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Studies exploring the brain correlates of behavioral symptoms in the frontotemporal dementia spectrum (FTD) have mainly searched for linear correlations with single modality neuroimaging data, either structural magnetic resonance imaging (MRI) or fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). We aimed at studying the two imaging modalities in combination to identify nonlinear co-occurring patterns of atrophy and hypometabolism related to behavioral symptoms. We analyzed data from 93 FTD patients who underwent T1-weighted MRI, FDG-PET imaging, and neuropsychological assessment including the Neuropsychiatric Inventory, Frontal Systems Behavior Scale, and Neurobehavioral Rating Scale. We used a data-driven approach to identify the principal components underlying behavioral variability, then related the identified components to brain variability using a newly developed method fusing maps of grey matter volume and FDG metabolism. A component representing apathy, executive dysfunction, and emotional withdrawal was associated with atrophy in bilateral anterior insula and putamen, and with hypometabolism in the right prefrontal cortex. Another component representing the disinhibition versus depression/mutism continuum was associated with atrophy in the right striatum and ventromedial prefrontal cortex for disinhibition, and hypometabolism in the left fronto-opercular region and sensorimotor cortices for depression/mutism. A component representing psychosis was associated with hypometabolism in the prefrontal cortex and hypermetabolism in auditory and visual cortices. Behavioral symptoms in FTD are associated with atrophy and altered metabolism of specific brain regions, especially located in the frontal lobes, in a hierarchical way: apathy and disinhibition are mostly associated with grey matter atrophy, whereas psychotic symptoms are mostly associated with hyper-/hypo-metabolism., Competing Interests: Declarations. Ethics approval and patients consents statement: Written informed consent for the study, approved by the NINDS Institutional Review Board and in accordance with the Declaration of Helsinki, was obtained from a family member. Assent from the patient was always required in all circumstances. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The monoiodoacetate-induced rat model of osteoarthritis knee pain is widely used. However, there are between-study differences in the pain behavioural endpoints assessed and in the dose of intraarticular monoiodoacetate administered. This study evaluated the robustness of gait analysis as a pain behavioural endpoint in the chronic phase of this model, in comparison with mechanical hyperalgesia in the injected (ipsilateral) joint and development of mechanical allodynia in the ipsilateral hind paws. Groups of Sprague-Dawley rats received a single intraarticular injection of monoiodoacetate at 0.5, 1, 2 or 3 mg or vehicle (saline) into the left (ipsilateral) knee joint. An additional group of rats were not injected (naïve group). The pain behavioural methods used were gait analysis, measurement of pressure algometry thresholds in the ipsilateral knee joints, and assessment of mechanical allodynia in the ipsilateral hind paws using von Frey filaments. These pain behavioural endpoints were assessed premonoiodoacetate injection and for up to 42-days postmonoiodoacetate injection in a blinded manner. Body weights were also assessed as a measure of general health. Good general health was maintained as all rats gained weight at a similar rate for the 42-day study period. In the chronic phase of the model (days 9-42), intraarticular monoiodoacetate at 3 mg evoked robust alterations in multiple gait parameters as well as persistent mechanical allodynia in the ipsilateral hind paws. For the chronic phase of the monoiodoacetate-induced rat model of osteoarthritis knee pain, gait analysis, such as mechanical allodynia in the ipsilateral hind paws, is a robust pain behavioural measure., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The externalizing spectrum is characterized by disinhibition, impulsivity, antisocial-aggressive behavior as well as substance (mis)use. Studies in forensic samples and mentally impaired children suggested that higher rates of externalization are linked to lower cortisol stress responses and altered affect-related neural activation. In this fMRI-study, we investigated whether externalizing behavior in healthy participants is likewise associated with altered cortisol responses and neural activity to stress. Following a quasi-experimental approach, we tested healthy participants (N = 61, 31 males) from the higher versus lower range of the non-clinical variation in externalization (31 participants with high externalization) as assessed by the subscales disinhibition and meanness of the Triarchic-Psychopathy-Measure. All participants were exposed to ScanSTRESS, a standardized psychosocial stress paradigm for scanner environments. In both groups, ScanSTRESS induced a significant rise in cortisol levels with the high externalization group showing significantly lower cortisol responses to stress than the low externalization group. This was mainly driven by males. Further, individual increases in cortisol predicted neural response differences between externalization groups, indicating more activation in the dorsal striatum in low externalization. This was primarily driven by females. In contrast, post-hoc analysis showed that hypothalamic-pituitary-adrenal axis hyporeactivity in males was associated with prefrontal and hippocampal activation. Our data substantiate that individuals from the general population high on externalization, show reduced cortisol stress responses. Furthermore, dorsal striatum activity as part of the mesolimbic system, known to be sensitive to environmental adversity, seems to play a role in externalization-specific cortisol stress responses. Beyond that, a modulating influence of gender was disclosed., (© 2021 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

