A Comparative Evaluation of Error Processing Performance and its Relationship with Cognitive Function in Patients with Alzheimer's Disease, Individuals with Mild Cognitive Impairment, and Normal Controls Using the Event-Related Potentials.

Background: Some pathological changes occur in patients with Alzheimer's disease (AD) prior to the onset of clinical symptoms. Objective: In the present study, we aimed to investigate the potential of event-related potential (ERP) components in error processing performance as a neuromarker of mild cognitive impairment (MCI) and transition to AD and their relation with cognitive functions. Methods: We conducted an evaluation of 16 patients diagnosed with AD, 16 patients with MCI, and 15 normal controls using three subtests from the Cambridge Neuropsychological Testing Automated Battery (CANTAB). The ERP components of error processing were extracted and compared among the three groups using a modified version of the Eriksen flanker task. Additionally, we assessed the correlation between the cognitive results and the ERP components. Results: Significant differences were observed among the three groups in terms of providing correct responses following errors and the amplitude of error-related negativity (ERN). These differences were also significant between all paired groups. Regarding other ERP components of error processing and the peak latency of ERN, no significant differences were observed among the three groups. The findings revealed that the spatial working memory and new learning were correlated with the amplitude of ERN. Conclusions: In the context of error processing performance, both the accuracy of responses following an error and the amplitude of ERN can be considered as indicators of MCI and its progression to AD. The present findings do not support the use of other error processing components as differential markers in the three groups.

Concurrent and Discriminant Validity of the Farsi Translation of the Social Responsiveness Scale-Second Edition (SRS-2) and Social Communication Questionnaire (SCQ).

Objective: Early detection of autism spectrum disorder (ASD) can lead to earlier intervention and greater improvement of children's quality of life and performance; hence, the use of screening tools is essential to facilitate the diagnosis process. The aim of the present study was to determine the clinical and differential validity of Social Responsiveness Scale-Second Edition (SRS-2) and Social Communication Questionnaire (SCQ) in a group of children and adolescents with autism spectrum disorder compared to a normal developmental group. Method : The study was conducted in Roozbeh Hospital involving 52 children with ASD and 53 typically developing (TD) children, aged between 4-12 years. Their parents completed the SRS-2 and SCQ. These children were also interviewed using the Childhood Autism Rating Scale, 2nd Edition (CARS-2) and Asperger Syndrome Diagnostic Scale (ASDS). After completion, the results were analyzed using the SPSS Version 18 software and a significant level of 0.05. Results: The average age of children in the autism group was 7.5 ± 2.7 years, while in the typically developing (TD) children group, it was 7.7 ± 2.3 years (P = 0.656). A positive correlation coefficient was observed between the CARS questionnaire score, the SRS questionnaire score, the SCQ questionnaire score, and the ASDS (P < 0.01). In the SRS questionnaire, the area under the ROC curve was 0.976, and in the SCQ questionnaire it was 0.953, both of which had a good and significant diagnostic value (P < 0.001). A sensitivity of 0.942 and specificity of 0.811 for the cut-off point of 62.5 were obtained in the SRS questionnaire. Additionally, a sensitivity of 0.865 and specificity of 0.925 for the cut-off point of 15.5 were achieved in the SCQ questionnaire. Conclusion: The SRS-2 and the SCQ are sensitive and specific tools for identifying and discriminating children with autism spectrum disorder.

Association of verbal and non-verbal theory of mind abilities with non-coding variants of OXTR in youth with autism spectrum disorder and typically developing individuals: a case-control study.

