptoms (MDS), recent studies have demonstrated reduced internalizing and externalizing problems for those who have attended formal childcare (i.e., center-based, family-based childcare). However, these studies did not consider whether childcare attendance is associated with benefits for the child only or also with reduced MDS. Using a four-wave longitudinal cross-lagged model, we evaluated whether formal childcare attendance was associated with MDS or child behavior problems and whether it moderated longitudinal associations between MDS and child behavior problems and between child behavior problems and MDS. The sample was drawn from a population-based cohort study and consisted of 908 biologically related mother–child dyads, followed from 5 months to 5 years. Attending formal childcare was not associated with MDS or child behavior problems but moderated the association between MDS at 3.5 years and child internalizing and externalizing problems at 5 years as well as between girls' externalizing problems at 3.5 years and MDS at 5 years. No other moderation of formal childcare was found. Findings suggest that attending formal childcare reduces the risks of behavior problems in the context of MDS but also the risk of MDS in the context of girls' externalizing problems. [ABSTRACT FROM AUTHOR]

Presenilin 1 gene (PSEN1) mutations are the most common cause of familial Alzheimer's disease (FAD). One of the most abundant FAD mutations, PSEN1 A431E, has been reported to be associated with spastic paraparesis in about half of its carriers, but the determining mechanisms of this phenotype are still unknown. In our study we characterized three A431E mutation carriers, one symptomatic and two asymptomatic, from a Mexican family with a history of spastic paraparesis in all of its affected members. At cognitive assessment and MRI, the symptomatic subject showed an atypical non-amnestic mild cognitive impairment with visuospatial deficits, olfactory dysfunction and significant parieto-occipital brain atrophy. Furthermore, we found several periventricular white matter hyperintensities whose progression pattern and localization correlated with their motor impairment, cognitive profile, and non-motor symptoms. Together, our data suggests that in this family the A431E mutation leads to a divergent neurological disorder in which cognitive deterioration was clinically exceeded by motor impairment and that it involves early glial and vascular pathological changes. [ABSTRACT FROM AUTHOR]

Although disturbing dreams are prevalent in youth and are associated with psychopathology, little is known about their developmental course and risk factors. We aimed to examine the association between early social environment and subsequent disturbing dream frequency across adolescence as moderated by early negative emotionality. Measures of children's early social environment and negative emotionality were collected from the mothers of 410 children (5–42 months old) and measures of disturbing dream frequency directly from the children (13–18 years old). Preliminary steps identified subgroups of families with distinct profiles of social environment using latent variable mixture modeling, and captured changes in disturbing dream frequency using latent growth modeling. Regression and moderation analyses were conducted to test the study objectives. Results showed that the diverse family patterns were best captured by two profiles reflecting adverse and positive social environments and that overall disturbing dream frequency decreased during adolescence. Moderation analyses showed that when early negative emotionality was higher, DD frequency was not only more elevated in an adverse environment, but lower in a positive environment. These results indicate that the development of disturbing dreams is most strongly associated with a combination of individual and environment factors. Our study adds to the literature by refining our conception of individual traits and disturbing dream development and has implications for the prevention of bad dreams, nightmares, and associated psychopathologies. [ABSTRACT FROM AUTHOR]

Differences between monolingual and multilingual vocabulary development have been observed but few studies provide a longitudinal perspective on vocabulary development before and following school entry. This study compares vocabulary growth profiles of 106 multilingual children to 211 monolingual peers before and after school entry to examine whether: (1) school entry coincides with different rates of vocabulary growth compared to prior to school entry, (2) compared to monolingual peers, multilingual children show different vocabulary sizes or rates of vocabulary growth, (3) the age of onset of second-language acquisition for multilingual children is associated with vocabulary size or rate of vocabulary growth, and (4) the sociolinguistic context of the languages spoken by multilingual children is associated with vocabulary size or rate of vocabulary growth. Results showed increases in vocabulary size across time for all children, with a steeper increase prior to school entry. A significant difference between monolingual and multilingual children who speak a minority language was observed with regards to vocabulary size at school entry and vocabulary growth prior to school entry, but growth rate differences were no longer present following school entry. Taken together, results suggest that which languages children speak may matter more than being multilingual per se. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both. Methods: In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age. Results: The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction. Conclusions: These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse. [ABSTRACT FROM AUTHOR]

This study examined whether interactions of parental knowledge of adolescent's whereabouts with impulsivity and sensation seeking in the prediction of adolescent substance use supported the diathesis-stress or differential susceptibility model in 230 15-year old adolescents (53% girls). Interactions between impulsivity and parental knowledge supported the diathesis-stress model with high impulsivity as a vulnerability factor: when impulsivity was higher, low levels of parental knowledge were associated with higher levels of substance use. Interactions between sensation seeking and parental knowledge supported differential susceptibility with low sensation seeking as a susceptibility factor; low parental knowledge was associated with higher substance use and high parental knowledge with lower substance use when sensation seeking was lower. Our results show that impulsivity and sensation seeking should be considered independently. Results support previous research suggesting that impulsivity in adolescence may act as a vulnerability factor and suggests that low sensation seeking may be a susceptibility factor. [ABSTRACT FROM AUTHOR]

The present study examined 1) whether the associations between cannabis use (CU) age of onset and drug abuse by 28 y remain when controlling for risk factors in childhood, adolescence and early adulthood; and 2) the developmental pathways from early risk factors to drug abuse problems. Participants from a longitudinal sample of boys of low socioeconomic status ( N = 1,030) were followed from 6 to 28 y. We examined the self-reported CU onset between the ages of 13 and 17 y and drug abuse symptoms by 28 y. The odds of developing any drug abuse symptoms by 28 y were reduced by 31% for each year of delayed CU onset (OR = 0.69). Cannabis, alcohol and other drug frequency at 17 y mediated this association. Still, even when taking that frequency of use into account, adolescents who started using cannabis before 15 y were at a higher risk of developing drug abuse symptoms by age 28 y. Significant indirect effects were found from early adolescent delinquency and affiliation with deviant friends to drug abuse symptoms at 28 y through CU age of onset and substance use frequency at 17 y. The results suggest more clearly than before that prevention programs should aim at delaying CU onset to prevent or reduce drug abuse in adulthood. Furthermore, prevention programs targeting delinquency and/or affiliation with deviant friends in childhood or early adolescence could indirectly reduce substance abuse in adulthood without addressing substance use specifically. [ABSTRACT FROM AUTHOR]

