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Importance: The Coronavirus Disease (COVID-19) pandemic has significantly impacted mental health outcomes. While the frequency of anxiety and depressive symptoms has increased in the whole population, the relationship between COVID-19 and new psychiatric diagnoses remains unclear., Objective: To compare the population incidence rate of emergence of de novo psychiatric disorders in 2020 compared to the previous years, and to compare the incidence rate of new psychiatric disorder diagnoses between people with vs without COVID-19., Design, Setting, and Participants: This study utilized administrative claims data from the Clinformatics® Data Mart database, licensed from Optum®. The study is a cross-sectional analysis that compared the incidence rate of new psychiatric disorders in 2020 vs. 2018 and 2019 in the entire insured population database. Subsequently, the incidence of new psychiatric disorders in people with vs. without COVID-19 during 2020 was analyzed., Exposure: The exposures included diagnosis and severity of COVID-19 infection., Main Outcomes Measures: The dependent variables of interest were the incidence rates of new psychiatric disorders, specifically schizophrenia spectrum disorders, mood disorders, anxiety disorders, and obsessive-compulsive disorder., Results: The population studied included 10,463,672 US adults (mean age 52.83, 52% female) who were unique people for the year of 2020. Incidence of newly diagnosed psychiatric disorders per 1,000 individuals in the 2020 whole population were 28.81 (CI: 28.71, 28.92) for anxiety disorders, 1.04 (CI: 1.02, 1.06) for schizophrenia disorders, 0.42 (CI: 0.41, 0.43) for OCD and 28.85 (CI: 28.75, 28.95) for mood disorders. These rates were not significantly higher than 2018 or 2019. When comparing incidence rates between COVID-19 vs. non-COVID-19 populations in 2020, the rates were significantly higher in the COVID-19 population: 46.89 (CI: 46.24, 47.53) for anxiety, 49.31 (CI: 48.66, 49.97) for mood disorders, 0.57 (CI: 0.50, 0.65) for OCD, and 3.52 (CI: 3.34, 3.70) for schizophrenia. COVID-19 severity was significantly associated with new diagnoses of schizophrenia, anxiety and mood disorders in multivariate analyses., Conclusions: Compared to 2018 and 2019, in 2020 there was no increased incidence of new psychiatric disorders in the general population based on insurance claims data. Importantly, people with COVID-19 were more likely to be diagnosed with a new psychiatric disorder, most notably disorders with psychosis, indicating a potential association between COVID-19 and mental/brain health., Competing Interests: The authors have declared that no competing interests exist. Dr Soares reported receiving grants from Compass Pathways and Relmada; and personal fees from Boehringer Ingelheim, Merck, and Johnson & Johnson outside the submitted work.

Brazilian native fruits are a rich source of polyphenolic compounds that can act as anti-inflammatory and antioxidant agents. Here, we determined the polyphenolic composition, anti-inflammatory mechanism of action, antioxidant activity and systemic toxicity in Galleria mellonella larvae of Eugenia selloi B.D.Jacks. (synonym Eugenia neonitida Sobral) extract (Ese) and its polyphenol-rich fraction (F3) obtained through bioassay-guided fractionation. Phenolic compounds present in Ese and F3 were identified by LC-ESI-QTOF-MS. The anti-inflammatory activity of Ese and F3 was tested in vitro and in vivo through NF-κB activation, cytokine release and neutrophil migration assays. The samples were tested for their effects against reactive species (ROO•, O2•-, HOCl and NO•) and for their toxicity in Galleria mellonella larvae model. The presence of hydroxybenzoic acid, ellagitannins and flavonoids was identified. Ese and F3 reduced NF-κB activation, cytokine release and neutrophil migration, with F3 being three-fold more potent. Overall, F3 exhibited strong antioxidant effects against biologically relevant radicals, and neither Ese nor F3 were toxic to G. mellonella larvae. In conclusion, Ese and F3 revealed the presence of phenolic compounds that decreased the inflammatory parameters evaluated and inhibited reactive oxygen/nitrogen species. E. selloi is a novel source of bioactive compounds that may provide benefits for human health., Competing Interests: The authors have declared that no competing interests exist.

Background: Somatic complaints are often the presenting symptoms of major depressive disorder (MDD) in the outpatient context, because this may go unrecognized. It is well understood that MDD carries an increased risk of suicide. This study aimed to identify the risk factors and association with both MDD and suicidality among Han Chinese outpatients., Methods: A multicenter study was carried out in 5189 outpatient adults (≥18 years old) in four general hospitals in Guangzhou, China. The 1392 patients who had the Patient Health Questionnaire-9 (PHQ-9) score ≥ 5, indicating depressive symptoms were offered an interview with a psychiatrist by the Mini International Neuropsychiatric Interview (MINI); 819 patients consented and completed the MINI interview. MINI module B was used to assess suicidality. Stepwise binary logistic models were used to estimate the relationship between a significant risk factor and suicide or MDD. According to with or without MDD, the secondary analysis was performed using the logistic regression model for the risk of suicidility., Results: The current prevalence of MDD and the one month prevalence of suicidality were 3.7% and 2.3% respectively. The odds ratio of suicidality in women was more than twice that in men (OR = 2.62; 95% CI 1.45-4.76). Other risk factors which were significantly associated with suicidality were: living alone, higher education, self-reported depression, getting psychiatric diagnoses (MDD, anxiety disorders, and bipolar disorders). Significant risk factors for MDD were also noticed, such as comorbid anxiety disorders, self-reported anxiety, insomnia, suicidal ideation., Limitation: It's a cross-sectional study in outpatient clinics using self-report questionnaires., Conclusion: This study provides valuable data about the risk factors and association of MDD and suicide risk in adult outpatients in Han Chinese. Those factors allow better the employment of preventative measures.

Immune dysfunction has been implicated in the pathophysiology of schizophrenia. Leukocyte migration to the site of inflammation is a fundamental step of immune response which involves P-, E-, and L-selectins. Elevated selectin levels have been reported in un-medicated first-episode patients with schizophrenia but not in medicated patients with multi-episode schizophrenia. We measured fasting plasma soluble P-, E-, and L-selectin in 39 medicated patients with multi-episode schizophrenia and 19 healthy controls. In patients, psychotic symptom severity and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and the NIH Toolbox Cognitive Test Battery respectively. C-reactive protein (CRP) and Body Mass Index (BMI) were measured in patients and controls. Comparison of selectin levels between patients and controls was done with t-tests and linear regression. Pearson correlation coefficients between plasma selectins and PANSS and cognitive measures were calculated. Geometric mean plasma soluble L-selectin level was lower in patients compared to controls from unadjusted (606.7 ± 1.2 ng/ml vs. 937.7 ± 1.15 ng/ml, p < 0.001) and adjusted analyses (β = 0.59; CI 0.41 to 0.88, p = 0.011). There was a trend towards higher plasma soluble P-selectin in patients compared to controls (90.4 ± 1.2ng/ml vs. 71.8 ± 1.2ng/ml, p = 0.059) in the unadjusted analysis. There was no association between the selectins and psychotic symptoms or cognitive function in the patients. In addition, the selectins were not significantly associated with CRP or BMI. The limitations of this study include small sample size and unavailability of information on medications and blood cell counts. The potential utility of soluble L-selectin as a biomarker of antipsychotic exposure in patients with schizophrenia and the concomitant change in immune response with the use of antipsychotics should be further evaluated.

Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Aerobiology is a branch of biology that studies microorganisms passively transferred by the air. Bacteria, viruses, fungal spores, tiny insects, and pollen grains are samples of microorganisms. Pollen grains classification is essential in medicine, agronomy, economy, etc. It is performed traditionally (manually) and automatically. The automated approach is faster, more accurate, cost-effective, and with less human intervention than the manual method. In this paper, we introduce a Residual Cognitive Attention Network (RCANet) for the automated classification of pollen grains microscopic images. The suggested attention block, Ventral-Dorsal Ateetntion Block (VDAB), is designed based on the ventral (temporal) and dorsal (parietal) pathways of the occipital lobe. It is embedded in each Basic Block of the architecture of ResNet18. The VDAB is composed of ventral and dorsal attention blocks. The ventral and dorsal streams detect the structure and location of the pollen grain, respectively. According to the mentioned pathways, the Ventral Attention Block (VAB) extracts the channels related to the shape of the pollen grain, and the Dorsal Attention Block (DAB) is focused on its position. Three publicly pollen grains datasets including the Cretan Pollen Dataset (CPD), Pollen13K, and Pollen23E are employed for experiments. The ResNet18 and the proposed method (RCANet) are trained on the datasets and the proposed RCANet obtained higher performance metrics than the ResNet18 in the test step. It achieved weighted F1-score values of 98.69%, 97.83%, and 98.24% with CPD, Pollen13K, and Pollen23E datasets, respectively. [ABSTRACT FROM AUTHOR]

