Evaluating the Interrater Reliability of the Icelandic Version of K-SADS-PL DSM-5.

The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) is a valuable tool for diagnosing mental disorders in children and adolescents. Previous studies have examined its interrater reliability, but there is limited information on individual disorders, on the updated DSM-5 version. This study aims to analyse the interrater reliability of the Icelandic translation of K-SADS-PL, DSM-5 version. K-SADS-PL was administered to a clinical sample of outpatients from the Icelandic Anxiety Centre for Children, Adolescents, and Young Adults, and The Department of Child and Adolescent Psychiatry at Landspítali, the National University Hospital in Reykjavík, Iceland. In total, 135 patients aged 6-18 were included in this study. We assessed the interrater reliability using Cohen's κ, with results ranging from poor to excellent (0.3-1.0), though most disorders showed excellent reliability (κ > 0.75). The Icelandic translation of the DSM-5 K-SADS-PL is generally reliable when used by properly trained post-graduate students, which supports its use in clinical settings.

Evaluating Prophylactic Effect of Bovine Colostrum on Intestinal Barrier Function in Zonulin Transgenic Mice: A Transcriptomic Study.

The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various tissues. Recent research has suggested that specific dietary components may influence the function of the intestinal barrier, potentially offering a means to prevent or mitigate inflammatory disorders. However, the precise mechanism underlying these effects remains unclear. Bovine colostrum (BC), the first milk from cows after calving, is a natural source of nutrients with immunomodulatory, anti-inflammatory, and gut-barrier fortifying properties. This novel study sought to investigate the transcriptome in BC-treated Zonulin transgenic mice (Ztm), characterized by dysbiotic microbiota, intestinal hyperpermeability, and mild hyperactivity, applying RNA sequencing. Seventy-five tissue samples from the duodenum, colon, and brain of Ztm and wild-type (WT) mice were dissected, processed, and RNA sequenced. The expression profiles were analyzed and integrated to identify differentially expressed genes (DEGs) and differentially expressed transcripts (DETs). These were then further examined using bioinformatics tools. RNA-seq analysis identified 1298 DEGs and 20,952 DETs in the paired (Ztm treatment vs. Ztm control) and reference (WT controls) groups. Of these, 733 DEGs and 10,476 DETs were upregulated, while 565 DEGs and 6097 DETs were downregulated. BC-treated Ztm female mice showed significant upregulation of cingulin (Cgn) and claudin 12 (Cldn12) duodenum and protein interactions, as well as molecular pathways and interactions pertaining to tight junctions, while BC-treated Ztm males displayed an upregulation of transcripts like occludin (Ocln) and Rho/Rac guanine nucleotide exchange factor 2 (Arhgf2) and cellular structures and interfaces, protein-protein interactions, and organization and response mechanisms. This comprehensive analysis reveals the influence of BC treatment on tight junctions (TJs) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway gene expressions. The present study is the first to analyze intestinal and brain samples from BC-treated Ztm mice applying high-throughput RNA sequencing. This study revealed molecular interaction in intestinal barrier function and identified hub genes and their functional pathways and biological processes in response to BC treatment in Ztm mice. Further research is needed to validate these findings and explore their implications for dietary interventions aimed at improving intestinal barrier integrity and function. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).

Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study): A protocol for an observational longitudinal case-control study.

