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.

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.

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.

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).

Depressive symptoms among metabolically healthy and unhealthy overweight/obese individuals: a comparative study.

Background: Although a growing body of evidence suggests an association between obesity and depressive disorder, the association remains inconclusive. Metabolically healthy obese (MHO) phenotype, defined by favorable lipid profile, and normal insulin sensitivity, blood pressure, may be considered as a possible explanation for these inconsistencies. Accordingly, this study aimed to compare depression score among metabolic unhealthy obese (MUO) and age- and sex-matched healthy controls. Methods: In this comparative study including 157 Iranian adults, we assigned participants into three groups (non-obese metabolic healthy group, MHO and MUO) according to the BMI cutoff and MetS criteria. Depressive symptoms were assessed by Beck Depression Inventory. Analysis was done using SPSS version 14.0. All variables are expressed as means ± SD. One-way ANOVA and multiple linear regression were used for data analysis. Results: After adjustment for sex, marital status and educational level, MUO participants had significantly higher Beck depression score (P= 0.036) compared to MHO and non-obese metabolic healthy groups. After adjustment for demographic variables, there was a significant association between waist circumference (ß = 0.142, p=0.023), BMI (ß= 0.347, p= 0.037), FBS (ß= 0.096, p< 0.001), and the number of MetS components (ß= 1.71, p= 0.002) with depression score. Conclusion: MHO was a benign phenotype in relation to depression.

Comparing Efficacy and Side Effects of Memantine vs. Risperidone in the Treatment of Autistic Disorder.

Introduction: This study was aimed to compare the efficacy and side effects of memantine, an antagonist of the NMDA receptor of glutamate, with risperidone given the fact that glutamate has been noted for its possible effects in the pathogenesis of autism. Risperidone, an atypical antipsychotic, has been approved by FDA for the management of irritability associated with autism. Methods: 30 children, aged 4-17 years, entered an 8-week, randomized trial. Patients were randomly assigned to receive either risperidone or memantine. Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Clinical Global Impressions - Improvement (CGI-I) and Clinical Global Impression-Severity (CGI-S) scales were used to assess behavioral symptoms of the patients. Results: Both risperidone and memantine reduced the scores of 4 subscales of ABC as well as the 10-item and the total score of CARS significantly. However, differences between the 2 drugs in the scores of each evaluating scale were not found to be significant. Relatively, larger number of patients on risperidone showed "very much improvement" when assessed by CGI-I scale when compared with those on memantine. Discussion and conclusion: The present study suggests that memantine may have beneficial effects in the treatment of many core symptoms of autism. Therefore, memantine may be considered as a potential medication in the treatment of those autistic children who do not respond or cannot tolerate side effects of risperidone.

The effects of probiotics on mental health and hypothalamic-pituitary-adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers.

OBJECTIVE: The aim of this study was to determine effects of probiotic yogurt and multispecies probiotic capsule supplementation on mental health and hypothalamic-pituitary-adrenal axis in petrochemical workers. METHODS: The present randomized double-blind, placebo-controlled trial was conducted on 70 petrochemical workers. Subjects were randomly divided into three groups to receive 100 g/day probiotic yogurt + one placebo capsule (n = 25) or one probiotic capsule daily + 100 g/day conventional yogurt (n = 25) or 100 g/day conventional yogurt + one placebo capsule (n = 20) for 6 weeks. Mental health parameters including general health questionnaire (GHQ) and depression anxiety and stress scale (DASS) scores were measured. Fasting blood samples were obtained at the beginning and 6 weeks after the intervention to quantify hypothalamic-pituitary-adrenal axis. RESULTS: After 6 weeks of intervention, a significant improvement of GHQ was observed in the probiotic yogurt (18.0 ± 1.5 vs. 13.5 ± 1.9, P = 0.007) and in the probiotic capsule group (16.9 ± 1.8 vs. 9.8 ± 1.9, P = 0.001), as well as a significant improvement in DASS scores in the probiotic yogurt (23.3 ± 3.7 vs. 13.0 ± 3.7, P = 0.02) and the probiotic capsule group (18.9 ± 3.2 vs. 9.4 ± 4.0, P = 0.006). However, there was no significant improvement in the conventional yogurt group (P = 0.05 for GHQ and P = 0.08 for DASS). DISCUSSION: The consumption of probiotic yogurt or a multispecies probiotic capsule had beneficial effects on mental health parameters in petrochemical workers.

Zinc monotherapy increases serum brain-derived neurotrophic factor (BDNF) levels and decreases depressive symptoms in overweight or obese subjects: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Previous studies have shown a positive effect of zinc as an adjunctive therapy on reducing depressive symptoms. However, to our knowledge, no study has examined the effect of zinc monotherapy on mood. The aim of the present study was to determine the effects of zinc monotherapy on depressive symptoms and serum brain-derived neurotrophic factor (BDNF) levels in overweight or obese subjects. METHODS: Fifty overweight or obese subjects were randomly assigned into two groups and received either 30 mg zinc or placebo daily for 12 weeks. At baseline and post-intervention, depression severity was assessed using Beck depression inventory II (BDI II), and serum BDNF and zinc levels were determined by enzyme-linked immunosorbent assay and atomic absorption spectrophotometry, respectively. RESULTS: The trial was completed with 46 subjects. After a 12-week supplementation, serum zinc and BDNF levels increased significantly in the zinc-supplemented group compared with the placebo group. BDI scores declined in both the groups at the end of the study, but reduction in the zinc-supplemented group was significantly higher than the placebo group. More analysis revealed that following supplementation, BDI scores decreased in subgroup of subjects with depressive symptoms (BDI ≥ 10) (n = 30), but did not change in the subgroup of non-depressed subjects (BDI < 10) (n = 16). Moreover, a significant inverse correlation was observed between serum BDNF levels and depression severity in all participants. Interestingly, a significant positive correlation was found between serum BDNF and zinc levels at baseline. CONCLUSION: Zinc monotherapy improves mood in overweight or obese subjects most likely through increasing BDNF levels.