Proprioceptive impairments occur in approximately 50–64% of people following stroke. While much is known about the grey matter structures underlying proprioception, our understanding of the white matter correlates of proprioceptive impairments is less well developed. It is recognised that behavioural impairments post-stroke are often the result of disconnection between wide-scale brain networks, however the disconnectome associated with proprioception post-stroke is unknown. In the current study, white matter disconnection was assessed in relation to performance on a robotic arm position matching (APM) task. Neuroimaging and robotic assessments of proprioception were collected for 203 stroke survivors, approximately 2-weeks post-stroke. The robotic assessment was performed in a KINARM Exoskeleton robotic device and consisted of a nine-target APM task. First, the relationship between white matter tract lesion load and performance on the APM task was assessed. Next, differences in the disconnectome between participants with and without impairments on the APM task were examined. Greater lesion load to the superior longitudinal fasciculus (SLF II and III), arcuate fasciculus (all segments) and fronto-insular tracts were associated with worse APM task performance. In those with APM task impairments, there was, additionally, disconnection of the posterior corpus callosum, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus and optic radiations. This study highlights an important perisylvian white matter network supporting proprioceptive processing in the human brain. It also identifies white matter tracts, important for relaying proprioceptive information from parietal and frontal brain regions, that are not traditionally considered proprioceptive in nature. [ABSTRACT FROM AUTHOR]

Finding an interpretable and compact representation of complex neuroimaging data is extremely useful for understanding brain behavioral mapping and hence for explaining the biological underpinnings of mental disorders. However, hand-crafted representations, as well as linear transformations, may inadequately capture the considerable variability across individuals. Here, we implemented a data-driven approach using a three-dimensional autoencoder on two large-scale datasets. This approach provides a latent representation of high-dimensional task-fMRI data which can account for demographic characteristics whilst also being readily interpretable both in the latent space learned by the autoencoder and in the original voxel space. This was achieved by addressing a joint optimization problem that simultaneously reconstructs the data and predicts clinical or demographic variables. We then applied normative modeling to the latent variables to define summary statistics ('latent indices') and establish a multivariate mapping to non-imaging measures. Our model, trained with multi-task fMRI data from the Human Connectome Project (HCP) and UK biobank task-fMRI data, demonstrated high performance in age and sex predictions and successfully captured complex behavioral characteristics while preserving individual variability through a latent representation. Our model also performed competitively with respect to various baseline models including several variants of principal components analysis, independent components analysis and classical regions of interest, both in terms of reconstruction accuracy and strength of association with behavioral variables. [ABSTRACT FROM AUTHOR]

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD. [ABSTRACT FROM AUTHOR]

Advancements in brain imaging techniques have significantly expanded the size and complexity of real-time neuroimaging and behavioral data. However, identifying patterns, trends and synchronies within these datasets presents a significant computational challenge. Here, we demonstrate an approach that can translate time-varying neuroimaging data into unique audiovisualizations consisting of audible representations of dynamic data merged with simplified, color-coded movies of spatial components and behavioral recordings. Multiple variables can be encoded as different musical instruments, letting the observer differentiate and track multiple dynamic parameters in parallel. This representation enables intuitive assimilation of these datasets for behavioral correlates and spatiotemporal features such as patterns, rhythms and motifs that could be difficult to detect through conventional data interrogation methods. These audiovisual representations provide a novel perception of the organization and patterns of real-time activity in the brain, and offer an intuitive and compelling method for complex data visualization for a wider range of applications. [ABSTRACT FROM AUTHOR]

Introduction: Adult and pediatric patients admitted to intensive care units (ICUs) requiring invasive ventilatory support, sedation, and muscle blockade may present neuromusculoskeletal deterioration. Different physical rehabilitation interventions have been studied to evaluate their effectiveness in improving critically ill patients' outcomes. Given that many published systematic reviews (SRs) aims to determine the effectiveness of different types of physical rehabilitation interventions, it is necessary to group them systematically and assess the methodological quality of SRs to help clinicians make better evidence-based decisions. This overview of SRs (OoSRs) aims to map the existing evidence and to determine the effectiveness of physical rehabilitation interventions to improve neuromusculoskeletal function and other clinical outcomes in adult and pediatric critically ill patients. Methods: An OoSRs of randomized and non-randomized clinical trials involving critically ill adult and pediatric patients receiving physical rehabilitation intervention will be conducted. A sensitive search of MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Cochrane Library, Epistemonikos, and other search resources will be conducted. Two independent reviewers will conduct study selection, data extraction, and methodological quality assessment. Discrepancies will be resolved by consensus or a third reviewer. The degree of overlap of studies will be calculated using the corrected covered area. The methodological quality of the SRs will be measured using the AMSTAR-2 tool. The GRADE framework will report the certainty of evidence by selecting the "best" SR for each physical rehabilitation intervention and outcome. Discussion: The findings of this overview are expected to determine the effectiveness and safety of physical rehabilitation interventions to improve neuromusculoskeletal function in adult and pediatric critically ill patients based on a wide selection of the best available evidence and to determine the knowledge gaps in this topic by mapping and assessing the methodological quality of published SRs. Registration number: CRD42023389672. [ABSTRACT FROM AUTHOR]

The caudate nucleus has been thought to be involved in the control of motor commands by the cerebrum, and recent studies suggest that it may play a role in the control of attachment behavior, cognition, emotion, and mental functions. Implied by the basal ganglia's involvement in the execution, planning and control of movement, the caudate nucleus functions in a situation-dependent manner where processing of external stimuli is important on the basis of learning and memory. Sensory processing, which determines the response to external stimuli, has been shown to be related to various brain regions but it remains unknown how sensory processing is associated with the structure of the caudate nucleus and white matter microstructures of the caudate. Using four diffusion parameters derived from diffusion tensor imaging (DTI) (i.e., fractional anisotropy (FA), mean diffusivity (MD), axonal diffusivity (AD), and radial diffusivity (RD)) and the Adolescent/Adult Sensory Profile (AASP) questionnaire of 99 healthy subjects [42 males and 57 females; mean age:26.9 years, standard deviation 6.9], we investigated the relationship between white matter structure in the caudate nucleus and sensory processing. In consistent with what had been suggested by the results of previous studies, we found significant correlations between AD, MD and tactile sensation. Furthermore, we found a significant correlation between AD, MD and tactile sensory avoidance, the AASP sub-scores regarding the tactile senses. To the best of our knowledge, this is the first study to show that DTI diffusion parameters correlate with AASP scores in specific brain regions. [ABSTRACT FROM AUTHOR]

Being a close family or friend of someone with bipolar disorder (BD) can lead to experiences of increased stress, anxiety and depressive symptoms related to the burden of caring. However, the lived experience of being a carer for a person with BD has not received significant research attention. This study aimed to gain further insight into the experiences of individuals in an informal caring role for someone with BD and determine what additional information and support these people need to take care of both themselves and the person they are caring for. Fifteen qualitative interviews were carried out with carers discussing their lived experiences with utilising coping strategies and supporting someone with BD. Following the interviews, thematic analysis was used to identify five key themes. These themes were: Separation of the person and the disorder, carer health and coping strategies, unpredictability and variability of symptoms, carer disillusionment and silencing, and story sharing and support needs. Overall, the findings highlighted the need for increased in-person and online support specifically tailored for carers with loved ones experiencing BD. [ABSTRACT FROM AUTHOR]

Bipolar Disorder (BD) has recently been related to a process of accelerated aging, with shortened leukocyte telomere length (LTL) in this population. It has also been observed that the suicide rate in BD patients is higher than in the general population, and more recently the telomere length variation has been described as shorter in suicide completers compared with control subjects. Objectives The aim of the present study was to investigate if there is an association between LTL and BD in families where two or more members have BD including clinical symptomatology variables, along with suicide behavior. Methods Telomere length and single copy gene ratio (T/S ratio) was measured using quantitative polymerase chain reaction in a sample of 143 relatives from 22 families, of which 60 had BD. The statistical analysis was performed with a polygenic mixed model. Results LTL was associated with suicidal ideation (p = 0.02) as that there is an interaction between suicidal ideation and course of the disorder (p = 0.02). The estimated heritability for LTL in these families was 0.68. In addition, covariates that relate to severity of disease, i.e. suicidal ideation and course of the disorder, showed an association with shorter LTL in BD patients. No difference in LTL between BD patients and healthy relatives was observed. Conclusion LTL are shorter in subjects with familial BD suggesting that stress related sub-phenotypes possibly accelerate the process of cellular aging and correlate with disease severity and suicidal ideation. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a complex mental health condition that results in several obstacles including disabilities, loss of productivity, and economic burdens on both patients and society. Etiopathogenesis of MDD involves several factors such as sociodemographic, genetic, and biological determinants. However, any suitable biomarkers for risk assessment of depression have not been established yet. Alterations of cytokine are assumed to be involved in the pathophysiology and severity of the depressive disorder. Therefore, we aimed to evaluate serum adiponectin and interleukin-8 (IL-8) among MDD patients in Bangladesh. Methods: We recruited a total of 63 MDD patients and 94 age-sex matched healthy controls (HCs) in the present study. MDD patients were enrolled from a tertiary care teaching hospital, Dhaka, Bangladesh, and HCs from surrounding parts of Dhaka city. A psychiatrist assessed all the study participants following the criteria mentioned in the DSM-5. We applied the Hamilton depression (Ham-D) rating scale to assess the depression severity. Serum adiponectin and IL-8 levels were determined using ELISA kits (BosterBio, USA). Results: The mean serum concentration of adiponectin was decreased (30.67±4.43 μg/mL vs. 53.81±5.37 μg/mL), and the IL-8 level was increased (160.93±14.84 pg/mL vs. 88.68±6.33 pg/mL) in MDD patients compared to HCs. Sex-specific scatters plot graphs showed the distribution of adiponectin and IL-8 levels with Ham-D scores in MDD patients. Also, ROC curve analysis demonstrated good predictive performances of serum adiponectin and IL-8 for MDD with the area under the curve (AUC) as 0.895 and 0.806, respectively. Conclusion: The present study findings suggest that alterations of serum adiponectin and IL-8 levels in MDD patients might be involved in the disease process. Therefore, we can use these changes of cytokines in serum levels as early risk assessment tools for depression. The present study findings should be considered preliminary. We propose further interventional studies to evaluate the exact role of adiponectin and IL-8 in depression. [ABSTRACT FROM AUTHOR]

