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Introduction: Currently, major depressive disorder (MDD) treatment plans are based on trial-and-error, and remission rates remain low. A strategy to replace trial-and-error and increase remission rates could be treatment stratification. We explored the heartbeat-evoked potential (HEP) as a biomarker for treatment stratification to either antidepressant medication or rTMS treatment. Methods: Two datasets were analyzed: (1) the International Study to Predict Optimized Treatment in Depression (iSPOT-D; n = 1,008 MDD patients, randomized to escitalopram, sertraline, or venlafaxine, and n = 336 healthy controls) and (2) a multi-site, open-label rTMS study (n = 196). The primary outcome measure was remission. Cardiac field artifacts were removed from the baseline EEG using independent component analysis (ICA). The HEP-peak was detected in a bandwidth of 20 ms around 8 ms and 270 ms (N8, N270) after the R-peak of the electrocardiogram signal. Differences between remitters and non-remitters were statistically assessed by repeated-measures ANOVAs for electrodes Fp1, Cz, and Oz. Results: In the venlafaxine subgroup, remitters showed a lower HEP around the N8 peak than non-remitters on electrode site Cz (p = 0.004; d = 0.497). The rTMS group showed a non-significant difference in the opposite direction (d = −0.051). Retrospective stratification to one of the treatments based on the HEP resulted in enhanced treatment outcome prediction for venlafaxine (+22.98%) and rTMS (+10.66%). Conclusion: These data suggest that the HEP could be used as a stratification biomarker between venlafaxine and rTMS; however, future out-of-sample replication is warranted.

Introduction Little is known about smoking cessation among gender minority populations compared to cisgender individuals (whose gender matches their sex assigned at birth). We examined differences between smokers from gender minority populations, cis-women, and cis-men in the heaviness of smoking, quit intentions, use of cessation assistance, quit attempts (ever tried and number), and triggers for thinking about quitting. Aims and Methods We used cross-sectional data from the 2020 International Tobacco Control Netherlands Survey. Among smoking respondents, we distinguished (1) cis-women (female sex, identified as women, and having feminine gender roles; n = 670), (2) cis-men (male sex, identified as men, and having masculine gender roles; n = 897), and (3) gender minorities (individuals who were intersex, who identified as nonbinary, genderqueer, had a sex/gender identity not listed, whose gender roles were not feminine or masculine, or whose gender identity and/or roles were not congruent with sex assigned at birth; n = 220). Results Although gender minorities did not differ from cis-women and cis-men in the heaviness of smoking, plans to quit smoking, and quit attempts, they were significantly more likely to use cessation assistance (20% in the past 6 months) than cis-women (12%) and cis-men (9%). Gender minorities were also significantly more likely to report several triggers for thinking about quitting smoking, for example, quit advice from a doctor, an anti-smoking message/campaign, and the availability of a telephone helpline. Conclusion Despite equal levels of quit attempts and heaviness of smoking, gender minority smokers make more use of smoking assistance, and respond stronger to triggers for thinking about quitting smoking. Implications Smoking cessation counselors should be sensitive to the stressors that individuals from any minority population face, such as stigmatization, discrimination, and loneliness, and should educate their smoking clients on effective coping mechanisms to prevent relapse into smoking after they experience these stressors. Developing tailored smoking cessation programs or campaigns specifically for gender minority populations can also be useful. Based on the results of our subgroup analyses, programs or campaigns for younger gender minority smokers could focus on the availability of telephone helplines and on how friends and family think about their smoking behavior.

The assessment of performance validity is essential in any neuropsychological evaluation. However, relatively few measures exist that are based on attention performance embedded within routine cognitive tasks. The present study explores the potential value of a computerized attention test, the Cognitrone, as an embedded validity indicator in the neuropsychological assessment of early retirement claimants. Two hundred and sixty-five early retirement claimants were assessed with the Word Memory Test (WMT) and the Cognitrone. WMT scores were used as the independent criterion to determine performance validity. Speed and accuracy measures of the Cognitrone were analyzed in receiver operating characteristics (ROC) to classify group membership. The Cognitrone was sensitive in revealing attention deficits in early retirement claimants. Further, 54% (n = 143) of the individuals showed noncredible cognitive performance, whereas 46% (n = 122) showed credible cognitive performance. Individuals failing the performance validity assessment showed slower (AUC = 79.1%) and more inaccurate (AUC = 79.5%) attention performance than those passing the performance validity assessment. A compound score integrating speed and accuracy revealed incremental value as indicated by AUC = 87.9%. Various cut scores are suggested, resulting in equal rates of 80% sensitivity and specificity (cut score = 1.297) or 69% sensitivity with 90% specificity (cut score = 0.734). The present study supports the sensitivity of the Cognitrone for the assessment of attention deficits in early retirement claimants and its potential value as an embedded validity indicator. Further research on different samples and with multidimensional criteria for determining invalid performance are required before clinical application can be suggested.

A crucial aspect of any clinical trial is using the right outcome measure to assess treatment efficacy. Compared to the rapidly evolved understanding and measurement of pathophysiology in preclinical and early symptomatic stages of Alzheimer's disease (AD), relatively less progress has been made in the evolution of clinical outcome assessments (COAs) for those stages. The current paper aims to provide a benchmark for the design and evaluation of COAs for use in early AD trials. We discuss lessons learned on capturing cognitive changes in predementia stages of AD, including challenges when validating novel COAs for those early stages and necessary evidence for their implementation in clinical trials. Moving forward, we propose a multi-step framework to advance the use of more effective COAs to assess clinically meaningful changes in early AD, which will hopefully contribute to the much-needed consensus around more appropriate outcome measures to assess clinical efficacy of putative treatments. HIGHLIGHTS: We discuss lessons learned on capturing cognitive changes in predementia stages of AD. We propose a framework for the design and evaluation of performance based cognitive tests for use in early AD trials. We provide recommendations to facilitate the implementation of more effective cognitive outcome measures in AD trials.

Background: Research on the association between physical inactivity and cognitive decline and dementia is dominated by studies with short-term follow-up, that might be biased by reverse causality. Objective: Investigate the long-term association between physical activity, cognition, and the rate of age-associated cognitive decline. Methods: We investigated the association between late-life physical activity and executive functioning and rate of decline of executive abilities during follow-up of up to 16 years, in 3553 participants of the prospective Rotterdam Study cohort. Measurement took place in 1997–1999, 2002–2004, 2009–2011, and 2014–2015. Results: At baseline (age ± 72 years), higher levels of physical activity were associated with higher levels of executive functioning (adjusted mean difference = 0.03, 95% CI: 0.00 ; 0.06, p = 0.03). This difference remained intact up to 16 years of follow-up. The level of physical activity at baseline was unrelated to the rate of decline of executive abilities over time, in the whole group (adjusted mean difference in change time*physical activity = 0.00, 95% CI: -0.00 ; 0.01, p = 0.31). However, stratification by APOE genotype showed that the accelerated decline of executive abilities observed in those with the ApoE-ε4 allele might be attenuated by higher levels of physical activity in late adulthood (ApoE-ε4 carriers: B time*physical activity = 0.01, 95% CI: 0.00 ; 0.01, p = 0.03). Conclusion: Higher levels of physical activity in late adulthood are related to higher levels of executive functioning, up to 16 years of follow-up. Accelerated decline of executive abilities observed in those with the ApoE-ε4 allele might be mitigated by higher levels of physical activity.

