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Differences between hands in motor performance are associated with differences in the interaction of inhibitory connections of homologous parts of the cerebral hemispheres. Modulation of these inhibitory connections in the right and left primary motor cortex (M1) may alter manual performance asymmetries. To investigate this assumption, eleven right-handed male university students performed a discrete aiming task in a digitizing tablet under three experimental conditions: dominant M1 inhibition, non-dominant M1 inhibition, and sham. The Transcranial Direct Current Stimulation technique was used to increase or decrease participants' M1 excitability. We used a within-subject design, in which we counterbalanced the order of conditions and the order of the starting hand among participants. The performance-dependent variables were: reaction time, movement time, and radial error, while kinematic variables were: peak velocity, relative time to peak velocity, and number of discontinuities in acceleration in the final homing phase. Results showed changes in asymmetry related to reaction time, movement time, and relative time to peak velocity. The interaction between M1 modulation and hemispheric specialization produced specific changes in these variables. Taken together, these findings revealed that modulation of the dominant and non-dominant M1 affects manual performance asymmetries. [ABSTRACT FROM AUTHOR]

In aiming movements the limb position drifts away from the defined target after some trials without visual feedback, a phenomenon defined as proprioceptive drift (PD). There are no studies investigating the association between the posterior parietal cortex (PPC) and PD in aiming movements. Therefore, cathodal and sham transcranial direct current stimulation (tDCS) were applied to the left PPC concomitantly with the performance of movements with or without vision. Cathodal tDCS applied without vision produced a higher level of PD and higher rates of drift accumulation while it decreased peak velocity and maintained the number of error corrections, not affecting movement amplitude. The proprioceptive information seems to produce an effective reference to movement, but with PPC stimulation it causes a negative impact on position. [ABSTRACT FROM AUTHOR]

The functional role of the primary motor cortex (M1) in the production of movement parameters, such as length, direction and force, is well known; however, whether M1 is associated with the parametric adjustments in the absolute timing dimension of the task remains unknown. Previous studies have not applied tasks and analyses that could separate the absolute (variant) and relative (invariant) dimensions. We applied transcranial direct current stimulation (tDCS) to M1 before motor practice to facilitate motor learning. A sequential key-pressing task was practiced with two goals: learning the relative timing dimension and learning the absolute timing dimension. All effects of the stimulation of M1 were observed only in the absolute dimension of the task. Mainly, the stimulation was associated with better performance in the transfer test in the absolute dimension. Taken together, our results indicate that M1 is an important area for learning the absolute timing dimension of a motor sequence. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examinethe association between polymorphism in thecatechol-O-methyltransferase(COMT) gene and Alzheimer's disease (AD) in a Brazilianpopulation. The case-control method was used to study the association between AD and geneticvariants of COMT. Six tag single-nucleotide polymorphisms(SNPs) in the COMT gene were genotyped by RT-PCR. Ourfindings showed that the 6 tag SNPs analyzed in this study were not associated with AD at the alleleand genotype levels in comparison with the control group. No statistical difference was foundbetween groups with and without behavioral and psychological symptoms of dementia (BPSD). Ourresults do not support the hypothesis that the polymorphisms of theCOMT gene may be associated with susceptibility to AD withand without BPSD. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

An imbalance in dopamine-mediated neurotransmission is a hallmark physiological feature of neuropsychiatric disorders, such as schizophrenia. Recent evidence demonstrates that dopamine D2 receptors, which are the main target of antipsychotics, modulate the activity of the protein kinase Akt, which is known to be downregulated in the brain of patients with schizophrenia. Akt has an important role in the regulation of cellular processes that are critical for neurodevelopment, including gene transcription, cell proliferation, and neuronal migration. Thus, it is possible that during brain development, altered Akt-dependent dopamine signaling itself may lead to defects in neural circuit formation. Here, we used a zebrafish model to assess the direct impact of altered dopamine signaling on brain development and larval motor behavior. We demonstrate that D2 receptor activation acutely suppresses Akt activity by decreasing the level of pAkt(Thr308) in the larval zebrafish brain. This D2-dependent reduction in Akt activity negatively regulates larval movement and is distinct from a D1-dependent pathway with opposing affects on motor behavior. In addition, we show that D2-dependent suppression of Akt activity causes a late onset change in GSK3b activity, a known downstream target of Akt signaling. Finally, altered D2 receptor signaling, or direct inhibition of Akt activity, causes a significant decrease in the size of the GABAergic neuron population throughout most of the brain. Our observations suggest that D2 receptor signaling suppresses Akt-GSK3b activity, which regulates GABAergic neuron development and motor behavior. [ABSTRACT FROM AUTHOR]

Abstract: GDNF (glial-cell-line derived neurotrophic factor) is a potent neurotrophic factor for dopaminergic neurons. Neuropsychiatric diseases and their treatments are associated with alterations in the levels of both GDNF and its receptor family (GDNF family receptor alpha or GFRA). GFRA1, GFRA2 and GFRA3 are located in chromosomal regions with suggestive linkage to schizophrenia. In this study we analyzed polymorphisms located in all four known GFRA genes and examined association with schizophrenia and clozapine response. We examined SNPs across the genes GFRA1-4 in 219 matched case-control subjects, 85 small nuclear families and 140 schizophrenia patients taking clozapine for 6months. We observed that GFRA3 rs11242417 and GFRA1 rs11197557 variants were significantly associated with schizophrenia after combining results from both schizophrenia samples. Furthermore, we found an overtransmission of the G–C GFRA1 rs7920934-rs730357 haplotype to subjects with schizophrenia and association of A–T–G–G GFRA3 rs10036665-rs10952-rs11242417-rs7726580 with schizophrenia in the case-control sample. On the other hand, GFRA2 variants were not associated with schizophrenia diagnosis but subjects carrying T–G–G rs1128397-rs13250096-rs4567028 haplotype were more likely to respond to clozapine treatment. The statistical significance of results survived permutation testing but not Bonferroni correction. We also found nominally-significant evidence for interactions between GFRA1, 2 and 3 associated with schizophrenia and clozapine response, consistent with the locations of these three genes within linkage regions for schizophrenia. [Copyright &y& Elsevier]