Obesity can result from excess intake in response to environmental food cues, and stress can drive greater intake and body weight. We used a novel fMRI task to explore how obesity and stress influenced appetitive responses to relatively minimal food cues (words representing food items, presented similarly to a chalkboard menu). Twenty-nine adults (16F, 13M), 17 of whom had obesity and 12 of whom were lean, completed two fMRI scans, one following a combined social and physiological stressor and the other following a control task. A food word reactivity task assessed subjective food approach (wanting) as well as food avoidant (restraint) responses, along with neural responses, to words denoting high energy-density (ED) foods, low-ED foods, and non-foods. A multi-item ad-libitum meal followed each scan. The obese and lean groups demonstrated differences as well as similarities in activation of appetitive and attention/self-regulation systems in response to food vs. non-food, and to high-ED vs. low-ED food words. Patterns of activation were largely similar across stress and non-stress conditions, with some evidence for differences between conditions within both obese and lean groups. The obese group ate more than the lean group in both conditions. Our results suggest that neural responses to minimal food cues in stressed and non-stressed states may contribute to excess consumption and adiposity. [ABSTRACT FROM AUTHOR]

Early mobilization, which includes active / passive motion in bed along with mobilization out of bed, is recommended to prevent the development of intensive care unit acquired-weakness (ICU-AW) for patients with critical illness on the intensive care unit. To date, the impact of passive motion of the lower extremities in sedated and ventilated patients remains unclear. The aim of the study is to systematically review and summarize the currently available randomized controlled trials in English or German language on the impact of passive motion of the lower extremities in sedated and ventilated patients ≥ 18 years in the intensive care unit on musculature, inflammation and immune system and the development of intensive care unit-acquired weakness and to evaluate the replicability of interventions and the methodological quality of included studies. A systematic literature search was performed up to 20th February 2022 in the databases Medline, Embase, Cochrane Library, CINAHL and PEDro. The description of the intervention (TIDieR checklist) and the methodological quality (Downs and Black checklist) were assessed. Five studies were included in the qualitative syntheses. On average, the studies were rated with 6.8 out of 12 points according to the TIDieR checklist. For the methodological quality an average of 19.8 out of 27 points on the Downs and Black checklist was reported. The results of included studies indicated that muscle loss may be reduced by passive manual movement, passive cycling and passive motion on a continuous passive motion-unit. In addition, positive effects were reported on the reduction of nitrosative stress and the immune response. The impact on the development of ICU-AW remains unclear. In conclusion, passive movement show a slight tendency for beneficial changes on cellular level in sedated and ventilated patients in the ICU within the first days of admission, which may indicate a reduction of muscle wasting and could prevent the development of ICU-AW. Future randomized controlled trials should use larger samples, use complete intervention description, use a comparable set of outcome measures, use rigorous methodology and examine the effect of passive motion on the development of ICU-AW. [ABSTRACT FROM AUTHOR]

Eastern cottonwood (Populus deltoides W. Bartram ex Marshall) and hybrid poplars are well-known bioenergy crops. With advances in tree breeding, it is increasingly necessary to find economical ways to identify high-performing Populus genotypes that can be planted under different environmental conditions. Photosynthesis and leaf nitrogen content are critical parameters for plant growth, however, measuring them is an expensive and time-consuming process. Instead, these parameters can be quickly estimated from hyperspectral leaf reflectance if robust statistical models can be developed. To this end, we measured photosynthetic capacity parameters (Rubisco-limited carboxylation rate (Vcmax), electron transport-limited carboxylation rate (Jmax), and triose phosphate utilization-limited carboxylation rate (TPU)), nitrogen per unit leaf area (Narea), and leaf reflectance of seven taxa and 62 genotypes of Populus from two study plantations in Mississippi. For statistical modeling, we used least absolute shrinkage and selection operator (LASSO) and principal component analysis (PCA). Our results showed that the predictive ability of LASSO and PCA models was comparable, except for Narea in which LASSO was superior. In terms of model interpretability, LASSO outperformed PCA because the LASSO models needed 2 to 4 spectral reflectance wavelengths to estimate parameters. The LASSO models used reflectance values at 758 and 935 nm for estimating Vcmax (R2 = 0.51 and RMSPE = 31%) and Jmax (R2 = 0.54 and RMSPE = 32%); 687, 746, and 757 nm for estimating TPU (R2 = 0.56 and RMSPE = 31%); and 304, 712, 921, and 1021 nm for estimating Narea (R2 = 0.29 and RMSPE = 21%). The PCA model also identified 935 nm as a significant wavelength for estimating Vcmax and Jmax. Therefore, our results suggest that hyperspectral leaf reflectance modeling can be used as a cost-effective means for field phenotyping and rapid screening of Populus genotypes because of its capacity to estimate these physicochemical parameters. [ABSTRACT FROM AUTHOR]

Hormonal fluctuations, such as the perinatal period, may increase susceptibility of women to depression, which in turn exert a negative impact on child's neurodevelopment, becoming a risk factor in development of neuropsychiatric disorders. Moreover, the use of antidepressants during this critical period presents a serious health concern for both the mother and the child, due to the consequences of treatment in terms of the reliability and safety for the proper neurodevelopment of the organism being not well known. Atypical antidepressants, such as mirtazapine, that targets both serotonergic and noradrenergic systems in the central nervous system (CNS), represent a novel focus of research due to its unique pharmacological profile. The aim of this work was to study the effects of maternal depression and/or perinatal antidepressant mirtazapine treatment on the neurobehavioral development of the offspring. Pre-gestationally chronically stressed or non-stressed Wistar rat dams were treated with either mirtazapine (10 mg/kg/day) or vehicle during pregnancy and lactation followed by analysis of offspring's behavior at juvenile and adolescent age. We found mirtazapine induced significant alterations of nursing behavior. In offspring, pregestational stress (PS) had an anxiogenic effect on adolescent males (p≤0.05) and increased their active behavior in forced swim test (p≤0.01). Interaction between pregestational stress and mirtazapine treatment variously induced anxiolytic changes of juvenile (p≤0.05) and adolescent (p≤0.05) females and impairment of spatial memory (p≤0.01) in adolescent females as well. Hippocampal density of synaptophysin, pre-synaptic protein marker, was decreased mainly by mirtazapine treatment. In conclusion, our results show mirtazapine induced significant alterations in maternal behavior and several sex- and age-dependent changes in neurobehavioral development of offspring caused by both prenatal mirtazapine treatment and/or chronic pregestational stress. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder is a mental illness in which manic and depressive states are repeated, causing psychosocial dysfunction. Manic/hypomanic episodes cause problems with interpersonal, social and financial activities, but there is limited evidence regarding the predictors of manic/hypomanic episodes in real-world clinical practice. Methods: The multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was administered in an observational study that was conducted to accumulate evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked to complete a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics by conducting a retrospective medical record survey. Our study extracted baseline patient characteristics from September to October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. We investigated the presence or absence of manic/hypomanic episodes over the course of one year from baseline to September-October 2017. Results: In total, 2231 participants were included in our study, 29.1% of whom had manic/hypomanic episodes over the course of one year from baseline. Binomial logistic regression analysis revealed that the presence of manic/hypomanic episodes was correlated with lower baseline GAF scores, rapid cycling, personality disorder, bipolar I disorder, and a mood state with manic or mixed features. Substance abuse was also a risk factor for manic episodes. There was no significant association between a baseline antidepressant prescription and manic/hypomanic episodes. Conclusions: In Japan, 29.1% of outpatients with bipolar disorder had manic/hypomanic episodes over the course of one year. Our study suggested that a low GAF score, rapid cycling, personality disorder, bipolar I disorder, substance abuse, and baseline mood state could be predictors of manic/hypomanic episodes. Based on our findings, an antidepressant prescription is not a predictor of manic/hypomanic episodes. [ABSTRACT FROM AUTHOR]