With the growing population and rapid change in the social environment, nurses in China are suffering from high rates of stress; however, the neural mechanism underlying this occupation related stress is largely unknown. In this study, mental status was determined for 81 nurses and 61 controls using the Symptom Checklist 90 (SCL-90) scale. A subgroup (n = 57) was further scanned by resting-state functional MRI with two sessions. Based on the SCL-90 scale, "somatic complaints" and "diet/sleeping" exhibited the most prominent difference between nurses and controls. This mental health change in nurses was further supported by the spatial independent component analysis on functional MRI data. First, dynamic functional connectome analysis identified two discrete connectivity configurations (States I and II). Controls had more time in the State I than II, while the nurses had more time in the State II than I. Second, nurses showed a similar static network topology as controls, but altered dynamic properties. Third, the symptom-imaging correlation analysis suggested the functional alterations in nurses as potential imaging biomarkers indicating a high risk for "diet/sleeping" problems. In summary, this study emphasized the high risk of mental deficits in nurses and explored the underlying neural mechanism using dynamic brain connectome, which provided valuable information for future psychological intervention., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Past research has found a relationship between the apolipoprotein E (APOE) e4 allele and worse neurobehavioral functioning following mild traumatic brain injury (MTBI) in civilian populations. The purpose of this study was to examine this relationship in service members and veterans (SMVs) following MTBI. Participants were 151 SMVs (103 uncomplicated MTBI; 48 Injured Controls [IC]) prospectively enrolled in the DVBIC-TBICoE 15-Year Longitudinal TBI Study. Participants completed a battery of self-reported neurobehavioral symptom measures on average 76.2 months post-injury (SD = 31.8). APOE genotyping was undertaken using non-fasting blood samples. Participants were classified into four subgroups based on injury (MTBI vs. IC) and APOE e4 allele status (e4 present/absent). In the IC group, there were no significant differences across APOE e4 status subgroups for all measures. In the MTBI group, participants with the APOE e4 allele had significantly worse scores on measures of depression, pain, anxiety, grief, positive well-being, social participation, and resilience compared to those without the e4 allele (d = .44 to d = .69). When comparing the number of 'clinically elevated' neurobehavioral measures simultaneously, the MTBI/e4 present subgroup consistently had a higher number of elevated measures compared to the MTBI/e4 absent, IC/e4 present, and IC/e4 absent subgroups. The APOE e4 allele was associated with poorer neurobehavioral outcome in SMVs in the chronic phase of recovery following MTBI. APOE e4 could be incorporated into screening tools to predict SMVs at risk for poor long-term neurobehavioral outcome in an effort to provide early intervention to improve long-term clinical outcome., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Brain predicted age difference, or BrainPAD, compares chronological age to an age estimate derived by applying machine learning (ML) to MRI brain data. BrainPAD studies in youth have been relatively limited, often using only a single MRI modality or a single ML algorithm. Here, we use multimodal MRI with a stacked ensemble ML approach that iteratively applies several ML algorithms (AutoML). Eligible participants in the Healthy Brain Network (N = 489) were split into training and test sets. Morphometry estimates, white matter connectomes, or both were entered into AutoML to develop BrainPAD models. The best model was then applied to a held-out evaluation dataset, and associations with psychometrics were estimated. Models using morphometry and connectomes together had a mean absolute error of 1.18 years, outperforming models using a single MRI modality. Lower BrainPAD values were associated with more symptoms on the CBCL (p corr  = .012) and lower functioning on the Children's Global Assessment Scale (p corr  = .012). Higher BrainPAD values were associated with better performance on the Flanker task (p corr  = .008). Brain age prediction was more accurate using ComBat-harmonized brain data (MAE = 0.26). Associations with psychometric measures remained consistent after ComBat harmonization, though only the association with CGAS reached statistical significance in the reduced sample. Our findings suggest that BrainPAD scores derived from unharmonized multimodal MRI data using an ensemble ML approach may offer a clinically relevant indicator of psychiatric and cognitive functioning in youth., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Parvalbumin (PV)-expressing neurons have been implicated in the pathology of autism spectrum disorders (ASD). Loss of PV expression and/or reduced number of PV-expressing neurons have been reported not only in genetic and environmental rodent models of ASD, but also in post-mortem analyses of brain tissues from ASD vs. healthy control human subjects. PV-expressing neurons play a pivotal role in the maintenance of the balance between excitation and inhibition within neural circuits in part because of their fast-spiking properties. Their high firing rate is mostly regulated by the voltage-gated potassium channel Kv3.1. It is yet unknown whether disturbances in the electrophysiological properties of PV-expressing neurons per se can lead to behavioral disturbances. We assessed locomotor activity, social interaction, recognition and memory, and stereotypic behaviors in Kv3.1 wild-type (WT) and knockout (KO) mice. We then used Western Blot analyses to measure the impact of Kv3.1 deficiency on markers of GABA transmission (PV and GAD67) and neural circuit activity (Egr1). Deficiency in Kv3.1 channel is sufficient to induce social deficits, hyperactivity and stereotypic behaviors. These behavioral changes were independent of changes in GAD67 levels and associated with increased levels of PV protein in the prefrontal cortex and striatum. These findings reveal that a loss of PV expression is not a necessary factor to induce an ASD-like phenotype in mice and support the need for further investigation to fully understand the contribution of PV-expressing neurons to ASD pathology., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate the associations between psychopathological characteristics of children and adolescents with primary headache, as measured by the Strengths and Difficulties Questionnaire (SDQ), and treatment outcomes., Methods: A cohort study was conducted on 124 pediatric patients with primary headache. At the first consultation, the SDQ was completed by the parents. The analysis of treatment efficacy was conducted on 90 patients with a follow-up period of at least one year. Treatment responders were defined as those who showed 50% reduction in the headache frequency. First, an analysis of the SDQ total scores and five subscales, among the migraine and tension-type headache groups, was conducted for 124 participants. Second, the association between the SDQ scores and treatment outcomes in the groups with periods of improvement of less than three months and three months or more were analyzed in 90 patients., Results: Migraine patients displayed more difficulties than strengths in terms of the total score (p = .004) and in the emotional symptoms subscale (p = .012) compared with tension-type headache patients. Migraine patients who required more than three months to show improvement displayed more peer problems (p = .020), while tension-type headache patients who required more than three months to show improvement displayed fewer conduct problems (p = .007)., Conclusion: Evaluation of patient characteristics using the SDQ at first consultation can predict the treatment outcome. Moreover, it can help provide appropriate initial treatment and improve outcome of primary headache in children., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Dysregulated autonomic nervous system (ANS) activity has been associated with adolescent risk-taking and internalizing behavior, but previous results in community samples have been mixed. We investigated whether ANS activity was associated with higher risk-taking and internalizing behavior in young adolescents (age 11/12; n = 875), and whether adolescents' gender, parents' parenting style or a combination of both moderated these associations. Adolescents and their parents were recruited as part of the population-based, longitudinal Amsterdam Born Children and their Development (ABCD) study. Risk-taking behavior was assessed with the Balloon Analogue Risk Task and the personality characteristics sensation seeking and impulsivity, measured with the Substance Use Risk Profile Scale (SURPS). Internalizing behavior was assessed via the SURPS subscales anxiety sensitivity and hopelessness. Authoritative (AUTH-SW) and authoritarian (AUTH-S) parenting styles were measured with the Parenting Styles and Dimensions Questionnaire. Resting ANS activity was assessed via heart rate and respiratory sinus arrhythmia (RSA). Hierarchical, multivariable regression analyses showed higher RSA, but not heart rate, being associated with higher risk-taking behavior and sensation seeking. The associations between ANS activity and risk-taking variables were not significantly moderated by gender, parenting, or interactions between gender and parenting. Our findings suggest that RSA activity may be a relevant factor in mild to moderate risk-taking behavior in adolescents from the general population, regardless of their gender or the type of parenting they experience., (© 2021 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Background: Prader-Willi syndrome (PWS) is a rare genetic disorder that in many cases is associated with mental health disorders, in addition to characteristic symptoms such as hyperphagia. The current Sars-CoV-2 coronavirus pandemic has led to massive restrictions in health care and social life worldwide. People with PWS represent a particularly vulnerable population group to these restrictions, with unknown impact on their mental health., Methods: We conducted an online questionnaire to assess the impact of the restrictions associated with the COVID-19 pandemic on the mental health of people with PWS., Results: One hundred and eight caregivers completed the survey about individuals with PWS. Individuals with PWS > 6 years (n = 89) were included for evaluation with regard to psychopathological change. Respondents frequently reported an increase in psychopathological symptoms associated with PWS during the lockdown, with 51.7% reporting increased temper outbursts, 43.8% showing signs of sadness, 38.2% being anxious, 55.0% more irritable, and 39.3% showing more food seeking behaviour. Adjusted for the type of accommodation food seeking behaviour and irritability is increased to a significantly lesser extent in people with PWS accommodated in specialised care facilities compared with those living in their family home. No significant difference could be found between the sexes., Conclusion: The COVID-19 pandemic has had a significant effect on the mental health of individuals with PWS, evidenced by an increase in behaviours associated with PWS, including temper outbursts, food-seeking, and irritability, which again underlines their need for specialised care. Individuals living with their families were particularly vulnerable, indicating that they and their families are in special need of support., (© 2021 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disibilities and John Wiley & Sons Ltd.)

Objectives: To test for cerebellar involvement in motor and nonmotor impairments in Parkinson disease (PD) and to determine patterns of metabolic correlations with supratentorial brain structures, we correlated clinical motor, cognitive, and psychiatric scales with cerebellar metabolism., Methods: We included 90 patients with PD. Motor, cognitive, and psychiatric domains were assessed, and resting-state 18 FDG-PET metabolic imaging was performed. The motor, cognitive, and psychiatric scores were entered separately into a principal component analysis. We looked for correlations between these 3 principal components and cerebellar metabolism. Furthermore, we extracted the mean glucose metabolism value for each significant cerebellar cluster and looked for patterns of cerebrum-cerebellum metabolic correlations., Results: Severity of impairment was correlated with increased metabolism in the anterior lobes and vermis (motor domain); the right crus I, crus II, and declive (cognitive domain); and the right crus I and crus II (psychiatric domain). No results survived multiple testing corrections regarding the psychiatric domain. Moreover, we found distributed and overlapping, but not identical, patterns of metabolic correlations for motor and cognitive domains. Specific supratentorial structures (cortical structures, basal ganglia, and thalamus) were strongly correlated with each of the cerebellar clusters., Conclusions: These results confirm the role of the cerebellum in nonmotor domains of PD, with differential but overlapping patterns of metabolic correlations suggesting the involvement of cerebello-thalamo-striatal-cortical loops., (© 2021 American Academy of Neurology.)