BACKGROUND: The ability to attribute mental states to others is called theory of mind (ToM) and is a substantial component of social cognition. This ability is abnormally developed in individuals with autism spectrum disorder (ASD). Several studies over the past decade have identified the oxytocin receptor gene (OXTR) and its variants as promising components for explaining the molecular mechanisms underlying Theory of Mind (ToM). The main aim of this study is to examine the association between rs2268498 and rs53576, two functional single nucleotide polymorphisms (SNPs), and verbal and non-verbal ToM in children and adolescents with ASD and a group of typically developing youth. METHODS: The study involved 44 children and adolescents with high-functioning ASD aged 8 to 18 years old and 44 TD individuals who were matched on age and sex. In all participants, blood samples were collected and rs2268498 and rs53576 were genotyped. Happe's Strange Stories test and the moving shapes paradigm were used to measure verbal and non-verbal ToM in all participants. RESULTS: The results of permutation tests and logistic regression suggested that in TD group, rs2268498 AA carriers showed significant higher scores in variables representing verbal ToM (ToM stories and appropriateness score) whereas, in ASD group, rs53576 AA carriers exhibited significant better performance in parameters related to non-verbal ToM (ToM general rule and intentionality score). The results of hierarchical clustering in both groups support the findings by distinguishing between language-related and language-independent aspects of ToM. CONCLUSIONS: In the present study, we examined the association between rs2268498 and rs53576 and social functioning in individuals with ASD and TD group. We found preliminary evidence that rs2268498 and rs53576 are associated with ToM related abilities in healthy individuals as well as in autistic individuals. Accordingly, rs2268498 and rs53576 may play an important role in predicting ToM capabilities. It will be necessary to conduct further research to address the association of genetic variants with a deficit in ToM in individuals with ASD.

The Brain Networks Basis for Deductive and Inductive Reasoning: A Functional Magnetic Resonance Imaging Study.

Introduction: Frontoparietal (FPN) and cingulo-opercular network (CON) control cognitive functions needed in deductive and inductive reasoning via different functional frameworks. The FPN is a fast intuitive system while the CON is slow and analytical. The default-interventionist model presents a serial view of the interaction between intuitive and analytic cognitive systems. This study aims to examine the activity pattern of the FPN and CON from the perspective of the default-interventionist model via reasoning. Methods: We employed functional magnetic resonance imaging (fMRI) to investigate cingulo-opercular and frontoparietal network activities in 24 healthy university students during Raven and Wason reasoning tasks. Due to the different operation times of the CON and FPN, the reaction time was assessed as a behavioral factor. Results: During Raven's advanced progressive matrices (RAPM) test, both the CON and FPN were activated. Also, with the increase in the difficulty level of the Raven test, a linear increase in response time was observed. In contrast, during the Wason's selection task (WST) test, only the activity of FPN was observed. Conclusion: The results of the study support the hypothesis that the default-interventionist model of dual-process theory provides an accurate explanation of the cognitive mechanisms involved in reasoning. Thus, the response method (intuitive/analytical) determines which cognitive skills and brain regions are involved in responding. Highlights: The cingulo-opercular and fronto-parietal networks (FPNs) control cognitive functions and processes.The frontoparietal network is a fast intuitive system that utilizes short-time attention which is compatible with type 1 processing. In contrast, the cingulo-opercular network (CON) is an analytical time-consuming system that utilizes attention and working memory for a longer time, compatible with type 2 processing.The default-interventionist model of a dual-process theory states that our behaviors are controlled by type 1 processing unless we are confronted with novel and complex problems in which we have no prior experiences. Plain Language Summary: The present study examined the activity of two task-based brain networks through performing diffrent type of reasoning tasks. Fronto-parietal and Cingulo-opercular are the two task-based brain networks that are responsible for cognitive control. These two brain networks direct the way to use cognitive skills and executive functions which are necessary to perform cognitive tasks especially higher-order ones as reasoning tasks. Since the two types of inductive and deductive reasoning tasks requier two different bottom-up and top-down cognitive control respectively, different cognitive skills would be needed which affect the activity of fronto-parietal and cingulo-opercular brain networks. Our results showed that through inductive reasoning task which examined by RAVEN, both of the fronto-parietal and cingulo-opercular brain networks were activated but deductive reasoning task which examined by Wason Selection Card test, just the fronto-parietal brain network was activated. It seems that in the case of deductive reasoninf task, there is a higher probability of errors which lead to giving less correct responses. Based on our results, subjects paid not enough attention to details, so had failure to update informations that leaded to responding with errors. Inactivity of cingulo-opercular network through dedeuctive reasoning task clearly showed that the bottom-up cognitive control did not happen successfully. As a result of that, information processing did not proceed properly.