The Apicomplexa protozoan Toxoplasma gondii is a mandatory intracellular parasite and the causative agent of toxoplasmosis. This illness is of medical importance due to its high prevalence worldwide and may cause neurological alterations in immunocompromised persons. In chronically infected immunocompetent individuals, this parasite forms tissue cysts mainly in the brain. In addition, T. gondii infection has been related to mental illnesses such as schizophrenia, bipolar disorder, depression, obsessive-compulsive disorder, as well as mood, personality, and other behavioral changes. In the present study, we evaluated the kinetics of behavioral alterations in a model of chronic infection, assessing anxiety, depression and exploratory behavior, and their relationship with neuroinflammation and parasite cysts in brain tissue areas, blood-brain-barrier (BBB) integrity, and cytokine status in the brain and serum. Adult female C57BL/6 mice were infected by gavage with 5 cysts of the ME-49 type II T. gondii strain, and analyzed as independent groups at 30, 60 and 90 days postinfection (dpi). Anxiety, depressive-like behavior, and hyperactivity were detected in the early (30 dpi) and long-term (60 and 90 dpi) chronic T. gondii infection, in a direct association with the presence of parasite cysts and neuroinflammation, independently of the brain tissue areas, and linked to BBB disruption. These behavioral alterations paralleled the upregulation of expression of tumor necrosis factor (TNF) and CC-chemokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β and CCL5/RANTES) in the brain tissue. In addition, increased levels of interferon-gamma (IFNγ), TNF and CCL2/MCP-1 were detected in the peripheral blood, at 30 and 60 dpi. Our data suggest that the persistence of parasite cysts induces sustained neuroinflammation, and BBB disruption, thus allowing leakage of cytokines of circulating plasma into the brain tissue. Therefore, all these factors may contribute to behavioral changes (anxiety, depressive-like behavior, and hyperactivity) in chronic T. gondii infection. [ABSTRACT FROM AUTHOR]

Background: Patients admitted to intensive care units (ICU) are at an increased risk of developing immobility related complications. Physiotherapists are challenged to employ preventive and rehabilitative strategies to combat these effects. Passive limb range of motion (PROM) exercises- a part of early mobilization-aid in maintaining joint range of motion and functional muscle strength and forms a part of treatment for patients in ICU. However, there is a lack of evidence on practice of PROM exercises on patients admitted to ICU in the United Arab Emirates (UAE). This study aimed at exploring practices regarding the same in UAE. Methods: This survey, conducted from January 2021 to February 2021 in College of Physiotherapy, Sharjah University studied practice of physiotherapists in the intensive care units. Physiotherapists currently working in ICU completed an online questionnaire composed of forty-two questions about physiotherapy service provision, assessment and intervention in the intensive care units. Results: 33 physiotherapists completed the survey. 66.6% of respondents routinely assessed PROM for all the patients in ICU referred for physiotherapy. 84.8% of them assessed all the joints. More than half of the respondents (57.8%) reported that they administered PROM regularly to all the patients. According to 63.6% respondents, maintaining joint range of motion was the main reason for performing PROM. Responses pertaining to sets and repetitions of PROM were variable ranging from 1–6 sets and from 3 to 30 repetitions. Personal experience, resources/financial consideration and research findings were found to have influence on the practice. Conclusions: PROM was found to be one of the frequently used mobilization techniques administered by physiotherapists in the intensive care units and was mostly performed after assessment. Maintaining joint range of motion was the main aim for performing PROM. Variability was found in the sets and repetitions of PROM administered. Various factors influenced the practice of PROM. [ABSTRACT FROM AUTHOR]

The serial feature-positive discrimination task requires the subjects to respond differentially to the identical stimulus depending on the temporal context given by a preceding cue stimulus. In the present study, we examined the involvement of the M1 muscarinic acetylcholine receptors using a selective M1 antagonist VU0255035 in the serial feature-positive discrimination task of eyeblink conditioning in mice. In this task, mice received a 2-s light stimulus as the conditional cue 5 or 6 s before the presentation of a 350-ms tone conditioned stimulus (CS) paired with a 100-ms peri-orbital electrical shock (cued trials), while they did not receive the cue before the presentation of the CS alone (non-cued trials). Each day mice randomly received 30 cued and 30 non-cued trials. We found that VU0255035 impaired acquisition of the conditional discrimination as well as the overall acquisition of the conditioned response (CR) and diminished the difference in onset latency of the CR between the cued and non-cued trials. VU0255035 administration to the control mice after sufficient learning did not impair the pre-acquired conditional discrimination or the CR expression itself. These effects of VU0255035 were almost similar to those with the scopolamine in our previous study, suggesting that among the several types of muscarinic acetylcholine receptors, the M1 receptors may play an important role in the acquisition of the conditional discrimination memory but not in mediating the discrimination itself after the memory had formed in the eyeblink serial feature-positive discrimination learning. [ABSTRACT FROM AUTHOR]

Objective: To identify abnormalities of regional cerebral blood flow (rCBF) in individuals with obsessive-compulsive disorder (OCD) by conducting a voxel-based analysis of pseudo-continuous arterial spin labeling (pCASL) perfusion images. Materials and methods: This prospective study included 23 OCD patients (nine males, 14 females; age 21–62 years; mean ± SD 37.2 ± 10.7 years) diagnosed based on DSM-IV-TR criteria and 64 healthy controls (27 males, 37 females; age 20–64 years; mean ± SD 38.3 ± 12.8 years). Subjects were recruited from October 2011 to August 2017. Imaging was performed on a 3T scanner. Quantitative rCBF maps generated from pCASL images were co-registered and resliced with the three-dimensional T1-weighted images, and then spatially normalized to a brain template and smoothed. We used statistical nonparametric mapping to assess the differences in rCBF and gray matter volume between the OCD and control groups. The significance level was set at the p-value <0.05 with family-wise error rate correction for multiple comparisons. Results: Compared to the control group, there were significant rCBF reductions in the right putamen, right frontal operculum, left midcingulate cortex, and right temporal pole in the OCD group. There were no significant between-group differences in the gray matter volume. Conclusion: The pCASL imaging noninvasively detected physiologically disrupted areas without structural abnormalities in OCD patients. The rCBF reductions observed in these regions in OCD patients could be associated with the pathophysiology of OCD. [ABSTRACT FROM AUTHOR]

Aims: Smaller hippocampal volumes are among the most consistently reported neuroimaging findings in schizophrenia. However, little is known about hippocampal volumes in people who report psychotic experiences. This study investigated differences in hippocampal volume between young people without formal diagnoses who report psychotic experiences (PEs) and those who do not report such experiences. This study also investigated if any differences persisted over two years. Methods: A nested case-control study of 25 adolescents (mean age 13.5 years) with reported PEs and 25 matched controls (mean age 13.36 years) without PEs were drawn from a sample of 100 local schoolchildren. High-resolution T1-weighted anatomical imaging and subsequent automated cortical segmentation (Freesurfer 6.0) was undertaken to determine total hippocampal volumes. Comprehensive semi-structured clinical interviews were also performed including information on PEs, mental diagnoses and early life stress (bullying). Participants were invited for a second scan at two years. Results: 19 adolescents with PEs and 19 controls completed both scans. Hippocampal volumes were bilaterally lower in the PE group compared to the controls with moderate effects sizes both at baseline [left hippocampus p = 0.024 d = 0.736, right hippocampus p = 0.018, d = 0.738] and at 2 year follow up [left hippocampus p = 0.027 d = 0.702, right = 0.048 d = 0.659] throughout. These differences survived adjustment for co-morbid mental disorders and early life stress. Conclusions: Psychotic experiences are associated with total hippocampal volume loss in young people and this volume loss appears to be independent of possible confounders such as co-morbid disorders and early life stress. [ABSTRACT FROM AUTHOR]

