Search

Introduction Bipolar Disorder (BD) is a complex psychiatric condition that typically manifests during late adolescence and early adulthood. Over the past two decades, international studies have reported that BD often goes unrecognized and untreated for several years, which can lead to negative clinical and functional outcomes. However, the components of delay in the diagnosis and treatment of BD in adolescents and young adults and various factors influencing those components have not been systematically explored. Objectives To determine the known factors that contribute to delays in the treatment of BD in adolescents and young adults and identify current knowledge gaps. Methods A conceptual framework based on the Model of Pathways to Treatment by Scott and colleagues was used as a foundation for our search and extraction strategy to ensure all components of delay and potential factors influencing each component are explored. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline (PRISMA-ScR) to systematically search the electronic databases of MEDLINE (OVID), EMBASE, PsycINFO and CINAHL for peer-reviewed original research articles published from January 01, 2000 through March 29, 2023. Inclusion was restricted to studies with quantitative or qualitative data on individuals diagnosed with bipolar spectrum disorders with symptomatic onset or study participation between the ages of 13-24. Grey literature and studies not published in English were excluded due to resource limitations. Two independent reviewers screened the references retrieved by the literature search based on our inclusion criteria. The findings of included studies were summarized in a narrative and tabular form according to component of delay. Results Our search yielded 5180 unique citations, of which 44 articles met our inclusion criteria. We present findings on the patient, illness, and healthcare provider/mental health system factors contributing to the delays in illness appraisal, help-seeking, diagnosis, and treatment. Conclusions To the best of our knowledge, this is the first systematic scoping review to explore the potential factors that influence delays in the treatment of BD in adolescents and young adults. Findings from this review will inform clinical practice and policy. We also demonstrate the utility of a systematic approach to identifying the components of delay, from symptom recognition through treatment, as a methodology to help identify knowledge gaps to inform future research. Disclosure of Interest None Declared

Objective: People with bipolar disorder (BD) often show inaccurate subjective ratings of their objective cognitive function. However, it is unclear what information individuals use to formulate their subjective ratings. This study evaluated whether people with BD are likely using information about their crystallized cognitive abilities (which involve an accumulated store of verbal knowledge and skills and are typically preserved in BD) or their fluid cognitive abilities (which involve the capacity for new learning and information processing in novel situations and are typically impaired in BD) to formulate their subjective cognitive ratings., Method: Eighty participants diagnosed with BD and 55 control volunteers were administered cognitive tests assessing crystallized and fluid cognitive abilities. Subjective cognitive functioning was assessed with the Cognitive Failures Questionnaire (CFQ), daily functioning was rated using the Multidimensional Scale of Independent Functioning (MSIF) and the Global Assessment of Functioning Scale (GAF), and quality of life was assessed with the Quality of Life in Bipolar Disorder scale (QoL.BD)., Results: The BD group exhibited considerably elevated subjective cognitive complaints relative to controls. Among participants with BD, CFQ scores were associated with fluid cognitive abilities including measures of memory and executive function, but not to crystallized abilities. After controlling for objective cognition and depression, higher cognitive complaints predicted poorer psychosocial outcomes., Conclusions: Cognitive self-reports in BD may represent a metacognitive difficulty whereby cognitive self-appraisals are distorted by a person's focus on their cognitive weaknesses rather than strengths. Moreover, negative cognitive self-assessments are associated with poorer daily functioning and diminished quality of life.

Background: e-Health tools using validated questionnaires to assess outcomes may facilitate measurement-based care for psychiatric disorders. MoodFX was created as a free online symptom tracker to support patients for outcome measurement in their depression treatment. We conducted a pilot randomized evaluation to examine its usability, and clinical utility., Methods: Patients presenting with a major depressive episode (within a major depressive or bipolar disorder) were randomly assigned to receive either MoodFX or a health information website as the intervention and control condition, respectively, with follow-up assessment surveys conducted online at baseline, 8 weeks and 6 months. The primary usability outcomes included the percentage of patients with self-reported use of MoodFX 3 or more times during follow up (indicating minimally adequate usage) and usability measures based on the System Usability Scale (SUS). Secondary clinical outcomes included the Quick Inventory of Depressive Symptomatology, Self-Rated (QIDS-SR) and Patient Health Questionnaire (PHQ-9)., Results: Forty-nine participants were randomized (24 to MoodFX and 25 to the control condition). Of the 23 participants randomized to MoodFX who completed the user survey, 18 (78%) used MoodFX 3 or more times over the 6 months of the study. The mean SUS score of 72.7 (65th-69th percentile) represents good usability. Compared to the control group, the MoodFX group had significantly better improvement on QIDS-SR and PHQ-9 scores, with large effect sizes and higher response rates at 6 months. There were no differences between conditions on other secondary outcomes such as functioning and quality of life., Conclusion: MoodFX demonstrated good usability and was associated with reduction in depressive symptoms. This pilot study supports the use of digital tools in depression treatment., Competing Interests: Declaration of Conflicting InterestsRWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Abbvie, Asia-Pacific Economic Cooperation, Bausch, BC Leading Edge Foundation, Brain Canada, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, CB Solutions, Carnot, Genome BC, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Michael Smith Foundation for Health Research, MITACS, Neurotorium, Ontario Brain Institute, Otsuka, Pfizer/Viatris, Shanghai Mental Health Center, Unity Health, Vancouver Coastal Health Research Institute, and VGH-UBCH Foundation. AD was partly supported by an unrestricted fellowship grant from Janssen Canada and has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: AbbVie, Canadian Institutes of Health Research and Otsuka. JJN was partially supported by a Marshall/Institute of Mental Health Fellowship Award and received unrestricted research funding from the BC Cancer Foundation, with funds originating from Pfizer. KK is supported as a health professional investigator by Michael Smith Health Research Foundation of BC, Vancouver Coastal Health Research Institute and VGH & UBC Hospital Foundation and has previously served on the scientific advisory board of AbbVie. EEM has received support for patient education activities from Otsuka-Lundbeck. LNY has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: AbbVie, Alkermes, Allergan, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Dainippon Sumitomo Pharma, GlaxoSmithKline, Intracellular Therapies, Lundbeck, Merck, Otsuka, Sanofi, and Sunovion. VWL, VCE, JS, DKD, DDG, AA, EMT and JKM have no disclosures.