Aims: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. Design, Setting and Participants: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. Measurements: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. Findings: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. Conclusions: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options., Medical Research Future Fund (MRFF) MRF1141214, National Health and Medical Research Council (NHMRC) of Australia GNT2009464

Background: The clinical staging model states that psychosis develops through subsequent stages of illness severity. To better understand what drives illness progression, more extensive comparison across clinical stages is needed. The current paper presents an in-depth characterization of individuals with different levels of risk for psychosis (i.e., different early clinical stages), using a multimethod approach of cross-sectional assessments and daily diary reports.Methods: Data came from the Mirorr study that includes N = 96 individuals, divided across four subgroups (n1 = 25, n2 = 27, n3 = 24, and n4 = 20). These subgroups, each with an increasing risk for psychosis, represent clinical stages 0-1b. Cross-sectional data and 90-day daily diary data on psychopathology, well-being, psychosocial functioning, risk and protective factors were statistically compared across subgroups (stages) and descriptively compared across domains and assessment methods.Results: Psychopathology increased across subgroups, although not always linearly and nuanced differences were seen between assessment methods. Well-being and functioning differed mostly between subgroup 1 and the other subgroups, suggesting differences between non-clinical and clinical populations. Risk and protective factors differed mostly between the two highest and lowest subgroups, especially regarding need of social support and coping, suggesting differences between those with and without substantial psychotic experiences. Subgroup 4 (stage 1b) reported especially high levels of daily positive and negative psychotic experiences.Conclusions: Risk for psychosis exists in larger contexts of mental health and factors of risk and protection that differ across stages and assessment methods. Taking a broad, multi-method approach is an important next step to understand the complex development of youth mental health problems.

Contains fulltext : 281504.pdf (Publisher’s version ) (Open Access) Antisocial and aggressive behaviors show considerable heritability and are central to disruptive behavior disorders (DBDs), but are also frequently observed in attention deficit hyperactivity disorder (ADHD). While the amygdala is implicated as a key neural structure, it remains unclear whether common genetic variants underlie this brain-behavior association. We hypothesized that polygenic (risk) scores for antisocial and aggressive behaviors (ASB-PRS) would be related to amygdala morphology. Using the Broad Antisocial Behavior Consortium genome-wide association study (GWAS; mostly population based cohorts), we calculated ASB-PRS in the NeuroIMAGE I ADHD case-control sample with varying levels of DBD symptomatology (n=679 from 379 families, aged 7 - 29). We first investigated associations of several ASB-PRS p value thresholds with the presence of DBD symptoms and self-reported antisocial behavior (ASB) to determine the threshold for further analyses. This PRS was then related to amygdala volume and shape using regression and vertex-wise analyses. Our results showed associations of ASB-PRS with the presence of DBD symptoms, self-reported ASB, and left basolateral amygdala shape, independent of ADHD symptom severity and ADHD-PRS, with a relative outward displacement of the vertices. No associations of ASB-PRS, DBD symptoms or self-reported ASB with amygdala volume were found. Our results indicate that genetic risk for antisocial and aggressive behaviors is related to amygdala shape alterations, and point to genetic sharing across different DBD and ASB and aggression-related phenotypes as a spectrum of genetically related quantitative traits. Additionally, our findings support the utility of vertex-based shape analyses in genetic studies of ASB, aggression, and DBDs.

Importance: Neurofibrillary tangles composed of aggregated tau protein are one of the neuropathological hallmarks of Alzheimer disease (AD) and correlate with clinical disease severity. Monoclonal antibodies targeting tau may have the potential to ameliorate AD progression by slowing or stopping the spread and/or accumulation of pathological tau. Objective: To evaluate the safety and efficacy of the monoclonal anti-tau antibody semorinemab in prodromal to mild AD. Design, Setting, and Participants: This phase 2 randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted between October 18, 2017, and July 16, 2020, at 97 sites in North America, Europe, and Australia. Individuals aged 50 to 80 years (inclusive) with prodromal to mild AD, Mini-Mental State Examination scores between 20 and 30 (inclusive), and confirmed β-amyloid pathology (by positron emission tomography or cerebrospinal fluid) were included. Interventions: During the 73-week blinded study period, participants received intravenous infusions of placebo or semorinemab (1500 mg, 4500 mg, or 8100 mg) every 2 weeks for the first 3 infusions and every 4 weeks thereafter. Main Outcomes and Measures: The primary outcomes were change from baseline on the Clinical Dementia Rating-Sum of Boxes score from baseline to week 73 and assessments of the safety and tolerability for semorinemab compared with placebo. Results: In the modified intent-to-treat cohort (n = 422; mean [SD] age, 69.6 [7.0] years; 235 women [55.7%]), similar increases were seen on the Clinical Dementia Rating-Sum of Boxes score in the placebo (n = 126; Δ = 2.19 [95% CI, 1.74-2.63]) and semorinemab (1500 mg: n = 86; Δ = 2.36 [95% CI, 1.83-2.89]; 4500 mg: n = 126; Δ = 2.36 [95% CI, 1.92-2.79]; 8100 mg: n = 84; Δ = 2.41 [95% CI, 1.88-2.94]) arms. In the safety-evaluable cohort (n = 441), similar proportions of participants experienced adverse events in the placebo (130 [93.1%]) and semorinemab (1500 mg: 89 [88.8%]; 4500 mg: 132 [94.7%]; 8100 mg: 90 [92.2%]) arms. Conclusions and Relevance: In participants with prodromal to mild AD in this randomized clinical trial, semorinemab did not slow clinical AD progression compared with placebo throughout the 73-week study period but did demonstrate an acceptable and well-tolerated safety profile. Additional studies of anti-tau antibodies may be needed to determine the clinical utility of this therapeutic approach. Trial Registration: ClinicalTrials.gov Identifier: NCT03289143.

Impairments in executive functions (EFs) are common across disorders and can greatly affect daily functioning. Frontal-midline (FM) theta neurofeedback (NF) has been shown effective in enhancing EFs in healthy adults, prompting interest in exploring its potential as an alternative treatment for EFs in (sub)clinical samples. This study aims to determine the effects of FM theta NF on EFs in a sample of 58 adults (aged 20-60 years) with pronounced subjective EF complaints in daily life. Using a pre/post/follow-up design with a sham NF group, the present study assessed upregulation of FM theta in an eight-session individualized FM theta NF training and its immediate and long-term transfer effects on objective and subjective measures of EFs. These included behavioral performance on EF tasks assessing working memory updating (N-back task), set-shifting (Switching task), conflict monitoring (Stroop task), and response inhibition (Stop-signal task), as well as FM theta power during these tasks, and subjective EFs in daily life (BRIEF-A). The results indicate that there are only differences in FM theta self-upregulation between the NF group and sham group when non-responders are excluded from the analysis. Regarding behavioral transfer effects, NF-specific improvements are found in working memory updating reaction time (RT) and conflict monitoring RT variability at six-month follow-up, but not immediately after the NF training. The effects on FM theta power during the EF tasks and subjective changes in EFs in daily life were not specific to the NF training. As a next step, research should identify the best biomarkers to stratify NF training, as well as explore ways to improve NF responsiveness, for instance by increasing neuroplasticity.