The main objective of this prospective longitudinal study was to investigate bidirectional associations between adolescent cannabis use (CU) and neurocognitive performance in a community sample of 294 young men from ages 13 to 20 years. The results showed that in early adolescence, and prior to initiation to CU, poor short-term and working memory, but high verbal IQ, were associated with earlier age of onset of CU. In turn, age of CU onset and CU frequency across adolescence were associated with (a) specific neurocognitive decline in verbal IQ and executive function tasks tapping trial and error learning and reward processing by early adulthood and (b) lower rates of high-school graduation. The association between CU onset and change in neurocognitive function, however, was found to be accounted for by CU frequency. Whereas the link between CU frequency across adolescence and change in verbal IQ was explained (mediated) by high school graduation, the link between CU frequency and tasks tapping trial and error learning were independent from high school graduation, concurrent cannabis and other substance use, adolescent alcohol use, and externalizing behaviors. Findings support prevention efforts aimed at delaying onset and reducing frequency of CU. [ABSTRACT FROM AUTHOR]

This study investigated the transactional relations between vocabulary and disruptive behaviors (DB; physical aggression and opposition/rule breaking/theft and vandalism), during the transition to formal schooling, using a community sample of 572 children. Cross-lagged panel model analyses were used to examine bidirectional relationships, comparing physical aggression to non-aggressive DB. Transactional associations between vocabulary and DB were observed, coinciding with school entry. Lower vocabulary in preschool (60mo.) was predictive of higher physical aggression scores in kindergarten. In turn, higher physical aggression in kindergarten was predictive of lower vocabulary in 1st grade. For non-aggressive DB, recurrent associations were found. Lower verbal skills in preschool (42mo.) and kindergarten predicted higher non-aggressive DB scores later in preschool and in 1st grade respectively. In turn, higher non-aggressive DB in kindergarten predicted lower vocabulary scores in 1st grade. In contrast to transactional paths from vocabulary to DB, transactional paths from DB to vocabulary observed after the transition to elementary school remained significant after controlling for comorbid hyperactivity, impulsivity and inattention behaviors, suggesting these links were specific to aggressive and non-aggressive DB. Practical implications for prevention are discussed. [ABSTRACT FROM AUTHOR]

Recent brain imaging studies have found changes in subcortical regions in presymptomatic autosomal dominant Alzheimer's disease (ADAD). These regions are also affected in sporadic Alzheimer's disease (sAD), but whether such changes are seen in early-stage disease is still uncertain. In this review, we discuss imaging studies published in the past 12 years that have found evidence of subcortical involvement in early-stage ADAD and/or sAD. Several papers have reported amyloid deposition in the striatum of presymptomatic ADAD mutation carriers, prior to amyloid deposition elsewhere. Altered caudate volume has also been implicated in early-stage ADAD, but findings have been variable. Less is known about subcortical involvement in sAD: the thalamus and striatum have been found to be atrophied in symptomatic patients, but their involvement in the preclinical phase remains unclear, in part due to the difficulties of studying this stage in sporadic disease. Longitudinal imaging studies comparing ADAD mutation carriers with individuals at high-risk for sAD may be needed to elucidate the significance of subcortical involvement in different AD clinical stages. [ABSTRACT FROM AUTHOR]

Background: The causes of phenotypic heterogeneity in familial Alzheimer's disease with autosomal dominant inheritance are not well understood. We aimed to characterise clinical phenotypes and genetic associations with APP and PSEN1 mutations in symptomatic autosomal dominant familial Alzheimer's disease (ADAD).Methods: We retrospectively analysed genotypic and phenotypic data (age at symptom onset, initial cognitive or behavioural symptoms, and presence of myoclonus, seizures, pyramidal signs, extrapyramidal signs, and cerebellar signs) from all individuals with ADAD due to APP or PSEN1 mutations seen at the Dementia Research Centre in London, UK. We examined the frequency of presenting symptoms and additional neurological features, investigated associations with age at symptom onset, APOE genotype, and mutation position, and explored phenotypic differences between APP and PSEN1 mutation carriers. The proportion of individuals presenting with various symptoms was analysed with descriptive statistics, stratified by mutation type.Findings: Between July 1, 1987, and Oct 31, 2015, age at onset was recorded for 213 patients (168 with PSEN1 mutations and 45 with APP mutations), with detailed history and neurological examination findings available for 121 (85 with PSEN1 mutations and 36 with APP mutations). We identified 38 different PSEN1 mutations (four novel) and six APP mutations (one novel). Age at onset differed by mutation, with a younger onset for individuals with PSEN1 mutations than for those with APP mutations (mean age 43·6 years [SD 7·2] vs 50·4 years [SD 5·2], respectively, p<0·0001); within the PSEN1 group, 72% of age at onset variance was explained by the specific mutation. A cluster of five mutations with particularly early onset (mean age at onset <40 years) involving PSEN1's first hydrophilic loop suggests critical functional importance of this region. 71 (84%) individuals with PSEN1 mutations and 35 (97%) with APP mutations presented with amnestic symptoms, making atypical cognitive presentations significantly more common in PSEN1 mutation carriers (n=14; p=0·037). Myoclonus and seizures were the most common additional neurological features; individuals with myoclonus (40 [47%] with PSEN1 mutations and 12 [33%] with APP mutations) were significantly more likely to develop seizures (p=0·001 for PSEN1; p=0·036 for APP), which affected around a quarter of the patients in each group (20 [24%] and nine [25%], respectively). A number of patients with PSEN1 mutations had pyramidal (21 [25%]), extrapyramidal (12 [14%]), or cerebellar (three [4%]) signs.Interpretation: ADAD phenotypes are heterogeneous, with both age at onset and clinical features being influenced by mutation position as well as causative gene. This highlights the importance of considering genetic testing in young patients with dementia and additional neurological features in order to appropriately diagnose and treat their symptoms, and of examining different mutation types separately in future research.Funding: Medical Research Council and National Institute for Health Research. [ABSTRACT FROM AUTHOR]