Objective: When confronted with major threats, people often experience decline in well-being. The central purpose of this study was to identify mechanisms underlying change of well-being in times of threat, using the example of the COVID-19 pandemic, with a focus on appraisals of the pandemic and affective states, stress, as well as mindfulness in daily life., Method: We conducted a study across 3.5 weeks, including pretest, posttest, and a diary phase in-between. We worked with a sample of 460 adults, pre- and post-test information, as well as 7,189 observations from the diary phase., Results: Results showed that deterioration in mental health symptoms across the duration of the study was associated with (a) change towards less fortunate appraisals of the pandemic and (b), more negative affect and less mindfulness in daily life. Furthermore, appraisals of the pandemic at pretest predicted experiences in daily life, with more negative appraisals of the pandemic predicting more negative affect and stressor occurrence as well as less mindfulness., Conclusions: These findings speak to the dynamic nature of well-being and appraisals in times of threat, and highlight the role of experiences in daily life in changes in well-being., (© 2020 Wiley Periodicals LLC.)

Seasonal affective disorder has been associated with sleep problems, young age, and an evening chronotype. A chronotype refers to an individual's preference in the timing of their sleep-wake cycle, as well as the time during the sleep-wake cycle when a person is most alert and energetic. Seasonality refers to season-dependent fluctuations in sleep length, social activity, mood, weight, appetite, and energy level. Evening chronotype is more common in young adults and morning chronotype more common in the elderly. This study aimed to estimate the differential contribution of chronotype and age on seasonality. A sample of n=410 participants were included in the study. The age groups showed significantly different results according to sleep parameters, depression, anxiety, stress, seasonality, and chronotype. The oldest group (>59 years) showed the lowest scores on all of these scales. According to a path analysis, chronotype and age predict propensity for seasonality. However, sleep problems were linked to chronotype but not to age. Older adults seem to be more resistant to seasonal changes that are perceived as a problem than young and middle aged adults. Future studies would benefit from considering cultural aspects and examine seasonality, chronotype, depression, and insomnia in longitudinal designs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cognitive and behavioural flexibility permit the appropriate adjustment of thoughts and behaviours in response to changing environmental demands. Brain mechanisms enabling flexibility have been examined using non-invasive neuroimaging and behavioural approaches in humans alongside pharmacological and lesion studies in animals. This work has identified large-scale functional brain networks encompassing lateral and orbital frontoparietal, midcingulo-insular and frontostriatal regions that support flexibility across the lifespan. Flexibility can be compromised in early-life neurodevelopmental disorders, clinical conditions that emerge during adolescence and late-life dementias. We critically evaluate evidence for the enhancement of flexibility through cognitive training, physical activity and bilingual experience.

Background: Cough is a defense mechanism that protects the airways and lungs in response to airway irritation. The sensory neurons involved in detecting airway irritants and the neural pathways mediating cough share similarities with those that encode pain from the body. Painful conditioning stimuli applied to one body site are known to reduce the perception of pain at another. However, whether the neural regulation of cough is influenced by painful stimuli is not known., Research Question: What are the behavioral and neural outcomes of painful conditioning stimuli on urge-to-cough (UTC) and cough evoked by inhaled capsaicin?, Study Design and Methods: Sixteen healthy participants underwent psychophysical testing and functional MRI while completing a series of capsaicin inhalations to induce UTC and cough. The responses associated with capsaicin inhalation without pain were compared with those after the application of painful conditioning stimuli., Results: Significant decreases were seen behaviorally of 18.7% ± 17.3% (P < .001) and 47.0% ± 30.8% (P < .001) in participants' UTC ratings and cough frequencies, respectively, during the application of pain. UTC ratings were reduced by 24.2% ± 36.5% (P < .005) and increased by 67% ± 40% (P < .001) for capsaicin and saline inhalation, respectively, during the scanning session. Painful conditioning stimuli were associated with widespread decreases in regional brain responses to capsaicin inhalation (P < .001). Several brain regions showed levels of reduced activation attributable to painful conditioning that correlated with related changes in behavioral responses during scanning (R 2  = 0.53)., Interpretation: Pain-related decreases of cough and UTC are accompanied by widespread changes in brain activity during capsaicin inhalation, suggesting that pain can modify the central processing of inputs arising from the airways. A mechanistic understanding of how cough and pain processing interact within the brain may help develop more effective therapies to reduce unwanted coughing., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Aims: Neurogranin (NRGN) is a postsynaptic protein kinase substrate that binds calmodulin in the absence of calcium. Recent studies suggest that NRGN is involved in neuropsychiatric disorders, including schizophrenia, ADHD, and Alzheimer's disease. Previous behavioral studies of Nrgn knockout (Nrgn KO) mice identified hyperactivity, deficits in spatial learning, impaired sociability, and decreased prepulse inhibition, which suggest that these mice recapitulate some symptoms of neuropsychiatric disorders. To further validate Nrgn KO mice as a model of neuropsychiatric disorders, we assessed multiple domains of behavioral phenotypes in Nrgn KO mice using a comprehensive behavioral test battery including tests of homecage locomotor activity and nesting behavior., Methods: Adult Nrgn KO mice (28-54 weeks old) were subjected to a battery of comprehensive behavioral tests, which examined general health, nesting behavior, neurological characteristics, motor function, pain sensitivity, locomotor activity, anxiety-like behavior, social behavior, sensorimotor gating, depression-like behavior, and working memory., Results: The Nrgn KO mice displayed a pronounced decrease in nesting behavior, impaired motor function, and elevated pain sensitivity. While the Nrgn KO mice showed increased locomotor activity in the open field test, these mice did not show hyperactivity in a familiar environment as measured in the homecage locomotor activity test. The Nrgn KO mice exhibited a decreased number of transitions in the light-dark transition test and decreased stay time in the center of the open field test, which is consistent with previous reports of increased anxiety-like behavior. Interestingly, however, these mice stayed on open arms significantly longer than wild-type mice in the elevated plus maze. Consistent with previous studies, the mutant mice exhibited decreased prepulse inhibition, impaired working memory, and decreased sociability., Conclusions: In the current study, we identified behavioral phenotypes of Nrgn KO mice that mimic some of the typical symptoms of neuropsychiatric diseases, including impaired executive function, motor dysfunction, and altered anxiety. Most behavioral phenotypes that had been previously identified, such as hyperlocomotor activity, impaired sociability, tendency for working memory deficiency, and altered sensorimotor gating, were reproduced in the present study. Collectively, the behavioral phenotypes of Nrgn KO mice detected in the present study indicate that Nrgn KO mice are a valuable animal model that recapitulates a variety of symptoms of neuropsychiatric disorders, such as schizophrenia, ADHD, and Alzheimer's disease., (© 2020 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsycho Pharmacology.)

Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale multivariate neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an α brain atlas and a β brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify and separate mediators that potentially positively and negatively mediate symptoms and psychosis, respectively, and quantify the effect of each neural mediator on disease development. Taken together, these results paint a brain-wide picture of neural markers that are potentially mediating behavioral symptoms and the development of psychotic disorders; additionally, they underscore a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological system., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In addition to motor disability, another characteristic feature of Parkinson disease is the early appearance of psychiatric symptoms, including apathy, depression, anxiety and cognitive deficits; treatments for these symptoms are limited by the development of adverse effects such as impulse-control disorders. In this context, we investigated the orphan G protein-coupled receptor 88 (GPR88) as a novel therapeutic target., Methods: We used lentiviral-mediated expression of specifically designed microRNA to knock down Gpr88 in a translational male rat model of early Parkinson disease obtained by dopamine loss in the dorsolateral striatum as a result of 6-hydroxydopamine lesions. We evaluated the impact of Gpr88 knockdown on the Parkinson disease model using behavioural, immunohistochemical and in situ hybridization studies., Results: Knockdown of Gpr88 in associative territories of the dorsal striatum efficiently reduced alterations in mood, motivation and cognition through modulation of the regulator of the G-protein signalling 4 and of the truncated splice variant of the FosB transcription factor. Knockdown of Gpr88 also reduced allostatic changes in striatal activity markers that may be related to patterns observed in patients and that provide support for an "overload" hypothesis for the etiology of the psychiatric symptoms of Parkinson disease., Limitations: Behavioural tests assessing specific cognitive and motivational parameters are needed to further characterize the effects of the lesion and of Gpr88 knockdown in early-stage and advanced Parkinson disease models, presenting more extensive dopamine loss. Additional studies focusing on the direct and indirect striatal output pathways are also required, because little is known about the signalling pathways regulated by GPR88 in different striatal cell types., Conclusion: GPR88 may constitute a highly relevant target for the treatment of the psychiatric symptoms of Parkinson disease., Competing Interests: None declared., (© 2021 Joule Inc. or its licensors.)

The Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) is a commonly administered battery for assessing intellectual and cognitive abilities. Despite its popularity, construct validation studies primarily utilize the WAIS-IV normative sample rather than ecologically-valid clinical samples. The current study expands the literature on the validity of WAIS-IV by testing a bifactor model in such a sample. We examined archival data from 300 concurrent psychological evaluations performed at a university-based community clinic. Participants received the full WAIS-IV standard battery. Consistent with recent literature, confirmatory factor analyses (CFAs) favored a direct hierarchical model, where the g factor has a direct influence on WAIS-IV subtest performance and index scores explain only modest degrees of residual variance. Results challenge traditional intelligence nosologies and suggest consideration of a two-step method of WAIS-IV interpretation in clinical samples, whereby the Full Scale IQ score (FSIQ) score is examined first and individual subtest scores are analyzed second.

Huntington's disease is associated with motor, cognitive and behavioral dysfunction. Behavioral symptoms may present before, after, or simultaneously with clinical disease manifestation. The relationship between age of onset and behavioral symptom presentation and severity was explored using the Enroll-HD database. Manifest individuals (n = 4469) were initially divided into three groups for preliminary analysis: early onset (<30 years; n = 479); mid-adult onset (30-59 years; n = 3478); and late onset (>59 years; n = 512). Incidence of behavioral symptoms reported at onset was highest in those with early onset symptoms at 26% (n = 126), compared with 19% (n = 678) for mid-adult onset and 11% (n = 56) for late onset (P < 0.0001). Refined analysis, looking across the continuum of ages rather than between categorical subgroups found that a one-year increase in age of onset was associated with a 5.6% decrease in the odds of behavioral symptoms being retrospectively reported as the presenting symptom (P < 0.0001). By the time of study enrollment, the odds of reporting severe behavioral symptoms decreased by 5.5% for each one-year increase in reported age of onset. Exploring environmental, genetic and epigenetic factors that affect age of onset and further characterizing types and severity of behavioral symptoms may improve treatment and understanding of Huntington's disease's impact on affected individuals., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bacteria, archaeae, fungi and viruses of the intestinal microbiome play an important role as symbionts in the complex human ecosystem. Parasites, which account for about 40 % of the earth's biodiversity, depend on hosts to complete their life cycle. This article explains how they use them and which signalling pathways play a role in this, using toxoplasmosis and malaria as examples. The parasitic manipulation hypothesis is based on impressive observations in the wild and under laboratory conditions, especially in invertebrates. For the assumption of an adaptive manipulation, every step from the genotype, the translated messenger, and its source via the used signalling pathways to the altered host behaviour must be proven. The assumption of an adaptive manipulation of humans by T. gondii in the sense of a cause-effect relationship is not proven. Alternative explanations include the inflammatory and immunological processes on the host side, which change the neuronal signal transduction as concomitant symptoms of an infection. Even without confirmation of parasitic manipulation in humans, it could be worthwhile to further investigate the observed associations in order to develop new possibilities for diagnosis and therapy, e. g. for schizophrenia., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objective: To compare clinical traits of suicidal vulnerability among in-patients with suicidal behavior disorder (SBD) with and without borderline personality disorder (BPD)., Method: we recruited adult patients with SBD, consecutively and voluntarily hospitalized in a specialized unit for affective disorders and suicidal behavior between July and October 2016. Ninety-two inpatients having attempted suicide within the past 2 years were divided into two subgroups according to the presence or absence of BPD. Clinical vulnerability traits for suicidal behavior were assessed., Results: Half of the patients with SBD also had BPD. Patients with BPD were nine times more likely to be major suicide repeaters compared to those without. They were also more likely to display clinical and psychological vulnerability traits for suicidal behavior, even after considering potential confounders. Emotional dysregulation, shame-proneness, impulsiveness, preoccupied attachment pattern, and childhood trauma were high in both groups, but significantly increased in those with (vs. without) BPD status. Psychological traits remained stable in SBD-BPD patients, regardless of the time since the last suicide attempt (i.e. SBD in recent vs. early remission)., Conclusions: Clinical and psychological traits associated with suicidal vulnerability are present in all SBD patients compared to non-suicidal populations, but comorbidity with BPD is associated with particularly high scores. BPD could be considered as a specifier for SBD diagnoses.

In this study, 285 adults who met criteria for trichotillomania (TTM) via self-report completed an online, cross-sectional survey examining antecedent phenomenological experiences pertaining to hair pulling along with measures of TTM severity and experiential avoidance (i.e., avoidance of or escape from unwanted thoughts or feelings). Results showed a heterogeneous depiction of antecedent experiences. Subsequent analyses revealed that certain antecedents were not significantly related to TTM severity but were significantly correlated with higher levels of experiential avoidance. In particular, four of five classes of antecedents (i.e., bodily sensations, physical symptoms, mental anxiety, and general uncomfortableness) were significantly related to greater experiential avoidance. The authors conclude that treatments may need to be designed to address specific private antecedents, and that this may be done through targeting experiential avoidance.

This study tested the potential mediating roles of various cognitive abilities in middle childhood (i.e., short-term memory [STM], sustained attention, and inhibitory control) in the associations between home learning environment in early childhood and child adjustment in multiple domains during early adolescence (i.e., internalizing and externalizing problems, language skills, and social competence), based on data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development ( N = 1,364). Results demonstrated that the quality of home learning environment at 36 and 54 months was directly related to externalizing problems, social competence, and language skills at the 6th grade. Early home learning environment was also associated negatively with externalizing behavior problems at the 6th grade specifically via child sustained attention at 3rd grade. Additionally, the associations between early home learning environment and child language skills in early adolescence were mediated by STM, sustained attention, and inhibitory control in middle childhood. This study contributes to an increased specificity in the understanding of the roles of cognitive abilities in the far-reaching and comprehensive implications of early home learning environment for child later behavioral, social, and language development. Our findings suggest that training parents to appropriately build early home learning environment during the early years of life may yield benefits in the long run as it is a potential avenue to foster child later cognitive development and may ultimately facilitate child adaptation during the stressful, transitional stage of early adolescence. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The overarching aim of this study was to develop and validate a new scale (i.e., the Praise, Indulgence, and Status Parenting Scale [PISPS]) to measure modern parenting practices and behaviors consistent with instilling ideals of specialness (i.e., the notion that one is special), self-esteem, and status in children. In 2 studies on emerging adults (Study 1: N  = 582, M age = 19.46; Study 2: N  = 464, M age = 19.58), the PISPS was developed and validated using classical test theory (Study 1) and further refined using item-response theory (Study 2). Results from both studies indicated a 3-factor structure with factors differentially linked with correlates of interest including parenting strategies, self-esteem, narcissism, entitlement, and internalizing symptoms. Study 3 further validated the PISPS in a sample of parents ( N  = 638, M age = 35.79) reporting on their parenting and their child's emotion regulation and symptoms of psychopathology. Overall, findings support the PISPS, its psychometric properties, and its unique contribution to child symptoms.