Aim: To assess neurodevelopment in young patients with biliary atresia (BA) and to determine the predictive value of General Movement Assessment (GMA) at infant age for neurodevelopmental impairments at toddler age. Method: Infants diagnosed with BA were prospectively included in a longitudinal study. Neurodevelopmental status was previously assessed before Kasai porto-enterostomy (KPE) and one month after KPE using Prechtl's GMA, including motor optimality scores. At 2–3 years, neurodevelopment was assessed using the Bayley Scales of Infant Development, and compared to the Dutch norm population. The predictive value of GMA at infant age for motor skills and cognition at toddler age was determined. Results: Neurodevelopment was assessed in 41 BA patients. At toddler age (n = 38, age 29 ± 5 months, 70 % liver transplantation), 13 (39 %) patients scored below-average on motor skills, and 6 (17 %) patients on cognition. Abnormal GMA after KPE predicted both below-average motor skills and cognitive score at toddler age (sensitivity, 91 % and 80 %; specificity 83 % and 67 %; negative predictive value, 94 % and 94 %; and, positive predictive value, 77 % and 33 %, resp.). Interpretation: One-third of toddlers with BA show impaired motor skills. GMA post-KPE has a high predictive value to identify infants with BA at risk of neurodevelopmental impairments.

BACKGROUND: Post-transplant anaemia and reduced muscle mass and strength are highly prevalent in kidney transplant recipients (KTRs). Decreased haemoglobin levels, a marker of anaemia, could adversely affect muscle mass and strength through multiple mechanisms, among others, through diminished tissue oxygenation. We aimed to investigate the association between haemoglobin levels with muscle mass and strength in KTRs.METHODS: We included stable KTRs from the TransplantLines Biobank and Cohort study with a functional graft ≥1 year post-transplantation. Muscle mass was assessed using 24 h urinary creatinine excretion rate (CER) and bioelectrical impedance analysis (BIA). Muscle strength was assessed with a handgrip strength test using a dynamometer and, in a subgroup (n = 290), with the five-times sit-to-stand (FTSTS) test. We used multivariable linear and logistic regression analyses to investigate the associations of haemoglobin levels with muscle mass and strength.RESULTS: In 871 included KTRs [median age 58 (interquartile range (IQR), 48-66)] years; 60% men; eGFR 51 ± 18 mL/min/1.73 m2 ) who were 3.5 (1.0-10.2) years post-transplantation, the mean serum haemoglobin level was 13.9 ± 1.8 g/dL in men and 12.8 ± 1.5 g/dL in women. Lower haemoglobin levels were independently associated with a lower CER (std. β = 0.07, P = 0.01), BIA-derived skeletal muscle mass (std. β = 0.22, P < 0.001), handgrip strength (std. β = 0.15, P < 0.001), and worse FTSTS test scores (std. β = -0.17, P = 0.02). KTRs in the lowest age-specific and sex-specific quartile of haemoglobin levels had an increased risk of being in the worst age-specific and sex-specific quartile of CER (fully adjusted OR, 2.09; 95% CI 1.15-3.77; P = 0.02), handgrip strength (fully adjusted OR, 3.30; 95% CI 1.95-5.59; P < 0.001), and FTSTS test score (fully adjusted OR, 7.21; 95% CI 2.59-20.05; P < 0.001).CONCLUSIONS: Low haemoglobin levels are strongly associated with decreased muscle mass and strength in KTRs. Future investigation will need to investigate whether maintaining higher haemoglobin levels may improve muscle mass and strength in KTRs.

A decade of research has both illustrated the need for accurate clinical assessment of adult ADHD and brought forward a series of validity indicators assisting this diagnostic process. Several of these indicators have been embedded into Conners’ Adult ADHD Rating Scales (CAARS). As their different theoretical underpinnings offer the opportunity of possible synergy effects, the present study sought to examine whether the item- or index-wise combination of multiple validity indicators benefits classification accuracy. A sample of controls (n = 856) and adults with ADHD (n = 72) answered the CAARS, including the ADHD Credibility Index (ACI) honestly, while a group of instructed simulators (n = 135) completed the instrument as though they had ADHD. First, original CAARS items, which are part of the CAARS Infrequency Index (CII), and items drawn from the ACI were combined into a new CII-ACI-Compound Index. Secondly, existing validity indicators, including suspect T-score elevations and the CII, were considered in combination. Both approaches were evaluated in terms of sensitivity and specificity. The combination of four CII and five ACI items into the CII-ACI-Compound Index yielded a sensitivity between 41 and 51% and an estimated specificity above 87%. Suspect T-score elevations on all three DSM scales emerged as another potentially useful validity indicator with a sensitivity of 45 to 46% and a specificity > 90%. Deeming examinees non-credible whenever two or more validity indicators showed suspect results ensured low false-positive rates ( 11% of misclassified adults with ADHD). Depending on whether high specificity or high sensitivity is prioritized, such combined considerations offer valuable additions to individual validity indicators. High sensitivity provided by “either/or” combinations could prove useful in screening settings, whereas high stakes settings could benefit from “and” combinations.

This study investigated whether visually impaired cyclists, compared to cyclists without visual limitations, take other, potentially safer routes to destinations in their own living environment and whether they ride at a lower speed. In total, 19 matched pairs of a visually impaired cyclist and a normally sighted peer from the same neighbourhood recorded their everyday bicycle rides, using GPS action cameras. In addition, they completed an 'assigned ride', a ride for which only a starting and an ending point were provided by the researcher. A risk-assessment procedure showed that the route taken by visually impaired cyclists during this assigned ride was not less risky than the route taken by the normally sighted cyclists. Analysis of the everyday rides showed that, on average, cyclists with a visual impairment more frequently (i.e. for longer periods) cycled at a speed below 10 km/h compared to cyclists without visual impairment. Also, the visually impaired participants' cruising speed was 1.4 km/h lower than that of their normally sighted counterparts. In conclusion, no evidence was found that visually impaired cyclists compensate strategically by taking different, potentially safer routes than normally sighted cyclists when riding in their own environment. They may (unconsciously) compensate tactically for their visual function limitations by riding at a lower speed when necessary. Mobility trainers in vision rehabilitation as well as road designers could apply these findings to optimise the cycling mobility of visually impaired people.

et al., Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging., The ENIGMA-Plasticity Working Group is part of the ENIGMA World Aging Center, funded by NIA grants R56 AG058854 and R01 AG058854. The ENIGMA Consortium core funding was supported by NIH Consortium Grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centers of Excellence. 1000BRAINS: 1000BRAINS is a population-based cohort based on the Heinz-Nixdorf Recall Study and is supported, in part, by the German National Cohort. We thank the Heinz Nixdorf Foundation (Germany) for their generous support in terms of the Heinz Nixdorf Study. The authors are supported by the Initiative and Networking Fund of the Helmholtz Association (Svenja Caspers) and the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 785907 (Human Brain Project SGA2; Svenja Caspers, Sven Cichon and Katrin Amunts). This work was further supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under the auspices of the e:Med Program (grant 01ZX1314A; Sven Cichon) and by the Swiss National Science Foundation (SNSF, grant 156791; Sven Cichon). The authors acknowledge grants supporting their work from the European Union’s Horizon 2020 Research and Innovation Programme (H2020/2014–2020) under grant agreements 667302 (CoCA), 728018 (Eat2beNICE), 785907 (HBP SGA2) and 772376 (EScORIAL) and the Netherlands ALS Foundation.Additional support is received from the European Community’s Seventh Framework Programme (FP7/2007—2013) under grant agreements n° 602805 (Aggressotype), n° 603016 (MATRICS), n° 602450 (IMAGEMEND) and n° 278948 (TACTICS) and from the European Community’s Horizon 2020 Programme (H2020/2014—2020) under grant agreements n° 643051 (MiND) and n° 667302 (CoCA). FP7 Ideas: the European Research Council (ERC-230374 to D.B.). This work was supported by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012 and PI19/024), co-financed by ERDF Funds from the European Commission, ‘A way of making Europe’, CIBERSAM; Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), European Union Structural Funds; European Union Seventh Framework Program under grant agreements FP7- HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN) and European Union H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking (grant agreement 115916, Project PRISM and grant agreement 777394, Project AIMS-2-TRIALS), Fundación Familia Alonso, Fundación Alicia Koplowitz and Fundación Mutua Madrileña. The Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders) (695313). The FP7 project MATRICS (603016). The research leading to these results also received support from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement 278948 (TACTICS), 602805 (Aggressotype), 603016 (MATRICS) and 602450 (Imagemend) and the Innovation Medicine Initiative grants 115300 (EU-AIMS) and 777394 (AIMS-2-TRIALS).PAFIP: PAFIP was supported by the Instituto de Salud Carlos III (PI14/00639, PI14/00918 and PI17/01056) and Fundación Instituto de Investigación Marqués de Valdecilla (NCT0235832 and NCT025KG Jebsen Stiftelsen and H2020 CoMorMent (847776).34363). European Union Marie Curie Research Training Network (MRTN-CT-2006-035987).