The traditional view that mental disorders are distinct, categorical disorders has been challenged by evidence that disorders are highly comorbid and exist on a continuum (e.g., Caspi et al., 2014; Tackett et al., 2013). The first objective of this study was to use structural equation modeling to model the structure of psychopathology in an adolescent community-based sample (N = 2,144) including conduct disorder, attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), obsessive-compulsive disorder, eating disorders, substance use, anxiety, depression, phobias, and other emotional symptoms, assessed at 16 years. The second objective was to identify common personality and cognitive correlates of psychopathology, assessed at 14 years. Results showed that psychopathology at 16 years fit 2 bifactor models equally well: (a) a bifactor model, reflecting a general psychopathology factor, as well as specific externalizing (representing mainly substance misuse and low ADHD) and internalizing factors; and (b) a bifactor model with a general psychopathology factor and 3 specific externalizing (representing mainly ADHD and ODD), substance use and internalizing factors. The general psychopathology factor was related to high disinhibition/impulsivity, low agreeableness, high neuroticism and hopelessness, high delay-discounting, poor response inhibition and low performance IQ. Substance use was specifically related to high novelty-seeking, sensation-seeking, extraversion, high verbal IQ, and risk-taking. Internalizing psychopathology was specifically related to high neuroticism, hopelessness and anxiety-sensitivity, low novelty-seeking and extraversion, and an attentional bias toward negatively valenced verbal stimuli. Findings reveal several nonspecific or transdiagnostic personality and cognitive factors that may be targeted in new interventions to potentially prevent the development of multiple psychopathologies. (PsycINFO Database Record [ABSTRACT FROM AUTHOR]

The traditional view that mental disorders are distinct, categorical disorders has been challenged by evidence that disorders are highly comorbid and exist on a continuum (e.g., Caspi et al., 2014; Tackett et al., 2013). The first objective of this study was to use structural equation modeling to model the structure of psychopathology in an adolescent community-based sample (N = 2,144) including conduct disorder, attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), obsessive-compulsive disorder, eating disorders, substance use, anxiety, depression, phobias, and other emotional symptoms, assessed at 16 years. The second objective was to identify common personality and cognitive correlates of psychopathology, assessed at 14 years. Results showed that psychopathology at 16 years fit 2 bifactor models equally well: (a) a bifactor model, reflecting a general psychopathology factor, as well as specific externalizing (representing mainly substance misuse and low ADHD) and internalizing factors; and (b) a bifactor model with a general psychopathology factor and 3 specific externalizing (representing mainly ADHD and ODD), substance use and internalizing factors. The general psychopathology factor was related to high disinhibition/impulsivity, low agreeableness, high neuroticism and hopelessness, high delay-discounting, poor response inhibition and low performance IQ. Substance use was specifically related to high novelty-seeking, sensation-seeking, extraversion, high verbal IQ, and risk-taking. Internalizing psychopathology was specifically related to high neuroticism, hopelessness and anxiety-sensitivity, low novelty-seeking and extraversion, and an attentional bias toward negatively valenced verbal stimuli. Findings reveal several nonspecific or transdiagnostic personality and cognitive factors that may be targeted in new interventions to potentially prevent the development of multiple psychopathologies. [ABSTRACT FROM AUTHOR]

Both individual and environmental factors predict externalizing behaviors and substance use (EB-SU); however, different patterns of interaction among these factors may have different implications. This review first examines how temperament and the family environment interact in the prediction of adolescent EB-SU. Second, studies are reviewed according to two theoretical models: (1) diathesis–stress, i.e., certain individual characteristics are linked to vulnerability and later problems in adverse environments; (2) differential susceptibility, i.e., these characteristics are linked to susceptibility, predicting problems in adverse environments, but also better than average outcomes in good environments. Fourteen studies focusing on the prediction of EB-SU at ages 12–18 were selected through a literature search. Results showed that certain temperament traits (high levels of impulsivity and disinhibition; low levels of effortful control, negative affect, fearfulness and shyness), hereby designated as “adventurous” disposition, were associated with higher levels of EB-SU in adverse family environments. Some studies also showed that children with “adventurous” temperament traits in positive environments had the lowest levels of EB-SU. This suggests that prevention of EB-SU might target family factors such as parenting and focus on children with “adventurous” temperament traits. Further, studies that supported the differential susceptibility model were those assessing temperament and the family environment in childhood and studies that supported the diathesis–stress model assessed these variables in adolescence. It is thus possible that some of these “adventurous” temperament traits, with regard to EB-SU, would be indicators of susceptibility to both enriched and adverse environments in childhood but no longer in adolescence, when they would only be indicators of vulnerability to adverse environments. [ABSTRACT FROM AUTHOR]

Temperament and parental practices (PP) are important predictors of adolescent alcohol use (AU); however, less is known about how they combine to increase or decrease risk of AU. This study examined whether age 6 temperament (i.e., impulsivity and inhibitory control) interacted with age 6 coercive PP and/or age 14 parental monitoring to predict AU at 15 years among 209 adolescents. Results showed that low parental monitoring was associated with more frequent AU and that coercive PP interacted with impulsivity to predict AU. This interaction was examined as a function of two models that were not studied before in the prediction of AU: the diathesis–stress model (i.e., impulsive children are more “vulnerable” to adverse PP than those with an easy temperament); and the differential susceptibility model (i.e., impulsive children are also more likely to benefit from good PP). Results supported the differential susceptibility model by showing that impulsive children were not only at higher risk for AU when combined with high coercive PP but also benefit from the absence of coercive PP. This supports the suggestion that the conception of certain temperament characteristics, or in this case impulsivity, as a “vulnerability” for adolescent AU, may need revision because it misrepresents the malleability it may imply. [ABSTRACT FROM PUBLISHER]