Aim: To: (1) provide greater insight into the psychological and social impact of a range of demyelinating disorders, (2) explore differences between disorders, and (3) provide direction for future research., Method: Studies were identified by searching online databases. Studies that explored the psychological, emotional, or social impact of a range of demyelinating disorders in childhood, including acute disseminated encephalomyelitis (ADEM), optic neuritis, transverse myelitis, and multiple sclerosis, were included and screened independently by three authors. Data on the design, sample characteristics, psychosocial measures, key findings, and methodological strengths and limitations were extracted. Twenty-five studies were included in the narrative synthesis., Results: Demyelinating disorders are associated with lower quality of life, affecting young people's emotional, social, school, and behavioural functioning. There is a high prevalence of psychiatric disorders and fatigue, particularly in multiple sclerosis. Subtle differences exist in the psychological presentation between different demyelinating disorders, with clear gaps in the research for the long-term psychosocial impact of monophasic conditions., Interpretation: The difference between the impact of monophasic and relapsing demyelinating disorders on psychosocial functioning is unclear. Future research should aim to identify the psychosocial impact across disorders and over time, ensure that services are capturing those patients who may benefit from tailored interventions., What This Paper Adds: Prevalence of psychiatric diagnoses in paediatric demyelinating disorders is higher than controls. Depression and emotional concerns are elevated in paediatric demyelinating disorders. Demyelinating disorders impact children's quality of life across school, social, and physical functioning., (© 2020 Mac Keith Press.)

Early case series suggest that about one-third of patients with COVID-19 present with neurological manifestations, including cerebrovascular disease, reported in 2%-6% of hospitalised patients. These are generally older patients with severe infection and comorbidities. Here we discuss the case of a previously fit and well 39-year-old man who presented with fever and respiratory symptoms, evolving in pneumonia with hypoxia but only requiring continuous positive airway pressure. After resolution of the respiratory disease, the patient developed focal neurology and was found to have bilateral occipital, thalamic and cerebellar infarcts. A diagnosis of COVID-19 central nervous system vasculopathy was made. He developed a florid neuropsychiatric syndrome, including paranoia, irritability, aggression and disinhibition, requiring treatment with antipsychotics and transfer to neurorehabilitation. Neuropsychometry revealed a wide range of cognitive deficits. The rapid evolution of the illness was matched by fast resolution of the neuropsychiatric picture with mild residual cognitive impairment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Functional interconnections between brain regions define the "connectome" which is of central interest for understanding human brain function. Resting-state functional magnetic resonance (rsfMRI) work has revealed changes in static connectivity related to age, sex, cognitive abilities and psychiatric symptoms, yet little is known how these factors may alter the information flow. The commonly used approach infers functional brain connectivity using stationary coefficients yielding static estimates of the undirected connection strength between brain regions. Dynamic graphical models (DGMs) are a multivariate model with dynamic coefficients reflecting directed temporal associations between nodes, and can yield novel insight into directed functional connectivity. Here, we leveraged this approach to test for associations between edge-wise estimates of direction flow across the functional connectome and age, sex, intellectual abilities and mental health. We applied DGM to investigate patterns of information flow in data from 984 individuals from the Human Connectome Project (HCP) and 10,249 individuals from the UK Biobank. Our analysis yielded patterns of directed connectivity in independent HCP and UK Biobank data similar to those previously reported, including that the cerebellum consistently receives information from other networks. We show robust associations between information flow and age and sex for several connections, with strongest effects of age observed in the sensorimotor network. Visual, auditory and sensorimotor nodes were also linked to mental health. Our findings support the use of DGM as a measure of directed connectivity in rsfMRI data and provide new insight into the shaping of the connectome during aging., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The purpose of this study was to examine long-term neurobehavioural symptom reporting following mild, moderate, severe, or penetrating TBI in U.S. military service members and veterans (SMV). Participants were 445 SMVs divided into four groups: 158 uncomplicated mild TBI ("unMTBI" group), 105 penetrating, severe, moderate, or complicated mild TBI ("smcTBI" group), 101 injured controls (IC), and 81 non-injured controls (NIC). Two independent cohorts were examined that included participants 5-years or 10-year post-injury. Participants completed the TBI-Quality of Life, Neurobehavioural Symptom Inventory, and Post-traumatic Stress Disorder Checklist. At 5-years and 10-years post-injury, there were significant main effects for the majority of measures (all p 's < .005). At 10-years post-injury, the NIC group had consistently better scores compared to the IC, unMTBI, and smcTBI groups. At 5-years post-injury, either (a) the IC and NIC group had better scores compared to both TBI groups, or (b) the NIC group had better scores compared to the IC, unMTBI, and smcTBI groups. A high proportion of SMVs reported poor long-term neurobehavioural symptoms following TBI or bodily injury without TBI. Injured SMVs (regardless of injury type) can have long-term symptoms that impact mental health and overall quality of life requiring long-term follow-up and care.

Background: Alternating hemiplegia of childhood often manifests severe or extreme behavioral problems, the nature of which remains to be fully characterized., Methods: We analyzed 39 consecutive patients with alternating hemiplegia of childhood for occurrence of behavioral problems and categorized those by severity: mild (not requiring intervention), moderate (requiring intervention but no risk), severe (minor risk to self, others, or both), and extreme (major risk). We then analyzed behavioral manifestations, concurrent morbidity, and medication responses in patients with severe or extreme symptoms., Results: Two patients had mild behavioral problems, five moderate, 10 severe, six extreme, and 16 none. Extreme cases exhibited disruptive behaviors escalating to assaults. Triggers, when present, included peer-provocation, low frustration tolerance, limits set by others, and sleep disruption. Reversible psychotic symptoms occurred in two patients: in one triggered by infection and trihexyphenidyl, and in another triggered by sertraline. Of the 16 patients with severe or extreme symptoms, 13 had concurrent neuropsychiatric diagnoses. Occurrence of severe or extreme symptoms did not correlate with age, puberty, severity of intellectual disability, or mutation status (P > 0.05). A multidisciplinary team including mental health professionals comanaged all patients with severe or extreme symptoms with either behavioral therapy, medications, or both. When considering medications prescribed to more than four patients, medicines that demonstrated efficacy or partial efficacy in more than 50% of patients were alpha-adrenergic agonists and selective-serotonin-reuptake-inhibitors., Conclusions: Patients with alternating hemiplegia of childhood (41%) often experience severe or extreme behavioral problems and, rarely, medication-triggered psychotic symptoms. These observations are consistent with current understanding of underlying alternating hemiplegia of childhood brain pathophysiology. Increasing awareness of these behavioral problems facilitates alternating hemiplegia of childhood management and anticipatory guidance., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study aimed to assess whether callous-unemotional traits (CU) are associated with deficits in emotion recognition independent of externalizing behavior and whether such deficits can be explained by aberrant attention. As previous studies have produced inconsistent results, the current study included two different emotion recognition paradigms and assessed the potential influence of factors such as processing speed and attention. The study included N = 94 children (eight to 14 years) with an oversampling of children with conduct problems (CP) and varying levels of CU-traits. Independent of externalizing behavior, CU-traits were associated with slower recognition of angry, sad and fearful facial expressions but not with higher error rates. There was no evidence that the association between CU-traits and emotion processing could be explained by misguided attention. Our results implicate that in children with high levels of CU-traits emotion recognition deficits depend on deficits in processing speed.