Hesperidin reduces depressive symptoms in post-coronary artery bypass graft patients with mild depression.

Previous studies have shown that hesperidin may have beneficial effects on depression; however, to the best of our knowledge, no clinical trial has yet been conducted in this area. The aim of the present study was, therefore, to determine the effects of hesperidin on depression, serum brain-derived neurotrophic factor (BDNF), and serum cortisol levels in post-coronary artery bypass graft (CABG) patients. Toward this goal, 73 post-CABG patients with depression symptoms were enrolled. The participants were randomly divided into two groups to receive either 200 mg/day hesperidin (n = 38) or placebo (n = 35) for 12 weeks. Depressive symptoms, serum BDNF, and cortisol levels were then assessed at the baseline and after intervention. Beck Depression Inventory-II (BDI-II) was also used to determine the severity of depression. Sixty-six patients completed the trial. Hesperidin decreased depression severity after 12 weeks, as compared to placebo (p = .004), but serum BDNF and cortisol were not statistically significantly different in the two groups after the intervention. Subgroup analyses also showed that, while in the patients with mild depression, the score of BDI-II was significantly different in the hesperidin and placebo groups after intervention; there was no difference in the severity of depression between the two groups in patients with moderate-to-severe depression. To conclude, a dose of 200 mg/day hesperidin may reduce depressive symptoms after 12 weeks in post-CABG patients with mild depression.

Fronto-Cerebellar Neurometabolite Alterations After Methylphenidate in Children and Adolescents With ADHD: A Proton Magnetic Resonance Spectroscopy Study.

OBJECTIVE: The fronto-cerebellar circuit is involved in ADHD pathophysiology. Methylphenidate, as a first-line medication for ADHD, affects different brain regions, however, its effect on the fronto-cerebellar circuit is not investigated sufficiently. We aimed to investigate the effect of 8-week treatment with methylphenidate on neurometabolite ratios in the fronto-cerebellar circuit in ADHD participants using magnetic resonance spectroscopy (MRS). METHODS: Fifteen drug-naïve ADHD children and adolescents were enrolled in the present study. Two single-voxel MR spectra were acquired from the right dorsolateral prefrontal cortex (DLPFC) and left Crus 1, before and after the medication. Also, neuropsychological and behavioral assessments were administered. RESULTS: After medication, the glutamate/creatine in the DLPFC and the choline/creatine in the Crus 1 decreased in the ADHD participants. CONCLUSION: These findings propose that methylphenidate-induced metabolite changes in the fronto-cerebellar circuit could be associated with improvement in cognitive/behavioral characteristics in ADHD. Also, results highlighted cerebellar engagement in ADHD pathophysiology.

Features and effects of computer-based games on cognitive impairments in children with autism spectrum disorder: an evidence-based systematic literature review.

INTRODUCTION: Children with Autism Spectrum Disorder (ASD) have different cognitive and intelligence profiles than typical developing individuals. Some of these children need cognitive rehabilitation. This study's main purpose is to provide a systematic review about applying computerized cognitive games for autistic children and to determine the effectiveness of such interventions. MATERIAL AND METHODS: A thorough search of the ISI Web of Science, Medline (through PubMed), Scopus, IEEE Xplore, and APA PsycInfo databases was performed for articles published from inception to May 17, 2022. RESULTS: Of 1746 papers, 28 studies were found to be eligible in this systematic review. Fifteen studies (53.57%) compared a Control Group (CG) with Experimental Groups (EGs), while 13 papers (46.42%) evaluated only the impact of the applied intervention in an experimental group. Major domains of cognitive functions are divided into five main categories: 1. Executive functions, 2. Social cognition/emotions, 3. Attention/concentration, 4. Learning and memory, and 5. Language. In 42.85% (12 studies) of the screened papers, social cognition and emotions were assessed after cognitive rehabilitation. The highest rate of effects reported by studies were related to social cognition enhancement. Of the total number of included studies, 17 studies reported a positive effect at all scales, of which nine were quasi-experimental, and seven were fully experimental. CONCLUSION: Using suitable computerized game-based solutions could enhance cognition indexes in autistic children. Hence, further investigation is needed to determine the real effectiveness of these novel technologies.