Abstract: Tardive dyskinesia (TD) is a motor adverse effect of chronic antipsychotic medication. It has been suggested to involve dopamine neurotransmission system changes. AKT1 acts downstream of the D2 receptor that is blocked by all antipsychotics to some degree. The AKT1 gene has not been investigated in TD. We examined eight polymorphisms spanning the AKT1 gene and their association with TD in our schizophrenia sample of 193 Caucasians, 76 of which with TD. AKT1 polymorphisms and haplotypes were not significantly associated with TD. However, we detected a significant interaction between rs6275 of DRD2 and rs3730358 of AKT1 (p <1×10−5). [Copyright &y& Elsevier]

A number of human and animal studies implicate GSK3 in the pathophysiology and genetics of schizophrenia. In general, the data suggest that phosphorylation levels of GSK3β are reduced in schizophrenia, resulting in increased GSK3β activity. Since GSK3β regulation is altered in schizophrenia, polymorphic variation in this gene may affect susceptibility to schizophrenia or treatment response. To analyze GSK3β genetic variants for association with schizophrenia and clozapine response. We examined GSK3β markers in 185 matched case–control subjects, 85 small nuclear families, and 150 schizophrenia patients treated with clozapine for 6 months. Three markers (rs7624540, rs4072520, and rs6779828) showed genotypic association with schizophrenia in the case–control sample. We did not observe any family and clozapine response association with a specific allele, genotype, or haplotype. Our results suggest that GSK3β polymorphisms might be involved in schizophrenia risk but do not appear to play a significant role in clozapine response. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, internalizing and externalizing symptoms have impacted the quality of life of children and adolescents. This cross-sectional study evaluated children's quality of life using parental reports, observing associations with mental health problems and sociodemographic variables. Some behavioral measures were linked to lower quality of life, particularly depression symptoms, relationship problems, and inattention. Multiple regression models indicated that reduced children's quality of life (R 2 = 36%) was associated with higher levels of internalizing (r = −0.46) and externalizing (r = −0.23) behavioral problems and younger parents (r = −0.08). Children with previous mental disorder diagnoses had lower quality of life than those without (p < 0.001). In summary, children's quality of life during the COVID-19 pandemic was linked to current mental health, parental age, and previous history of mental disorders. [ABSTRACT FROM AUTHOR]

DARPP-32 (dopamine and cAMP-regulated phosphoprotein Mr. 32 kDa) is a phosphoprotein that is modulated by multiple receptors integrating intracellular pathways and playing roles in various physiological functions. It is regulated by dopaminergic receptors through the cAMP/protein kinase A (PKA) pathway, which modulates the phosphorylation of threonine 34 (Thr34). When phosphorylated at Thr34, DARPP-32 becomes a potent protein phosphatase-1 (PP1) inhibitor. Since dopamine is involved in the development of GABAergic neurons and DARPP-32 is expressed in the developing brain, it is possible that DARPP-32 has a role in GABAergic neuronal development. We cloned the zebrafish darpp-32 gene (ppp1r1b) gene and observed that it is evolutionarily conserved in its inhibitory domain (Thr34 and surrounding residues) and the docking motif (residues 7–11 (KKIQF)). We also characterized darpp-32 protein expression throughout the 5 days post-fertilization (dpf) zebrafish larval brain by immunofluorescence and demonstrated that darpp-32 is mainly expressed in regions that receive dopaminergic projections (pallium, subpallium, preoptic region, and hypothalamus). We demonstrated that dopamine acutely suppressed darpp-32 activity by reducing the levels of p-darpp-32 in the 5dpf zebrafish larval brain. In addition, the knockdown of darpp-32 resulted in a decrease in the number of GABAergic neurons in the subpallium of the 5dpf larval brain, with a concomitant increase in the number of DAergic neurons. Finally, we demonstrated that darpp-32 downregulation during development reduced the motor behavior of 5dpf zebrafish larvae. Thus, our observations suggest that darpp-32 is an evolutionarily conserved regulator of dopamine receptor signaling and is required for the formation of GABAergic neurons in the developing telencephalon. • Zebrafish darpp-32 gene (ppp1r1b) is evolutionarily conserved in its inhibitory domain and the docking motif. • Darpp-32 is mainly expressed in regions that receive dopaminergic projections in the zebrafish telencephalon. • Dopamine regulates darpp-32 activity by reducing the levels of p-darpp-32 in the zebrafish larval brain • Darpp-32 downregulation during development decreases the number of GABAergic neurons in the subpallium and the motor behavior. [ABSTRACT FROM AUTHOR]

Although telomere attrition is associated with the process of normal ageing, shorter telomere length (TL) has been associated with acute and chronic stressors. A neurobiological factor hypothesised to be responsible for this accelerated attrition is the dysregulation of the cortisol stress response, which can induce DNA damage affecting DNA telomeric caps. Marked sex differences are reported in both the cortisol stress response and telomere dynamics, yet no explicit investigation of sex specificity on the relationship between cortisol and TL exists. This study used mathematical equation modelling to describe the relationship between diurnal cortisol levels and telomere length within the context of sex, in a healthy population. Cortisol awakening responses (CAR) were measured via ELISA methodology in fifty‐one healthy participants (28 males, 23 females). qPCRs determined TL from genomic DNA extracted from saliva. To assess the effect of free cortisol on relative TL ratio, a semi‐log regression plot of the two variables trended for sex were fitted using spline curves. Results demonstrated significant differences between males and females in the relationship defining CAR and TL association (p = 0.03). These results suggest the relationship is not linear and can be represented as a complex arcsin function, and that the patterns are opposite in males and females. Males demonstrate a positive correlation, with higher levels of CAR being associated with longer telomere sequences. Females demonstrated a negative correlation. Future studies must carefully take into consideration moderating factors such as sex, and sex hormones across the lifespan when investigating telomere length. [ABSTRACT FROM AUTHOR]