Recent studies indicate that the interplay between diet, intestinal microbiota composition, and intestinal permeability can impact mental health. More than 10% of children and adolescents in Iceland suffer from mental disorders, and rates of psychotropics use are very high. The aim of this novel observational longitudinal case-control study, "Meals, Microbiota and Mental Health in Children and Adolescents (MMM-Study)" is to contribute to the promotion of treatment options for children and adolescents diagnosed with mental disorders through identification of patterns that may affect the symptoms. All children and adolescents, 5-15 years referred to the outpatient clinic of the Child and Adolescent Psychiatry Department at The National University Hospital in Reykjavik, Iceland, for one year (n≈150) will be invited to participate. There are two control groups, i.e., sex-matched children from the same postal area (n≈150) and same parent siblings (full siblings) in the same household close in age +/- 3 years (n<150). A three-day food diary, rating scales for mental health, and multiple questionnaires will be completed. Biosamples (fecal-, urine-, saliva-, blood samples, and buccal swab) will be collected and used for 16S rRNA gene amplicon sequencing of the oral and gut microbiome, measurements of serum factors, quantification of urine metabolites and host genotype, respectively. For longitudinal follow-up, data collection will be repeated after three years in the same groups. Integrative analysis of diet, gut microbiota, intestinal permeability, serum metabolites, and mental health will be conducted applying bioinformatics and systems biology approaches. Extensive population-based data of this quality has not been collected before, with collection repeated in three years' time, contributing to the high scientific value. The MMM-study follows the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) guidelines. Approval has been obtained from the Icelandic National Bioethics Committee, and the study is registered with Clinicaltrials.gov. The study will contribute to an improved understanding of the links between diet, gut microbiota and mental health in children through good quality study design by collecting information on multiple components, and a longitudinal approach. Furthermore, the study creates knowledge on possibilities for targeted and more personalized dietary and lifestyle interventions in subgroups. Trial registration numbers: VSN-19-225 & NCT04330703.

Prophylactic Effect of Bovine Colostrum on Intestinal Microbiota and Behavior in Wild-Type and Zonulin Transgenic Mice.

The microbiota-gut-brain axis (MGBA) involves bidirectional communication between intestinal microbiota and the gastrointestinal (GI) tract, central nervous system (CNS), neuroendocrine/neuroimmune systems, hypothalamic-pituitary-adrenal (HPA) axis, and enteric nervous system (ENS). The intestinal microbiota can influence host physiology and pathology. Dysbiosis involves the loss of beneficial microbial input or signal, diversity, and expansion of pathobionts, which can lead to loss of barrier function and increased intestinal permeability (IP). Colostrum, the first milk from mammals after birth, is a natural source of nutrients and is rich in oligosaccharides, immunoglobulins, growth factors, and anti-microbial components. The aim of this study was to investigate if bovine colostrum (BC) administration might modulate intestinal microbiota and, in turn, behavior in two mouse models, wild-type (WT) and Zonulin transgenic (Ztm)-the latter of which is characterized by dysbiotic microbiota, increased intestinal permeability, and mild hyperactivity-and to compare with control mice. Bioinformatics analysis of the microbiome showed that consumption of BC was associated with increased taxonomy abundance (p = 0.001) and diversity (p = 0.004) of potentially beneficial species in WT mice and shifted dysbiotic microbial community towards eubiosis in Ztm mice (p = 0.001). BC induced an anxiolytic effect in WT female mice compared with WT female control mice (p = 0.0003), and it reduced anxiogenic behavior in Ztm female mice compared with WT female control mice (p = 0.001), as well as in Ztm male mice compared with WT BC male mice (p = 0.03). As evidenced in MGBA interactions, BC supplementation may well be applied for prophylactic approaches in the future. Further research is needed to explore human interdependencies between intestinal microbiota, including eubiosis and pathobionts, and neuroinflammation, and the potential value of BC for human use. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).

Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis.

Worldwide, up to 20% of children and adolescents experience mental disorders, which are the leading cause of disability in young people. Research shows that serum zonulin levels are associated with increased intestinal permeability (IP), affecting neural, hormonal, and immunological pathways. This systematic review and meta-analysis aimed to summarize evidence from observational studies on IP in children diagnosed with mental disorders. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the Cochrane Library, PsycINFO, PubMed, and the Web of Science identified 833 records. Only non-intervention (i.e., observational) studies in children (<18 years) diagnosed with mental disorders, including a relevant marker of intestinal permeability, were included. Five studies were selected, with the risk of bias assessed according to the Newcastle-Ottawa scale (NOS). Four articles were identified as strong and one as moderate, representing altogether 402 participants providing evidence on IP in children diagnosed with attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). In ADHD, elevated serum zonulin levels were associated with impaired social functioning compared to controls. Children with ASD may be predisposed to impair intestinal barrier function, which may contribute to their symptoms and clinical outcome compared to controls. Children with ASD, who experience gastro-intestinal (GI) symptoms, seem to have an imbalance in their immune response. However, in children with OCD, serum zonulin levels were not significantly different compared to controls, but serum claudin-5, a transmembrane tight-junction protein, was significantly higher. A meta-analysis of mean zonulin plasma levels of patients and control groups revealed a significant difference between groups (p = 0.001), including the four studies evaluating the full spectrum of the zonulin peptide family. Therefore, further studies are required to better understand the complex role of barrier function, i.e., intestinal and blood-brain barrier, and of inflammation, to the pathophysiology in mental and neurodevelopmental disorders. This review was PROSPERO preregistered, (162208).