Examining the Dominant Presence of Brain Grey Matter in Autism During Functional Magnetic Resonance Imaging.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with symptoms appearing from early childhood. Behavioral modifications, special education, and medicines are used to treat ASD; however, the effectiveness of the treatments depends on early diagnosis of the disorder. The primary approach in diagnosing ASD is based on clinical interviews and valid scales. Still, methods based on brain imaging could also be possible diagnostic biomarkers for ASD. Methods: To identify the amount of information the functional magnetic resonance imaging (fMRI) reveals on ASD, we reviewed 292 task-based fMRI studies on ASD individuals. This study is part of a systematic review with the registration number CRD42017070975. Results: We observed that face perception, language, attention, and social processing tasks were mainly studied in ASD. In addition, 73 brain regions, nearly 83% of brain grey matter, showed an altered activation between the ASD and normal individuals during these four tasks, either in a lower or a higher activation. Conclusion: Using imaging methods, such as fMRI, to diagnose and predict ASD is a great objective; research similar to the present study could be the initial step.

Evaluating the Effects of Rivastigmine on Decision-Making in Patients with Mild Cognitive Impairment by Cambridge Neuropsychological Test Automated Battery (CANTAB); A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Decision-making is a complex process, and most studies showed that patients with mild cognitive impairment (MCI) make worse decisions than healthy people. Objectives: This study aims to evaluate the effect of rivastigmine on the decision-making of MCI patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB) tests. Methods: The study was conducted at the Roozbeh Hospital neurology clinic, and 30 patients with mild cognitive impairment over 40 years old were randomly recruited to receive rivastigmine or placebo twice daily for 12 weeks. The initial dose of rivastigmine or placebo was 1.5 mg twice daily and was increased to 3 mg twice daily per patient compliance. A CANTAB test was conducted before and following the intervention. Results: The mean age of patients in the rivastigmine group was 58.93 ± 10.88, and in the placebo group was 59.33 ± 10.34. The median MMSE (Mini-Mental State Examination) was 26 (IQR = 25 - 26) in both groups. Patients in the rivastigmine group showed significant differences in all subgroup tests of CGT, IST, and SST except in risk adjustment in the CGT test, discrimination in the IST test, and median correct RT on the go trial and SSRT in the SST test. The most commonly reported adverse effects were gastrointestinal complications. Conclusions: According to the results, rivastigmine significantly improved the primary decision-making outcomes in comparison with placebo.

Evaluation of fronto-cerebellar neurometabolites in youth with ADHD compared to the healthy group and their associations with cognitive and behavioral characteristics: A proton magnetic spectroscopy study.

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders, characterized by specific cognitive and behavioral symptoms. A fronto-cerebellar circuit is implicated in ADHD, and despite its role in cognitive/behavioral aspects, the neurochemical alterations in this circuit are not well understood. The present study aimed to compare neurometabolite ratios of the fronto-cerebellar circuit between ADHD and control participants, using proton magnetic resonance spectroscopy (1H MRS), and investigate whether neurometabolites related to cognitive/behavioral characteristics. Fifteen children and adolescents with ADHD and 19 healthy control participants were enrolled in this study. Two single voxel spectra localized in the right dorsolateral prefrontal cortex (DLPFC) and left Crus 1 were taken using PRESS sequence. Also, neuropsychological performance and behavioral characteristics were evaluated. Results revealed that ADHD group had different choline/creatine and glutamate/creatine ratios in the fronto-cerebellar circuit, compared to healthy controls. The current study also found significant correlations between neurometabolite ratios in the both region of interests (ROIs) and cognitive/behavioral characteristics. These results suggest that alterations in fronto-cerebellar metabolites may be related to cognitive and behavioral deficits in ADHD, and also, our findings highlight that the cerebellum may be involved in the pathophysiology of ADHD.

Normative Data and Reliability of the Moving Shapes Paradigm.