The metal hyperaccumulator Azolla filiculoides is accompanied by a microbiome potentially supporting plant during exposition to heavy metals. We hypothesized that the microbiome exposition to selected heavy metals will reveal metal tolerant strains. We used Next Generation Sequencing technique to identify possible metal tolerant strains isolated from the metal-treated plant (Pb, Cd, Cr(VI), Ni, Au, Ag). The main dominants were Cyanobacteria and Proteobacteria constituting together more than 97% of all reads. Metal treatment led to changes in the composition of the microbiome and showed significantly higher richness in the Pb-, Cd- and Cr-treated plant in comparison with other (95–105 versus 36–44). In these treatments the share of subdominant Actinobacteria (0.4–0.8%), Firmicutes (0.5–0.9%) and Bacteroidetes (0.2–0.9%) were higher than in non-treated plant (respectively: 0.02, 0.2 and 0.001%) and Ni-, Au- and Ag-treatments (respectively: <0.4%, <0.2% and up to 0.2%). The exception was Au-treatment displaying the abundance 1.86% of Bacteroidetes. In addition, possible metal tolerant genera, namely: Acinetobacter, Asticcacaulis, Anabaena, Bacillus, Brevundimonas, Burkholderia, Dyella, Methyloversatilis, Rhizobium and Staphylococcus, which form the core microbiome, were recognized by combining their abundance in all samples with literature data. Additionally, the presence of known metal tolerant genera was confirmed: Mucilaginibacter, Pseudomonas, Mycobacterium, Corynebacterium, Stenotrophomonas, Clostridium, Micrococcus, Achromobacter, Geobacter, Flavobacterium, Arthrobacter and Delftia. We have evidenced that A. filiculoides possess a microbiome whose representatives belong to metal-resistant species which makes the fern the source of biotechnologically useful microorganisms for remediation processes. [ABSTRACT FROM AUTHOR]

Objective: To identify the differences between persons with schizophrenia (PWS) and general population in France in terms of oral health treatment (tooth scaling, dental treatment and tooth extraction) and the factors associated with these differences. Methods: This retrospective cohort study included PWS identified from a representative sample of 1/97th of the French population (general sample of beneficiaries). PWS were identified from 2014 data by an algorithm that included: F2 diagnostic codes in the register of long-term diseases in 2014 AND {(at least three deliveries of antipsychotics in 2014) OR (F20 diagnostic codes as a main or associated diagnosis in hospital discharge abstracts in 2012 or 2013 (hospital data for medicine, surgery and obstetrics)}. Follow-up dental care was explored for all people over a period of 3 years (2014 to 2017). Results: In 2014, 580,219 persons older than 15 years were identified from the 96 metropolitan departments in France; 2,213 were PWS (0.4%). Fewer PWS were found along a diagonal line from north-east to south-west France, and the highest numbers were located in urban departments. PWS were more often male (58.6% vs 48.7%, p<0.001). They were less likely to have had tooth scaling but more likely to have undergone a dental extraction. In one third of departments, more than 50% of PWS had at least one tooth scaling over a three-year period; the rate of dental extraction in these departments ranged from 6 to 23%. Then, a quarter of the departments in which 40 to 100% of PWS had had at least one dental extraction (2/8) presented a rate of tooth scaling ranging from 0 to 28% over the study period. Conclusions: Compared with the general population, PWS were less likely to have had tooth scaling and dental treatment but more likely to have undergone dental extraction. [ABSTRACT FROM AUTHOR]

A recently developed risk calculator for bipolar disorder (BD) accounts for clinical and parental psychopathology. Yet, it is understood that both familial predisposition and early life adversity contribute to the development of BD. How the interplay between these two factors influence emotion and reward processing networks in youth at risk for BD remains unclear. In this exploratory analysis, offspring of BD parents performed emotion and reward processing tasks while undergoing a fMRI scan. Risk calculator score was used to assess risk for developing BD in the next 5 years. Environmental risk was tabulated using the Stressful Life Events Schedule (SLES). Emotion and reward processing networks were investigated for genetic and/or environment interactions. Interaction effects were found between risk calculator scores, negative SLES score and activity in right amygdala and bilateral fusiform gyri during the emotion processing task, as well as activity in the fronto-, striatal, and parietal regions during the reward processing task. Our findings are preliminary; however, they support the unique and interactive contributions of both familial and environmental risk factors on emotion and reward processing within OBP. They also identify potential neural targets to guide development of interventions for youth at greatest risk for psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Physical therapy can prevent functional impairments and improve the quality of life of patients after hospital discharge. However, the effect of early mobilization on patients with a critical illness remains unclear. This study was performed to assess the evidence available regarding the effect of early mobilization on critically ill patients in the intensive care unit (ICU). Methods: Electronic databases were searched from their inception to March 21, 2019. Randomized controlled trials (RCTs) comprising critically ill patients who received early mobilization were included. The methodological quality and risk of bias of each eligible trial were assessed using the Cochrane Collaboration tool. Data were extracted using a standard collection form each included study, and processed using the Mantel-Haenszel (M-H) or inverse-variance (I-V) test in the STATA v12.0 statistical software. Results: A total of 1,898 records were screened. Twenty-three RCTs comprising 2,308 critically ill patients were ultimately included. Early mobilization decreased the incidence of ICU-acquired weakness (ICU-AW) at hospital discharge (three studies, 190 patients, relative risk (RR): 0.60, 95% confidence interval (CI) [0.40, 0.90]; p = 0.013, I2 = 0.0%), increased the number of patients who were able to stand (one study, 50 patients, 90% vs. 62%, p = 0.02), increased the number of ventilator-free days (six studies, 745 patients, standardized mean difference (SMD): 0.17, 95% CI [0.02, 0.31]; p = 0.023, I2 = 35.5%) during hospitalization, increased the distance the patient was able to walk unassisted (one study, 104 patients, 33.4 (0–91.4) meters vs. 0 (0–30.4) meters, p = 0.004) at hospital discharge, and increased the discharged-to-home rate (seven studies, 793 patients, RR: 1.16, 95% CI [1.00, 1.34]; p = 0.046). The mortality (28-day, ICU and hospital) and adverse event rates were moderately increased by early mobilization, but the differences were statistically non-significant. However, due to the substantial heterogeneity among the included studies, and the low quality of the evidence, the results of this study should be interpreted with caution. Publication bias was not identified. Conclusions: Early mobilization appears to decrease the incidence of ICU-AW, improve the functional capacity, and increase the number of ventilator-free days and the discharged-to-home rate for patients with a critical illness in the ICU setting. [ABSTRACT FROM AUTHOR]

Introduction: Identifying modifiable risk factors for Alzheimer’s disease (AD) is critical for research. Data mining may be a useful tool for finding new AD associated factors. Methods: We included all patients over 49 years of age, hospitalized in France in 2008 (without dementia) and in 2014. Dependent variable was AD or AD dementia diagnosis in 2014. We recoded the diagnoses of hospital stays (in ICD-10) into 137 explanatory variables.To avoid overweighting the "age" variable, we divided the population into 7 sub-populations of 5 years. Results: We analyzed 1,390,307 patients in the PMSI in 2008 and 2014: 55,997 patients had coding for AD or AD dementia in 2014 (4.04%). We associated Alzheimer disease in 2014 with about 20 variables including male sex, stroke, diabetes mellitus, mental retardation, bipolar disorder, intoxication, Parkinson disease, depression, anxiety disorders, alcohol, undernutrition, fall and 3 less explored variables: intracranial hypertension (odd radio [95% confidence interval]: 1.16 [1.12–1.20] in 70–80 years group), psychotic disorder (OR: 1.09 [1.07–1.11] in 70–75 years group) and epilepsy (OR: 1.06 [1.05–1.07] after 70 years). Discussion: We analyzed 137 variables in the PMSI identified some well-known risk factors for AD, and highlighted a possible association with intracranial hypertension, which merits further investigation. Better knowledge of associations could lead to better targeting (identifying) at-risk patients, and better prevention of AD, in order to reduce its impact. [ABSTRACT FROM AUTHOR]

Cortical thickness and gyrification abnormalities in anorexia nervosa (AN) have been recently described, but no attempt has been made to explore their organizational patterns to characterize the neurobiology of the disorder in the different stages of its course. The aim of this study was to explore cortical thickness and gyrification patterns by means of graph theory tools in 38 patients with AN, 20 fully recovered patients, and 38 healthy women (HC). All participants underwent high-resolution magnetic resonance imaging. Connectome properties were compared between: 1) AN patients and HC, 2) fully recovered patients and HC, 3) patients with a full remission at a 3-year follow-up assessment and patients who had not recovered. Small-worldness was greater in patients with acute AN in comparison to HC in both cortical thickness and gyrification networks. In the cortical thickness network, patients with AN also showed increased Local Efficiency, Modularity and Clustering coefficients, whereas integration measures were lower in the same group. Patients with a poor outcome showed higher segregation measures and lower small-worldness in the gyrification network, but no differences emerged for the cortical thickness network. For both cortical thickness and gyrification patterns, regional analyses revealed differences between patients with different outcomes. Different patterns between cortical thickness and gyrification networks are probably due to their peculiar developmental trajectories and sensitivity to environmental influences. The role of gyrification network alterations in predicting the outcome suggests a role of early maturational processes in the prognosis of AN. [ABSTRACT FROM AUTHOR]