Familial Alzheimer's disease (FAD) treatment trials raise interest in the variable occurrence of cerebral amyloid angiopathy (CAA); an emerging important factor in amyloid-modifying therapy. Previous pathological studies reported particularly severe CAA with postcodon 200 PSEN1 mutations and amyloid beta coding domain APP mutations. As CAA may manifest as white matter hyperintensities (WMH) on magnetic resonance imaging, particularly posteriorly, we investigated WMH in 52 symptomatic FAD patients for associations with mutation position. WMH were visually rated in 39 PSEN1 (18 precodon 200); 13 APP mutation carriers and 25 healthy controls. Ten PSEN1 mutation carriers (5 precodon 200) had postmortem examination. Increased WMH were observed in the PSEN1 postcodon 200 group and in the single APP patient with an amyloid beta coding domain (p.Ala692Gly, Flemish) mutation. WMH burden on MRI correlated with severity of CAA and cotton wool plaques in several areas. The precodon 200 group had younger ages at onset, decreased axonal density and/or integrity, and a greater T-lymphocytic response in occipital deep white matter. Mutation site contributes to the phenotypic and pathological heterogeneity witnessed in FAD. [ABSTRACT FROM AUTHOR]

Amyloid-related imaging abnormalities (ARIA), thought to reflect immune responses to vascular amyloid, have been detected in several amyloid-modifying therapy trials for Alzheimer's disease (AD). We report a case of ARIA developing spontaneously during the course of Presenilin 1 (PSEN1)-associated familial AD (FAD), in an APOE4 homozygous patient. Severe cerebral amyloid angiopathy with associated inflammation was subsequently found at autopsy. Recognition that ARIA may arise spontaneously during FAD and of the potential risk factors for its development are important observations given the recent launch of amyloid-modifying therapy trials for FAD. [ABSTRACT FROM AUTHOR]

Amyloid-related imaging abnormalities (ARIA), thought to reflect immune responses to vascular amyloid, have been detected in several amyloid-modifying therapy trials for Alzheimer's disease (AD). We report a case of ARIA developing spontaneously during the course of Presenilin 1 (PSEN1)-associated familial AD (FAD), in an APOE4 homozygous patient. Severe cerebral amyloid angiopathy with associated inflammation was subsequently found at autopsy. Recognition that ARIA may arise spontaneously during FAD and of the potential risk factors for its development are important observations given the recent launch of amyloid-modifying therapy trials for FAD. [ABSTRACT FROM AUTHOR]

Longitudinal and family-based research suggests that conduct disorder, substance misuse, and ADHD involve both unique forms of dysfunction as well as more specific dysfunctions unique to each condition. Using direct measures of brain function, this study also found evidence in both unique and disorder-specific perturbations. [ABSTRACT FROM AUTHOR]

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by impaired higher visual processing skills; however, motor features more commonly associated with corticobasal syndrome may also occur. We investigated the frequency and clinical characteristics of motor features in 44 PCA patients and, with 30 controls, conducted voxel-based morphometry, cortical thickness, and subcortical volumetric analyses of their magnetic resonance imaging. Prominent limb rigidity was used to define a PCA-motor subgroup. A total of 30% (13) had PCA-motor; all demonstrating asymmetrical left upper limb rigidity. Limb apraxia was more frequent and asymmetrical in PCA-motor, as was myoclonus. Tremor and alien limb phenomena only occurred in this subgroup. The subgroups did not differ in neuropsychological test performance or apolipoprotein E4 allele frequency. Greater asymmetry of atrophy occurred in PCA-motor, particularly involving right frontoparietal and peri-rolandic cortices, putamen, and thalamus. The 9 patients (including 4 PCA-motor) with pathology or cerebrospinal fluid all showed evidence of Alzheimer's disease. Our data suggest that PCA patients with motor features have greater atrophy of contralateral sensorimotor areas but are still likely to have underlying Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background It has been reported that mania may be associated with superior cognitive performance. In this study, we test the hypothesis that manic symptoms in youth separate along two correlated dimensions and that a symptom constellation of high energy and cheerfulness is associated with superior cognitive performance. Method We studied 1755 participants of the IMAGEN study, of average age 14.4 years ( SD = 0.43), 50.7% girls. Manic symptoms were assessed using the Development and Wellbeing Assessment by interviewing parents and young people. Cognition was assessed using the Wechsler Intelligence Scale For Children ( WISC- IV) and a response inhibition task. Results Manic symptoms in youth formed two correlated dimensions: one termed exuberance, characterized by high energy and cheerfulness and one of undercontrol with distractibility, irritability and risk-taking behavior. Only the undercontrol, but not the exuberant dimension, was independently associated with measures of psychosocial impairment. In multivariate regression models, the exuberant, but not the undercontrolled, dimension was positively and significantly associated with verbal IQ by both parent- and self-report; conversely, the undercontrolled, but not the exuberant, dimension was associated with poor performance in a response inhibition task. Conclusions Our findings suggest that manic symptoms in youth may form dimensions with distinct correlates. The results are in keeping with previous findings about superior performance associated with mania. Further research is required to study etiological differences between these symptom dimensions and their implications for clinical practice. [ABSTRACT FROM AUTHOR]

A child presents with eye pathology. Underlying is a major eating disorder connected to a genetic abnormality. Serious bone pathology develops and a connection to vitamin A supplementation is investigated. [ABSTRACT FROM AUTHOR]