Objective: Moving Shapes paradigm is a test that evaluates intentionality as a theory of mind (ToM) component. This study aimed to assess the normative data and reliability of this test in a community sample of 9-11-year-old children. Method : A total of 398 children aged between 9 and 11 years were recruited from mainstream elementary schools through a random cluster sampling. All participants were evaluated using the Moving Shapes paradigm. To evaluate test-retest reliability, the test was administered again after 2-4 weeks. Results: The intentionality mean score was 29.70 (+5.88) out of 60. There was no significant difference between girls and boys in test scores. Age was not significantly related to the paradigm variables scores. Ten percent of the participants achieved the scores below 22, and 10% above 37. Cronbach's Alfa was 0.40 for the intentionality score. The test-retest reliability was fair to good (0.43 - 0.79) for different groups of animations. The inter-rater agreement was 80%. Conclusion: The study found that the Moving shapes paradigm is a reliable instrument to evaluate intentionality in normal school-aged children.

The Reliability of the Social Responsiveness Scale-2 in an Iranian Typically Developing Group of Children.

Objective: The Social Responsiveness Scale-2 (SRS-2) is a well-known screening instrument to assess autistic spectrum symptoms quantitatively. This study assessed the different types of reliability of the Farsi translation of the scale. Method : This scale was translated into Farsi and back translated considering all aspects of methodology in translation. Then, based on stratified sampling, 533 7-11-year-old students were randomly selected from the mainstream schools located in the central parts of Tehran, the capital of Iran. For all the students, SRS-2 was completed by both the parents and teachers. To check retest reliability, the test was administered again for 15% of the total participants after a 2-4 week-period. Cronbach's alpha coefficient, split-half" and Gottman" methods, and intra-class correlation coefficient (ICC) were used. Results: The mean total raw score was 48.47 (±23.63) and 53.17 (±27.33) in the sequence of the parents and teachers' reports. The internal consistency (Cronbach's alpha; 0.86 and 0.89), test-retest reliability (ICC; 0.72 and 0.83 for parents and teacher' ratings, respectively), and interrater reliability (ICC; 0.72) showed well-accepted measurement performance. Conclusion: The findings indicated that the Farsi SRS-2 can be used as a reliable instrument to measure social responsiveness as autistic symptoms in Iranian child population.

Cross-Cultural Validation and Normative Data of the Social Responsiveness Scale in a Group of Iranian General Child Population.

This study aimed to assess the validity and normative statistics of the Farsi version of the Social Responsiveness Scale-2 (SRS-2). Among the mainstream elementary schools, 191 boys and 342 girls with a mean age of 9.46 (+ 1.72) years were recruited. Teachers and parents completed the SRS-2. The parents also answered the Social Communication Questionnaire (SCQ) and the Vineland Adaptive Behavior Scale (VABS). There were not any significant differences regarding the parents' and teachers' ratings of the SRS mean scores in terms of gender, academic level, and age. The SRS was significantly correlated with the SCQ (0.438) and VABS (- 0.142) mean scores. The study supported the validity of the SRS as a screening instrument for social communication problems in Farsi-speaking school-aged children.

Effects of zinc, vitamin D, and their co-supplementation on mood, serum cortisol, and brain-derived neurotrophic factor in patients with obesity and mild to moderate depressive symptoms: A phase II, 12-wk, 2 × 2 factorial design, double-blind, randomized, placebo-controlled trial.