Background: The mechanisms underlying autism spectrum disorder (ASD) remain unclear, and clinical biomarkers are not yet available for ASD. Differences in dysregulated proteins in ASD have shown little reproducibility, which is partly due to ASD heterogeneity. Recent studies have demonstrated that subgrouping ASD cases based on clinical phenotypes is useful for identifying candidate genes that are dysregulated in ASD subgroups. However, this strategy has not been employed in proteome profiling analyses to identify ASD biomarker proteins for specific subgroups. Methods: We therefore conducted a cluster analysis of the Autism Diagnostic Interview-Revised (ADI-R) scores from 85 individuals with ASD to predict subgroups and subsequently identified dysregulated genes by reanalyzing the transcriptome profiles of individuals with ASD and unaffected individuals. Proteome profiling of lymphoblastoid cell lines from these individuals was performed via 2D-gel electrophoresis, and then mass spectrometry. Disrupted proteins were identified and compared to the dysregulated transcripts and reported dysregulated proteins from previous proteome studies. Biological functions were predicted using the Ingenuity Pathway Analysis (IPA) program. Selected proteins were also analyzed by Western blotting. Results: The cluster analysis of ADI-R data revealed four ASD subgroups, including ASD with severe language impairment, and transcriptome profiling identified dysregulated genes in each subgroup. Screening via proteome analysis revealed 82 altered proteins in the ASD subgroup with severe language impairment. Eighteen of these proteins were further identified by nano-LC-MS/MS. Among these proteins, fourteen were predicted by IPA to be associated with neurological functions and inflammation. Among these proteins, diazepam-binding inhibitor (DBI) protein was confirmed by Western blot analysis to be expressed at significantly decreased levels in the ASD subgroup with severe language impairment, and the DBI expression levels were correlated with the scores of several ADI-R items. Conclusions: By subgrouping individuals with ASD based on clinical phenotypes, and then performing an integrated transcriptome-proteome analysis, we identified DBI as a novel candidate protein for ASD with severe language impairment. The mechanisms of this protein and its potential use as an ASD biomarker warrant further study. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) is essential for timely treatment. Machine learning and multivariate pattern analysis (MVPA) for the diagnosis of brain disorders are explicitly attracting attention in the neuroimaging community. In this paper, we propose a voxel-wise discriminative framework applied to multi-measure resting-state fMRI (rs-fMRI) that integrates hybrid MVPA and extreme learning machine (ELM) for the automated discrimination of AD and MCI from the cognitive normal (CN) state. Materials and methods: We used two rs-fMRI cohorts: the public Alzheimer’s disease Neuroimaging Initiative database (ADNI2) and an in-house Alzheimer’s disease cohort from South Korea, both including individuals with AD, MCI, and normal controls. After extracting three-dimensional (3-D) patterns measuring regional coherence and functional connectivity during the resting state, we performed univariate statistical t-tests to generate a 3-D mask that retained only voxels showing significant changes. Given the initial univariate features, to enhance discriminative patterns, we implemented MVPA feature reduction using support vector machine-recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO), in combination with the univariate t-test. Classifications were performed by an ELM, and its efficiency was compared to linear and nonlinear (radial basis function) SVMs. Results: The maximal accuracies achieved by the method in the ADNI2 cohort were 98.86% (p<0.001) and 98.57% (p<0.001) for AD and MCI vs. CN, respectively. In the in-house cohort, the same accuracies were 98.70% (p<0.001) and 94.16% (p<0.001). Conclusion: From a clinical perspective, combining extreme learning machine and hybrid MVPA applied on concatenations of multiple rs-fMRI biomarkers can potentially assist the clinicians in AD and MCI diagnosis. [ABSTRACT FROM AUTHOR]

Functional connectivity (FC) characterizes brain activity from a multivariate set of N brain signals by means of an NxN matrix A, whose elements estimate the dependence within each possible pair of signals. Such matrix can be used as a feature vector for (un)supervised subject classification. Yet if N is large, A is highly dimensional. Little is known on the effect that different strategies to reduce its dimensionality may have on its classification ability. Here, we apply different machine learning algorithms to classify 33 children (age [6-14 years]) into two groups (healthy controls and Attention Deficit Hyperactivity Disorder patients) using EEG FC patterns obtained from two phase synchronisation indices. We found that the classification is highly successful (around 95%) if the whole matrix A is taken into account, and the relevant features are selected using machine learning methods. However, if FC algorithms are applied instead to transform A into a lower dimensionality matrix, the classification rate drops to less than 80%. We conclude that, for the purpose of pattern classification, the relevant features should be selected among the elements of A by using appropriate machine learning algorithms. [ABSTRACT FROM AUTHOR]

Background: Brain-derived neurotrophic factor (BDNF) is widely expressed in the brain and plays an important role in neuronal maintenance, plasticity, and neurogenesis. Prior studies have found that decreased serum BDNF levels are associated with perceived stress, depression, or sleep disturbances in humans. Study objectives: To elucidate whether the serum BDNF levels and BDNF genotype were associated with the sleep pattern in healthy young adults. Methods: The study group consisted of 79 healthy paid volunteers (45 men, 34 women) aged 20 to 29 years. Serum BDNF levels were measured with an enzyme-linked immunosorbent assay, and a single-nucleotide polymorphism (Val66Met) in the BDNF gene was assessed with a TaqMan assay. Details of the sleep pattern were obtained from 1-week sleep/wake records. Results: Serum BDNF levels were significantly associated with sleep parameters on weekends, whereas no such association was found on weekdays. On weekends, longer total sleep time and time in bed, and later mid-sleep time were associated with lower serum BDNF levels. The difference between mid-sleep time on weekdays and that on weekends, otherwise known as social jetlag, was negatively associated with serum BDNF levels. Met/Met homozygotes of the BDNF Val66Met polymorphism had significantly longer time in bed on weekends than Val/Val homozygotes. Heterozygotes did not differ from Val/Val homozygotes. Conclusions: We first found that serum BDNF levels and the BDNF Val66Met polymorphism in healthy young adults were associated with the sleep pattern on weekends but not with that on weekdays, suggesting that the systems involved in BDNF control may be linked to endogenous sleep characteristics rather than the socially constrained sleep schedule in healthy young adults. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects a large number of people throughout the world. Anxiety, depression and fatigue are common symptoms of SLE that substantially contribute to decreased quality of life. This study investigates the interplay between physical and psychiatric manifestations of lupus. To this end, an SLE patient cohort was examined for correlations between clinical presentation, laboratory tests, and psychological indicators. Methods: Seventy-two lupus patients were evaluated for psychological status using a battery of instruments, including assessments for fatigue (CFS & FSS), depression (HADS), anxiety (HADS), overall health (SF-36 & PSQI) and intimate relationship satisfaction (RAS & CSI). Scores from these assessments were correlated with lupus clinical profiles and laboratory test values. Results: The prevalence of depression in the SLE patient cohort was 41.7%, as measured by the hospital depression and anxiety scale. The study identified that pain (p = 0.001), body mass index (p = 0.026), Chalder’s fatigue scale (p < 0.001), fatigue severity scale (p < 0.001), and anxiety (p = 0.001) are all positively correlated with depression in SLE patients. Total complement (CH50) (p = 0.032), and SF-36 physical and mental characteristic assessments are negatively correlated with depression. Longitudinal analysis indicated that the disease related complaint alopecia (p = 0.008) and relationship assessment scale scores (p = 0.004) may also be correlated to depression in SLE patients. Multivariant scrutiny of the clinical and psychosocial characteristics identified the fatigue severity scale (p = 0.026), SF-36 physical function (p = 0.040), physical role function (0.030), and mental health (p = 0.002) as the best indicators directly correlated with depression for the SLE cohort. Conclusion: These results reveal the influence of physical manifestations of lupus including fatigue, pain, body mass index and anxiety, as well as decreased physical and mental function, on depression. Fatigue is the strongest factor correlated with depression in SLE patients in the cohort. Both physical and social/psychological aspects likely contribute to the depression and anxiety in lupus. [ABSTRACT FROM AUTHOR]

Background: Depression is prevalent in primary biliary cholangitis (PBC) patients. Our aims were to examine the effects of depression and antidepressants on hepatic outcomes of PBC patients. Methods: We used the UK Health Improvement Network database to identify PBC patients between 1974 and 2007. Our primary outcome was one of three clinical events: decompensated cirrhosis, liver transplantation and death. We assessed depression and each class of antidepressant medication in adjusted multivariate Cox proportional hazards models to identify independent predictors of outcomes. In a sensitivity analysis, the study population was restricted to PBC patients using ursodeoxycholic acid (UDCA). Results: We identified 1,177 PBC patients during our study period. In our cohort, 86 patients (7.3%) had a depression diagnosis prior to PBC diagnosis, while 79 patients (6.7%) had a depression diagnosis after PBC diagnosis. Ten-year incidence of mortality, decompensated cirrhosis, and liver transplantation were 13.4%, 6.6%, and 2.0%, respectively. In our adjusted models, depression status was not a predictor of poor outcomes. After studying all classes of antidepressants, using the atypical antidepressant mirtazapine after PBC diagnosis was significantly protective (Adjusted HR 0.23: 95% CI 0.07–0.72) against poor liver outcomes (decompensation, liver transplant, mortality), which remained statistically significant in patients using UCDA (HR 0.21: 95% CI 0.05–0.83). Conclusions: In our study, depression was not associated with poor clinical outcomes. However, using the antidepressant mirtazapine was associated with decreased mortality, decompensated cirrhosis and liver transplantation in PBC patients. These findings support further assessment of mirtazapine as a potential treatment for PBC patients. [ABSTRACT FROM AUTHOR]