Abstract: Associating with substance using peers is generally considered as one of the most important predictors of adolescent substance use. However, peer association does not affect all adolescents in the same way. To better understand when and under what conditions peer association is most linked with adolescent substance use (SU), this review focuses on the factors that may operate as moderators of this association. The review highlighted several potential moderators reflecting adolescents' individual characteristics (e.g., pubertal status, genes and personality), peer and parental factors (e.g., nature of relationships and parental monitoring), and contextual factors (e.g., peer, school and neighborhood context). As peer association is a broad concept, important methodological aspects were also addressed in order to illustrate how they can potentially bias interpretation. Taking these into account, we suggest that, while the effects of some moderators are clear (e.g., parental monitoring and sensation seeking), others are less straightforward (e.g., neighborhood) and need to be further examined. This review also provides recommendations for addressing different methodological concerns in the study of moderators, including: the use of longitudinal and experimental studies and the use of mediated moderation. These will be key for developing theory and effective prevention. [Copyright &y& Elsevier]

Most research linking early pubertal development to substance use has focused on the effects of pubertal timing (age at which a certain stage of pubertal development is reached or pubertal status at a particular age--related to the maturation disparity hypothesis), but little research has focused on pubertal tempo (rate of growth through pubertal stages--related to the maturation compression hypothesis). However, both timing and tempo have not only been identified as important components of pubertal development, with different predictors, but have also been shown to be independently associated with other adolescent psychopathologies. Using latent growth-curve modeling, this study examined how pubertal status at age 12 and pubertal tempo (between 11 and 13 years) related to substance use from 15 to 16 years in boys from low socioeconomic backgrounds (N = 871). Results showed that both pubertal status at age 12 and tempo were significant predictors of increased levels of substance use and problems in mid to late adolescence. In an attempt to identify mechanisms that may explain the association between pubertal development and substance use it was found that sensation seeking partially mediated the association between pubertal status at age 12 and substance use behaviors. Impulse control was found to moderate the association sensation seeking had with marijuana use frequency, with high sensation-seeking scores predicting higher marijuana use frequency only at low levels of impulse control. These findings highlight the importance of considering multiple sources of individual variability in the pubertal development of boys and provide support for both the maturational disparity and compression hypotheses. [ABSTRACT FROM AUTHOR]

Amyloid imaging studies of presymptomatic familial Alzheimer's disease have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. This study aimed to investigate whether there are associated volume and diffusivity changes in these subcortical structures during the presymptomatic and symptomatic stages of familial Alzheimer's disease. As the thalamus and striatum are involved in neural networks subserving complex cognitive and behavioural functions, we also examined the diffusion characteristics in connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers underwent volumetric and diffusion tensor magnetic resonance imaging, neuropsychological and clinical assessments; 10 were symptomatic, 10 were presymptomatic and on average 5.6 years younger than their expected age at onset; 20 healthy control subjects were also studied. We conducted region of interest analyses of volume and diffusivity changes in the thalamus, caudate, putamen and hippocampus and examined diffusion behaviour in the white matter tracts of interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and tract-based spatial statistics were also used to provide unbiased whole-brain analyses of group differences in volume and diffusion indices, respectively. We found that reduced volumes of the left thalamus and bilateral caudate were evident at a presymptomatic stage, together with increased fractional anisotropy of bilateral thalamus and left caudate. Although no significant hippocampal volume loss was evident presymptomatically, reduced mean diffusivity was observed in the right hippocampus and reduced mean and axial diffusivity in the right cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial and in particular radial diffusivity, with reduced fractional anisotropy, in all of the white matter tracts of interest. The symptomatic group also showed atrophy and increased mean diffusivity in all of the subcortical grey matter regions of interest, with increased fractional anisotropy in bilateral putamen. We propose that axonal injury may be an early event in presymptomatic Alzheimer's disease, causing an initial fall in axial and mean diffusivity, which then increases with loss of axonal density. The selective degeneration of long-coursing white matter tracts, with relative preservation of short interneurons, may account for the increase in fractional anisotropy that is seen in the thalamus and caudate presymptomatically. It may be owing to their dense connectivity that imaging changes are seen first in the thalamus and striatum, which then progress to involve other regions in a vulnerable neuronal network. [ABSTRACT FROM AUTHOR]

Amyloid imaging studies of presymptomatic familial Alzheimer’s disease have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. This study aimed to investigate whether there are associated volume and diffusivity changes in these subcortical structures during the presymptomatic and symptomatic stages of familial Alzheimer’s disease. As the thalamus and striatum are involved in neural networks subserving complex cognitive and behavioural functions, we also examined the diffusion characteristics in connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers underwent volumetric and diffusion tensor magnetic resonance imaging, neuropsychological and clinical assessments; 10 were symptomatic, 10 were presymptomatic and on average 5.6 years younger than their expected age at onset; 20 healthy control subjects were also studied. We conducted region of interest analyses of volume and diffusivity changes in the thalamus, caudate, putamen and hippocampus and examined diffusion behaviour in the white matter tracts of interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and tract-based spatial statistics were also used to provide unbiased whole-brain analyses of group differences in volume and diffusion indices, respectively. We found that reduced volumes of the left thalamus and bilateral caudate were evident at a presymptomatic stage, together with increased fractional anisotropy of bilateral thalamus and left caudate. Although no significant hippocampal volume loss was evident presymptomatically, reduced mean diffusivity was observed in the right hippocampus and reduced mean and axial diffusivity in the right cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial and in particular radial diffusivity, with reduced fractional anisotropy, in all of the white matter tracts of interest. The symptomatic group also showed atrophy and increased mean diffusivity in all of the subcortical grey matter regions of interest, with increased fractional anisotropy in bilateral putamen. We propose that axonal injury may be an early event in presymptomatic Alzheimer’s disease, causing an initial fall in axial and mean diffusivity, which then increases with loss of axonal density. The selective degeneration of long-coursing white matter tracts, with relative preservation of short interneurons, may account for the increase in fractional anisotropy that is seen in the thalamus and caudate presymptomatically. It may be owing to their dense connectivity that imaging changes are seen first in the thalamus and striatum, which then progress to involve other regions in a vulnerable neuronal network. [ABSTRACT FROM AUTHOR]