Objective: Genetic variability significantly impacts metabolism, weight gain, and feeding behaviors, predisposing individuals to obesity. This study explored how variations in key genes related to obesity—FOXO3A (forkhead box O3), AMPK (protein kinase AMP‐activated), and POMC (proopiomelanocortin)—are associated with extreme obesity (EOB). Methods: We conducted a case–control study with 251 EOB patients and 212 healthy controls with a body mass index (BMI) of less than 25 kg/m2. We genotyped 10 single nucleotide variants (SNVs) using TaqMan‐based assays. Results: Four SNVs—rs1536057 in FOXO3A, rs103685 in AMPK, rs934778, and rs6545975 in POMC—were associated with an increased risk of EOB. The strongest association was observed with rs934778 (POMC), which had a maximum odds ratio (OR) of 5.26 (95% CI: 2.86–9.09). While these genetic variations are closely linked to EOB, they do not affect serum glucose, triglycerides, HDL, LDL, BMI, or waist circumference. Conclusions: These findings indicate that factors beyond traditional metabolic pathways, potentially related to feeding behavior or hormonal regulation, may also link these genetic variations to obesity. Further research in a larger sample is essential to validate these findings and explore their potential to guide clinical interventions and public health strategies. [ABSTRACT FROM AUTHOR]

• Antipsychotics may impact gut microbiota, but this connection is little understood. • Most studies reported changes in gut microbiota after antipsychotic treatment. • Further understanding on the subject may help to optimize treatment. Antipsychotics (APs) have been increasingly prescribed for psychiatric disorders from schizophrenia to disruptive behavioral conditions. These drugs have been associated with considerable side effects, such as weight gain, and increasing evidence has also indicated that its use impacts gut microbiota (GM), although this connection is still little understood. To assess APs effects on the GM of patients starting or ongoing treatment, a systematic review was carried out in PubMed and Scopus databases. Twelve articles were considered eligible for the review, which investigated the effects of risperidone (5 studies), quetiapine (3), amilsupride (1), olanzapine (1), and unspecified atypical drugs (2). Eleven reported changes in GM in response to APs, and associations between the abundance of bacterial groups and different metabolic parameters were described by most of them. However, the studies were noticeably heterogeneous considering design, methods, and results. In this way, the effects of APs on GM composition and diversity were inconclusive. Despite the uncertain interactions, a more comprehensive understanding on how microbiota is affected by APs may help to optimize treatment, potentially minimizing side effects and improving adherence to treatment. [ABSTRACT FROM AUTHOR]

Background Yoga can be used as a complementary intervention to conventional treatments, whether pharmacological or non-pharmacological. Sustained practice of yoga can generate a series of benefits for individuals quality of life and improve their physical fitness. Objective To investigate the potential effects of yoga as an adjunct intervention in conditions involving impulse control issues, such as attention deficit hyperactivity disorder (ADHD), borderline personality disorder, bipolar affective disorder, and substance use disorders. Methods We performed a systematic review of placebo-controlled, randomized trials of yoga in patients with impulsivity. PubMed, Web of Science, and Science Direct databases were searched for trials published up to January, 2023. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Results Out of 277 database results, 6 RCT were included in this systematic review. To assess the level of attention and impulsiveness, the following scales were analyzed: Barratt Impulsiveness, UPPS-P Impulsive Behavior scale, Conners' Continuous Performance Test II and Conners' Parent Rating Scale-Revised: Long. Conclusions Yoga didn't have a significant improvement in impulsivity when compared to placebo. There are many tools to assess impulsivity, but they mean different concepts and domains consisting in a weakness on comparison of yoga effects. [ABSTRACT FROM AUTHOR]

Abstract: In traumatic brain injury (TBI), cerebral edema and hemorrhage are factors involved in the determination of the clinical presentation and outcome. The aquaporin 4 (AQP4) water channel is abundant in mammalian brain and there is a growing body of evidence suggesting that this protein plays a major role in the control of water flow within the central nervous system. Previous studies examined the influence of genetic variants in cerebral edema of TBI. However, to our knowledge, there are no previous studies of molecular variations of the AQP4 gene and its association with TBI. Thus, we sought to investigate if the clinical presentation and outcome of TBI could be influenced by the presence of mutations on exon 4 of the AQP4 gene. One hundred and two patients were enrolled in this study. A neurologist assessed the clinical severity at admission according to the GCS followed by a brain computer tomography (CT) scan. Then, DNA was extracted from blood cells and exon 4 of the AQP4 gene amplified by the polymerase chain reaction and directly sequenced. On discharge, GOS was assigned by a neurologist blind to the CGS on admission. We did not find any variation in exon 4 of the AQP4 gene in our considerable large sample. Despite this negative result, there is a strong biological rationale for the involvement of AQP4 gene in brain edema regulation and, as consequence, in TBI. Therefore, further studies should be performed, including the assessment of the other three exons of the AQP4 gene. [Copyright &y& Elsevier]

Several letters to the editor are presented in response to several articles including one on lithium and topiramate association in the treatment of comorbid pathological gambling and bipolar disorder, coping and resilience in refugees from the Sudan, and the metabolic syndrome in drug-naive first-episode psychosis treated with atypical antipsychotics.