Objectives: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well-characterized individuals with BD in North America, Europe, and Australia., Methods: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta-analyses with generalized linear mixed methods were conducted to identify prescription patterns., Results: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD-I (60%; vs. BD-II = 33%). Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First-generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD-II (47%) compared to BD-I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort., Conclusions: Mood-stabilizing anticonvulsants, second-generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first-generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence-based guidelines to help improve treatment practices in BD., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Bipolar Disorder (BD) is a complex psychiatric condition that typically manifests during late adolescence and early adulthood. Over the past two decades, international studies have reported that BD often goes unrecognized and untreated for several years, which can lead to negative clinical and functional outcomes. However, the components of delay in the diagnosis and treatment of BD and various factors influencing those components have not been systematically explored., Objectives: The scoping review described in this protocol aims to map the existing literature on potential factors that influence delays in the treatment of BD in adolescents and young adults, in order to identify the knowledge gaps and future research and policy priorities., Methods: This protocol for a systematic scoping review will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline (PRISMA-ScR). We will search the electronic databases of MEDLINE (OVID), EMBASE, PsycINFO and CINAHL for peer-reviewed primary research articles published in academic journals. Grey literature will not be explored due to resource limitations. A conceptual framework based on the Model of Pathways to Treatment by Scott and colleagues was used as a foundation for our search and extraction strategy to ensure all components of delay and potential factors influencing each component are explored. Two independent reviewers will screen the references retrieved by the literature search and select relevant studies based on our inclusion criteria. The data from included studies will be synthesized into a narrative summary, and implications for future research, practice and policy will be discussed., Discussion: To the best of our knowledge, this will be the first scoping review to explore the potential factors that influence delays in the treatment of BD in adolescents and young adults. We intend to disseminate the review results through academic conferences and publication in a peer-reviewed journal., Competing Interests: Kamyar Keramatian has served on the scientific advisory board of AbbVie. John-Jose Nunez has received research funding from an unrestricted research grant from Pfizer Canada. Emma Morton and Alexander Levit have no competing interests to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Keramatian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bipolar disorder is a complex and heterogeneous psychiatric condition that affects more than 2% of the population. The assessment and treatment of bipolar disorder can be a challenge for clinicians, given its clinical complexity and the rapidly changing treatment landscape with the growing range of treatment options that are becoming available for various phases of the illness. To help clinicians navigate the complexity involved in the assessment and management of bipolar disorder, the guidelines of the 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) synthesized the evidence on the efficacy, safety, and tolerability of treatments for bipolar disorder and translated it into first-, second-, and third-line treatment recommendations. The main objective of this contribution is to provide clinicians with a summary of the 2018 CANMAT/ISBD guideline recommendations with the addition of any new evidence for the treatment of bipolar disorder across the lifespan., Competing Interests: Dr. Yatham is a consultant for, has received speaker fees from, sits on the advisory board of, and/or receives research funding from AbbVie, Alkermes, Allergan, Canadian Network for Mood and Anxiety Treatments, Canadian Institutes of Health Research, Dainippon Sumitomo Pharma, Gedeon Richter, Intracellular Therapies, Lundbeck, Merck, Otsuka, Sanofi, and Sunovion over the past 3 years. Dr. Keramatian has been on an advisory board for AbbVie. Dr. Chithra reports no financial relationships with commercial interests., (Copyright © 2023 by the American Psychiatric Association.)

Aims: This study aimed to systematically review the literature on neuroanatomical predictors of future problematic drinking in adolescents., Methods: Using PRISMA guidelines, a systematic review was conducted to evaluate neuroanatomical predictors of problematic alcohol consumption in adolescents. EMBASE, MEDLINE, and PsycINFO databases were searched from inception to 6 January 2023. Studies were included if they were original, had a prospective design, had a sample size of at least 12, had a follow-up period of at least 1 year, had at least one structural neuroimaging scan before 18 with no prior alcohol use, and had alcohol use as the primary outcome. Studies were excluded if they had animals only and were not in English. Risk of bias was conducted using the CASP tool., Results: Out of 1412 studies identified, 19 studies met the criteria, consisting of 11 gray matter (n = 4040), 5 white matter (n = 319), and 3 assessing both (n = 3608). Neuroanatomical predictors of future problematic drinking in adolescents were reported to be distributed across various brain regions such as the orbitofrontal cortex and paralimbic regions. However, the findings were largely heterogeneous., Conclusions: This is the first systematic review to map out the existing literature on neuroanatomical predictors of problematic drinking in adolescents. Future research should focus on the aforementioned regions to determine their role in predicting future problematic drinking with more certainty., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Appropriate interventions for psychiatric conditions that commonly emerge during adolescence and early adulthood play a crucial role in modifying both acute risks as well as long-term outcomes. Substance use disorder is a common comorbidity during the early stages of mood and psychotic disorders that further heightens acute risks and is considered a negative prognostic factor. New presentations of mood and psychotic symptoms with co-occurring substance use are inherently challenging to formulate due to the uncertainty surrounding the relative impact of multiple intrinsic and extrinsic factors. Given such uncertainty, it is natural for clinicians to rely on heuristics to guide assessment and management. These heuristics however may bring about premature diagnostic closure by favouring the primacy of substance use, which in turn can result in a missed window of opportunity for a timely and appropriate intervention. We caution clinicians against over-attributing early symptoms of mood and psychotic disorders to substances use alone., Competing Interests: Conflicts of interest Dr. Keramatian is supported as a health professional investigator by Michael Smith Health Research BC, Vancouver Coastal Health Research Institute and VGH & UBC Hospital Foundation. He has previously served on the scientific advisory board of AbbVie., (Copyright © 2023 Canadian Academy of Child and Adolescent Psychiatry.)

Depression is the most commonly experienced mood state over the life span in individuals with bipolar disorder (BD) and is the primary driver of functional impairment and suicidality in BD. Despite this, there are few effective treatments for BD depression, with only a handful of atypical anti-psychotics and inconsistent evidence for traditional mood stabilizing agents. There have been few major 'breakthroughs' in the treatment of BD depression, and until recently, few agents that work via novel mechanisms of action to exert therapeutic effects. Here, we review treatments for BD depression which are emergent or on the horizon. Included are new atypical anti-psychotics, glutamate modulators (ketamine and cycloserine/lurasidone), neurosteroid modulators (zuranolone), anti-inflammatories and mitochondrial modulators, cannabidiol (CBD) and psilocybin. New atypical anti-psychotics lumateperone and cariprazine have demonstrated efficacy in large-scale, placebo-controlled, double-blind randomized controlled trials (RCT) in treatment of BD depression. Non-racemic amisulpride showed potential therapeutic benefit in one RCT which requires replication. Three small RCTs examined the efficacy of intravenous ketamine in BD depression and showed rapid antidepressant and anti-suicidal effects after a single infusion. Anti-inflammatory and mitochondrial modulators show inconsistent evidence for efficacy. There are currently no adequately powered RCTs of zuranolone, psilocybin or CBD in BD depression to support their use. While there are potentially efficacious, mechanistically novel agents on the horizon, they require further study and validation. Further investigation on how these agents may impact specific subgroups of patients will also advance the field., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Bipolar disorder (BD) in youth often goes unrecognized and therefore untreated. However, little is known about pathways to treatment of youth with BD and factors that influence the time taken for each stage of these pathways. In this article, we use the conceptual framework by Scott and colleagues called the Model of Pathways to Treatment as a foundation to explore the components of delay in the diagnosis and treatment of youth with BD. The total time from the onset of symptoms until treatment initiation was divided into four sequential intervals; i.e., the Appraisal, the Help-seeking, the Diagnostic and the Pre-treatment intervals and potential disease, patient, and healthcare system/provider factors that influence each interval were identified. This multidimensional conceptual framework can offer a systematic approach to understanding and exploring barriers to early identification and interventions in BD, which is a crucial step in the development of strategies to facilitate prompt diagnosis and treatment. We hope this work contributes to the discussion on delayed diagnosis and treatment of youth with BD and provides a roadmap to inform future research studies and policy decisions., Competing Interests: KK has been on advisory board for AbbVie. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Keramatian and Morton.)