Early diagnosis is critical for individuals with Alzheimer's disease (AD) in clinical practice because its progress is irreversible. In the existing literature, support vector machine (SVM) has always been applied to distinguish between AD and healthy controls (HC) based on neuroimaging data. But previous studies have only used a single SVM to classify AD and HC, and the accuracy is not very high and generally less than 90%. The method of random support vector machine cluster was proposed to classify AD and HC in this paper. From the Alzheimer's Disease Neuroimaging Initiative database, the subjects including 25 AD individuals and 35 HC individuals were obtained. The classification accuracy could reach to 94.44% in the results. Furthermore, the method could also be used for feature selection and the accuracy could be maintained at the level of 94.44%. In addition, we could also find out abnormal brain regions (inferior frontal gyrus, superior frontal gyrus, precentral gyrus and cingulate cortex). It is worth noting that the proposed random support vector machine cluster could be a new insight to help the diagnosis of AD. [ABSTRACT FROM AUTHOR]

Background: Structural imaging studies of borderline personality disorder (BPD) have found regions of reduced cortical volume, but these have varied considerably across studies. Reduced hippocampus and amygdala volume have also been a regular finding in studies using conventional volumetric measurement. How far comorbid major depression, which is common in BPD and can also affect in brain structure, influences the findings is not clear. Methods: Seventy-six women with BPD and 76 matched controls were examined using whole-brain voxel-based morphometry (VBM). The hippocampus and amygdala were also measured, using both conventional volume measurement and VBM within a mask restricted to these two subcortical structures. Lifetime history of major depression was assessed using structured psychiatric interview. Results: At a threshold of p = 0.05 corrected, the BPD patients showed clusters of volume reduction in the dorsolateral prefrontal cortex bilaterally and in the pregenual/subgenual medial frontal cortex. There was no evidence of volume reductions in the hippocampus or amygdala, either on conventional volumetry or using VBM masked to these regions. Instead there was evidence of right-sided enlargement of these structures. No significant structural differences were found between patients with and without lifetime major depression. Conclusions: According to this study, BPD is characterized by a restricted pattern of cortical volume reduction involving the dorsolateral frontal cortex and the medial frontal cortex, both areas of potential relevance for the clinical features of the disorder. Previous findings concerning reduced hippocampus and amygdala volume in the disorder are not supported. Brain structural findings in BPD do not appear to be explainable on the basis of history of associated lifetime major depression. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the behavioral effects of chronic (six weeks) nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose) administration (in order to mimic heavy human abuse), and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break), applied alone and simultaneously with ND, in male rats (n = 40). Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV) content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF) test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone) and in elevated plus maze (EPM) test (decrease in frequency and cumulative duration in open arms, and total exploratory activity), that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region), followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters), and in evoked beam-walking test (increase in time to cross the beam), compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system) may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols. [ABSTRACT FROM AUTHOR]

Introduction: Although schizophrenia (SCZ) and bipolar disorder (BD) share elements of pathology, their neural underpinnings are still under investigation. Here, structural Magnetic Resonance Imaging (MRI) data collected from a large sample of BD and SCZ patients and healthy controls (HC) were analyzed in terms of gray matter volume (GMV) using both voxel based morphometry (VBM) and a region of interest (ROI) approach. Methods: The analysis was conducted on two datasets, Dataset1 (802 subjects: 243 SCZ, 176 BD, 383 HC) and Dataset2, a homogeneous subset of Dataset1 (301 subjects: 107 HC, 85 BD and 109 SCZ). General Linear Model analyses were performed 1) at the voxel-level in the whole brain (VBM study), 2) at the regional level in the anatomical regions emerged from the VBM study (ROI study). The GMV comparison across groups was integrated with the analysis of GMV correlates of different clinical dimensions. Results: The VBM results of Dataset1 showed 1) in BD compared to HC, GMV deficits in right cingulate, superior temporal and calcarine cortices, 2) in SCZ compared to HC, GMV deficits in widespread cortical and subcortical areas, 3) in SCZ compared to BD, GMV deficits in insula and thalamus (p<0.05, cluster family wise error corrected). The regions showing GMV deficits in the BD group were mostly included in the SCZ ones. The ROI analyses confirmed the VBM results at the regional level in most of the clusters from the SCZ vs. HC comparison (p<0.05, Bonferroni corrected). The VBM and ROI analyses of Dataset2 provided further evidence for the enhanced GMV deficits characterizing SCZ. Based on the clinical-neuroanatomical analyses, we cannot exclude possible confounding effects due to 1) age of onset and medication in BD patients, 2) symptoms severity in SCZ patients. Conclusion: Our study reported both shared and specific neuroanatomical characteristics between the two disorders, suggesting more severe and generalized GMV deficits in SCZ, with a specific role for insula and thalamus. [ABSTRACT FROM AUTHOR]

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a debilitating mental health problem hampering the child’s development. The underlying causes include both genetic and environmental factors and may differ between individuals. The efficacy of diet treatments in ADHD was recently evaluated in three reviews, reporting divergent and confusing conclusions based on heterogeneous studies and subjects. To address this inconsistency we conducted a systematic review of meta-analyses of double-blind placebo-controlled trials evaluating the effect of diet interventions (elimination and supplementation) on ADHD. Methods: Our literature search resulted in 14 meta-analyses, six of which confined to double-blind placebo-controlled trials applying homogeneous diet interventions, i.e. artificial food color (AFC) elimination, a few-foods diet (FFD) and poly-unsaturated fatty acid (PUFA) supplementation. Effect sizes (ES) and Confidence intervals (CI) of study outcomes were depicted in a forest plot. I2 was calculated to assess heterogeneity if necessary and additional random effects subgroup meta-regression was conducted if substantial heterogeneity was present. Results: The AFC ESs were 0.44 (95% CI: 0.16–0.72, I2 = 11%) and 0.21 (95% CI: -0.02–0.43, I2 = 68%) [parent ratings], 0.08 (95% CI: -0.07–0.24, I2 = 0%) [teacher ratings] and 0.11 (95% CI: -0.13–0.34, I2 = 12%) [observer ratings]. The FFD ESs were 0.80 (95% CI: 0.41–1.19, I2 = 61%) [parent ratings] and 0.51 (95% CI: -0.02–1.04, I2 = 72%) [other ratings], while the PUFA ESs were 0.17 (95% CI: -0.03–0.38, I2 = 38%) [parent ratings], -0.05 (95% CI: -0.27–0.18, I2 = 0%) [teacher ratings] and 0.16 (95% CI: 0.01–0.31, I2 = 0%) [parent and teacher ratings]. Three meta-analyses (two FFD and one AFC) resulted in high I2 without presenting subgroup results. The FFD meta-analyses provided sufficient data to perform subgroup analyses on intervention type, resulting in a decrease of heterogeneity to 0% (diet design) and 37.8% (challenge design). Conclusion: Considering the small average ESs PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment, while further research is required for AFC elimination before advising this intervention as ADHD treatment. The average FFD ES is substantial, offering treatment opportunities in subgroups of children with ADHD not responding to or too young for medication. Further FFD research should focus on establishing the underlying mechanisms of food (e.g. incrimination of gut microbiota) to simplify the FFD approach in children with ADHD. [ABSTRACT FROM AUTHOR]

Background: Body Integrity Identity Disorder (BIID) is a condition in which individuals perceive a mismatch between their internal body scheme and physical body shape, resulting in an absolute desire to be either amputated or paralyzed. The condition is hypothesized to be of congenital nature, but evidence for a neuro-anatomical basis is sparse. Methods: We collected T1-weighted structural magnetic resonance imaging scans on a 3T scanner in eight individuals with BIID and 24 matched healthy controls, and analyzed the data using voxel-based morphometry. Results: The results showed reduced grey matter volume in the left dorsal and ventral premotor cortices and larger grey matter volume in the cerebellum (lobule VIIa) in individuals with BIID compared to controls. Conclusion: The premotor cortex and cerebellum are thought to be crucial for the experience of body-ownership and the integration of multisensory information. Our results suggest that BIID is associated with structural brain anomalies and might result from a dysfunction in the integration of multisensory information, leading to the feeling of disunity between the mental and physical body shape. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) symptoms frequently occur in individuals with attention-deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural brain correlates, knowledge of the structural brain profile of individuals with ADHD with raised ASD symptoms is limited. The presence of ASD-like symptoms was measured by the Children's Social Behavior Questionnaire (CSBQ) in a sample of typically developing controls (n = 154), participants with ADHD (n = 239), and their unaffected siblings (n = 144) between the ages of 8 and 29. Structural magnetic resonance imaging (MRI) correlates of ASD ratings were analysed by studying the relationship between ASD ratings and grey matter volumes using mixed effects models which controlled for ADHD symptom count and total brain volume. ASD ratings were significantly elevated in participants with ADHD relative to controls and unaffected siblings. For the entire group (participants with ADHD, unaffected siblings and TD controls), mixed effect models revealed that the left caudate nucleus volume was negatively correlated with ASD ratings (t = 2.83; P = 0.005). The current findings are consistent with the role of the caudate nucleus in executive function, including the selection of goals based on the evaluation of action outcomes and the use of social reward to update reward representations. There is a specific volumetric profile associated with subclinical ASD-like symptoms in participants with ADHD, unaffected siblings and controls with the caudate nucleus and globus pallidus being of critical importance in predicting the level of ASD-like symptoms in all three groups. [ABSTRACT FROM AUTHOR]