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.

Therapeutic effects of vitamin D as adjunctive therapy to fluoxetine in patients with major depressive disorder.

OBJECTIVE: To compare the therapeutic effects of vitamin D3 plus fluoxetine and fluoxetine alone in patients with major depressive disorder. METHODS: In the present double-blind, randomized, placebo-controlled trial, 42 patients with a diagnosis of major depressive disorder based on DSM-IV criteria were randomly assigned into two groups to receive daily either 1500 IU vitamin D3 plus 20 mg fluoxetine or fluoxetine alone for 8 weeks. Depression severity was assessed at 2-week intervals using the 24-item Hamilton Depression Rating Scale (HDRS) as a primary outcome measure and the 21-item Beck Depression Inventory (BDI) as a secondary outcome measure. Serum 25(OH) vitamin D was measured at baseline and after intervention. RESULTS: Forty patients completed the trial. A two-way repeated-measures analysis of variance showed that depression severity based on HDRS and BDI decreased significantly after intervention, with a significant difference between the two groups. The vitamin D + fluoxetine combination was significantly better than fluoxetine alone from the fourth week of treatment. CONCLUSIONS: In the present 8-week trial, the vitamin D + fluoxetine combination was superior to fluoxetine alone in controlling depressive symptoms.

Memantine-induced speech problems in two patients with autistic disorder.

Stuttering is a complex speech disorder. There are two forms of stuttering: developmental stuttering and acquired stuttering. Developmental stuttering is a disorder of early childhood but acquired stuttering can develop at any age. Some medications can induce or deteriorate stuttering as an adverse effect. There are several reports of stuttering due to psychotropic drugs. Memantine, a glutamate antagonist used in the treatment of Alzheimer's disease, has also been studied for the treatment of autism spectrum disorders. This report presents deterioration of stuttering and speech problem in two children with autistic disorder who were receiving memantine. Based on our knowledge, this is the first time these adverse drug reactions have been attributed to memantine. In conclusion clinicians should consider that speech problems including stuttering may be due to the consumption of memantine, especially, in children may be a side effect of memantine especially in children.

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.

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.

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.

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.

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.

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.

Duloxetine in the treatment of adolescents with attention deficit/hyperactivity disorder: an open-label study.

OBJECTIVE: The main aim of this study was to explore the efficacy and safety of duloxetine, a serotonin and norepinephrine reuptake inhibitor, in the treatment of adolescents with attention deficit/hyperactivity disorder (ADHD). METHODS: Seventeen adolescents aged 11-18 years, diagnosed with ADHD, participated in this 6-week open-label study. Duloxetine was given in doses of 30 mg/day in the first week and 60 mg/day from week 2 to the end of the study. Conners' Parent Rating Scale-Revised (CPRS-R) short form was used to assess the efficacy of the therapy. RESULTS: A significant reduction in ADHD symptoms measured by CPRS-R was observed. This reduction was evident from week 4 of the study. In addition, the decrease was significant in all four subscales of CPRS-R including inattention, oppositionality, hyperactivity and ADHD index. In terms of side effects, duloxetine was generally safe and well tolerated. CONCLUSIONS: The results of this open-label study suggest a promise of duloxetine in the treatment of youth with ADHD. Further controlled studies with larger samples are required to evaluate the efficacy of duloxetine in children and adolescents with ADHD.

Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder.

Treatment studies have suggested that omega-3 fatty acids (omega-3 FAs) as monotherapy or adjunctive treatment have therapeutic effects in depression. The authors recently reported a study in which fluoxetine and eicosapentaenoic acid (EPA), which is an omega-3 fatty acid, appeared to be equally effective in controlling depressive symptoms and their combination was superior to either of them alone. Regulation of hypothalamus-pituitary-adrenal (HPA) axis activity and reduction of inflammatory cytokines are among several biological mechanisms which potentially explain the impact of omega-3 FAs on depression. In the present study, plasma cortisol and serum interleukin-1beta (IL-1 beta) and interleukin-6 (Il-6) were measured in patients with a diagnosis of major depressive disorder (MDD) participating in aforementioned trial to determine the effects of 8 weeks of treatment of depression with 1000 mg EPA alone or in combination with 20 mg fluoxetine on HPA axis activity and inflammatory cytokine production and compare the changes in these variables with those of treating with 20 mg fluoxetine alone. Forty-two patients were included in analysis. Two-way repeated measures analysis of variance (ANOVA) showed that plasma cortisol decreased significantly after 8 weeks of intervention without significant difference among the groups. There was no interaction between group and response to treatment over time in the cortisol response based on three-way ANOVA. Serum concentrations of IL-1beta and IL-6 did not change significantly after intervention. In conclusion, EPA alone or in combination with fluoxetine, as well as fluoxetine alone decreased serum cortisol after 8 weeks of treatment in patients with major depression disorder (MDD) without any significant effect of response to treatment. Serum IL-1beta and IL-6 did not change significantly after intervention. These findings suggest that EPA may exert its therapeutic effects through reduction of cortisol.