Previous research has shown an association between cognitive control deficits and problematic behavior such as antisocial behavior and substance use, but little is known about the predictive value of cognitive control for treatment outcome. The current study tests whether selected markers of baseline cognitive control predict (1) treatment completion of a day treatment program involving a combination of approaches for multiproblem young adults and (2) daytime activities a year after the start of treatment, over and above psychological, social, and criminal characteristics. We assessed individual, neurobiological, and neurobehavioral measures, including functional brain activity during an inhibition task and two electroencephalographic measures of error processing in 127 male multiproblem young adults (age 18-27 years). We performed two hierarchical regression models to test the predictive power of cognitive control for treatment completion and daytime activities at follow-up. The overall models did not significantly predict treatment completion or daytime activities at follow-up. However, activity in the anterior cingulate cortex (ACC) during response inhibition, years of regular alcohol use, internalizing problems, and ethnicity were all significant individual predictors of daytime activity at follow-up. In conclusion, cognitive control could not predict treatment completion or daytime activities a year after the start of treatment over and above individual characteristics. However, results indicate a direct association between brain activity during response inhibition and participation in daytime activities, such as work or school, after treatment. As adequate baseline inhibitory control is associated with a positive outcome at follow-up, this suggests interventions targeting cognitive control might result in better outcomes at follow-up.

Parkinson's disease (PD) is characterized by overlapping motor, neuropsychiatric, and cognitive symptoms. Worse performance in one domain is associated with worse performance in the other domains. Commonality analysis (CA) is a method of variance partitioning in multiple regression, used to separate the specific and common influence of collinear predictors. We apply, for the first time, CA to the functional connectome to investigate the unique and common neural connectivity underlying the interface of the symptom domains in 74 non-demented PD subjects. Edges were modeled as a function of global motor, cognitive, and neuropsychiatric scores. CA was performed, yielding measures of the unique and common contribution of the symptom domains. Bootstrap confidence intervals were used to determine the precision of the estimates and to directly compare each commonality coefficient. The overall model identified a network with the caudate nucleus as a hub. Neuropsychiatric impairment accounted for connectivity in the caudate-dorsal anterior cingulate and caudate-right dorsolateral prefrontal-right inferior parietal circuits, while caudate-medial prefrontal connectivity reflected a unique effect of both neuropsychiatric and cognitive impairment. Caudate-precuneus connectivity was explained by both unique and shared influence of neuropsychiatric and cognitive symptoms. Lastly, posterior cortical connectivity reflected an interplay of the unique and common effects of each symptom domain. We show that CA can determine the amount of variance in the connectome that is unique and shared amongst motor, neuropsychiatric, and cognitive symptoms in PD, thereby improving our ability to interpret the data while gaining novel insight into networks at the interface of these symptom domains., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

The dysregulation of the inflammatory response, including pro-inflammatory molecules, produces neuropsychiatric symptoms and depression-like behavior, including withdrawal from the physical and social environment. Genetic variants that enhance immune reactivity may thus increase inflammatory and withdrawn reactions to stress. Here we investigated a functional polymorphism of Interferon Gamma gene (IFNG +874 T > A, rs2430561) as moderator of the relationship between mothers' distress exposure and children's withdrawn behavior at preschool age. Participants were 198 Portuguese preschool children (mean age = 57.98 months). Exposure to mother's distress was assessed using the Brief Symptom Inventory, and withdrawn behavior with the Caregiver Teacher Report Form. All children provided saliva samples for genotyping. Contrary to expecations based on prior work, the rs2430561 AA genotype-not the T variant-interacted with (high levels of) mothers' distress exposure, to increase children's withdrawn behavior. No significant main effects were detected. The polymorphism in Interferon Gamma gene showed specific environmental stressor-dependent effects on withdrawn behavior during childhood, ones which are interpreted in light of the "behavioral immune system" hypothesis, and which proved inconsistent with diathesis-stress thinking., (© 2020 Wiley Periodicals, Inc.)

Background: There is growing evidence that children with motor difficulties are at risk of psychosocial problems and vice versa. However, it is not clear how far different aspects of motor function are predictive of psychosocial well-being in the context of other powerful factors, such as family upset, that are known to affect psychosocial development., Aims: To investigate the role of basic motor skills and primary reflex persistence in young children with severe emotional and behavioural difficulties (EBD)., Sample: From a total sample of 225 children, three groups were selected: children excluded from school (severe EBD) (n = 29), a male comparison group (n = 38), and a female comparison group (n = 45). The groups were matched (at group level) on age, IQ, and level of social disadvantage., Method: All of the selected children completed a range of standardized motor, cognitive, social, and behavioural measures, as well as a clinical protocol for primary reflex persistence., Results: Children with severe EBD had significant levels of motor difficulties, primary reflex persistence, and family upset, as well as significant literacy problems, attention deficits, and raised levels of hyperactivity/impulsivity relative to the comparison groups. A hierarchical multiple regression analysis revealed that basic motor skills, primary reflex persistence, family upset, hyperactivity, and literacy were all significant predictors of psychosocial functioning., Conclusions: The findings suggest that motor difficulties and primary reflex persistence may act as independent stressors of psychosocial functioning in children with EBD. We suggest that specific movement interventions should be adopted to complement existing provision for children at risk of psychosocial problems., (© 2019 The British Psychological Society.)

Objective : Suicidal individuals are a heterogeneous population and may differ in systematic ways in their responsiveness to stress. The primary aim of the present study was to identify whether a different pattern of physiological stress response exists among adult suicide attempters with a history of behavioral problems during childhood and adolescence, which earlier studies have related to both decreased activity of the HPA axis and to suicidal behaviors. Method : Seventy-eight participants with Borderline Personality Disorder were assessed using the SCID-II, and completed self-report measures assessing their history of suicide attempts, history of aggressive behaviors, depressive symptoms, history of lifetime abuse and demographics. Participants' cortisol reactivity was assessed using the Trier Social Stress Test . Results : Analyses indicated that suicide attempters with a history of behavioral problems in youth (n = 30) had a significantly lower response to stress than both suicide attempters without such a history (n = 26) and non-attempters (n = 22), when controlling for lifetime history of abuse. The groups did not differ in basal cortisol. Conclusions : These findings suggest a unique subtype of suicide attempter among those with Borderline Personality Disorder, characterized by a blunted physiological stress response.

Posterior reversible encephalopathy syndrome (PRES) is a clinically and radiologically diagnosed disorder distinguished by subcortical vasogenic cerebral edema. To date, its presentation has been described through summarized neurological categories, such as seizures, headaches, "confusion," and "altered mental function." This retrospective case series identified all cases of clinically confirmed, radiologically diagnosed PRES resulting in treatment in a large teaching hospital from 2010 to 2019. The authors conducted a search for the term "reversible encephalopathy" in the hospital clinical radiology information system, followed by an audit of scan reports and clinical records. The most common reasons for psychiatric referral were addictions, acute psychosis, depression, suicidality, and treatment refusal. Multidisciplinary staff should consider PRES as a rare, organic differential diagnosis for acute mental state changes. Physicians should be aware of elevated rates of post-PRES psychiatric symptoms and consider whether psychiatric consultation may enhance recovery.