OBJECTIVE: The aim of this study was to investigate the effects of zinc, vitamin D, and their co-supplementation versus placebo on changes in the Beck Depression Inventory II (BDI-II) score, serum cortisol level, and brain-derived neurotrophic factor (BDNF) in obese/overweight patients with depressive symptoms. METHOD: This 2 × 2 factorial, double-blind, randomized, placebo-controlled trial with obese/overweight patients with depressive symptoms was conducted in the Endocrinology and Metabolism Research Center (EMRC), Vali-Asr, Emam Khomeini Hospital between July 2016 and February 2017. The intervention period was 12 wk. There were 140 randomized participants who were obese or overweight (mean ± SD, 38.35± 6.70 y of age; mean ± SD body mass index, 30.1 ± 3.78 kg/m2) with BDI ≥ 10. Participants were randomly assigned to one of four groups in a 1:1:1:1 ratio: 2000 IU/d vitamin D + zinc placebo; 30 mg/d zinc gluconate + vitamin D placebo; 2000 IU/d vitamin D + 30 mg/d zinc gluconate; or vitamin D placebo + zinc placebo for 12 wk. RESULTS: We analyzed 125 participants, and a significant decrease in BDI-II was found among those who received zinc, vitamin D, or joint zinc-vitamin D supplements compared with the placebo group (P < 0.001). Zinc was significantly more effective than vitamin D on decreasing the depression score. Supplementation with zinc, vitamin D, or a combination of the two had no significant effects on serum cortisol (P = 0.974) or BDNF (P = 0.076). Fifteen patients discontinued participation owing to pregnancy (n = 1), severe anemia (n = 1), and unspecified unwillingness to continue (n = 13). CONCLUSION: Supplementation with zinc, vitamin D, or in combination for 12 wk yielded significant beneficial effects on the BDI-II score in obese or overweight patients with BDI-II ≥10.

A new semi-nonverbal task glance, moderate role of cognitive flexibility in ADHD children's theory of mind.

Introduction: Studies have documented both executive functions (EF) impairment in children with Attention Deficit / Hyperactivity Disorders (ADHD) and Theory of Mind (ToM), yielding mixed results, possibly because of a variety of tasks used, all requiring different levels of language skills.Aim: To investigate the relationship between ToM and EF with non-language-based tasks.Methods: Thirty ADHD (7-9 years old) were compared to thirty controls (age and IQ matched). Participants' ToM was assessed using the Animated Triangles task and two EF tasks, namely spatial control test, the Stockings Of Cambridge (SOC) and rule and acquisition test, the Intra-Extra Dimensional set shift (IED)-from the neuropsychological battery of the Cambridge Neuropsychological Test Automated Battery (CANTAB).Results: ADHD group had a significant ToM and EF impairment relative to the control group. ToM was not significantly correlated with EF; however, the performance on IED tasks affected the performance on ToM tasks.Discussion: The study provides evidence for a link between the abilities to attribute correct mental states to others, planning and shifting attention in ADHD children, suggesting the ability to rely on cognitive flexibility in the face of a changing environment plays a role in explaining the association between ToM and EF.

Choice Quality as a Function of Decision Accuracy and Search Cost.

Objective: A prominent challenge in modeling choice is specification of the underlying cognitive processes. Many cognitive-based models of decision-making draw substantially on algorithmic models of artificial intelligence and thus rely on associated metaphors of this field. In contrast, the current study avoids metaphors and aims at a first-hand identification of the behavioral elements of a process of choice. Method : We designed a game in Mouselab resembling the real-world procedure of choosing a wife. 17 male subjects were exposed to cost-benefit decision criteria that closely mimic their societal respective conditions. Results: The quality of choice index was measured with respect to its sensitivity to the final outcomes as well as process tracing of decisions. The correlation between this index and individual components of process tracing are discussed in detail. The choice quality index can be configured as a function of expected value and utility. In our sample the quality of choice with an average of 75.98% (SD: ±12.67) suggests that subjects obtained close to 76% of their expected gains. Conclusion: The quality of choice index, therefore, may be used for comparison of different conditions where the variables of decision-making are altered. The analysis of results also reveals that the cost of incorrect choice is significantly correlated with expected value (0.596, sig = 0.012) but not with utility. This means that when sub-jects face higher costs prior to making a decision, there exists a corresponding higher expectation of gains, i.e., higher expected value.

Bumetanide Therapeutic Effect in Children and Adolescents With Autism Spectrum Disorder: A Review Study.