Understanding the neural mechanisms of emotional reactivity in Attention-Deficit/Hyperactivity Disorder (ADHD) may help develop more effective treatments that target emotion dysregulation. In adult ADHD, emotion regulation problems cover a range of dimensions, including emotional reactivity (ER). One important process that could underlie an impaired ER in ADHD might be impaired working memory (WM) processing. We recently demonstrated that taxing WM prior to the exposure of emotionally salient stimuli reduced physiological and subjective reactivity to such cues in heavy drinkers, suggesting lasting effects of WM activation on ER. Here, we investigated neural mechanisms that could underlie the interaction between WM and ER in adult ADHD participants. We included 30 male ADHD participants and 30 matched controls. Participants performed a novel functional magnetic resonance imaging paradigm in which active WM-blocks were alternated with passive blocks of negative and neutral images. We demonstrated group-independent significant main effects of negative emotional images on amygdala activation, and WM-load on paracingulate gyrus and dorsolateral prefrontal cortex activation. Contrary to earlier reports in adolescent ADHD, no impairments were found in neural correlates of WM or ER. Moreover, taxing WM did not alter the neural correlates of ER in either ADHD or control participants. While we did find effects on the amygdala, paCG, and dlPFC activation, we did not find interactions between WM and ER, possibly due to the relatively unimpaired ADHD population and a well-matched control group. Whether targeting WM might be effective in participants with ADHD with severe ER impairments remains to be investigated.

Alexithymia has been characterized as an impaired ability of emotion processing and regulation. The definition of alexithymia does not include a social component. However, there is some evidence that social cognition may be compromised in individuals with alexithymia. Hence, emotional impairments associated with alexithymia may extend to socially relevant information. Here, we recorded electrophysiological responses of individuals meeting the clinically relevant cutoff for alexithymia (ALEX; n = 24) and individuals without alexithymia (NonALEX; n = 23) while they viewed affective scenes that varied on the dimensions of sociality and emotional valence during a rapid serial visual presentation task. We found that ALEX exhibited lower accuracy and larger N2 than NonALEX in the perception of social negative scenes. Source reconstruction revealed that the group difference in N2 was localized at the dorsal anterior cingulate cortex. Irrespective of emotional valence, ALEX showed stronger alpha power than NonALEX in social but not non-social conditions. Our findings support the hypothesis of social processing being selectively affected by alexithymia, especially for stimuli with negative valence. Electrophysiological evidence suggests altered deployment of attentional resources in the perception of social-specific emotional information in alexithymia. This work sheds light on the neuropsychopathology of alexithymia and alexithymia-related disorders.

OBJECTIVE: Behavioral parent training is an evidence-based intervention for children with attention-deficit/hyperactivity disorder (ADHD), but it is unknown which of its components are most effective. This meta-regression analysis investigated which specific behavioral techniques that parents learn in parent training are associated with effects on parental outcomes. METHOD: A search was performed for randomized controlled trials on parent training for children with ADHD, with positive parenting, negative parenting, parenting sense of competence, parent-child relationship quality, and parental mental health as outcome measures. After screening 23,026 publications, 29 studies contributing 138 effect sizes were included (N = 2,345). For each study, the dosage of 39 behavioral techniques was derived from intervention manuals, and meta-regression determined which techniques were related to outcomes. RESULTS: Parent training had robust small- to medium-sized positive effects on all parental outcomes relative to control conditions, both for unblinded and probably blinded measures. A higher dosage of techniques focusing on the manipulation of antecedents of behavior was associated with better outcomes on parenting sense of competence and parental mental health, and a higher dosage of techniques focusing on reinforcement of desired behaviors was related to larger decreases in negative parenting. Higher dosages of psychoeducation were negatively related to parental outcomes. CONCLUSION: Although techniques were not investigated in isolation, the results suggested that manipulation of antecedents of behavior and reinforcement techniques are key components of parent training for children with ADHD in relation to parental outcomes. These exploratory findings may help to strengthen and tailor parent training interventions for children with ADHD. ispartof: Journal Of The American Academy Of Child And Adolescent Psychiatry vol:61 issue:4 pages:478-494 ispartof: location:United States status: Published online

BACKGROUND: Altered cholinergic innervation plays a putative role in cognitive impairment in Parkinson's disease (PD) at least in advanced stages. Identification of the relationship between cognitive impairment and cholinergic innervation early in the disease will provide better insight into disease prognosis and possible early intervention.OBJECTIVE: The aim was to assess regional cholinergic innervation status in de novo patients with PD, with and without cognitive impairment.METHODS: Fifty-seven newly diagnosed, treatment-naive, PD patients (32 men, mean age 64.6 ± 8.2 years) and 10 healthy controls (5 men, mean age 54.6 ± 6.0 years) were included. All participants underwent cholinergic [18 F]fluoroethoxybenzovesamicol positron emission tomography and detailed neuropsychological assessment. PD patients were classified as either cognitively normal (PD-NC) or mild cognitive impairment (PD-MCI). Whole brain voxel-based group comparisons were performed.RESULTS: Results show bidirectional cholinergic innervation changes in PD. Both PD-NC and PD-MCI groups showed significant cortical cholinergic denervation compared to controls (P CONCLUSION: Altered cholinergic innervation is already present in de novo patients with PD. Posterior cortical cholinergic losses were present in all patients independent of cognitive status. Higher-than-normal binding in cerebellar, frontal, and subcortical regions in cognitively intact patients may reflect compensatory cholinergic upregulation in early-stage PD. Limited or failing cholinergic upregulation may play an important role in early, clinically evident cognitive impairment in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

IntroductionIron deficiency (ID) is common and has been associated with an excess mortality risk in kidney transplant recipients (KTRs). In patients with chronic heart failure and ID, intravenous iron improves exercise capacity and quality of life. Whether these beneficial effects also occur in KTRs is unknown. The main objective of this trial is to address whether intravenous iron improves exercise tolerance in iron-deficient KTRs.Methods and analysisThe Effect of Ferric Carboxymaltose on Exercise Capacity after Kidney Transplantation study is a multicentre, double-blind, randomised, placebo-controlled clinical trial that will include 158 iron-deficient KTRs. ID is defined as plasma ferritin 3+/mL, intravenously) or placebo (0.9% sodium chloride solution) every 6 weeks, four dosages in total. The primary endpoint is change in exercise capacity, as quantified by the 6 min walk test, between the first study visit and the end of follow-up, 24 weeks later. Secondary endpoints include changes in haemoglobin levels and iron status, quality of life, systolic and diastolic heart function, skeletal muscle strength, bone and mineral parameters, neurocognitive function and safety endpoints. Tertiary (explorative) outcomes are changes in gut microbiota and lymphocyte proliferation and function.Ethics and disseminationThe protocol of this study has been approved by the medical ethical committee of the University Medical Centre Groningen (METc 2018/482;) and is being conducted in accordance with the principles of the Declaration of Helsinki, the Standard Protocol Items: Recommendations for Interventional Trials checklist and the Good Clinical Practice guidelines provided by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Study results will be disseminated through publications in peer-reviewed journals and conference presentations.Trial registration numberNCT03769441.