Objective: The dual-pathway model has been proposed to explain the heterogeneity in symptoms of attention deficit hyperactivity disorder (ADHD) by two independent psychological pathways based on distinct brain circuits. The authors sought to test whether the hypothesized cognitive and motivational pathways have separable neural correlates., Methods: In a longitudinal community-based cohort of 1,963 adolescents, the neuroanatomical correlates of ADHD were identified by a voxel-wise association analysis and then validated using an independent clinical sample (99 never-medicated patients with ADHD, 56 medicated patients with ADHD, and 267 healthy control subjects). The cognitive and motivational pathways were assessed by neuropsychological tests of working memory, intrasubject variability, stop-signal reaction time, and delay discounting. The associations were tested between the identified neuroanatomical correlates and both ADHD symptoms 2 years later and the polygenic risk score for ADHD., Results: Gray matter volumes of both a prefrontal cluster and a posterior occipital cluster were negatively associated with inattention. Compared with healthy control subjects, never-medicated patients, but not medicated patients, had significantly lower gray matter volumes in these two clusters. Working memory and intrasubject variability were associated with the posterior occipital cluster, and delay discounting was independently associated with both clusters. The baseline gray matter volume of the posterior occipital cluster predicted the inattention symptoms in a 2-year follow-up and was associated with the genetic risk for ADHD., Conclusions: The dual-pathway model has both shared and separable neuroanatomical correlates, and the shared correlate in the occipital cortex has the potential to serve as an imaging trait marker of ADHD, especially the inattention symptom domain.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive head impacts (RHI), such as those received in contact/collision sports, blast injury in military veterans, and domestic violence. Currently, CTE can only be diagnosed following death. Although the clinical features of former boxers have been described for almost a century, and there is increasing evidence of long-term cognitive and neuropsychiatric impairments in living former American football players, the specific clinical presentation associated with underlying CTE neuropathology remains unclear. These features include diverse and nonspecific changes in cognition, mood, behavior, and motor functioning. Currently, there are no validated and widely accepted clinical diagnostic criteria. Proposed criteria are primarily based on retrospective telephonic interviews with the next of kin of individuals who were diagnosed with CTE postmortem. Prospective studies involving individuals presumably at high risk for CTE are underway; these will hopefully clarify the clinical features and course of CTE, allow the diagnostic criteria to be refined, and lead to the development and validation of in vivo biomarkers. This article reviews what is currently known about the clinical presentation of CTE and describes the evolution of this knowledge from early case reports of "punch drunk" boxers through larger case series of neuropathologically confirmed CTE. This article concludes with a discussion of gaps in research and future directions to address these areas., Competing Interests: None., (Thieme. All rights reserved.)

Background: Living with a progressive disease as muscular dystrophy (MD) can be challenging for the patient and the entire family from both emotional and practical point of view. We aimed to extend our previously published data about mental health in patients with MDs, also investigating coping profiles of both themselves and their parents. Furthermore, we wanted to verify whether psychological adaptation of patients can be predicted by coping strategies, taking also into account physical impairment, cognitive level and socioeconomic status., Methods: 112 patients with MDs, aged 2-32 were included. Their emotional and behavioural features were assessed through parent- and self-report Achenbach System for Empirically Based Assessment questionnaires and Strength and Difficulties Questionnaires. Development and Well-Being Assessment or Autism Diagnostic Observation Schedule were administered to confirm suspected diagnoses. Coping profile of both parents and patients was assessed through the self-administered New Italian Version of the Coping Orientation to the Problems Experienced questionnaire and its relationship with emotional/behavioural outcome was examined in linear regression analyses., Results: High prevalence of intellectual disability and autism spectrum disorders was confirmed in Duchenne MD. Despite the high rate of internalizing symptomatology, we did not report higher rate of psychopathological disorders compared to general population. Parents tend to rely more on positive reinterpretation and less on disengagement coping. Avoidance coping, whether used by parents or patients, and ID, predicted increased emotional/behavioural problems., Conclusions: Psychosocial interventions should address problems of anxiety and depression that people with MDs frequently experience, even through fostering parents' and childrens' engagement coping over disengagement coping.

P3 amplitude reductions, commonly elicited in oddball paradigms, have been associated with both internalizing (e.g., depression and anxiety) and externalizing problems (e.g., substance use, aggression, and impulsivity). Recent factor analytic models have focused on the shared variance between internalizing and externalizing problems as a potentially important separable psychopathology construct (a general psychopathology factor, or p-factor). To assess neurophysiological markers of this shared variance, we examined P3 amplitude to target and novel stimuli in an undergraduate sample with a range of internalizing and externalizing problems. Participants (N = 125) completed a rotated heads visual oddball paradigm, with IAPS pictures serving as infrequent novel stimuli. Results replicated P3 amplitude reduction relative to both target and novel stimuli separately for internalizing and externalizing problems, and found that the shared variance across internalizing and externalizing was significantly related to lower P3 amplitude to novels, targets, and a factor score of target and novel P3 measures. The present results are consistent with the interpretation that a general or shared problem behavior factor accounts for much of the associations between reduced P3 amplitude and internalizing and externalizing problems., (© 2020 Society for Psychophysiological Research.)

Objective: To assess the long-term outcomes of patients with temporal lobe epilepsy and CSF anti-glutamate decarboxylase antibodies (GAD65-Abs)., Methods: We retrospectively analyzed the clinical records of 35 patients with temporal lobe epilepsy and CSF GAD65-Abs, collected from January 1993 to December 2016 and assessed cognitive impairment and seizure activity at last visit. Cognitive impairment was considered significant if impacting on daily life activities. Immunohistochemistry on rat brain slices and ELISA were used for antibody detection and titration., Results: Median age was 30 years (range 2-63), 32/35 (91%) patients were female, and median follow-up was 68 months (range 7-232). At presentation, 20 patients had isolated temporal lobe epilepsy and 15 patients had other limbic symptoms, including anterograde amnesia (n = 10) and behavioral disturbances (n = 5). Progressive clinical deterioration over follow-up was reported in 28/35 patients (80%), including gradual increase of memory impairment (n = 25), and apparition of behavioral disturbances (n = 4) or mood disorders (n = 18). At last follow-up, 24/35 (69%) patients had cognitive disturbances with an impact on patient's daily life activities, and 28/35 (80%) still had active seizures., Conclusion: Most patients with temporal lobe epilepsy and CSF GAD65-Abs develop a chronic disease with progressive cognitive impairment and refractory epilepsy regardless of the presence of additional limbic symptoms at onset.

Background: Prenatal stress has been associated with adverse outcomes in offspring, including elevated risk of psychopathology. Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis has been posited as a biological mechanism underlying such consequences. The present study aimed to examine whether dysregulation of the offspring HPA axis mediates the relationship between prenatal stress exposure and adolescent psychopathology., Methods: Five months after the Quebec ice storm of 1998, women who had been pregnant at the time of the storm completed questionnaires about their objective hardship and subjective distress from the disaster. A total of 45 of their children, exposed to the ice storm in utero, participated at 13 years of age. Adolescents completed the Trier Social Stress Test while providing salivary samples to measure circulating cortisol levels. Maternal report of adolescent behaviors was assessed with the Child Behavior Checklist., Results: Results from the study found that greater objective hardship was associated with elevated offspring cortisol reactivity at 13 years of age. Furthermore, greater subjective distress was associated with greater externalizing behaviors. While lower cortisol reactivity predicted greater externalizing behaviors, it did not mediate the association between maternal objective hardship or subjective distress and offspring externalizing or internalizing behaviors., Conclusions: Findings suggest that objective hardship in pregnancy has long-term implications for offspring HPA axis functioning, which is also associated with externalizing behaviors. While dysregulation of the offspring HPA axis did not mediate the association between prenatal stress and offspring psychopathological symptoms, further research is warranted to investigate programming of alternative biological systems., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study examined the transdiagnostic effect of acceptance and commitment therapy (ACT) on impulsive decision-making in a community sample. A total of 40 adults were randomized to eight individual sessions of ACT or an inactive control. Participants completed pre-, mid-, and post-assessments for psychological symptoms; overall behavior change; valued living; delay discounting; psychological flexibility; and distress tolerance. Data were analyzed with multilevel modeling of growth curves. Significant interaction effects of time and condition were observed for psychological flexibility, distress tolerance, psychological symptoms, and the obstruction subscale of valued living. No significant interaction effect was found for two delay discounting tasks nor the progress subscale of valued living. The ACT condition had a significantly larger reduction of problem behavior at post-assessment. The results support use of ACT as a transdiagnostic treatment for impulsive behaviors. The lack of change in delay discounting contrasts previous research.