Acute ischemic stroke is a sudden neurological event caused by brain ischemia. Patients with large vessel occlusion are at high risk of developing significant cerebral edema, which can lead to rapid neurological decline. The optimal timing for decompressive hemicraniectomy to prevent further brain damage is still uncertain. This study aimed to identify potential predictors of severe brain edema. The data indicate that specific cytokines may help identify patients with a higher risk of developing life-threatening brain swelling in the early phase post-stroke. The association between a positive biomarker and the outcome was calculated, and three biomarkers—S100B protein, MMP-9, and IL-10—were found to be significantly associated with malignant edema. A model was derived for early predicting malignant cerebral edema, including S100B protein and IL-1 beta. These findings suggest that molecular biomarkers related to the ischemic cascade may be a helpful way of predicting the development of malignant cerebral edema in ischemic stroke patients, potentially widening the time window for intervention and assisting in decision-making. In conclusion, this study provides insights into the molecular mechanisms of severe brain edema and highlights the potential use of biomarkers in predicting the course of ischemic stroke. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke is a sudden neurological event caused by brain ischemia. Patients with large vessel occlusion are at high risk of developing significant cerebral edema, which can lead to rapid neurological decline. The optimal timing for decompressive hemicraniectomy to prevent further brain damage is still uncertain. This study aimed to identify potential predictors of severe brain edema. The data indicate that specific cytokines may help identify patients with a higher risk of developing life-threatening brain swelling in the early phase post-stroke. The association between a positive biomarker and the outcome was calculated, and three biomarkers—S100B protein, MMP-9, and IL-10—were found to be significantly associated with malignant edema. A model was derived for early predicting malignant cerebral edema, including S100B protein and IL-1 beta. These findings suggest that molecular biomarkers related to the ischemic cascade may be a helpful way of predicting the development of malignant cerebral edema in ischemic stroke patients, potentially widening the time window for intervention and assisting in decision-making. In conclusion, this study provides insights into the molecular mechanisms of severe brain edema and highlights the potential use of biomarkers in predicting the course of ischemic stroke. [ABSTRACT FROM AUTHOR]

The Grooved Pegboard Test, in its standard use, has well-documented utility. However, a revised methodology needs further study, leading us to investigate whether duration of eye fixation could predict performance on different task conditions of the Grooved Pegboard Test (place and remove pegs) with the preferred and nonpreferred hands. Fifty-two right-handed undergraduate students (33 male and 19 female), with a mean age of 22.22 (±3.57) years, performed the Grooved Pegboard Test. SensoMotoric eye-tracking glasses with a binocular time resolution of 30 Hz were used to measure eye fixation. The videos were recorded in iView software, and data were analyzed using BeGaze software. The number and duration of eye fixations were statistically different with preferred and nonpreferred hands and also differed across tasks. Simple linear regression showed eye fixation duration to predict movement time in the place task (preferred hand: R²=31%; nonpreferred hand: R²=41%) and in the remove task (preferred hand: R²=11%; nonpreferred hand: R²=25%). Thus, duration of eye fixation during the Grooved Pegboard Test differentially predicted performance with each hand and on preferred and different subtests of this instrument. [ABSTRACT FROM AUTHOR]

The authors present insights on the relevance of neuroscience research networks for the field of science in Brazil. They note that the close communication between active researchers of linked specialties is one of the most productive assets of modern science. They note on the support by prominent scientists in Brazil for the development of psychiatry as an applied neuroscience discipline.

The article presents the case which highlights the efficacy of olanzapine in the management of catatonia in elderly bipolar patient in Brazil. Olanzapine can also be used as a maintenance treatment in bipolar disorder in old age. However, as recent concern about the use of atypical antipsychotics in elderly patients has been raised, vigilance must be maintained, especially towards metabolic effects of these drugs.

Objective: Childhood maltreatment (CM) is a significant risk factor for the development and severity of bipolar disorder (BD) with increased risk of suicide attempts (SA). This study evaluated whether a machine learning algorithm could be trained to predict if a patient with BD has a history of CM or previous SA based on brain metabolism measured by positron emission tomography. Methods: Thirty-six euthymic patients diagnosed with BD type I, with and without a history of CM were assessed using the Childhood Trauma Questionnaire. Suicide attempts were assessed through the Mini International Neuropsychiatric Interview (MINI-Plus) and a semi-structured interview. Restingstate positron emission tomography with 18F-fluorodeoxyglucose was conducted, electing only grey matter voxels through the Statistical Parametric Mapping toolbox. Imaging analysis was performed using a supervised machine learning approach following Gaussian Process Classification. Results: Patients were divided into 18 participants with a history of CM and 18 participants without it, along with 18 individuals with previous SA and 18 individuals without such history. The predictions for CM and SA were not significant (accuracy = 41.67%; p = 0.879). Conclusion: Further investigation is needed to improve the accuracy of machine learning, as its predictive qualities could potentially be highly useful in determining histories and possible outcomes of high-risk psychiatric patients. [ABSTRACT FROM AUTHOR]

Background: Attention Deficit/Hyperactivity Disorder (ADHD) is associated with a diversity of impairments and Oppositional Defiant Disorder (ODD) is a very frequent comorbidity. Parent Training, as an evidence-based intervention, seems effective in reducing externalizing/disruptive behaviors, possibly leading to a better prognosis. This clinical trial aims to evaluate the effectiveness of an online parent training model as a complementary treatment for ADHD and ODD. Methods: Patients and their families will be screened upon their entry into the Research Center of Impulsivity and Attention (NITIDA) at UFMG—Brazil. Ninety families whose children are male, between 6–12 years old, and have significant externalizing symptoms and whose primary caregiver have complete high school education will be invited to participate. Families will be randomized (1:1) into 03 groups: 1) standard care; 2) standard care + face-to-face parent training; 3) standard care + online parent training. Interventions are analogous, differing only in delivery format. In the face-to-face format, the intervention will be conducted by a specialized therapist and the online format will be carried out through a platform. There will be six sessions/modules, arranged on a weekly basis. Measures of externalizing symptoms, parental and children quality of life, parental stress and parenting style will be collected at baseline and after the intervention. Discussion: This clinical trial intends to verify the effects of a new, online, model of an evidence-based intervention, which would allow a wider access in the Brazilian context. Trial registration: Registered on Brazilian Registry of Clinical Trials (ReBEC). Number: RBR-6cvc85. July 24th (2020) 05:35 pm. [ABSTRACT FROM AUTHOR]