INTRODUCTION: Autism Spectrum Disorder (ASD) is characterized by several impairments in communications and social interactions, as well as restricted interests or stereotyped behaviors. Interventions applied for this disorder are based on multi-modal approaches, including pharmacotherapy. No definitive cure or medication has been introduced so far; therefore, researchers still investigate potential drugs for treating ASD. One of the new medications introduced for this purpose is bumetanide. The present article aimed to review the efficacy of this drug on the core symptoms of ASD and its potential side effects. METHODS: We searched all papers reported on pharmacokinetics, pharmacodynamics, efficacy, and adverse effects of bumetanide on animal models and humans with ASD. The papers were extracted from the main databases of PubMed, Web of Science, and Scopus. RESULTS: The findings revealed that cortical neurons have high Chloride ion (Cl-)i and excitatory actions of gamma-aminobutyric acid in the valproic acid animal model with ASD and mice with fragile X syndrome. Bumetanide, which has been introduced as a diuretic, is also a high-affinity-specific Na+-K+-Cl- cotransporter (NKCC1) antagonist that can reduce Cl- level. The results also indicate that bumetanide can attenuate behavioral features of autism in both animal and human models. Moreover, the studies showed that such medication could activate fusiform face area in individuals with ASD while viewing emotional faces. Also, recent findings suggest that a dose of 1 mg/d of this drug, taken twice daily, might be the best compromise between safety and efficacy. CONCLUSION: Recent studies provided some evidence that bumetanide can be a novel pharmacological agent in treating core symptoms of ASD. Future studies are required to confirm the efficacy of this medication in individuals with ASD.

Effects of Combining Medication and Pivotal Response Treatment on Aberrant Behavior in Children with Autism Spectrum Disorder.

Abstract: The purpose of this study was to investigate the effects of combined risperidone (RIS) and pivotal response treatment (PRT) on children with autism spectrum disorder (ASD). A total of 34 children diagnosed with ASD according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) (mean age of 12.36 years) were randomly assigned to either of two groups; the first group (n = 17) received combined PRT-RIS while the second group (n = 17) received RIS only. Behavioral problems were evaluated with the Aberrant Behavior Checklist (ABC), whereas global improvement (GI) was measured with the Clinical Global Impressions (CGI). Assessment of ABC was performed before intervention, after intervention (12 weeks), and following 3 months of the intervention (follow-up). Total ABC scores were seen to decrease in both groups after 3 months, as compared with the scores prior to the interventions. Also, in both groups, mean scores of behavioral problems after the intervention were not significantly different from those prior to the intervention, in all subscales but the inappropriate speech (p < 0.001). However, both groups showed significant differences in mean scores of ABC subscales in both of the post-intervention evaluation stages. It was concluded that the combination of behavioral and drug interventions can further improve behavioral problems, ultimately improving patient's communication and social skills.

Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized, double blind, placebo-controlled trial.

OBJECTIVES: Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD. METHODS: Sixty-two children aged 5-12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed. RESULTS: Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P < 0.05). Evening symptoms and total score of WPREMB scale were significantly different at weeks 4 and 8 between the two groups (P = 0.013, 0.016, respectively), but no differences were found in symptoms by CPRS and ADHD-RS scales. DISCUSSION: Vitamin D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism. The trial was registered in www.irct.ir is (IRCT201404222394N10).

Early Posterior Negativity as Facial Emotion Recognition Index in Children With Attention Deficit Hyperactivity Disorder.

INTRODUCTION: Studies indicate that children with Attention Deficit Hyperactivity Disorder (ADHD) have deficits in social and emotional functions. It can be hypothesized that these children have some deficits in early stages of facial emotion discrimination. Based on this hypothesis, the present study investigated neural correlates of early visual processing during emotional face recognition in this group compared with typically developing children using the Event-Related Potentials (ERPs). METHODS: Nineteen boys between the ages of 7 and 11 years diagnosed with ADHD (Combined type) based on DSM-IV-TR classification were compared with 19 typically developing children matched on age and gender. The participants performed an emotional face recognition task while their brain activities were recorded using the event-related potentials procedure. RESULTS: A significant reduction in the Early Posterior Negativity (EPN) for happy and angry faces has been revealed in ADHD children compared to normal ones (P<0.05). CONCLUSION: The present study supports the notion that individuals with ADHD have some impairments in early stage of emotion processing which can leading to their misinterpretation of emotion in faces.