Background: The mechanisms through which physical activity supports healthy brain function remain to be elucidated. One hypothesis suggests that increased brain-derived neurotrophic factor (BDNF) mediates some cognitive and mood benefits. This meta-analysis sought to determine the effect of exercise training on resting concentrations of BDNF in peripheral blood. Methods: MEDLINE, Embase, PsycINFO, SPORTDiscus, Rehabilitation & Sports Medicine Source, and CINAHL databases were searched for original, peer-reviewed reports of peripheral blood BDNF concentrations before and after exercise interventions ≥ 2 weeks. Risk of bias was assessed using standardized criteria. Standardized mean differences (SMDs) were generated from random effects models. Risk of publication bias was assessed using funnel plots and Egger’s test. Potential sources of heterogeneity were explored in subgroup analyses. Results: In 29 studies that met inclusion criteria, resting concentrations of peripheral blood BDNF were higher after intervention (SMD = 0.39, 95% CI: 0.17–0.60, p < 0.001). Subgroup analyses suggested a significant effect in aerobic (SMD = 0.66, 95% CI: 0.33–0.99, p < 0.001) but not resistance training (SMD = 0.07, 95% CI: -0.15–0.30, p = 0.52) interventions. No significant difference in effect was observed between males and females, nor in serum vs plasma. Conclusion: Aerobic but not resistance training interventions increased resting BDNF concentrations in peripheral blood. [ABSTRACT FROM AUTHOR]

Current therapies for depression consist primarily of pharmacological agents, including antidepressants, and/or psychiatric counseling, such as psychotherapy. However, light therapy has recently begun to be considered as an effective tool for the treatment of the neuropsychiatric behaviors and symptoms of a variety of brain disorders or diseases, including depression. One methodology employed in light therapy involves flickering photic stimulation within a specific frequency range. The present study investigated whether flickering and flashing photic stimulation with light emitting diodes (LEDs) could improve depression-like behaviors in a corticosterone (CORT)-induced mouse model of depression. Additionally, the effects of the flickering and flashing lights on depressive behavior were compared with those of fluoxetine. Rhythmical flickering photic stimulation at alpha frequencies from 9–11 Hz clearly improved performance on behavioral tasks assessing anxiety, locomotor activity, social interaction, and despair. In contrast, fluoxetine treatment did not strongly improve behavioral performance during the same period compared with flickering photic stimulation. The present findings demonstrated that LED-derived flickering photic stimulation more rapidly improved behavioral outcomes in a CORT-induced mouse model of depression compared with fluoxetine. Thus, the present study suggests that rhythmical photic stimulation at alpha frequencies may aid in the improvement of the quality of life of patients with depression. [ABSTRACT FROM AUTHOR]

Objective: To study the involvement of the anterior nuclei of the thalamus (ANT) as compared to the involvement of the hippocampus in the processes of encoding and recognition during visual and verbal memory tasks. Methods: We studied intracerebral recordings in patients with pharmacoresistent epilepsy who underwent deep brain stimulation (DBS) of the ANT with depth electrodes implanted bilaterally in the ANT and compared the results with epilepsy surgery candidates with depth electrodes implanted bilaterally in the hippocampus. We recorded the event-related potentials (ERPs) elicited by the visual and verbal memory encoding and recognition tasks. Results: P300-like potentials were recorded in the hippocampus by visual and verbal memory encoding and recognition tasks and in the ANT by the visual encoding and visual and verbal recognition tasks. No significant ERPs were recorded during the verbal encoding task in the ANT. In the visual and verbal recognition tasks, the P300-like potentials in the ANT preceded the P300-like potentials in the hippocampus. Conclusions: The ANT is a structure in the memory pathway that processes memory information before the hippocampus. We suggest that the ANT has a specific role in memory processes, especially memory recognition, and that memory disturbance should be considered in patients with ANT-DBS and in patients with ANT lesions. ANT is well positioned to serve as a subcortical gate for memory processing in cortical structures. [ABSTRACT FROM AUTHOR]

Background: Findings from family studies and recent genome-wide association studies have indicated overlap in the risk genes between schizophrenia and bipolar disorder (BD). After finding a linkage between the ST8SIA2 (ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sicalyltransferase 2 gene) locus (15q26) and mixed families with schizophrenia and BD, several studies have reported a significant association between this gene and schizophrenia or BD. We investigated the genetic association between ST8SIA2 and both schizophrenia and BD in the Korean population. Methods: A total of 582 patients with schizophrenia, 339 patients with BD, and 502 healthy controls were included. Thirty-one tag single nucleotide polymorphisms (SNPs) across the ST8SIA2 region and three other SNPs showing significant associations in previous studies were genotyped. The associations were evaluated by logistic regression analysis using additive, dominant, and recessive genetic models. Results: Fourteen of 34 SNPs showed a nominally significant association (p < 0.05) with at least one diagnostic group. These association trends were strongest for the schizophrenia and combined schizophrenia and bipolar I disorder (BD-I) groups. The strongest association was observed in rs11637898 for schizophrenia (p = 0.0033) and BD-I (p = 0.0050) under the dominant model. The association between rs11637898 and the combined schizophrenia and BD-I group (p = 0.0006, under the dominant model) remained significant after correcting for multiple testing. Discussion: We identified a possible role of ST8SIA2 in the common susceptibility of schizophrenia and BD-I. However, no association trend was observed for bipolar II disorder. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories. [ABSTRACT FROM AUTHOR]

The application of machine learning techniques to psychiatric neuroimaging offers the possibility to identify robust, reliable and objective disease biomarkers both within and between contemporary syndromal diagnoses that could guide routine clinical practice. The use of quantitative methods to identify psychiatric biomarkers is consequently important, particularly with a view to making predictions relevant to individual patients, rather than at a group-level. Here, we describe predictions of treatment-refractory depression (TRD) diagnosis using structural T1-weighted brain scans obtained from twenty adult participants with TRD and 21 never depressed controls. We report 85% accuracy of individual subject diagnostic prediction. Using an automated feature selection method, the major brain regions supporting this significant classification were in the caudate, insula, habenula and periventricular grey matter. It was not, however, possible to predict the degree of ‘treatment resistance’ in individual patients, at least as quantified by the Massachusetts General Hospital (MGH-S) clinical staging method; but the insula was again identified as a region of interest. Structural brain imaging data alone can be used to predict diagnostic status, but not MGH-S staging, with a high degree of accuracy in patients with TRD. [ABSTRACT FROM AUTHOR]

Valproate (VPA) has recently been shown to influence the behavioral effects of psycho-stimulants. Although glycogen synthase kinase 3β (GSK3β) signaling in the nucleus accumbens (NAc) plays a key role in mediating dopamine (DA)-dependent behaviors, there is less direct evidence that how VPA acts on the GSK3β signaling in the functionally distinct sub-regions of the NAc, the NAc core (NAcC) and the NAc shell (NAcSh), during psycho-stimulant-induced hyperactivity. In the present study, we applied locomotion test after acute methamphetamine (MA) (2 mg/kg) injection to identify the locomotor activity of rats received repeated VPA (300 mg/kg) pretreatment. We next measured phosphor-GSK3β at serine 9 and total GSK3β levels in NAcC and NAcSh respectively to determine the relationship between the effect of VPA on MA-induced hyperlocomotor and changes in GSK3β activity. We further investigated whether microinjection of VPA (300 μg/0.5 μl/side, once daily for 7 consecutive days) into NAcC or NAcSh could affect hyperactivity induced by MA. Our data indicated that repeated VPA treatment attenuated MA-induced hyperlocomotor, and the effect was associated with decreased levels of phosphorylated GSK3β at Ser 9 in the NAcC. Moreover, repeated bilateral intra-NAcC, but not intra-NAcSh VPA treatment, significantly attenuated MA-induced hyperactivity. Our results suggested that GSK3β activity in NAcC contributes to the inhibitory effects of VPA on MA-induced hyperactivity. [ABSTRACT FROM AUTHOR]