Icelandic translation and reliability data on the DSM-5 version of the schedule for affective disorders and schizophrenia for school-aged children - present and lifetime version (K-SADS-PL).

BACKGROUND: The Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL) is a semi-structured interview based on the Diagnostic and Statistical Manual of Mental Disorders (DSM), and assesses past and present symptoms in children aged 6-18 years old. It has been translated into more than 20 languages and is widely used in clinical work. The K-SADS-PL has recently been revised by adopting new DSM-5 disorders and modifying probes accordingly. However, research on this revision is critically limited. The objective of this study was to examine the inter-rater reliability of the DSM-5 K-SADS-PL when administered by postgraduate students after receiving thorough training and supervision. METHOD: The DSM-5 K-SADS-PL was applied in a clinical sample of two outpatient units: The outpatient unit of the Department of Child and Adolescent Psychiatry at the Landspítali University Hospital in Reykjavík, Iceland and The Icelandic Anxiety Centre for Children, Adolescents and Young Adults. RESULTS: Fourty-one (80%) consecutive patients aged 6-18 years consented and were included. Cohen's κ was calculated to estimate inter-rater reliability, with estimates ranging from fair to excellent (κ = 0.57-0.90), with most diagnoses in the excellent range (κ > 0.75). CONCLUSIONS: These results indicate that the Icelandic translation of the DSM-5 K-SADS-PL can be reliably administered by postgraduate students.

[A Review and Recommendations of Evidence-Based Treatments for Pediatric Obsessive-Compulsive Disorder].

UNLABELLED: Pediatric obsessive-compulsive disorder (OCD) is characterized by recurrent obsessions and compulsions. In this review we depict evidence-based treatments for pediatric OCD patients. We searched PubMed for relevant publications including randomized controlled trials, reviews, and expert guidelines. Substantial evidence for cognitive behavior therapy (CBT) and specific serotonin reuptake inhibitors (SSRIs) among treatment-naïve patients shows that both treatments are effective. CBT is significantly more effective than SSRI based on head-to-head trials. The evidence for CBT- or SSRI-resistant patients is limited but indicates that CBT and SSRI are effective treatments for CBT non-responders while a combination of CBT and SSRI is the most effective treatment for SSRI non-responders with no prior exposure to CBT. The current data support clinical guidelines indicating that when CBT expertise is present, one can successfully treat patients with CBT. CBT is also as effective as SSRI in non-responders after 14 weeks of CBT. The results did not indicate that combined treatment of CBT and SSRI is more effective than CBT delivered by experts. However, combined treatment is more effective than SSRI in SSRI non-responders. KEY WORDS: Obsessive-compulsive disorder, children and adolescents, treatment, Cognitive behavior therapy, selective serotonin reuptake inhibitors, atypical antipsychotics, treatment-resistant, treatment-refractory. Correspondence: Guðmundur Skarphedinsson, gudmundur.skarphedinsson@r-bup.no.

Screening efficiency of the self-report version of the Multidimensional Anxiety Scale for Children in a highly comorbid inpatient sample.

BACKGROUND: The Multidimensional Anxiety Scale for Children (MASC) is a widely used self-report questionnaire for the assessment of anxiety symptoms in children and adolescents with well documented predictive validity of the total score and subscales in internalizing and mixed clinical samples. However, no data exist on the screening efficiency in an inpatient sample of adolescents. AIM: To examine the psychometric properties and screening efficiency of the MASC in a high comorbid inpatient sample. METHOD: The current study used receiver operating characteristic (ROC) analyses to investigate the predictive value of the MASC total and subscale scores for the Schedule for Affective Disorders and Schizophrenia for School-age children-Present and Lifetime version (K-SADS-PL), DSM-IV diagnoses of generalized anxiety disorder (GAD), separation anxiety disorder (SAD) and social phobia (SoP) in a highly comorbid inpatient sample of adolescents (11-18 years). RESULTS: The MASC total score predicted any anxiety disorder (AD) and GAD moderately well. Physical symptoms predicted GAD moderately well. Social anxiety and separation anxiety/panic did not predict SoP or SAD, respectively. Physical symptoms and harm avoidance also predicted the presence of major depressive disorder. CONCLUSIONS: The findings support the utility of the MASC total score to predict the presence of any AD and GAD. However, the utility of the social anxiety and separation anxiety/panic subscales showed limited utility to predict the presence of SAD and SoP, respectively. The MASC has probably a more limited function in screening for AD among a highly comorbid inpatient sample of severely affected adolescents. Our results should be interpreted in the light of a small, mixed sample of inpatient adolescents.