BackgroundsDecision-making deficits have been reported as trans-diagnostic characteristics of vulnerability to suicidal behaviors, independent of co-existing psychiatric disorders. Individuals with suicidal behaviors often regret their decision to attempt suicide and may have impairments in future-oriented processing. However, it is not clear how people with suicidal dispositions use future-oriented cognition and past experience of regret to guide decision-making. Here, we examined the processes of regret anticipation and experience in subclinical youth with and without suicidal ideation during value-based decision-making.MethodsIn total, 80 young adults with suicidal ideation and 79 healthy controls completed a computational counterfactual thinking task and self-reported measures of suicidal behaviors, depression, anxiety, impulsivity, rumination, hopelessness, and childhood maltreatment.ResultsIndividuals with suicidal ideation showed a reduced ability to anticipate regret compared to healthy controls. Specifically, suicidal ideators’ experience of regret/relief was significantly different from that of healthy controls upon obtained outcomes, while their disappointment/pleasure experience was not significantly different from healthy controls.ConclusionThese findings suggest that young adults with suicidal ideation have difficulty predicting the consequences or the future value of their behavior. Individuals with suicidal ideation showed impairments in value comparison and flat affect to retrospective rewards, whereas individuals with high suicidality showed blunted affect to immediate rewards. Identifying the counterfactual decision-making characteristics of at-risk suicidal individuals may help to elucidate measurable markers of suicidal vulnerability and identify future intervention targets.

Investigating sex chromosome trisomies (SCTs) may help in understanding neurodevelopmental pathways underlying the risk for neurobehavioral problems and psychopathology. Knowledge about the neurobehavioral phenotype is needed to improve clinical care and early intervention for children with SCT. This is especially relevant considering the increasing number of early diagnosed children with the recent introduction of noninvasive prenatal screening. The TRIXY Early Childhood Study is a longitudinal study designed to identify early neurodevelopmental risks in children with SCT, aged 1–7 years. This review summarizes the results from the TRIXY Early Childhood Study, focusing on early behavioral symptoms in areas of autism spectrum disorder, attention-deficit hyperactivity disorder, and communication disorders, and underlying neurocognitive mechanisms in domains of language, emotion regulation, executive functioning, and social cognition. Behavioral symptoms were assessed through structured behavior observation and parental questionnaires. Neurocognition was measured using performance tests, eyetracking, and psychophysiological measures of arousal. In total, 209 children aged 1–7 years were included: 107 children with SCT (33 XXX, 50 XXY, and 24 XYY) and 102 age-matched population controls. Study outcomes showed early behavioral symptoms in young children with SCT, and neurocognitive vulnerabilities, already from an early age onward. Neurobehavioral and neurocognitive difficulties tended to become more pronounced with increasing age and were rather robust, independent of specific karyotype, pre/postnatal diagnosis, or ascertainment strategy. A more longitudinal perspective on neurodevelopmental ‘at-risk’ pathways is warranted, also including studies assessing the effectiveness of targeted early interventions. Neurocognitive markers that signal differences in neurodevelopment may prove to be helpful in this. Focusing on early development of language, social cognition, emotion regulation, and executive functioning may help in uncovering early essential mechanisms of (later) neurobehavioral outcome, allowing for more targeted support and early intervention.

The goal of this on the road driving study was to investigate how drivers adapt their behavior when driving with conditional vehicle automation (SAE L3) on different occasions. Specifically, we focused on changes in how fast drivers took over control from automation and how their gaze off the road changed over time. On each of three consecutive days, 21 participants drove for 50 min, in a conditionally automated vehicle (Wizard of Oz methodology), on a typical German commuting highway. Over these rides the take-over behavior and gaze behavior were analyzed. The data show that drivers’ reactions to non-critical, system initiated, take-overs took about 5.62 s and did not change within individual rides, but on average became 0.72 s faster over the three rides. After these self-paced take-over requests a final urgent take-over request was issued at the end of the third ride. In this scenario participants took over rapidly with an average of 5.28 s. This urgent take-over time was not found to be different from the self-paced take-over requests in the same ride. Regarding gaze behavior, participants’ overall longest glance off the road and the percentage of time looked off the road increased within each ride, but stayed stable over the three rides. Taken together, our results suggest that drivers regularly leave the loop by gazing off the road, but multiple exposures to take-over situations in automated driving allow drivers to come back into loop faster.

Purpose: Cognitive Adaptation Training (CAT) is a psychosocial intervention with demonstrated effectiveness. However, no validated fidelity instrument is available. In this study, a CAT Fidelity Scale was developed and its psychometric properties, including interrater reliability and internal consistency, were evaluated. Methods: The fidelity scale was developed in a multidisciplinary collaboration between international research groups using the Delphi method. Four Delphi rounds were organized to reach consensus for the items included in the scale. To examine the psychometric properties of the scale, data from a large cluster randomized controlled trial evaluating the implementation of CAT in clinical practice was used. Fidelity assessors conducted 73 fidelity reviews at four mental health institutions in the Netherlands. Results: After three Delphi rounds, consensus was reached on a 44-item CAT Fidelity Scale. After administration of the scale, 24 items were removed in round four resulting in a 20-item fidelity scale. Psychometric properties of the 20-item CAT Fidelity Scale shows a fair interrater reliability and an excellent internal consistency. Conclusions: The CAT fidelity scale in its current form is useful for both research purposes as well as for individual health professionals to monitor their own adherence to the protocol. Future research needs to focus on improvement of items and formulating qualitative anchor point to the items to increase generalizability and psychometric properties of the scale. The described suggestions for improvement provide a good starting point for further development.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder, with onset in childhood and a considerable likelihood to persist into adulthood. Our previous work has identified that across adults and adolescents with ADHD, gray matter volume (GMV) alteration in the frontal cortex was consistently associated with working memory underperformance, and GMV alteration in the cerebellum was associated with inattention. Recent knowledge regarding ADHD genetic risk loci makes it feasible to investigate genomic factors underlying these persistent GMV alterations, potentially illuminating the pathology of ADHD persistence. Based on this, we applied a sparsity-constrained multivariate data fusion approach, sparse parallel independent component analysis, to GMV variations in the frontal and cerebellum regions and candidate risk single nucleotide polymorphisms (SNPs) data from 341 unrelated adult participants, including 167 individuals with ADHD, 47 unaffected siblings, and 127 healthy controls. We identified one SNP component significantly associated with one GMV component in superior/middle frontal regions and replicated this association in 317 adolescents from ADHD families. The association was stronger in individuals with ADHD than in controls, and stronger in adults and older adolescents than in younger ones. The SNP component highlights 93 SNPs in long non-coding RNAs mainly in chromosome 5 and 21 protein-coding genes that are significantly enriched in human neuron cells. Eighteen identified SNPs have regulation effects on gene expression, transcript expression, isoform percentage, or methylation level in frontal regions. Identified genes highlight MEF2C, CADM2, and CADPS2, which are relevant for modulating neuronal substrates underlying high-level cognition in ADHD, and their causality effects on ADHD persistence await further investigations. Overall, through a multivariate analysis, we have revealed a genomic pattern underpinning the frontal gray matter variation related to working memory deficit in ADHD.