Objective: The current paper aims to review findings from developmental research that are related to adolescent substance-use and are considered key for improving theory and developing effective prevention. Method: A selective literature review of relevant developmental studies on adolescent substance-use was conducted. Results: Studies in epidemiology and developmental science focusing on developmental onset, developmental transitions, comorbidity among disorders, and endophenotypes have identified important trends, risk-factors for and consequences of adolescent substance-use, which have informed theoretical models of addiction. Furthermore, they have informed clinical practice by identifying childhood disorders and personality characteristics that can be targeted preventatively before substance-use problems have their onset. Conclusions: Developmental research has contributed significantly to the understanding of aetiology and treatment of substance-use disorders. By targeting early liability factors rather than substance-use problems later in adolescence, interventions could reduce the adverse impact substance-use has on the developing brain as well as other associated harms. [ABSTRACT FROM AUTHOR]

Background This study assessed the validity, sensitivity, and specificity of the Substance Use Risk Profile Scale ( SURPS), a measure of personality risk factors for substance use and other behavioral problems in adolescence. Methods The concurrent and predictive validity of the SURPS was tested in a sample of 1,162 adolescents (mean age: 13.7 years) using linear and logistic regressions, while its sensitivity and specificity were examined using the receiver operating characteristics curve analyses. Results Concurrent and predictive validity tests showed that all 4 brief scales-hopelessness (H), anxiety sensitivity ( AS), impulsivity ( IMP), and sensation seeking ( SS)-were related, in theoretically expected ways, to measures of substance use and other behavioral and emotional problems. Results also showed that when using the 4 SURPS subscales to identify adolescents 'at risk,' one can identify a high number of those who developed problems (high sensitivity scores ranging from 72 to 91%). And, as predicted, because each scale is related to specific substance and mental health problems, good specificity was obtained when using the individual personality subscales (e.g., most adolescents identified at high risk by the IMP scale developed conduct or drug use problems within the next 18 months [a high specificity score of 70 to 80%]). Conclusions The SURPS is a valuable tool for identifying adolescents at high risk for substance misuse and other emotional and behavioral problems. Implications of findings for the use of this measure in future research and prevention interventions are discussed. [ABSTRACT FROM AUTHOR]

Excess neuronal loss-atrophy-is an inevitable feature of Alzheimer's disease (AD). Following studies in the early 1990 s demonstrating that non-invasive imaging can be used to visualize excess volume loss, i.e., the consequences of atrophy in AD, a major interest has been improving and validating methods to quantify measures of atrophy from serially acquired magnetic resonance imaging. Here we summarize our experience of measuring the extent and pattern of atrophy to understand disease pathogenesis, particularly through studies of individuals with or destined to develop familial AD; to aid diagnosis; and as an outcome measure for treatment trials. As the field moves toward earlier diagnosis and prevention, we outline the important roles that we believe structural imaging will play alongside other biomarkers both in identifying individuals in the earliest stages of neurodegeneration and assessing the effects of novel therapies. [ABSTRACT FROM AUTHOR]

The article discusses the identification of posterior cortial atrophy (PCA), which is a chronic condition caused by Alzheimer's disease (AD). It states that early symptoms of PCA is related to vision which include difficulty in reading, difficulty in locating objects, and trouble in judging distance, volume and depth. It also notes that an early diagnosis of the disease may help the patient plan for an effective treatment in the future and find effective therapies for disease modification.

Tract-based spatial statistics (TBSS) is a popular method for the analysis of diffusion tensor imaging data. TBSS focuses on differences in white matter voxels with high fractional anisotropy (FA), representing the major fibre tracts, through registering all subjects to a common reference and the creation of a FA skeleton. This work considers the effect of choice of reference in the TBSS pipeline, which can be a standard template, an individual subject from the study, a study-specific template or a group-wise average. While TBSS attempts to overcome registration error by searching the neighbourhood perpendicular to the FA skeleton for the voxel with maximum FA, this projection step may not compensate for large registration errors that might occur in the presence of pathology such as atrophy in neurodegenerative diseases. This makes registration performance and choice of reference an important issue. Substantial work in the field of computational anatomy has shown the use of group-wise averages to reduce biases while avoiding the arbitrary selection of a single individual. Here, we demonstrate the impact of the choice of reference on: (a) specificity (b) sensitivity in a simulation study and (c) a real-world comparison of Alzheimer's disease patients to controls. In (a) and (b), simulated deformations and decreases in FA were applied to control subjects to simulate changes of shape and WM integrity similar to what would be seen in AD patients, in order to provide a "ground truth" for evaluating the various methods of TBSS reference. Using a group-wise average atlas as the reference outperformed other references in the TBSS pipeline in all evaluations. [ABSTRACT FROM AUTHOR]

Objective/background: Many studies have reported associations between disturbing dream occurrence and internalizing symptoms in adults, but the extent to which such associations also characterize adolescents remains unknown. The main goal of the present longitudinal study was to evaluate the strength and stability of the associations between disturbing dream frequency, suicidal ideation, and internalizing symptoms from ages 13 to 18.Methods: Participants (N = 434) drawn from two longitudinal birth cohort studies on child development in the province of Quebec, Canada, completed annual self-reports of disturbing dream frequency, suicidal ideation, and levels of depression and anxiety.Results: Two separate cross-lagged panel models for symptoms of depression and anxiety were conducted with both models showing similar results. In early adolescence, high levels of and higher change in disturbing dream frequency were associated with increased odds of reporting later suicidal ideation, whereas in mid to late adolescence, increased odds of reporting suicidal ideation at age 17 was associated with increased disturbing dream frequency at age 18. Across adolescence, increased levels of depression and anxiety were associated with increased odds of reporting later suicidal ideation and increased disturbing dream frequency.Conclusions: These findings support previous literature suggesting that disturbing dream frequency, depression, and anxiety, are risk factors for suicidal ideation throughout adolescence. The present longitudinal study allows for a refinement of our conceptualization of disturbing dream and their relation to suicide and internalizing symptoms throughout adolescence and suggests that the collection of information on disturbing dream and internalizing symptoms during early adolescence may help screen adolescents for suicide risk. [ABSTRACT FROM AUTHOR]