Background: Prefrontal dopamine is catabolized by the catechol-O-methyltransferase (COMT) enzyme. Current evidence suggests that the val/met single nucleotide polymorphism in the COMT gene can predict the efficiency of executive cognition in humans. Individuals carrying the val allele perform more poorly because less synaptic dopamine is available. Methodology/Principal Findings: We investigated the influence of the COMT polymorphism on motor performance in a task that requires different executive functions. We administered a manual aiming motor task that was performed under four different conditions of execution by 111 healthy participants. Participants were grouped according to genotype (met/met, met/val, val/val), and the motor performance among groups was compared. Overall, the results indicate that met/met carriers presented lower levels of peak velocity during the movement trajectory than the val carriers, but met/met carriers displayed higher accuracy than the val carriers. Conclusions/Significance: This study found a significant association between the COMT polymorphism and manual aiming control. Few studies have investigated the genetics of motor control, and these findings indicate that individual differences in motor control require further investigation using genetic studies. [ABSTRACT FROM AUTHOR]

Electronic media pervade modern life. Childhood is a crucial period for attentional development and the screen exposure time is increasing. This review aimed to understand the association between screen time and attention of children with typical development. A systematic review was conducted in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyzes PRISMA being registered at Prospero under number CRD42021228721. A search was performed in January 2021 with the following keywords: "screen time," "children," and "attention," combined with the operator AND, on databases PubMed, and PsycINFO. Four hundred and ninety-eight articles were identified, and 41 papers were fully read, of which 11 were included in this review. Most studies found associations between screen time and attention in children. Only one study reported that children with more screen time performed better in an attention task. The findings suggest that exposure to excessive screen time in children can be associated with attention problems. Parents and teachers may be involved in controlling screen exposure, especially after the extensive exposition to online classes, due to the pandemic. Further studies are needed to assess the influence of this overexposure on care over time. [ABSTRACT FROM AUTHOR]

Objective: To compare the distress level among Brazilian healthcare professionals during the Coronavirus disease 2019 (COVID-19) pandemic and estimate risks by sex, age, and occupation. Methods: In a longitudinal cohort design, a nationally distributed online survey was used to collect data from 10,490 active healthcare professionals who worked during the pandemic. Participants were mostly female, aged 18 to 82 years; 13 different health professions and all states of Brazil were represented. Results: The most frequent professions were psychology, dentistry, and nursing. The Brief Symptom Inventory (BSI) score suggested an increased distress perception among health professionals. Females showed poorer mental health than males, but the absolute rise in Global Severity Index (GSI) score was larger in males than in females. Younger adults reported more symptoms of psychological distress than older adults. The most impacted age group was between 30-39 years. Nurse technicians presented the highest risk of distress. Conclusion: Health professionals are essential to overcoming the pandemic; thus, their mental health status should be monitored, and features associated with increased distress should be identified. Our findings suggest distress risk should be stratified by occupation, age, and sex. Health professionals showed an increased distress perception. Women, individuals between the ages of 30 and 39, nursing personnel, and physicians were more likely to report distress compared with other health professionals. [ABSTRACT FROM AUTHOR]

Abstract: Background: Bipolar disorder (BD) is a complex disorder where genetic factors play a major role in its etiology. Probably, no other axis I diagnosis has a co-morbidity prevalence as high as BD. Since BDNF is involved in different ways in various psychiatric disorders we hypothesized that its genetic polymorphisms could be associated with the co-morbidity phenomenon in BD. Methods: We studied 320 subjects (160 BD patients and 160 healthy controls). Genotyping was performed using made-to-order TaqMan genotyping assays (rs4923463, rs6265, rs2049045, and rs7103411). Statistical analyses were performed using UNPHASED version 3.0.12 and Haploview 4.1. Results: No genotypic, allelic or haplotype differences were found between bipolar patients and healthy controls. Concerning exclusively the rs4923463 (G/G) there was a significant association with alcoholism (p=0.009), smoking (p=0.006) and violent suicide attempt (p=0.03). We further found that the G-G haplotype (rs4923463–rs2049045) (adjusted p=0.029) and the G-T haplotype (rs4923463–rs7103411) (adjusted p=0.029) were significantly more frequent in the group with alcoholism co-morbidity when compared with the group without this co-morbidity. Limitations: Sample size and retrospective assessment of suicide behavior and psychiatric comorbidities. Conclusions: The results obtained in our study indicate that BDNF variants may confer susceptibility to additional psychiatric diagnosis in BD. [Copyright &y& Elsevier]

Abstract: Background: Suicide prediction is a huge challenge for mental health workers. Structured interviews based on epidemiological and clinical factors don''t show effectiveness for suicide prevention. Biological markers, such as 5-HTTLPR, could help for identification of potential suicide attempters. Methods: We evaluated 198 bipolar patients and 103 health controls, using a structured interview according to DSM-IV criteria. Genotyping, blind of clinical assessment for identification of S carriers and structured interviews were performed in order to describe clinical and epidemiological factors which could be associated with suicide behavior. Statistical analyses were calculated by the x 2 test and logistic regression model. Results: We found that 26.77% and 16.67% had a lifetime history of non violent suicide attempt and violent suicide attempt, respectively. The clinical factors associated with violent and non violent suicide attempt had several differences. Violent suicide attempters had an earlier illness onset and had a higher number of psychiatric comorbidities (borderline personality disorder, panic disorder and alcoholism). The frequency of S allele carriers was higher only in those patients who had made a violent suicide attempt in their lifetime (x 2 =16.969; p =0.0001). In a logistic regression model including these factors, S allele carrier (5-HTTLPR) was the only factor associated with violent suicide attempt. Limitations: Sample size and retrospective assessment of suicide behavior history are the limitations of this study. Conclusions: Our study showed that serotonin polymorphism (5-HTTLPR) is strongly associated with violent suicidal behavior in BD patients. If confirmed, our results could be an important step to create a genetic tool for long-term suicide prediction. [Copyright &y& Elsevier]