Abstract: Concurrent substance use and mental health disorders in youth are a major public health concern and require specialized and comprehensive services. In this paper, a novel inpatient tertiary care facility serving youth aged 13 to 18 with significant concurrent substance use and mental health issues is introduced. The development of this unit was prompted by the opioid overdose crisis in British Columbia and serves as the third concurrent disorders unit in Canada catered specifically to an adolescent population. From its opening in 2017, preadmission and postadmission data from each patient was gathered with the aim of providing a robust image of the serviced patient population as well as the efficacy of this service model. Patients admitted to this program had significantly higher quality of life ( d = 0.65) and significantly lower suicidality ( d = 0.86) at discharge, compared with at admission. Patients identifying as female had significantly lower quality of life, higher suicidality, and higher prevalence of adverse childhood events compared with patients identifying as male. Results from this program evaluation outline the efficacy of a novel concurrent disorders program for youth while further providing an overview of clinical and relevant demographic characteristics from an underanalyzed patient population., Competing Interests: Author KK has served on the scientific advisory board of AbbVie. KK is also supported by the Vancouver Coastal Health Research Institute Investigator Award. Author LS and JC declare no conflicts of interest., (Copyright © 2022 National Association for Healthcare Quality.)

Introduction: This narrative review of systematic reviews and meta-analyses aims at compiling available evidence in various aspects of neurocognitive functioning in Bipolar Disorder (BD). Methods: We conducted a MEDLINE literature search and identified 38 relevant systematic reviews and metaanalyses. Results: Current evidence suggests that BD is associated with cognitive impairment across multiple domains and during all clinical states. However, there is a considerable cognitive heterogeneity within BD, which cannot be explained by clinical subtypes, and the pattern of neurocognitive impairment in BD overlaps with other psychiatric conditions such as major depression and schizophrenia. Residual depressive symptoms, poor clinical course and higher number of manic episodes may negatively impact cognitive performance, which is a major predictor of general functioning in BD. Evidence from available prospective studies does not support the notion of progressive cognitive decline in BD while some evidence exists to suggest patients may show some improvements in cognitive functioning following the first manic episode. Furthermore, a subset of patients may show premorbid cognitive abnormalities that could signal an early neurodevelopmental aetiology. Preliminary findings from small studies identify potential pro-cognitive effects of Cognitive Remediation, erythropoietin, intranasal insulin, lurasidone, mifepristone, repetitive Transcranial Magnetic Stimulation and transcranial Direct Current Stimulation in BD. Discussion: Longitudinal studies in high-risk individuals can provide a better understanding of the development and progression of neurocognitive impairment in BD. Largescale randomised control trials are needed to compare the pro-cognitive efficacy of various pharmacological and non-pharmacological interventions in different cognitive subgroups of patients at different stages of BD., Competing Interests: IJT has been serving as a consultant for Community Living British Columbia. LNY has been on speaker/advisory boards for, or has received research grants from Alkermes, AstraZeneca, Bristol Myers Squibb, CANMAT, CIHR, DSP, Eli Lilly, GlaxoSmithKline, Janssen, the Michael Smith Foundation for Health Research, Pfizer, Servier, Sunovion, and the Stanley Foundation., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: The diagnosis of Bipolar Disorder (BD) is frequently delayed. In this study, we aimed to examine the clinical and demographic factors associated with delayed diagnosis of BD, defined as the difference between the age at first mood episode (depressive, manic, or hypomanic) and the age at the correct diagnosis of BD, using data from a Canadian multicentre naturalistic study., Methods: The sample included 192 patients with Bipolar I Disorder (BD-I) and 127 with Bipolar II Disorder (BP-II) who participated in the Health Outcomes and Patient Evaluations in Bipolar Disorder (HOPE-BD) study. Sociodemographic characteristics and clinical features that had been previously associated with delayed diagnosis of BD were included in the analysis., Results: The median delay in diagnosis was 5.0 years in BD-I and 11.0 years in BD-II. Clinical factors such as earlier age of onset, lifetime suicide attempts and comorbid anxiety disorders were associated with a longer delay, whereas the presence of lifetime psychotic symptoms and psychiatric hospitalizations were associated with a shorter delay. Quantile regression analysis showed older age at which professional help was first sought and younger age of onset as predictors of increased delay in diagnosis of BD-I and BD-II. Depression as first episode predicted longer delay in diagnosis of BD-I but not BD-II., Conclusion: Our findings identified the ongoing lag in identification of a BD diagnosis and the clinical markers most associated with this delay, highlighting the need for implementation of strategies for early identification and interventions in BD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose of Review: Bipolar disorder is a highly heritable condition, which can progress from an asymptomatic period in at-risk individuals to a potentially debilitating illness. Identifying individuals who are at a high risk of developing bipolar disorder may provide an opportunity for early intervention to improve outcomes. The main objective of this systematic review is to provide an overview of prospective studies that evaluated the incidence and predictors of transitioning to bipolar disorder among high-risk individuals., Recent Findings: Twenty-three publications from 16 cohorts were included in the final review. Most studies focused on familial high-risk groups, while others either used clinical or a combination of clinical and genetic risk factors. The follow-up length was from 1 to 21 years and the rate of conversion to bipolar disorder was between 8 and 25% among different studies. Overall, the results suggest that a combination of genetic and clinical risk factors; namely, subthreshold (hypo)manic symptoms and elevated depressive symptoms, may be required to optimally predict conversion to bipolar disorder., Summary: The concept of high-risk for bipolar disorder is still in its infancy. Further discussions are needed to work towards an expert consensus on the high-risk criteria for bipolar disorder, taking into account both clinical and genetic risk factors., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Bipolar disorder (BD) is chronic psychiatric disorder associated with significant impairment in psychosocial functioning and quality of life. Although current pharmacological treatments for BD have improved its clinical management, many patients do not achieve remission, particularly those suffering from bipolar depression. In addition, available treatments are associated with a myriad of potential adverse effects, which highlights the need for novel therapeutic agents that can be effective for both phases of the illness with a reduced side effect burden. Cariprazine is a novel antipsychotic that is a dopamine D2/D3 partial agonist with a preference for D3 receptors. In this review, we examine the pharmacological properties, clinical efficacy and tolerability profile of cariprazine in patients with BD, taking into account the latest clinical trials data. We also review post hoc analyses addressing clinically relevant subgroups and symptom domains in BD. Current evidence suggests efficacy for cariprazine 3-12 mg/day in the treatment of acute manic and mixed episodes; for bipolar depression, the efficacy of cariprazine appears to be dose-related, with doses of 1.5-3 mg/day beneficial as monotherapy. Cariprazine is overall well-tolerated by patients in both manic and depressive episodes. Its most common side effects relative to placebo include akathisia, extrapyramidal symptoms and nausea. There are no metabolic concerns reported with cariprazine use. In summary, the latest evidence suggests that cariprazine is an effective and safe treatment option for BD., Competing Interests: AD was partly supported by an unrestricted fellowship grant from Janssen Canada. KK has no disclosures. AS has been on speaker/advisory boards for, or has received research grants from Abbvie, Allergan, CANMAT, CIHR, Janssen, and Otsuka. LY has been on speaker/advisory boards for, or has received research grants from Abbvie, Alkermes, Allergan, CANMAT, CIHR, Dainippon Sumitomo Pharma, Intracellular Therapies, Lundbeck, Merck, Otsuka, Sanofi, and Sunovion., (Copyright © 2021 Do, Keramatian, Schaffer and Yatham.)