Some recent researches have shown the important role of hair cortisol as a retrospective biomarker of chronic stress. The aim of this research was to investigate the relationship between hair cortisol levels and sociodemographic and psychological variables, such as perceived stress levels and psychopathological symptoms on a Spanish population. The sample consisted of 347 healthy people, 230 women and 117 men, with an average age of 33.39 years (SD = 12.63). Hair cortisol levels were measured by obtaining a hair sample. In addition, a psychological assessment composed by: Analogic-Visual Stress Scale, Perceived Stress Scale (PSS), Symptom Checklist 90 Revised (SCL-90-R) and the assessment of vital stressful events suffered, was carried out. The mean cortisol level was 108.93 pg/mg (SD = 66.43) in men, and 120.38 pg/mg (SD = 87.26) in women. The linear hierarchical regression showed that Analogic-Visual Stress Scale and perceived stress levels were related with higher hair cortisol levels (R2 = .032; t = 2.21; p = .029). Due to the relationship between daily stress levels, Analogic-Visual Stress Scale, anxiety sub-scale of SCL 90-R and perceived stress levels with hair cortisol levels, we conclude that there is a relation between perceived yourself stressed and the physiological levels.

Objectives: We examined serial mediating roles of low self-control and aggression in explaining relationships between levels of inattention and hyperactivity problems (IHPs) and severity of Internet gaming disorder (IGD) features when exposed to online games among adolescents without Attention deficit hyperactivity disorder (ADHD) stratified by gender using three-wave longitudinal study., Method: The sample comprised a total of 1,732 family dyads from a study that was conducted among seventh graders without diagnoses of ADHD at baseline. Levels of IHPs were assessed by the parent reported Korean version of the ADHD rating scale at baseline (wave1). Severity of IGD features was assessed by the Internet Game Use-Elicited Symptom Screen (IGUESS) at wave3. Both levels of self-control (wave1) and aggression (wave2) were assessed by self-report. The mediating role of low self-control and aggression in the relationships between level of IHPs and severity of IGD were evaluated using serial mediation analysis separately for each gender., Results: Levels of IHPs were related directly to severity of IGD features in both genders. The indirect effects via low self-control were also significant in both genders, however, the indirect effects via aggression was significant only in women. The serial mediation effect via low self-control and aggression between levels of IHPs and IGD features was significant in both genders (men, coefficient:0.009, 95%CI 0.005-0.019; women, coefficient:0.010, 95%CI:0.005-0.026)., Conclusion: We revealed a possible mechanism underlying a serial mediation chain from low self-control to aggression explaining the effects of IHPs on severity of IGD features. However, this conclusion should be taken with a caution, because the effect sizes were very low.

Objective: Persons with Huntington's disease (HD) often have communication difficulties and cognitive impairments, making mental health assessment difficult. Informants close to the patient are often included in assessments. The authors investigated effects of informant presence during assessment of persons with HD., Methods: Data for four subsamples from ENROLL-HD were examined: manifest for HD (N=4,109), premanifest (N=1,790), genotype negative (N=1,041), and family members with no genetic risk (N=974). Assessment interviews with and without an informant present were identified, and the subsamples were compared on three subscales of the short-form Problem Behaviors Assessment: affect, apathy, and irritability. Differences in scores between participant-only and informant-present interviews were examined via multiple regression, controlling for demographic, disease-related, and individual confounds., Results: Significant differences in apathy and irritability scores were found between participant-only and informant-present conditions for the premanifest, manifest, and genotype-negative subsamples. Affect subscale scores were not influenced by informant presence. When the analysis controlled for confounds, informant presence significantly increased irritability scores in the manifest, and genotype-negative groups and significantly increased apathy scores in the manifest group., Conclusions: Apathy may have been systemically underreported in participant-only interviews, which supports previous findings that persons with HD underreport mental health symptoms. When an informant was present, irritability scores were higher for both HD and non-HD individuals, suggesting that underreporting via self-report may be attributable to non-HD factors. Informant contributions to apathy assessments may be particularly important for persons with HD. Clinicians should note potential underreporting regarding irritability and affect, which was not remediated by informant presence.

Background: Over 80% of individuals suffering from Rett syndrome (RTT) are affected over their life period by sleeping disorders. Little is known about the impact of those on the quality of life and a clinical approach to the treatment of sleep disturbances is lacking., Aims: Primary aim was to assess sleep quality in children and adults. Secondary aim was to assess behavioral disorders and their relationship to sleep quality. The medication taken by the subjects was also included., Methods: Sleep quality and medication were assessed using the sleeping questionnaire for children with neurological and other complex diseases (SNAKE). Behavioral disorders were assessed by the Rett Syndrome Behavior Questionnaire (RSBQ). Questionnaires were sent to the 700 members of the Elternhilfe für Kinder mit Rett Syndrom in Deutschland e.V. (Rett Aid) of which 287 were included. Questionnaires were filled out by the primary caregivers., Results: Sleep quality was rated as very good to good by over 60% of caregivers in contrast to data available in the literature. Behavioral disorders related to regression such as loss of acquired hand skills ( p  = 0.046) and isolation ( p  = 0.002) were found to be associated with sleep quality. Melatonin showed a significant association ( p  = 0.007) with sleep quality., Conclusion: Our study showed sleep dysfunction to be less prevalent in RTT-affected individuals than evidence from past studies has suggested. Nevertheless, this remains a subjective assessment of sleep quality and therefore the need to find objective, disorder-specific parameters that measure sleep quality in RTT patients persists., Competing Interests: All authors reported no conflicts of interest concerning the manuscript., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The main purpose of this article is to demonstrate the co-occurrence of Axenfeld-Rieger anomaly and neuropsychiatric problems as clinical signs of genetically determined cerebral small vessel disease in two patients., Case Study: We report on two adolescent individuals with ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) presenting with neuropsychiatric symptoms. Both patients underwent cerebral magnetic resonance imaging showing white matter T2-hyperintensities involving different brain regions, suspective of cerebral small vessel disease. Genetic analysis revealed pathogenic mutations in the FOXC1 gene (patient 1) and the COL4A1 gene (patient 2), respectively., Conclusion: We report on the co-occurrence of ocular anterior segment dysgenesis (Axenfeld-Rieger anomaly) and neuropsychiatric symptoms as clinical signs of genetically determined cerebral small vessel disease in two patients. In both patients, the cerebral lesions involved the frontotemporal regions, brain regions that control social behavior as well as executive and cognitive function, highlighting the fact that neuropsychiatric symptoms may be early clinical presentations of cerebral small vessel disease. We further provide a review of monogenic causes of pediatric cerebral small vessel disease, emphasizing the links to childhood-onset neuropsychiatric disease., Competing Interests: Dr. Ziegler reports personal fees from Biogen, personal fees from Avexis, and personal fees from PTC, outside the submitted work., (Georg Thieme Verlag KG Stuttgart · New York.)