Abstract: Dopamine-and-cAMP-regulated neuronal phosphoprotein (32 kDa) (DARPP-32), encoded by PPP1R1B, is expressed in brain regions receiving dopaminergic projections, including the prefrontal cortex (PFC), and is implicated in the pathophysiology of schizophrenia. The broad functional capacity of DARPP-32 has potential relevance to both psychotic and negative symptoms of schizophrenia. We wished to determine if DARPP-32 gene expression and variation at selected SNPs correlated significantly with patient phenotypes. We performed RT-PCR to quantify DARPP-32 mRNA from brain samples (Brodmann Area 46) donated by the Stanley Medical Research Institute (SMRI, Array Collection): 35 from unaffected controls (UC), 35 from patients with schizophrenia (SCZ), and 35 with bipolar disorder (BP). Relative mRNA expression was calculated in relation to the housekeeping gene Cyclophilin. SNP genotyping was conducted by PCR on DNA obtained from Brodmann Area 46. We found a significant difference in gene expression levels between SCZ patients who died by suicide (SCZ-S) (n =6) vs. other causes of death (SCZ-NS) (P <0.004), as well as between SCZ-S and UC (P <0.04). We genotyped the intron SNP rs907094 and found that the SCZ-S group was more similar to UC than to the SCZ-NS population. DARPP-32 expression differences between SCZ-S, SCZ-NS, and UC populations are consistent with previous literature suggesting that serotonin system components are also altered in suicide. Work in a larger sample is needed to confirm these findings. [Copyright &y& Elsevier]

Human T cell leukemia virus type-I (HTLV-1) infection courses with a myelopathy, the tropical spastic paraparesis (HAM/TSP). In a case-control study, we compared the neuropsychological profile and functional characteristics in two case HTLV-1-infected groups (asymptomatic and with HAM/TSP) with a control group negative for HTLV-1. Subjects were paired for age, sex, and educational features. The case group differed from control group in neuropsychological measures such as in episodic memory recall, executive functions, and fine motor dexterity measure. Individuals with HAM/TSP have more depressive symptoms and worst performance in activities of daily living (ADL) presenting a less functionality. In multivariate models, the fine motor performance, the executive functioning, the recognition memory, and the depressive symptoms explained part of the variance in functionality. Those findings may contribute to understand of everyday life impairments and limitations of HTLV-1-infected population and to organize the rehabilitation. Once more, based in neuropsychological and functional data, we can reaffirm that HTLV-1 is never a benign condition, but sometimes it is only in a stage coursing with less symptoms. [ABSTRACT FROM AUTHOR]

The deposition of amyloid plaques is considered one of the main microscopic features of Alzheimer's disease (AD). Since plaque formation can precede extensive neurodegeneration and it is the main clinical manifestation of AD, it constitutes a relevant target for new treatment and diagnostic approaches. Micro-Raman spectroscopy, a label-free technique, is an accurate method for amyloid plaque identification and characterization. Here, we present a high spatial resolution micro-Raman hyperspectral study in transgenic APPswePS1ΔE9 mouse brains, showing details of AD tissue biochemical and histological changes without staining. First we used stimulated micro-Raman scattering to identify the lipid-rich halo surrounding the amyloid plaque, and then proceeded with spontaneous (conventional) micro-Raman spectral mapping, which shows a cholesterol and sphingomyelin lipid-rich halo structure around dense-core amyloid plaques. The detailed images of this lipid halo relate morphologically well with dystrophic neurites surrounding plaques. Principal Component Analysis (PCA) of the micro-Raman hyperspectral data indicates the feasibility of the optical biomarkers of AD progression with the potential for discriminating transgenic groups of young adult mice (6-month-old) from older ones (12-month-old). Frequency-specific PCA suggests that plaque-related neurodegeneration is the predominant change captured by Raman spectroscopy, and the main differences are highlighted by vibrational modes associated with cholesterol located majorly in the lipid halo. [ABSTRACT FROM AUTHOR]

Given the long subclinical stage of Alzheimer's disease (AD), the study of biomarkers is relevant both for early diagnosis and the fundamental understanding of the pathophysiology of AD. Biomarkers provided by Amyloid-β (Aβ) plaques have led to an increasing interest in characterizing this hallmark of AD due to its promising potential. In this work, we characterize Aβ plaques by label-free multimodal imaging: we combine two-photon excitation autofluorescence (TPEA), second harmonic generation (SHG), spontaneous Raman scattering (SpRS), coherent anti-Stokes Raman scattering (CARS), and stimulated Raman scattering (SRS) to describe and compare high-resolution images of Aβ plaques in brain tissues of an AD mouse model. Comparing single-laser techniques images, we discuss the origin of the SHG, which can be used to locate the plaque core reliably. We study both the core and the halo with vibrational microscopy and compare SpRS and SRS microscopies for different frequencies. We also combine SpRS spectroscopy with SRS microscopy and present two core biomarkers unexplored with SRS microscopy: phenylalanine and amide B. We provide high-resolution SRS images with the spatial distribution of these biomarkers in the plaque and compared them with images of the amide I distribution. The obtained spatial correlation corroborates the feasibility of these biomarkers in the study of Aβ plaques. Furthermore, since amide B enables rapid imaging, we discuss its potential as a novel fingerprint for diagnostic applications. [ABSTRACT FROM AUTHOR]

Abstract: NALCN (sodium leak channel, non-selective) is located on chromosome 13q (suggested linkage region for schizophrenia). We analyzed 21 polymorphisms in 464 schizophrenia subjects, 220 controls subjects and 119 small nuclear families. We observed nominal association with rs9518320 and rs9518331, suggesting that NALCN is not related to schizophrenia risk. [Copyright &y& Elsevier]