Early Onset Dystonia (EOD) is thought to result from basal ganglia dysfunction, structures also involved in non-motor functions, like regulation of behavior, mood and anxiety. Problems in these domains have been found in proxy-reports but not yet in self-reports of EOD patients. The main questions are whether proxy-reports differ from those of patients and how problems relate to everyday social functioning. Subjective complaints about executive problems (BRIEF) and symptoms of depression and anxiety (CBCL) were obtained through a cross-sectional questionnaire study conducted on 45 EOD patients. Scores were in the normal range in patients and proxies. Proxy-rated behavior regulation was correlated with the estimated number of friends and quality of relations. Proxy-reported scores of depression correlated with the quality of relations and were higher than self-reports of adolescent/young adult patients. EOD patients and proxies do not seem to experience problematic regulation of behavior, mood and anxiety. Still, our study revealed two important aspects: (1) all measures were related to the estimated quality of relations with others, relating questionnaires to everyday social functioning; (2) proxies reported more symptoms of depression than patients. This may indicate overestimation by proxies or higher sensitivity of proxies to these symptoms, implying underestimation of problems by patients.

BACKGROUND: Concerns exist regarding the impact of widely used clinical drugs on brain development. This study investigates long-term neurocognitive functioning in relation to frequently used drug exposure at the Pediatric Intensive Care Unit (PICU).METHODS: This study compared children aged 6-12 years with previous PICU admission (age ≤1 year) for bronchiolitis requiring mechanical ventilation (patient group, n = 65) to a demographically comparable control group (n = 76) on a broad range of neurocognitive outcomes. The patient group was selected because bronchiolitis seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself. The relation between exposure to sedatives, analgesics and anesthetics and neurocognitive outcomes was assessed by regression analyses.RESULTS: The patient group had lower intelligence than the control group (p CONCLUSIONS: Children with PICU admission for bronchiolitis requiring mechanical ventilation are at risk of adverse neurocognitive outcomes. This study found no evidence for a role of exposure to sedatives, analgesics or anesthetics. Findings underline the importance of long-term follow-up after PICU admission, even in the absence of disease with neurological manifestation.IMPACT: Animal studies have indicated that exposing the maturing brain to clinical drugs may cause neurodegeneration. Clinical studies show mixed evidence regarding the association between clinical drugs and neurocognitive outcomes. This study provides evidence for considerably lower neurocognitive functioning among children with a history of PICU admission for bronchiolitis compared to healthy peers. Bronchiolitis seldom manifests neurologically and is therefore not expected to affect neurocognitive functioning in itself. We found no evidence supporting a relation between drug exposure (i.e., sedatives, analgesics and anesthetics) and long-term neurocognitive outcomes. Findings underline the importance of structured follow-up after PICU admission.

Background Increasing physical activity is one of the most promising and challenging interventions to delay or prevent cognitive decline and dementia. Methods We conducted a randomized controlled trial to assess the effects of a physical activity intervention, aimed at increasing step count, in elderly with low levels of physical activity on measures of strength, balance, aerobic capacity, and cognition. Participants were assigned to 9 months of exercise counseling or active control. Results The intention-to-treat analyses show that the intervention, compared to control, increases the level of physical activity, but has no significant effect on physical fitness and cognition. Those who increased their physical activity with 35% or more show significant improvements in aerobic capacity, gait speed, verbal memory, executive functioning, and global cognition, compared to those who did not achieve a 35% increase. Limitations The number of participants that achieved the intended improvement was lower than expected. Conclusion Responder analyses suggest an improvement of physical fitness and cognition in those who achieved an increase in physical activity of at least 35%. Trial registration The trial protocol is registered at the Dutch Trial Register NL5675, August 1, 2016.

Introduction Visual complaints can have a vast impact on the quality of life of people with Parkinson’s disease (PD). In clinical practice however, visual complaints often remain undetected. A better understanding of visual complaints is necessary to optimize care for people with PD and visual complaints. This study aims at determining the prevalence of visual complaints experienced by a large outpatient cohort of people with PD compared to a control group. In addition, relations between visual complaints and demographic and disease-related variables are investigated. Methods The Screening Visual Complaints questionnaire (SVCq) screened for 19 visual complaints in a cohort of people with idiopathic PD (n = 581) and an age-matched control group without PD (n = 583). Results People with PD experienced significantly more complaints than controls, and a greater impact of visual complaints on their daily lives. Complaints that were most common (‘often/always’) were unclear vision (21.7%), difficulty reading (21.6%), trouble focusing (17.1%), and blinded by bright light (16.8%). Largest differences with controls were found for double vision, needing more time to see and having trouble with traffic participation due to visual complaints. Age, disease duration, disease severity, and the amount of antiparkinsonian medication related positively to the prevalence and severity of visual complaints. Conclusion Visual complaints are highly prevalent and occur in great variety in people with PD. These complaints progress with the disease and have a large impact on the daily lives of these people. Standardized questioning is advised for timely recognition and treatment of these complaints.

Objective: A special group of adults with Attention Deficit Hyperactivity Disorder (ADHD) are emerging adults with ADHD studying at university. These young adults typically have greater problems compared to their peers in many domains of life. High intelligence is therefore not protective for the impairments that ADHD is causing. To date, there is little knowledge on prevalence in university students. This study estimates the prevalence of ADHD symptoms in Dutch university students before and during COVID-19. Method: Students from the social science faculty of a Dutch university were recruited in four consecutive academic years. The four cohorts included n = 404 (2018), n = 277 (2019), n = 350 (2020), and n = 415 (2021), reaching a total of N = 1446. ADHD symptoms and prevalence rates of positive screenings were measured by means of a thorough screening with Conners’ Adult ADHD Rating Scale (CAARS) Long Form (Conners et al., 1999). Results: Prevalence rates varied between 7.6-15.4% for the ADHD DSM-IV scale and 3.6-6.3% for the ADHD index, and did not significantly differ before and during COVID-19. No effect for the four cohorts was found for the subscales Inattention/Memory problems, Hyperactive/Restlessness, Impulsivity/Emotional lability, and Problems with self-concept. Compared to normative scores, university students reported significantly more Inattention/Memory problems (d = .25) and Self-concept problems (d = .11) than average. Conclusions:Thorough screening across four cohorts of Dutch university students indicates considerable levels of ADHD symptoms with higher rates for the classic DSM-IV scale and lower rates for ADHD Index. University students report elevated levels of problems with Inattention/Memory and Self-concept. ADHD symptoms did not change across the period from pre to post-COVID pandemic. These findings highlight that there is a specific group of students needing support for adjusting and succeeding in academia, regardless of circumstances.