Gene × Environment interactions in autism spectrum disorders: role of epigenetic mechanisms.

Several studies support currently the hypothesis that autism etiology is based on a polygenic and epistatic model. However, despite advances in epidemiological, molecular and clinical genetics, the genetic risk factors remain difficult to identify, with the exception of a few chromosomal disorders and several single gene disorders associated with an increased risk for autism. Furthermore, several studies suggest a role of environmental factors in autism spectrum disorders (ASD). First, arguments for a genetic contribution to autism, based on updated family and twin studies, are examined. Second, a review of possible prenatal, perinatal, and postnatal environmental risk factors for ASD are presented. Then, the hypotheses are discussed concerning the underlying mechanisms related to a role of environmental factors in the development of ASD in association with genetic factors. In particular, epigenetics as a candidate biological mechanism for gene × environment interactions is considered and the possible role of epigenetic mechanisms reported in genetic disorders associated with ASD is discussed. Furthermore, the example of in utero exposure to valproate provides a good illustration of epigenetic mechanisms involved in ASD and innovative therapeutic strategies. Epigenetic remodeling by environmental factors opens new perspectives for a better understanding, prevention, and early therapeutic intervention of ASD.

Psychiatric disorders in an urban sample of preschool children.

BACKGROUND: To increase limited epidemiological knowledge of early childhood psychopathology, a study of prevalence estimates and demographic correlates of psychiatric disorders was conducted in a sample of preschool children. METHODS: In a two-stage study, parents of 339 children aged 4-6 years who came for a medical check-up at three primary care centres in Reykjavik were invited to participate. First, the participants were screened with Brigance Screens and the Strengths and Difficulties Questionnaire (SDQ) for parents and teachers. Subsequently, the children were tested with a short version of Wechsler Preschool and Primary Scales of Intelligence - Revised and their parents were interviewed with the Schedule for Affective Disorders and Schizophrenia for School Aged Children Present and Lifetime Version. Weighted prevalence estimates were calculated and logistic regression was used to analyse the association between risk factors and psychiatric disorders. RESULTS: Of those invited to participate, 317 (93.5%) were included in the screening and of those, 131 received a full diagnostic assessment. The final study sample included 151 girls (47.6%) and 166 boys (52.4%) who represented 11.6% of the total birth cohort in Reykjavik. Weighted prevalence of DSM-IV psychiatric disorders was 10.1% (95% CI 6.7-13.5%) and 57/317 or 18.0% (95% CI 13.8-22.2%), including elimination disorders. Anxiety disorders (5.7%) and attention deficit hyperactivity disorder (3.8%) were the most common disorders in this preschool sample. Poor physical health of parents and higher education was associated with DSM-IV psychiatric disorders of the children. SDQ Total Difficulties score was associated with male gender and poor physical health of parents. CONCLUSIONS: This study indicates that psychiatric disorders in preschool children are common and may be correlated with parental health factors.

Parent-youth agreement on symptoms and diagnosis: assessment with a diagnostic interview in an adolescent inpatient clinical population.