Background: While widespread grey matter (GM) changes are seen in bipolar I disorder (BD-I), it is unclear how early in the illness such changes emerge. To date there has been little synthesis of findings regarding longitudinal grey matter changes early in the course of BD-I. We conducted a systematic review to examine the evolution of GM changes in BD-I patients following the first episode of mania (FEM)., Methods: Following PRISMA guidelines, we conducted a systematic review of studies examining longitudinal changes in GM volume (GMV), cortical thickness and/or surface area in BD-I patients following FEM. We qualitatively synthesized results regarding longitudinal GM changes in BD-I patients., Results: Fifteen studies met inclusion criteria, all examining GMV changes. Longitudinal ACC volume decrease following FEM was the most replicated finding, but was only reported in 4 out of 7 studies that examined this region as part of a whole brain/region of interest analysis, with 2 of these positive studies using an overlapping patient sample. The impact of episode recurrence, medications, and other clinical factors was inconsistently examined., Limitations: The literature regarding GM changes early in BD-I is highly inconsistent, likely due to heterogeneity in participant characteristics, imaging methodology/analysis and duration of follow up., Conclusions: Though there was some suggestion that structural ACC changes may represent a marker for neuroprogression following FEM, results were too inconsistent to draw any conclusions. Larger longitudinal studies examining cortical thickness/surface area, and the influence of relevant clinical factors, are needed to better understand neuroprogression in early BD-I., (Copyright © 2021. Published by Elsevier B.V.)

Purpose of Review: Atypical antipsychotics are increasingly used in the treatment of bipolar disorder (BD). This systematic review provides an overview of recently published randomized controlled trials (RCTs) on the efficacy and safety of atypical antipsychotics in BD., Recent Findings: Several studies supported efficacy of quetiapine monotherapy in acute bipolar I (BDI) and bipolar II (BDII) depression. Moreover, quetiapine adjunctive therapy showed superior efficacy to placebo in treatment-resistant bipolar depression. Cariprazine 1.5 mg was effective in treating bipolar I depression. Aripiprazole 400 mg IM once monthly was effective in preventing manic episodes with minimal metabolic effects. In youth with BD, lurasidone was effective and well-tolerated for acute depression while asenapine showed efficacy in treating acute manic and mixed episodes. Recently published RCTs generally support the efficacy of atypical antipsychotics in different phases of BD. Future studies should focus on understudied populations including pediatric BD and geriatric BD and BDII, as well as a focus on cognitive functioning and quality of life measures.

Objectives: It has been proposed that different stages of bipolar disorder may be underpinned by distinct neurobiological substrates. However, structural neuroimaging studies in early stages of the illness are limited by small sample sizes yielding inconsistent findings. The purpose of this systematic review and meta-analysis, therefore, was to identify regional grey matter volume (GMV) changes that are consistently associated with first episode of mania (FEM)., Methods: Following PRISMA guidelines, we conducted a systematic search of the literature to identify Voxel-Based Morphometry (VBM) studies in FEM patients compared with healthy individuals. We then conducted a voxel-wise meta-analysis using Seed-based d-Mapping technique. Finally, we performed univariate meta-regression analyses to explore the potential effects of moderator variables including age, gender, and percentage of lithium users on GMV alterations., Results: We identified 15 VBM studies and included 12 studies in the meta-analysis. Four studies found no regional differences in GM volumes while other 11 studies reported volume changes in frontal and temporal regions as well as anterior cingulate cortex (ACC), cerebellum and basal ganglia. The meta-analysis revealed a single cluster of GMV reduction in bilateral pregenual ACC in patients with FEM compared to healthy individuals (P < .001). The Egger's test showed no evidence of publication bias at peak voxel level (P = .447). Meta-regression analyses revealed no significant effects of moderators evaluated., Conclusions: Structural brain changes are evident in the early stages of bipolar disorder. GMV reduction in bilateral pregenual ACC is the most consistent finding in VBM studies of FEM., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: Major depressive episodes in bipolar disorder are common and debilitating. Repetitive transcranial magnetic stimulation is well established in the treatment of major depressive disorder, and the intermittent theta burst stimulation (iTBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, iTBS has not been adequately studied in bipolar disorder and, therefore, its efficacy is uncertain., Objective: To determine whether iTBS to the left dorsolateral prefrontal cortex (LDLPFC) is safe and efficacious in the treatment of acute bipolar depression., Design, Setting, and Participants: This study was a double-blind, 4-week, randomized clinical trial of iTBS targeting the LDLPFC. Two Canadian academic centers recruited patients between 2016 and 2020. Adults with bipolar disorder type I or type II experiencing an acute major depressive episode were eligible if they had not benefited from a first-line treatment for acute bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments and were currently treated with a mood stabilizer, an atypical antipsychotic, or their combination. Seventy-one participants were assessed for eligibility, and 37 were randomized to daily sham iTBS or active iTBS using a random number sequence, stratified according to current pharmacotherapy. Data analysis was performed from April to September 2020., Interventions: Four weeks of daily active iTBS (120% resting motor threshold) or sham iTBS to the LDLPFC. Nonresponders were eligible for 4 weeks of open-label iTBS., Main Outcomes and Measures: The primary outcome was the change in score on the Montgomery-Asberg Depression Rating Scale from baseline to study end. Secondary outcomes included clinical response, remission, and treatment-emergent mania or hypomania., Results: The trial was terminated for futility after 37 participants (23 women [62%]; mean [SD] age, 43.86 [13.87] years; age range, 20-68 years) were randomized, 19 to sham iTBS and 18 to active iTBS. There were no significant differences in Montgomery-Asberg Depression Rating Scale score changes (least squares mean difference between groups, -1.36 [95% CI, -8.92 to 6.19; P = .91] in favor of sham iTBS), and rates of clinical response were low in both the double-blind phase (3 of 19 participants [15.8%] in the sham iTBS group and 3 of 18 participants [16.7%] in the active iTBS group) and open-label phase (5 of 21 participants [23.8%]). One active iTBS participant had a treatment emergent hypomania, and a second episode occurred during open-label treatment., Conclusions and Relevance: iTBS targeting the LDLPFC is not efficacious in the treatment of acute bipolar depression in patients receiving antimanic or mood stabilizing agents. Additional research is required to understand how transcranial magnetic stimulation treatment protocols differ in efficacy between unipolar and bipolar depression., Trial Registration: ClinicalTrials.gov Identifier: NCT02749006.

Objective: Distinct cognitive subgroups are seen in patients with long duration bipolar I disorder (BDI), possibly reflective of underlying pathophysiological differences. It is unknown whether such cognitive heterogeneity is present at illness onset. We applied latent class analysis (LCA) to cognitive test scores in first episode BDI patients. Exploratory analysis elucidated whether impaired subgroups were characterized by 'early neurodevelopmental' (low premorbid IQ and intracranial volume) versus 'later neurodevelopmental' (decline from premorbid to current IQ, changes in relative grey (GM)/white (WM) matter volumes) pathology., Methods: Recently recovered first manic episode BDI patients (n = 91) and healthy controls (HC, n = 63) comprised the study sample. LCA identified subgroups based on processing speed, verbal memory, non-verbal memory, executive functioning, attention and working memory scores. Subgroups were compared amongst each other and HC on premorbid/current IQ, intracranial (ICV), total brain and regional volumes., Results: Three cognitive subgroups emerged: (i) globally impaired (GI, n = 31), scoring 0.5-1 SD below demographically corrected norms across domains, (ii) selectively impaired (SI, n = 47), with predominant processing speed deficits and (iii) high performing (HP, n = 13), with above-average cognitive performance. GI patients showed a 'later neurodevelopmental' pattern, with normal ICV, significant decline from premorbid to current IQ, higher total GM and lower total WM (with respect to total brain volume) versus SI and HC (p = 0.003). GI patients had higher left frontal pole GM versus HC (p < 0.05, FWE corrected)., Conclusions: A globally impaired patient subgroup is identifiable in first episode BDI, possibly characterized by unique neurodevelopmental pathologic processes proximal to illness onset., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: It has been proposed that different stages of the bipolar disorder might have distinct neurobiological changes. However, the evidence for this has not been consistent, as the studies in early stages of the illness are limited by small sample sizes. The purpose of this study was to investigate the gray matter volume changes in bipolar patients who recently recovered from their first episode of mania (FEM)., Methods: Using a whole-brain voxel-based analysis, we compared the regional gray matter volumes of 61 bipolar patients who have recovered from their FEM in the past 3 months with 43 age- and gender-matched healthy participants. We also performed a series of subgroup analyses to determine the effects of hospitalization during the FEM, history of depressive episodes, and exposure to lithium., Results: No statistically significant difference was found between gray matter volumes of FEM patients and healthy participants, even at a more liberal threshold ( P < 0.001, uncorrected for multiple comparisons). Voxel-based subgroup analyses did not reveal significant gray matter differences except for a trend toward decreased gray matter volume in left lateral occipital cortex ( P < 0.001, uncorrected) in patients with a previous history of depression., Conclusion: This study represents the largest structural neuroimaging investigation of FEM published to date. Early stage of bipolar disorder was not found to be associated with significant gray matter volume changes. Our findings suggest that there might be a window of opportunity for early intervention strategies to prevent or delay neuroprogression in bipolar disorder.

Objectives: Cariprazine is a partial agonist at D2/D3 receptors that has been approved for the treatment of mania associated with bipolar disorder (BD). This meta-analysis aimed to assess the efficacy and tolerability of cariprazine in the treatment of BD., Methods: Randomized controlled trials investigating the efficacy of cariprazine in BD were included. Of the 391 studies yielded by search, 7 were included. The PRISMA protocol was followed and a set of analyses involving random-effects model with restricted maximum-likelihood estimator were used to synthesize effect sizes., Results: Cariprazine was associated with a moderate and significant reduction of manic symptoms based on YMRS change scores (SMD: -0.52; 95%CI: -0.82 to -0.21; P = .018). Cariprazine resulted in significantly higher remission (OR: 2.05; 95%CI: 1.61-2.61; P = .006) and response rates (OR: 2.31; 95%CI: 1.35-3.95; P = .021) for manic and mixed episodes compared with placebo. Both cariprazine 1.5 mg and 3 mg doses were associated with small but significant reduction in depressive symptoms assessed with MADRS scores (SMD: -0.26, 95%CI: -0.49 to -0.02; P = .040) (SMD: -0.21, 95%CI: -0.41 to -0.01; P = .045), respectively. Cariprazine was significantly associated with the development of adverse effects but not with dropouts due to these adverse effects, when compared to placebo., Conclusion: Cariprazine appears to be safe and efficacious in the treatment of acute mania and mixed episodes associated with BD. Cariprazine at doses of 1.5-3 mg/day is efficacious in acute bipolar depression but the effect sizes were smaller. Controlled studies evaluating its efficacy for prophylaxis are needed., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Lithium and valproate are commonly used either in monotherapy or in combination with atypical antipsychotics in maintenance treatment of bipolar I disorder; however, their comparative efficacy is not well understood. This study aimed to compare the efficacy of valproate and lithium on mood stability either in monotherapy or in combination with atypical antipsychotics., Methods: We performed a post hoc analysis using data from a 52-week randomized double-blind, placebo-controlled trial, that recruited 159 patients with recently remitted mania during treatment with lithium or valproate and adjunctive atypical antipsychotic therapy. Patients were randomized to discontinue adjunctive atypical antipsychotic at 0, 24 or 52 weeks., Results: No significant differences in efficacy were observed between valproate and lithium (hazard ratio: 0.99; 95% confidence interval: [0.66, 1.48]) in time to any mood event. Valproate with 24 weeks of atypical antipsychotic was significantly superior to valproate monotherapy in preventing any mood relapse (hazard ratio: 0.46; 95% confidence interval: [0.22, 0.97]) while lithium with 24 weeks of atypical antipsychotic was superior to lithium monotherapy in preventing mania (hazard ratio: 0.27; 95% confidence interval: [0.09, 0.85]) but not depression., Conclusion: Overall, this study did not find significant differences in efficacy between the two mood-stabilizing agents when used as monotherapy or in combination with atypical antipsychotics. However, study design and small sample size might have precluded from detecting an effect if true difference in efficacy existed. Further head-to-head investigations with stratified designs are needed to evaluate maintenance therapies.