Recent technological advancements allow monitoring of drivers’ behaviour and offer the opportunity for providing feedback. While this approach has been shown to have a positive effect on driver behaviour, whether it is accepted by drivers has not yet been extensively investigated. This questionnaire study examined the opinions of a sample of 628 Dutch drivers on the potential useof a monitoring and feedback system. The focus was on (1) whether drivers would be interested in being assessed, (2) whether data collection (i.e., monitoring) could be used for this purpose, and (3) which features the potential system must have in order to get accepted. The results showedthat participants were moderately enthusiastic about the prospect of receiving monitoring feedback: on average, their opinion was between neutral and positive. Professional drivers expressed slightly more positive opinions, but no demographic variable was strongly associated with acceptability. Many drivers rated themselves as good drivers already and had low sensitivity todata collection, i.e., participants indicated being used to data collection online. If they were to use a monitoring and feedback device, participants indicated a preference for data on speed and forward-facing video footage and a preference for personalisation. The use of a monitoring and feedback system can be considered as a trade-off between sharing personal data and receivingsupport to improve driving skills. Based on the participants’ reported online behaviour, it appears that the perceived costs associated with sharing data are small. The potential benefits of driver monitoring and feedback, however, are not salient to the participants, which may limit the use of such a system on the roads.

Purpose: To determine the test–retest reliability of the recently developed Hip Load metric, evaluate its construct validity, and assess the differences with Playerload during football-specific short-distance shuttle runs. Methods: Eleven amateur football players participated in 2 identical experimental sessions. Each session included 3 different shuttle runs that were performed at 2 pace-controlled running intensities. The runs consisted of only running, running combined with kicks, and running combined with jumps. Cumulative Playerload and Hip Loads of the preferred and nonpreferred kicking leg were collected for each shuttle run. Test–retest reliability was determined using intraclass correlations, coefficients of variation, and Bland–Altman analyses. To compare the load metrics with each other, they were normalized to their respective values obtained during a 54-m run at 9 km/h. Sensitivity of each load metric to running intensity, kicks, and jumps was assessed using separate linear mixed models. Results: Intraclass correlations were high for the Hip Loads of the preferred kicking leg (.91) and the nonpreferred kicking leg (.96) and moderate for the Playerload (.87). The effects (95% CIs) of intensity and kicks on the normalized Hip Load of the kicking leg (intensity: 0.95 to 1.50, kicks: 0.36 to 1.59) and nonkicking leg (intensity: 0.96 to 1.53, kicks: 0.06 to 1.34) were larger than on the normalized Playerload (intensity: 0.12 to 0.25, kicks: 0.22 to 0.53). Conclusions: The inclusion of Hip Load in training load quantification may help sport practitioners to better balance load and recovery.

Background Dissociative experiences commonly occur in schizophrenia spectrum disorders (SSD). Yet little is known about how dissociative experiences in SSD are related to SSD symptoms. Accordingly, we investigated the relations between dissociative experiences and SSD symptoms, focusing on symptoms bridging these 2 symptom clusters as well as their relation to reported trauma history. Study Design Network analyses were conducted on the responses of 248 individuals with an SSD who enrolled from multiple mental health centers in The Netherlands. Dissociative experiences were assessed via the Dissociative Experience Scale, SSD symptoms using the Positive and Negative Syndrome Scale, and trauma history through the Trauma History Questionnaire. Study Results The results indicated that dissociative symptoms in SSD are mostly independent of other symptoms, but that emotional distress bridges between the dissociative and SSD symptom clusters. Furthermore, results revealed associations between positive and negative SSD symptoms and trauma through emotional distress, whereas dissociative symptoms remained relatively isolated. Conclusion Because SSD symptoms and dissociative experiences clustered relatively independent from each other, our findings promote the idea of tailored treatment approaches for individuals with an SSD with frequent dissociative experiences, specifically targeting these symptoms.

Peer reviewed: True, More and more members of the autistic community and the research field are moving away from the idea that there will be a single biological or cognitive explanation for autistic characteristics. However, little is known about the complex dynamic processes that could explain why early difficulties in the language and motor domain often go hand-in-hand. We here study how language and motor skills develop simultaneously in the British Autism Study of Infant Siblings cohort of infants, and compare the way they are linked between children with and without developmental delays. Our results suggest that improvements in one domain go hand-in-hand with improvements in the other in both groups and show no compelling evidence for group differences in how motor skills relate to language and vice versa. We did observe a larger diversity in motor and language skills at 6 months, and because we found the motor and language development to be tightly linked, this suggests that even very small early impairments can result in larger developmental delays in later childhood. Greater variability at baseline, combined with very strong correlations between the slopes, suggests that dynamic processes may amplify small differences between individuals at 6months to result into large individual differences in autism symptomatology at 36 months.

Although cannabis use patterns differ between men and women, studies on sex differences on the effects of cannabis on the brain and cognitive control are largely lacking. Working memory (WM) is a component of cognitive control believed to be involved in the development and maintenance of addiction. In this study, we evaluated the association between cannabis use and WM (load) related brain activity in a large sample, enabling us to assess sex effects in this association. The brain activity of 104 frequent cannabis users (63% men) and 85 controls (53% men) was recorded during an N-back WM task. Behavioral results showed a significant interaction between WM load and group for both accuracy and reaction time, with cannabis users showing a relatively larger decrease in performance with increasing WM load. Cannabis users compared to controls showed a relatively smaller reduction in WM (load) related activity in the precuneus and posterior cingulate cortex at higher WM load. This WM (load) related activity was not associated with performance nor cannabis use and related problems. An exploratory analysis showed higher WM-related activity in the superior frontal gyrus in men compared to women. While cannabis users showed higher WM (load) related activity in central nodes of the default mode network, this was not directly attributable to group specific worsening of performance under higher cognitive load. Further research is necessary to assess whether observed group differences increase with higher cognitive load, how group differences relate to measures of cannabis use, and how sex affects these group differences.

Pain is one of the most common health problems and has a severe impact on quality of life. Yet, a suitable and efficient treatment is still not available for all patient populations suffering from pain. Interestingly, recent research shows that low threshold mechanosensory C-tactile (CT) fibres have a modulatory influence on pain. CT-fibres are activated by slow gentle stroking of the hairy skin, providing a pleasant sensation. Consequently, slow gentle stroking is known as affective touch. Currently, a clear overview of the way affective touch modulates pain, at a neural level, is missing. This review aims to present such an overview. To explain the interaction between affective touch and pain, first the neural basis of the affective touch system and the neural processing of pain will be described. To clarify these systems, a schematic illustration will be provided in every section. Hereafter, a novel model of interactions between affective touch and pain systems will be introduced. Finally, since affective touch might be suitable as a new treatment for chronic pain, possible clinical implications will be discussed.

Aim: To investigate the clinical relevance of the radiotherapy (RT) dose bath in patients treated for lower grade glioma (LGG).Methods: Patients (n = 17) treated with RT for LGG were assessed with neurocognitive function (NCF) tests and structural Magnetic Resonance Imaging (MRI) and categorized in subgroups based on tumour lateralisation. RT dose, volumetric results and cerebral microbleed (CMB) number were extracted for contralateral cerebrum, contralateral hippocampus, and cerebellum. The RT clinical target volume (CTV) was included in the analysis as a surrogate for focal tumour and other treatment effects. The relationships between RT dose, CTV, NCF and radiological outcome were analysed per subgroup.Results: The subgroup with left-sided tumours (n = 10) performed significantly lower on verbal tests. The RT dose to the right cerebrum, as well as CTV, were related to poorer performance on tests for processing speed, attention, and visuospatial abilities, and more CMB.In the subgroup with right-sided tumours (n = 7), RT dose in the left cerebrum was related to lower verbal memory performance, (immediate and delayed recall, r = -0.821, p = 0.023 and r = -0.937, p = 0.002, respectively), and RT dose to the left hippocampus was related to hippocampal volume (r = -0.857, p = 0.014), without correlation between CTV and NCF.Conclusion: By using a novel approach, we were able to investigate the clinical relevance of the RT dose bath in patients with LGG more specifically. We used combined MRI-derived and NCF outcome measures to assess radiation-induced brain damage, and observed potential RT effects on the left-sided brain resulting in lower verbal memory performance and hippocampus volume.

ObjectiveCognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their interrelations and combined effects on functional outcome have not been elucidated. We investigated the associations between cognitive and motor functions and their interactions and mediating effects on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH).MethodsParticipants of the Helsinki Small Vessel Disease Study (n=152) were assessed according to an extensive clinical, neuropsychological and MRI protocol. Cognitive composite scores for global cognition, processing speed, executive functions and memory were constructed from multiple tests within each domain. Physical examination included measures of gait speed, balance (single-leg-stance) and functional mobility (timed-up-and-go test). IADL was evaluated with a proxy-based Amsterdam IADL questionnaire and quality of life with a self-report EUROHIS-Qol index. Volumes of WMH and gray matter (GM) were obtained with automated segmentation. Sets of linear regression analyses were used to model the associations between motor and cognitive performances, WMH and GM volumes, and IADL and quality of life.ResultsDomain-specific cognitive and motor functions had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on IADL, but not on quality of life. In particular, low cognitive scores together with decline in the timed-up-and-go test and gait speed were strongly related to impaired IADL. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up-and-go performance.ConclusionThe results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than the individual effects of each of the two impairments. WMH and brain atrophy contribute to disability through cognitive and motor impairment.

Accessible Summary What is known on the subject? To date, the majority of the research regarding innovative psychosocial interventions in psychiatry focuses upon the development and effectiveness of the interventions. Despite the fact that these are important clinical and scientific contributions, only a small percentage of the evidence-based interventions reach clinical practice. Cognitive Adaptation Training (CAT) is an effective psychosocial intervention to increase daily functioning and cognitive functioning in people diagnosed with severe mental illness (SMI) in inpatient and outpatient psychiatric care. Despite knowledge on the intervention's effectiveness, systematic use of CAT in the daily routine of mental health nurses is insufficient. What the paper adds to existing knowledge? To date, no research is available that describes the factors associated to the implementation of CAT from a nursing perspective. This research also adds to the literature on rehabilitation in people diagnosed with SMI in an inpatient setting. The results contribute to the science of implementing interventions in long-term psychiatric care and may help future interventions in their implementation process. What are the implications for practice? This study highlights that multiple factors need to be considered when implementing an intervention in routine care and that it is a complicated process. Future implementation initiatives require ongoing training and supervision of CAT specialists, appointment of local champions to increase commitment among nursing staff and inclusion and commitment of management to overcome organizational barriers. Without acknowledging the presence of barriers to implementation and considering strategies to overcome these barriers, sustainable implementation is likely to be unsuccessful. Introduction Evidence-based interventions in psychiatry often fail to reach clinical practice. Cognitive Adaptation Training (CAT) is an evidence-based psychosocial intervention that aims to improve daily functioning of people diagnosed with a severe mental illness. Implementation of CAT remains challenging, despite demonstrated effectiveness. Aim Identifying facilitators and barriers of CAT on the intervention, nursing, and organizational levels, and investigating relationships between capability, opportunity, motivation, and appraisal using the COM-B model. Method The Measurement Instrument for Determinants of Innovations and CAT-specific questions were administered to 46 nurses. The relationship among capability, opportunity, motivation and appraisal was calculated using the Pearson's r correlation coefficient. Results Nine barriers (mostly organizational level) and 13 facilitators (mostly intervention and nursing level) were identified. Significant moderate correlations were found between capability and opportunity, capability and motivation, capability and appraisal and a strong correlation between motivation and appraisal. Discussion The results suggest that barriers at the organizational level should be removed and facilitators at intervention and nursing levels may be exploited to improve implementation. Implications for practice Future implementation initiatives require ongoing training and supervision of CAT specialists, appointment of local champions to increase commitment among nursing staff and inclusion and commitment of management to overcome organizational barriers.

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = −0.164 to −0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = −0.173 to −0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

Changes in physical and cognitive abilities not only challenge the driving ability of older adults, in some situations age-related changes in driving behaviour require other road users to adapt their behaviour to maintain a safe traffic situation. In this study, we aimed to map age-related differences in driving behaviour and assess the impact on other road users. A group younger and a group older adults drove four different routes containing challenging situations (e.g., merging into motorway traffic) in a driving simulator while measures of driving behaviour were collected. Other road users’ deceleration responses to the driver's behaviour were also collected as a measure of behavioural adaptation. Our results showed similar driving performance between young and older drivers when task complexity was low, but reduced performance in older drivers when tasks requirements increased. Lower driving speed and longer waiting times that were observed in older drivers can be interpreted as compensatory behaviour aimed at creating more time to lower task requirements. Crucially, in a non-time critical situation this compensatory behaviour was found to be successful, however in a time-critical situation (merging onto a motorway) this strategy had negative side effects because other road users had to decelerate in order to keep a safe distance. Our results show the importance of anticipation and adaptation by other road users for the success of older driver's strategies and traffic safety.

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Prior research suggests that autistic adults are at increased risk for developing the core motor components of Parkinson’s disease (i.e. parkinsonism) although knowledge is limited to date. Therefore, we explore: (1) the prevalence of both continuous self-reported motor features typical of parkinsonism and the screen positivity rate for parkinsonism in two samples of older autistic adults without a suspected intellectual disability: the Netherlands-Sample ( N = 296, 50–81 years; 183 males; 113 females) and the United States of America-Sample ( N = 209, 50–83 years; 100 males; 109 females), and (2) whether there are differences between those who Screen+ versus Screen− for parkinsonism. Within the Netherlands-Sample only, the age of onset of the motor features was investigated. Self-reported parkinsonism features were prevalent in both samples (the Netherlands-Sample ~17% screened positive, mean age of onset ranging from 35.9 to 50.4 years; the United States of America-Sample ~33% screened positive). Autistic adults (the Netherlands-Sample) screening positive encountered more health problems than those who screened negative. In both samples, autistic adults who screened positive did not differ on current antipsychotic medication use relative to those who screened negative. The next step is to determine whether a positive screen for parkinsonism on this self-report questionnaire also implies that there is a higher risk for idiopathic Parkinson’s disease. Lay abstract Autistic adults without a suspected intellectual disability reported several motor features such as having tremors, and stiffness in one’s legs which are considered to be part of a complex of motor features called parkinsonism. This so-called parkinsonism was remarkably prevalent in middle-aged and older autistic adults in two independent studies (Dutch study: 50–81 years, 183 males, 113 females, all adulthood diagnoses; the USA study: 50–83 years, 110 females, 109 males, majority adulthood diagnosis). Parkinsonism can be part of the progressive motor disease—Parkinson’s disease. Therefore, it is important that future studies, including in-person neurological assessment, determine if (and if so, why) autistic adults who report these motor features are at increased risk for developing Parkinson’s disease.