The proposed pathogenesis of Sydenham's chorea (SC) is an autoantibody-mediated basal ganglia dysfunction. Our study has shown that incubation of PC12 cells with complement-inactivated serum from SC patients was associated with a significant increase in Ca2+ levels evoked by KCl stimulus (mean ± SEM, 341.0 ± 8.7% of fluorescence intensity, arbitrary units) when compared with incubation with control serum (313.8 ± 8.7% of fluorescence intensity, arbitrary units; P = 0.01). The increase in Ca2+ levels determined by SC patients sera correlated directly with the enzyme-linked immunosorbent assay optical density values for anti-basal ganglia antibodies. Our study supports the hypothesis that antibodies against basal ganglia in SC may cause their dysfunction. © 2005 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Many neuropsychiatric disorders are associated with both dopaminergic (DAergic) and developmental hypotheses. Since DAergic receptors are expressed in the developing brain, it is possible that alterations in dopamine (DA) signaling may impair brain development and consequent behavior. In our previous study, using a zebrafish model, we showed that an increase of DA during the 3 to 5 days postfertilization (dpf) developmental window (an important window for GABAergic neuronal differentiation) affects the motor behavior of 5 dpf larvae. In this study, we set out to determine whether these behavioral alterations were sustained in larvae at older stages (7 and 14 dpf). To test this hypothesis, we chronically treated zebrafish larvae from 3 to 5 dpf with DA. After washing the drug, we recorded and analyzed the first 5 and 30 min of the motor behavior of 5, 7, and 14 dpf subjects. We analyzed mobile episodes, distance traveled, time mobile, distance traveled per mobile episode, time in movement per mobile episode, and distance traveled per time mobile. We showed, once again, that an increase of DA during the 3 to 5 dpf developmental window reduces the number of movement episodes initiated by 5 dpf larvae. We also detected a decrease of other motor behavior parameters in 5 dpf DA‐treated larvae. We observed that these alterations are sustained in the 7 dpf larvae. However, we did not see these general locomotor alterations in the 14 dpf larvae. Moreover, we detected a decrease of distance traveled and an increase of time of locomotion per episode in the first 5 min of behavioral analyses in 14 dpf DA‐treated larvae. To test if the alterations in the first 5 min were due to anxiety‐like behavior, we used a light/dark preference paradigm. We recorded 5dpf, 7dpf, and 14dpf larvae for 5 min and analyzed time of freezing, preference for light or dark, number of entries to the dark, percentage of time in the light. We observed that 5dpf larvae treated with DA showed more freezing, less passages to the dark, and more time spent in the light as compared to their control counterparts. But 7dpf and 14dpf larvae did not show these alterations. Taken overall, therefore, our results suggest that DA does play a role in the development of zebrafish motor behavior, and, furthermore, that some behaviors are more sensitive than others to the effects of DAergic imbalances during development. [ABSTRACT FROM AUTHOR]

Peripheral biomarker and post-mortem brains studies have shown alterations of neuronal calcium sensor 1 (Ncs-1) expression in people with bipolar disorder or schizophrenia. However, its engagement by psychiatric medications and potential contribution to behavioral regulation remains elusive. We investigated the effect on Ncs-1 expression of valproic acid (VPA), a mood stabilizer used for the management of bipolar disorder. Treatment with VPA induced Ncs-1 gene expression in cell line while chronic administration of this drug to mice increased both Ncs-1 protein and mRNA levels in the mouse frontal cortex. Inhibition of histone deacetylases (HDACs), a known biochemical effect of VPA, did not alter the expression of Ncs-1. In contrast, pharmacological inhibition or genetic downregulation of glycogen synthase kinase 3β (Gsk3β) increased Ncs-1 expression, whereas overexpression of a constitutively active Gsk3β had the opposite effect. Moreover, adeno-associated virus-mediated Ncs-1 overexpression in mouse frontal cortex caused responses similar to those elicited by VPA or lithium in tests evaluating social and mood-related behaviors. These findings indicate that VPA increases frontal cortex Ncs-1 gene expression as a result of Gsk3 inhibition. Furthermore, behavioral changes induced by Ncs-1 overexpression support a contribution of this mechanism in the regulation of behavior by VPA and potentially other psychoactive medications inhibiting Gsk3 activity. [ABSTRACT FROM AUTHOR]

Individuals who experience mild COVID-19 can suffer from long-lasting cognitive symptoms. Notably, 26% of these individuals experience difficulties with visuospatial abilities six months after infection. However, among those who initially exhibited visuoconstructive impairments, 66% showed improvement or complete reversal over time. Additionally, changes in cytokine levels, particularly CCL11, HGF, and CXCL10, were observed. These results suggest a potential link between ongoing cognitive issues and elevated levels of pro-inflammatory cytokines, which merits further investigation. [Display omitted] • Persistent Cognitive Challenges Post Mild COVID-19. • Recovery in Visuoconstructive Abilities Noted. • Link Between Cytokine Levels and Cognitive Issues. • Neuroinflammation's Role in Long COVID Explored. • Importance of Further Cytokine-Cognition Research Highlighted. [ABSTRACT FROM AUTHOR]

The global prevalence of Alzheimer's disease (AD) points to endemic levels, especially considering the increase of average life expectancy worldwide. AD diagnosis based on early biomarkers and better knowledge of related pathophysiology are both crucial in the search for medical interventions that are able to modify AD progression. In this study we used unsupervised spectral unmixing statistical techniques to identify the vibrational spectral signature of amyloid β aggregation in neural tissues, as early biomarkers of AD in an animal model. We analyzed spectral images composed of a total of 55 051 Raman spectra obtained from the frontal cortex and hippocampus of five bitransgenic APPswePS1ΔE9 mice, and colocalized amyloid β plaques by other fluorescence techniques. The Raman signatures provided a multifrequency fingerprint consistent with the results of synthesized amyloid β fibrils. The fingerprint obtained from unmixed analysis in neural tissues is shown to provide a detailed image of amyloid plaques in the brain, with the potential to be used as biomarkers for non-invasive early diagnosis and pathophysiology studies in AD on the retina. [ABSTRACT FROM AUTHOR]

• Neural stem cells are not equally plastic homogeneous cells, but rather a combination of distinct subpopulations. • The cerebrospinal fluid is an essential component of the neural stem cell niche. • Neural stem cells auto-regulate themselves. • Innervations release neurotransmitters to neural stem cells, and affect neural stem cell behavior. • The biggest challenge remains to study the neural stem cell niche in humans. In mammals, new neurons can be generated from neural stem cells in specific regions of the adult brain. Neural stem cells are characterized by their abilities to differentiate into all neural lineages and to self-renew. The specific microenvironments regulating neural stem cells, commonly referred to as neurogenic niches, comprise multiple cell populations whose precise contributions are under active current exploration. Understanding the cross-talk between neural stem cells and their niche components is essential for the development of therapies against neurological disorders in which neural stem cells function is altered. In this review, we describe and discuss recent studies that identified novel components in the neural stem cell niche. These discoveries bring new concepts to the field. Here, we evaluate these recent advances that change our understanding of the neural stem cell niche heterogeneity and its influence on neural stem cell function. [ABSTRACT FROM AUTHOR]