Purpose of Review: Mixed presentations in bipolar disorder have long posed clinical and nosological challenges. The DSM-5 mixed features specifier was developed to provide a more flexible and clinically relevant definition of mixed presentations compared with narrowly defined DSM-IV mixed episodes. However, there is little guidance on treating such presentations. Here, we summarize the evidence for biological treatments of DSM-5 and similarly defined mixed features (MFs)., Recent Findings: The literature on treating MFs is almost exclusively based on post hoc analyses. Within this limited evidence base is preliminary positive data for aripiprazole, asenapine, cariprazine, olanzapine, risperidone, and ziprasidone in treating acute mania with MFs, and cariprazine, lurasidone, olanzapine, and ziprasidone for depressive symptoms in depression with MFs. Divalproex may also be efficacious for acute mania with MFs. The few extant maintenance studies suggest that divalproex and olanzapine may have long-term efficacy in those with index MFs or for the prevention of MFs, respectively. The existing evidence suggests that clinicians consider atypical antipsychotics and divalproex for treating acute mixed presentations. However, adequately powered treatment trials-and studies of maintenance and neurostimulation therapies-are needed. Additionally, data-driven techniques to identify relevant symptom clusters may help improve our conceptualization of mixed presentations.

Background: Non-adherence to medications is a major determinant of poor outcome in bipolar disorder. Second-generation long-acting injectable (LAI) antipsychotics help ensure medication adherence which in turn can lead to more favourable outcomes. However, the role of these medications in bipolar disorder is not well established., Objective: We sought to review available evidence relating to the efficacy and safety of using second-generation LAI antipsychotics in bipolar disorder., Methods: PRISMA guidelines were followed to systematically review all clinical studies that reported on the efficacy and safety of second-generation LAI antipsychotics in patients with bipolar disorder. We searched Ovid Medline, PsycINFO, and Cochrane Central Register of Controlled Trials from inception to November 2018., Results: Of 459 identified citations, 53 studies were fully evaluated and 37 met our inclusion criteria. Overall, second-generation LAI antipsychotics were found to be well tolerated and effective for treatment of manic symptoms and preventing mood recurrences in adults with bipolar disorder. However, we found disparity in the evidence available for individual agents. While several randomized controlled trials (RCTs) reported on the use of risperidone LAI in bipolar disorder, we found only one RCT on the use of aripiprazole LAI, and none for use of paliperidone palmitate or olanzapine pamoate (evidence for the former is limited to one observational study and one case series, and for the latter to a single case report). Studies in children and adolescents were restricted to case reports and small open-label studies., Conclusion: Second-generation LAI antipsychotics, particularly risperidone and aripiprazole LAI, may be a safe and effective alternative to oral medications in the management of bipolar disorder.

Objectives: The neurobiological underpinnings of bipolar I disorder are not yet understood. Previous structural neuroimaging studies of bipolar disorder have produced rather conflicting results. We hypothesise that clinical sub-phenotypes of bipolar I disorder defined by their psychotic symptoms, especially those with mood-incongruent psychotic features, may have more extensive structural brain abnormalities., Methods: We investigated structural brain alterations in patients with first-episode mania (n = 55) with mood-congruent (n = 16) and mood-incongruent (n = 32) psychotic features, as well as those without psychotic symptoms (n = 7), relative to healthy subjects (n = 56)., Results: Total intracranial volume was significantly reduced in patients with mood-incongruent psychosis compared to healthy subjects while cerebrospinal fluid (CSF) volume was significantly increased. Patients with mood-congruent psychosis showed significant reduction in total white matter volume and significant CSF volume increase. Patients with psychosis had significant volume reduction in anterior cingulate and medial prefrontal cortices. Relative to mood-congruent psychotic features, mood-incongruent psychotic features were associated with volume reduction in the left middle temporal gyrus, right inferior parietal gyrus, right fusiform gyrus, left middle orbitofrontal gyrus and cerebellum., Conclusions: While preliminary, our findings suggest that the presence and type of psychosis in first-episode mania may be phenotypic markers of underlying biological variants of bipolar disorder.