Objective: To examine the long-term effects of a personality-targeted intervention on drinking quantity and frequency (QF). problem drinking, and personality-specific motivations for alcohol use in early adolescence. Method: A randomized control trial was carried out with 364 adolescents (median age 14) recruited from 13 secondary schools with elevated scores in Hopelessness, Anxiety-Sensitivity (AS). Impulsivity, and Sensation-Seeking. Participants were randomly assigned to a control no-intervention condition or a 2-session group coping skills intervention targeting 1 of 4 personality risk factors. The effects of the intervention on quantity/frequency (QF) of alcohol use, frequency of binge drinking, problem drinking, and motives were examined at 6, 12, 18, and 24 months postintervention. Results: Intent-to-treat repeated measures analyses revealed a significant overall intervention effect in reducing problem drinking symptoms, and a Time × Intervention effect on drinking QF and binge drinking frequency. Relative to the control group, the intervention group showed significantly reduced drinking and binge drinking levels at 6 months postintervention and reduced problem drinking symptoms for the full 24-month follow-up period (Cohen's d = 0.33). A significant Time × Intervention × Personality interaction was demonstrated for coping and enhancement drinking motives. In addition to an overall effect of intervention on coping motives, the AS group who received that intervention reported for coping motives compared with the AS control group at 12 and 24 months postintervention. Conclusions: This study provides further evidence showing that personality-targeted interventions reduce drinking behavior in adolescents in the short term. Novel findings were that the interventions were shown to produced long-term effects on drinking problems and personality-specific effects on drinking motives. [ABSTRACT FROM AUTHOR]

Externalising behaviours such as substance misuse (SM) and conduct disorder (CD) symptoms highly co-ocurr in adolescence. While disinhibited personality traits have been consistently linked to externalising behaviours there is evidence that these traits may relate differentially to SM and CD. The current study aimed to assess whether this was the case, after examining the nature of the relationship between SM and CD symptoms in an adolescent sample ( N = 392), using structural equation modelling. Similar to those found in adults (Krueger et al. Journal of Abnormal Psychology 116: 645-666, ), results showed that CD and SM symptoms were organized hierarchically, with symptoms explaining a single broad, coherent construct of externalising behaviour, but also explaining specific factors of SM and CD that vary independently from the general externalising factor. Furthermore, disinhibited personality traits related differentially to these factors, with results showing that, even controlling for inhibited personality traits, impulsivity was associated with CD and the common variance shared by CD and SM, while sensation seeking was specifically associated with SM only. Hopelessness was also associated with the common variance shared by SM and CD. Results confirm impulsivity, hopelessness and sensation seeking as key correlates of externalising behaviour problems in adolescence, identifying them as clear targets for intervention and prevention strategies. [ABSTRACT FROM AUTHOR]

A great deal of research has emerged on the comorbidity between alcohol misuse and psychological symptoms (e.g., depression, anxiety, and antisocial behavior or conduct disorder) in adolescence. Research has also shown that personality traits underlie vulnerability to alcohol use and psychological symptoms, but how personality moderates this association has not been comprehensively examined. The goals of this study are to clarify (i) whether early alcohol use effects the rate of change of psychological symptoms and vice versa, (ii) whether initial levels and rate of change in both domains vary according to individual differences in personality traits, and (iii) whether personality moderates the relationship between alcohol use and psychological symptoms. Self-reported alcohol use, depression, anxiety, and antisocial behavior were collected from 393 adolescents at four separate time points across an 18-month period. Parallel growth models were used to assess the main objectives of the study. Personality traits [anxiety sensitivity (AS), hopelessness (H), impulsivity (IMP), and sensation seeking (SS)] were included as time-invariant predictors of initial levels and rates of change of each construct. The results indicated that elevated levels of depression predicted faster rates of increase in alcohol use. Personality-specific relationships were demonstrated across all models. IMP was shown to moderate the relationship between alcohol use and depression, suggesting that adolescents who showed a susceptibility to elevated levels of IMP, and heavier drinking were less likely to demonstrate a normative decline in depression. Adolescents with higher levels of AS and anxiety were more likely to show a faster rate of increase in alcohol use. These results highlight the importance of examining personality traits in studying the associations between alcohol use and psychological symptoms. [ABSTRACT FROM AUTHOR]

Disinhibited traits, assessed both at the self-report and at the cognitive/behavioral levels, have been frequently implicated in externalizing behaviors, such as conduct disorder (CD), binge drinking, and drug use. However, self-report measures of disinhibition, such as impulsivity (IMP) and sensation seeking (SS), and cognitive measures of disinhibition are not often studied together in the same participants. Thus, it is still unclear how cognitive measures such as response inhibition and reward response bias relate to self-report measures of IMP and SS, and whether they can explain some of the association found between these self-report measures and specific facets of externalizing problems. The aim of this study was to assess whether cognitive measures of disinhibition relate to self-report measures of disinhibition and can mediate the specific relationships between self-report measures of disinhibition and CD symptoms, binge drinking and drug use in adolescence. Seventy-six adolescents were assessed on personality, substance use, and conduct problems every 6 months from 14 to 16 years of age and completed a test battery that included a Stop task, rewarded go/no-go task, digit span, and intelligence quotient tests at 16 years of age. Multiple regression analyses showed that self-report IMP at 14 and deficits in response inhibition were associated with a 2-year average CD symptoms score and that deficits in response inhibition partially mediated the association between self-report IMP and CD symptoms ( ab = 0.018 CI: 0.00002 to 0.04827). In contrast, SS and reward response bias were significantly associated with the unique variance in binge drinking, and that part of the overlap between SS and binge drinking was mediated by reward response bias ( ab = 0.019, CI: 0.00131 to 0.04662). Findings show a dissociation between inhibitory measures associated with CD symptoms and those associated with binge drinking, with 'cool' inhibitory and executive functions being associated with CD but 'hot,' reward-related disinhibition measures being specific mediators between SS and binge drinking. The findings support the theoretical conceptualization for dual cognitive/motivational pathways of disinhibition, in this case IMP and SS, and their unique association with externalizing behavior in adolescence. [ABSTRACT FROM AUTHOR]