• M1 anodal bi-hemispheric condition worsens performance of taekwondo athletes in the FSKT. • M1 anodal bi-hemispheric condition increase session-RPE in taekwondo athletes. • The M1 anodal bi-hemispheric condition did not change the performance on CMJ. Transcranial Direct Current Stimulation (tDCS) is a neuromodulatory technique that has been used as an ergogenic aid in exercise/sports performance. However, little is known about its effects on highly-trained subjects, as athletes. The present study aimed to verify the effects of bi-hemispheric anodal tDCS (a-tDCS) on the performance of taekwondo athletes. Additionally, we investigated the persistence of the effects of the a-tDCS one hour after it. Nineteen Taekwondo athletes received active or sham bi-hemispheric a-tDCS over the primary motor cortex (M1). a-tDCS was delivered at 1.5 mA for 15 min. Athletes performed Countermovement Jumps (CMJ) and the Frequency Speed of Kick Test (FSKT) immediately (Mo1) and one hour after stimulation (Mo2). The athletes also reported their session-rating of perceived exertion (session-RPE). The total number of kicks (TK) was higher in sham than in the active a-tDCS condition (p < 0.01). In addition, TK was higher at Mo2 than at Mo1 (p < 0.05). Similarly, the session-RPE was higher in the a-tDCS condition (p < 0.05) and was greater one-hour post-stimulation (p < 0.01). No differences were found for CMJ performance (p > 0.05). Thus, bi-hemispheric a-tDCS worsens performance of taekwondo athletes, and the effect remains present even 1 h after the stimulation. [ABSTRACT FROM AUTHOR]

• The sclerotic hippocampus and hippocampal subfields have significant lower volumes than non-sclerotic hippocampus. • The non-sclerotic hippocampus and its subfields volumes in MTLE patients are significantly lower than in healthy controls. • CA1 and CA4 atrophy are associated with better prognosis. • CA2-3 vol loss is not associated with prognosis. • Freesurfer software preoperative hippocampal subfields volume analysis can help to define the best surgical candidates. The International League Against Epilepsy (ILAE) classification system for hippocampal sclerosis (HS) is based on location and extent of hippocampal neuron loss. Specific subgroups have a better surgical prognosis. Automated hippocampal subfields segmentation and volume measure could be obtained from high field MRI and used to pre-operatively classify the patients in ILAE subgroups to define best candidates for surgery. This prospective study included 86 MTLE patients, candidates to surgical treatment and ten healthy volunteers. Volumetric analysis of the hippocampal sublayers was performed through the Freesurfer software, using 3 Teslas volumetric T1 weighted MRI. We correlated the hippocampal subfields measures with the seizure control after one year from surgery. Volume loss in Cornu Amonis (CA) 1 and 4 were related to better surgical outcome after one year. Atrophy in CA 2 and CA 3 did not improve the prognosis. These results are in agreement with the ILAE classification of hippocampal subfields sclerosis. [ABSTRACT FROM AUTHOR]

Children with Attention-Deficit Hyperactivity Disorder (ADHD) struggle to perform a host of daily activities. Many of these involve forceful interaction with objects and thus implicate dynamic touch. Therefore, deficits in dynamic touch could underlie functional difficulties presented by ADHD children. We investigated whether performance on a dynamic touch task (length perception by wielding) differ between children with ADHD and age-matched controls. We further examined whether this difference could be explained by fractal temporal correlations (wielding dynamics). Forty-two children (ADHD: 21; typically developing: 21) wielded unseen wooden rods and reported their perceived length in the form of magnitude productions. The rods varied in the magnitude of the first principal moment of inertia (I1). Three-dimensional displacements of hand and rod positions were submitted to Detrended Fluctuation Analysis to estimate trial-by-trial temporal correlations. Children with ADHD reported shorter length for rods with higher I1 than their typically developing peers, indicative of reduced sensitivity to mechanical information supporting dynamic touch. Importantly, temporal correlations in wielding dynamics moderated children’s usage of I1. This finding points to a role of exploratory movements in perceptual deficits presented by children with ADHD and, thus, should be considered a new potential target for interventions. [ABSTRACT FROM AUTHOR]

Neuromodulation of deep brain structures (deep brain stimulation) is the current surgical procedure for treatment of Parkinson's disease (PD). Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD. We were able to show that optogenetic activation of secondary (M2) motor cortex improves motor functions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved in motor control, and makes synaptic contacts with dopaminergic neurons. Strikingly, optogenetic activation of M2 neurons or axons into the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with l-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under l-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented that discusses reliability of working memory assessment in neurocognitive disorders.

The present study introduces the Extreme Climate Event Database (EXCEED), a picture database intended to induce emotionally salient stimuli reactions in the context of natural hazards associated with global climate change and related extreme events. The creation of the database was motivated by the need to better understand the impact that the increase in natural disasters worldwide has on human emotional reactions. This new database consists of 150 pictures divided into three categories: two negative categories that depict images of floods and droughts, and a neutral category composed of inanimate objects. Affective ratings were obtained using online survey software from 50 healthy Brazilian volunteers who rated the pictures according to valence and arousal, which are two fundamental dimensions used to describe emotional experiences. Valence refers to the appraisal of pleasantness conveyed by a stimulus, and arousal involves internal emotional activation induced by a stimulus. Data from picture rating, sex difference in affective ratings and psychometric properties of the database are presented here. Together, the data validate the use of EXCEED in research related to natural hazards and human reactions. [ABSTRACT FROM AUTHOR]