Objectives: Bipolar I disorder (BD-I) is associated with gray matter volume (GMV) alterations in neural regions important for emotional regulation. Reductions found in patients with multiple episodes are not seen at illness onset, suggesting that changes occur with illness progression, although no prospective studies to date have examined this. In the present study, we assessed GMV at baseline and one year following a first manic episode, examining the impact of episode recurrence on the trajectory of change., Methods: A total of 41 recently remitted first manic episode patients with BD-I and 25 healthy subjects (HS) underwent 3T magnetic resonance imaging at baseline and one year later. Using voxel-based morphometry, we compared GMV change between HS, patients who experienced a recurrence of a mood episode (BD recurr ), and patients in sustained remission (BD well )., Results: The GMV change from baseline to one year did not differ significantly between HS and the full BD-I group or BD well and HS. However, the BD recurr group had greater GMV loss than HS in left frontal and bilateral temporal regions, and BD well patients involving bilateral frontal, temporal and left parietal regions., Conclusions: GMV change early in the course of BD-I is associated with clinical outcome, such that neuroprogression found in patients who experience a recurrence of a mood episode is not seen in those with sustained remission. These findings have important implications for the treatment of BD-I as they suggest that prevention of recurrence might minimize neuroprogression of the disease, possibly requiring a multipronged early intervention approach to achieve this goal., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: This study aimed to simplify the diagnostic criteria of pre-hypertension (pre-HTN) and hypertension (HTN) in the pediatric age group, and to determine the accuracy of these simple indexes in a nationally-representative sample of Iranian children and adolescents., Method: The diagnostic accuracy of the indexes of systolic blood pressure-to-height ratio (SBPHR) and diastolic BPHR (DBPHR) to define pre-HTN and HTN was determined by the area under the curve of the receiver operator characteristic curves., Results: The study population consisted of 5,738 Iranian students (2,875 females) with mean (SD) age of 14.7 (2.4) years. The prevalences of pre-HTN and HTN were 6.9% and 5.6%. The optimal thresholds for defining pre-HTN were 0.73 in males and 0.71 in females for SBPHR, and 0.47 in males and 0.45 in females for DBPHR, respectively. The corresponding figures for HTN were 0.73, 0.71, 0.48, and 0.46, respectively. In both genders, the accuracies of SBPHR and DBPHR in diagnosing pre-HTN and HTN were approximately 80%., Conclusions: BPHR is a valid, simple, inexpensive, and accurate tool to diagnose pre-HTN and HTN in adolescents. The optimal thresholds of SBPHR and DBPHR were consistent with the corresponding figures in other populations of children and adolescents with different racial and ethnic backgrounds. Thus, it is suggested that the use of these indexes can be generalized in programs aiming to screen elevated blood pressure in the pediatric age group., (Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Background: This study aims to determine the association of some genetic polymorphisms in the relationship of air pollutants on the serum levels of thrombomodulin (TM) and tissue factor (TF) in a population-based sample of children and adolescents., Materials and Methods: This cross-sectional study was conducted among 110 participants (52.8% girls) with a mean age of 12.7 + 2.3 years, in Isfahan, Iran. Genotypes of TM G33-A and + 5466A > G polymorphisms were determined by the polymerase chain reaction - restriction length fragment polymorphism method (PCR-RFLP). The enzyme-linked immunosorbent assay (ELISA) was used for measurement of serum TM and TF., Results: THE FOLLOWING GENOTYPES WERE IDENTIFIED FOR TM: GG in 69.2%, GA in27.2%, and AA in 3.6% of the participants. Considering TF, 108 participants were homozygous for the + 5466A allele, and two subjects had + 5466AG genotype. The mean pollution standards index (PSI) value was at a moderate level; the mean particulate matter measured up to 10 μm (PM(10)); and ozone (O(3)), nitrogen dioxide, and sulfur dioxide were considerably high. The mean serum TF and TM levels were not significantly different among the participants with the aforementioned genotypes. Among participants exposed to high quartiles of O(3), PM(10), and PSI, the TM-33G / A polymorphism (GA + AA genotype) increased the Odds ratio (OR) of the low serum TM level. There was no statistically significant association in the areas of low pollution., Conclusion: The findings of our study support the synergistic effect of the TM-33G / A polymorphism and air pollutants on factors associated with the onset of the atherosclerosis. This might be confirmatory evidence for gene-environment interaction, and related effects on atherogenesis from early life.

Background: A school-based surveillance system entitled the childhood and adolescence surveillance and prevention of Adult Noncommunicable disease (CASPIAN) Study is implemented at national level in Iran. This paper presents the methods and primary findings of the third survey of this surveillance system., Methods: This national survey was performed in 2009-2010 in 27 provinces of Iran among 5570 students and one of their parents. In addition to physical examination, fasting serum was obtained. Body mass index was categorized based on the World Health Organization growth charts., Findings: Data of 5528 students (2726 girls, 69.37% urban, mean age 14.7 ± 2.4 years) were complete and are reported. Overall, 17.3% (17.3% of girls and 17.5% of boys) were underweight, and 17.7% (15.5% of girls and 19.9% of boys) were overweight or obese. Abdominal obesity was documented in 16.3% of students (17.8% of girls and 15% of boys). 57.6% of families consumed breads, the staple food for Iranians, prepared with white flour. Most families (43.8% in urban areas and 58.6% in rural areas) used solid hydrogenated fats. 22.7% of students did not add salt to the table food. 14.2% of students reported to have a regular daily physical activity for at least 30 min a day. Overall, 10.4% of students (11.7% in urban areas and 7.3% in rural areas) reported that they used tobacco products, often waterpipe. 32.8% of students experienced at least three times of bullying in the previous 3 months. During the year prior to the survey, 14.46% of students had an injury needing the interference by school health providers., Conclusion: This survey is confirmatory evidence on the importance of establishing surveillance systems for risk behaviors to implement action-oriented interventions.

Objective: University students' mental health affects not only their educational achievements, but also their professional future. The authors assessed the prevalence of suicidal ideation, depression, and aggression among students of three major universities in Isfahan, Iran., Methods: In 2008, 470 students were entered into the study using a convenience sampling method. The three measurement tools applied were Aggression Questionnaire (AGQ), Beck Depression Inventor (BDI), and Beck Scale for Suicide Ideation (BSSI)., Results: Suicidal ideation was present in 7.58% of the students, depression in 28.04%, and aggression in 30.11% of them. The ratio of depression to suicidal ideation was approximately 4:1. No significant difference in the mean scores of aggression, depression, and suicidal ideation was observed between the three universities. No significant relationships were found between mean scores of aggression, depression, and suicidal ideation with age and gender. There was no meaningful relationship between the mean scores of aggression and marriage status, but the mean scores of depression (P = 0.01) and suicidal ideation (P = 0.0001) were significantly lower in the married students compared to the single ones. Aggression was significantly associated with depression and suicidal ideation (P = 0.0001)., Conclusion: The frequency of suicidal ideation, aggression, and depression was less in our studied college students than in previous non-Iranian studies. The decreasing trend in reported frequency of mild depression during previous years is a noticeable finding. Yet, the findings seek more preventing programs among college students.

Background: This study aimed to establish a comprehensive screening and referral system for chronic non-communicable diseases (CNCD) in the routine primary health care, and to determine the prevalence of diabetes, pre-diabetes, metabolic syndrome, and dyslipidemia in adult population invited by public announcement to the Health clinics in Isfahan, Iran., Methods: This survey was conducted from March 2010, and the current paper presents data obtained until November 2011. To provide health services for prevention and control of CNCDs, with priority of type2 diabetes mellitus, Health clinics were established in different parts of Isfahan city with a population of approximately 2,100,000 in Iran. The general populations aged 30 years and above were invited to the Health clinics by public announcement., Results: A total of 198972 participants were screened. The mean age of participants was 47.8 years (48.5 men, 47.3 women), with a range of 1 to 95 years old and standard deviation of 12.3 years (12.7 men, 12.1 women). Overall, 22% of participants had impaired fasting glucose, 25% had hypercholesterolemia, 31% had hypertriglyceridemia, and 20% had metabolic syndrome., Conclusion: The high prevalence of dysglycemia and diabetes in our survey may serve as confirmatory evidence about the importance of mass screening and early diagnosis of CNCDs' risk factors. Our model of establishing Health clinics, as a comprehensive referral system in the routine primary health care can be adopted by Middle Eastern countries, where CNCDs notably diabetes are an emerging health problem.