Abstract: Background: Despite the adverse externalising risks associated with bullying victimisation, no study has investigated the underlying mechanisms of adolescent victims'' engagement with alcohol. This current study investigated the development of risky coping drinking motives as a mediator in the relationship between adolescent school victimisation and alcohol-related problem behaviour using a longitudinal design over 12months. Method: We recruited 324 participants, aged 13 to 15 from schools across London, England. Participants were surveyed during class time at 2 time points: baseline and 12months. At both time points participants answered questions related to bullying victimisation, alcohol-related problem behaviour, drinking motives and the quantity by frequency of alcohol consumption. Results: The relationships between victimisation, drinking and drinking motives were investigated using Pearson correlations. Path analysis showed that victimisation leads both directly and indirectly, through coping motives to alcohol-related problems, rather than to the quantity and frequency of alcohol use. Significance of mediation was tested using 5000 bias corrected and accelerated bootstrapped intervals. Baseline victimisation was significantly correlated with baseline alcohol-related problem behaviour and predictive of future problems at 12months. Drinking to cope at 12months partially mediated the relationship between baseline victimisation and alcohol-related problems at 12months. Conclusions: Results show that victims of bullying are drinking alcohol in a risky style, partly due to the development of self medicating drinking behaviour. Victims of bullying could therefore benefit from coping skills interventions targeting negative affect regulation in order to reduce the risk for future alcohol misuse. [Copyright &y& Elsevier]

Imaging plays an increasingly important role in both clinical practice and research in Alzheimer's disease. Clinically, there is growing appreciation that imaging provides not just exclusion of alternative pathologies, but also positive predictive, diagnostic, and prognostic information in dementia. Imaging can improve specificity of diagnosis in trial populations, facilitate research on the earlier stages of disease, and provide crucial information regarding drug safety and toxicity. With the advent of disease-modifying therapies, these properties acquire increasing importance. Furthermore, imaging biomarkers have the potential to serve as outcome measures of disease progression. A whole arsenal of imaging modalities has now been developed, each allowing a different aspect of the disease process to be explored. However, the limitations of each technique must also be appreciated. A multimodal approach, where imaging markers are combined, may be required to maximize the potential of imaging to enhance our understanding of Alzheimer's disease and to help find effective therapies. [ABSTRACT FROM AUTHOR]

With the prospect of prevention trials for familial Alzheimer's disease on the horizon, understanding the natural history of the illness has never been so important. Earlier this year in The Lancet Neurology, Acosta-Baena and colleagues published the results of the largest and longest retrospective study of pre-dementia clinical stages in familial Alzheimer's disease to date. By reviewing serial neuropsychological assessments of individuals from a large Colombian kindred affected by the E280A mutation in the Presenilin 1 gene, they defined three stages of predementia cognitive impairment. Using survival analyses, the authors estimated the median age at onset and rate of progression through each of these stages towards dementia and ultimately death. Their study provides valuable insights into the time course of cognitive decline associated with this mutation. Furthermore, the study highlights some of the challenges of defining pre-dementia clinical stages in familial Alzheimer's disease and the need for the field to develop a consistent terminology. [ABSTRACT FROM AUTHOR]

The prevalence of mental health problems represents a significant burden on school and community health resources as early as preschool. Reducing this burden requires a better understanding of the developmental mechanisms linking children's early vulnerabilities with mental health after the transition to formal schooling. The 3D-Transition Study (2017–2021) follows 939 participants from a pregnancy cohort in the province of Québec, Canada, as they transition to kindergarten and first grade to examine these mechanisms. Biannual assessments include completed questionnaires from 2 parents as well as teachers, parent-child observations, anthropometric measurements, and age-sensitive cognitive assessments. Saliva is also collected on 11 days over a 16-month period in a subsample of 384 participants to examine possible changes in child salivary cortisol levels across the school transition and their role in difficulties observed during the transition. A combination of planned missing-data designs is being implemented to reduce participant burden, where incomplete data are collected without introducing bias after the use of multiple imputation. The 3D-Transition Study will contribute to an evidence-based developmental framework of child mental health from pregnancy to school age. In turn, this framework can help inform prevention programs delivered in health-care settings during pregnancy and in child-care centers, preschools, and schools. [ABSTRACT FROM AUTHOR]

Background: Peroxisomes are central metabolic organelles that have key roles in fatty acid homoeostasis. As prostate cancer (PCa) is particularly reliant on fatty acid metabolism, we explored the contribution of peroxisomal β-oxidation (perFAO) to PCa viability and therapy response. Methods: Bioinformatic analysis was performed on clinical transcriptomic datasets to identify the perFAO enzyme, 2,4-dienoyl CoA reductase 2 (DECR2) as a target gene of interest. Impact of DECR2 and perFAO inhibition via thioridazine was examined in vitro, in vivo, and in clinical prostate tumours cultured ex vivo. Transcriptomic and lipidomic profiling was used to determine the functional consequences of DECR2 inhibition in PCa. Results: DECR2 is upregulated in clinical PCa, most notably in metastatic castrate-resistant PCa (CRPC). Depletion of DECR2 significantly suppressed proliferation, migration, and 3D growth of a range of CRPC and therapy-resistant PCa cell lines, and inhibited LNCaP tumour growth and proliferation in vivo. DECR2 influences cell cycle progression and lipid metabolism to support tumour cell proliferation. Further, co-targeting of perFAO and standard-of-care androgen receptor inhibition enhanced suppression of PCa cell proliferation. Conclusion: Our findings support a focus on perFAO, specifically DECR2, as a promising therapeutic target for CRPC and as a novel strategy to overcome lethal treatment resistance. [ABSTRACT FROM AUTHOR]