Pediatric pre-hypertension (pre-HTN) has a complex multifactorial etiology. Although most cases are secondary to other disorders, a substantial number of children and adolescents have primary or essential HTN and pre-HTN. The gene-gene and gene-environment interactions should be considered in this context. The strong relationship of pre-HTN with environmental factors such as air pollution, noise pollution and passive smoking and obesity suggest that its prevalence will be escalating.Exposure to ambient particulate matters may increase blood pressure (BP) within hours to days. The underlying biologic pathways include autonomic nervous system imbalance and arterial vascular dysfunction or vasoconstriction because of systemic oxidative stress and inflammation. Likewise, tobacco smoke exposure of pregnant mothers increases systolic BP of their offspring in early infancy. Parental smoking also independently affects systolic BP among healthy preschool children. Noise exposure, notably in night, is associated with catecholamine secretion, increased BP and a pre-HTN state even in pre-school age children.Excess weight is associated with dysfunction of the adipose tissue, consisting of enlarged hypertrophied adipocytes, increased infiltration by macrophages and variations in secretion of adipokines and free fatty acids. These changes would result in chronic vascular inflammation, oxidative stress, activation of the renin-angiotensin-aldosterone system and sympathetic response, and ultimately to pre-HTN from childhood.Prevention and control of the modifiable risk factors of pre-HTN from prenatal period can have long-term health impact on primordial and primary prevention of chronic non-communicable diseases. This review presents a general view on the diagnosis, prevalence and etiology of pre-HTN along with practical measures for its prevention and control.

Recent real-time fMRI (rt-fMRI) training studies have demonstrated that subjects can achieve improved control over localized brain regions by using real-time feedback about the level of fMRI signal in these regions. It has remained unknown, however, whether subjects can gain control over anterior prefrontal cortex (PFC) regions that support some of the most complex forms of human thought. In this study, we used rt-fMRI training to examine whether subjects can learn to regulate the rostrolateral prefrontal cortex (RLPFC), or the lateral part of the anterior PFC, by using a meta-cognitive awareness strategy. We show that individuals can achieve improved regulation over the level of fMRI signal in their RLPFC by turning attention towards or away from their own thoughts. The ability to achieve improved modulation was contingent on observing veridical real-time feedback about the level of RLPFC activity during training; a sham-feedback control group demonstrated no improvement in modulation ability and neither did control subjects who received no rt-fMRI feedback but underwent otherwise identical training. Prior to training, meta-cognitive awareness was associated with recruitment of anterior PFC subregions, including both RLPFC and medial PFC, as well as a number of other midline and posterior cortical regions. Following training, however, regulation improvement was specific to RLPFC and was not observed in other frontal, midline, or parietal cortical regions. These results demonstrate the feasibility of acquiring control over high-level prefrontal regions through rt-fMRI training and offer a novel view into the correspondence between observable neuroscientific measures and highly subjective mental states., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The prefrontal cortex (PFC) plays a crucial role in cognitive control and higher mental functions by maintaining working memory representations of currently relevant information, thereby inducing a mindset that facilitates the processing of such information. Using fMRI, we examined how the human PFC implements mindsets for information at varying levels of abstraction. Subjects solved anagrams grouped into three kinds of blocks (concrete, moderately abstract, and highly abstract) according to the degree of abstraction of their solutions. Mindsets were induced by cuing subjects at the beginning of every block as to the degree of abstraction of solutions they should look for. Different levels of abstraction were matched for accuracy and reaction time, allowing us to examine the effects of varying abstraction in the absence of variations in cognitive complexity. Mindsets for concrete, moderately abstract, and highly abstract information were associated with stronger relative recruitment of ventrolateral, dorsolateral, and rostrolateral PFC regions, respectively, suggesting a functional topography whereby increasingly anterior regions are preferentially associated with representations of increasing abstraction. Rather than being a structural property of the neurons in different prefrontal subregions, this relative specialization may reflect one of the principles according to which lateral PFC adaptively codes and organizes task-relevant information.

The functions of the rostrolateral prefrontal cortex (RLPFC) have recently become the target of multiple theories and empirical investigations. This region can be loosely defined as the lateral portion of Brodmann area (BA) 10. One of the challenges in testing theories about RLPFC functions is the difficulty in defining its boundaries when formulating predictions for its recruitment. Here we present a procedure that goes beyond the currently available anatomical definitions to attempt a functional localization of RLPFC. A combination of functional and anatomical criteria was employed, consistent with other localizer procedures. Functional localization was performed by comparing a relational condition involving relational matching to a control condition involving feature matching. It was expected that within an anatomically defined BA10 region, this procedure would produce functional activations in the lateral but not the medial subregions. The task was administered in the course of a single 13-min fMRI session. Results showed remarkable consistency, with all subjects activating RLPFC and activations consistently localized in the lateral part of BA10. These results demonstrate the practical feasibility of localizing RLPFC using a short procedure and a combination of functional and anatomical criteria. Such localization presents with a number of potential advantages for testing theories of RLPFC functions, including improved anatomical precision of experimental predictions, as well as the possibility of reduction in the rate of false-negative findings across studies. In addition, the results provide further support for the previously proposed functional dissociation between lateral and medial BA10.

Objective: Traumatic brain injury is one of the major causes of death and disability among young people. Methylphenidate, a neural stimulant and protective drug, which has been mainly used for childhood attention deficit/hyperactivity disorder, has shown some benefits in late psychosocial problems in patients with traumatic brain injury. Its effect on arousal and consciousness has been also revealed in the sub-acute phase of traumatic brain injury. We studied its effect on the acute phase of moderate and severe traumatic brain injury (TBI) in relation to the length of ICU and hospital admission., Patients and Methods: Severely and moderately TBI patients (according to inclusion and exclusion criteria) were randomized to treatment and control groups. The treatment group received methylphenidate 0.3mg/kg per dose PO BID by the second day of admission until the time of discharge, and the control group received a placebo. Admission information and daily Glasgow Coma Scale (GCS) were recorded. Medical, surgical, and discharge plans for patients were determined by the attending physician, blinded to the study., Results: Forty patients with severe TBI (GCS = 5-8) and 40 moderately TBI patients (GCS = 9-12) were randomly divided into treatment and control groups on the day of admission. In the severely TBI patients, both hospital and ICU length of stay, on average, were shorter in the treatment group compared with the control group. In the moderately TBI patients while ICU stay was shorter in the treatment group, there was no significant reduction of the period of hospitalization., Conclusion: There were no significant differences between the treatment and control groups in terms of age, sex, post resuscitation GCS, or brain CT scan findings, in either severely or moderately TBI patients. Methylphenidate was associated with reductions in ICU and hospital length of stay by 23% in severely TBI patients (P = 0.06 for ICU and P = 0.029 for hospital stay time). However, in the moderately TBI patients who received methylphenidate, there was 26% fall (P = 0.05) only in ICU length of stay.