Diagnostic information on adolescents may be elicited from both youths and their parents, especially for depressive and suicidal symptomatology. The objective of this study was to examine the degree of agreement between parent and adolescent reports of major psychiatric disorders, at the diagnostic and at the symptom level, in a severely affected inpatient clinical population. 64 parent-adolescent pairs were interviewed separately with the semi-structured diagnostic interview Kiddie-SADS-PL. Symptomatology was also assessed with 11 self-report and parent-report scales, all translated, adapted and in most cases validated in Iceland. A total of 25 subscales were included to assess emotional dimensions such as depression or anxiety and cognitive dimensions such as attention deficit or self-concept. Good agreement was found for social phobia and fair agreement for generalized anxiety disorder. Although parent-youth agreement was poor in most cases at the symptoms level, significant correlations indicated consistency for most severity scores, except those related to depressive symptomatology, attention deficit, separation anxiety or conduct disorder. The low agreement between reports of suicidal ideation is in line with results from previous studies and suggests that parents might under- or over-estimate this symptomatology. The combination of data obtained with diagnostic interviews and rating-scales confirmed results from prior empirical work, giving greater weight to parents' reports of observable behavior and to adolescents' reports of subjective experiences, especially depressive symptomatology. Our findings suggest that both parent and child informants are necessary to obtain adequate assessments in adolescents. Further research should explore the correspondence between discrepant diagnoses and external criteria such as parental psychopathology or parent-child relationships and attachment. Psychoanalysis could benefit from cognitive neuroscience and use cognitive assessments as interesting tools. Thus, cognitive assessments can show discrepant results according to parents' or adolescents' reports and can therefore shed light on the parent-child interaction and relational dynamics. Inversely, cognitive neuroscience could benefit from psychoanalysis by taking into account, when interpretating the scores, the relational dynamics and the personal history of the rater.

Validity of K-SADS-PL (Schedule for Affective Disorders and Schizophrenia for School-Age Children--Present and Lifetime Version) depression diagnoses in an adolescent clinical population.

BACKGROUND: Validity studies of the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) interview are modest in number given the international acceptance and extensive use of this instrument in epidemiological and treatment research. The results are somewhat mixed and limited, particularly for adolescent depression. AIMS: The objective of this study was to assess the convergent-divergent validity of the screen criteria and depression diagnoses (major depressive episode) generated with the diagnostic interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). METHODS: Participants were 86 consecutively admitted inpatients aged 12-17 years and their parents. Both convergent and divergent validity of the depression diagnoses were assessed against 11 standard self-report or parent-report rating scales, all of which had been translated, adapted and in most cases validated in Iceland. A total of 25 subscales were included in calculations. RESULTS: Convergent validity was confirmed, with adolescents who screened positive or met criteria for major depressive episode scoring higher than other patients did on scales assessing depressive symptoms. However, divergent validity was only partially supported in this highly comorbid inpatient sample. Severity based on number of diagnostic criteria met had a generally substantial correlation with the rating scales. CONCLUSIONS: This study provides a substantial additional amount of convergent-divergent validity data related to this extensively used diagnostic instrument.

An Icelandic version of the Kiddie-SADS-PL: translation, cross-cultural adaptation and inter-rater reliability.

The development of structured diagnostic instruments has been an important step for research in child and adolescent psychiatry, but the adequacy of a diagnostic instrument in a given culture does not guarantee its reliability or validity in another population. The objective of the study was to describe the process of cross-cultural adaptation into Icelandic of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (Kiddie-SADS-PL) and to test the inter-rater reliability of the adapted version. To attain cross-cultural equivalency, five important dimensions were addressed: semantic, technical, content, criterion and conceptual. The adapted Icelandic version was introduced into an inpatient clinical setting, and inter-rater reliability was estimated both at the symptom and diagnoses level, for the most frequent diagnostic categories in both international diagnostic classification systems (DSM-IV and ICD-10). The cross-cultural adaptation has provided an Icelandic version allowing similar understanding among different raters and has achieved acceptable cross-cultural equivalence. This initial study confirmed the quality of the translation and adaptation of Kiddie-SADS-PL and constitutes the first step of a larger validation study of the Icelandic version of the instrument.

Implementing the semi-structured interview Kiddie-SADS-PL into an in-patient adolescent clinical setting: impact on frequency of diagnoses.

BACKGROUND: Research is needed to establish the utility of diagnostic interviews in clinical settings. Studies comparing clinical diagnoses with diagnoses generated with structured instruments show generally low or moderate agreement and clinical diagnostic assignment (e.g. admission or chart diagnoses) are often considered to underdiagnose disorders. The objective of this study was to evaluate the impact of implementing the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (Kiddie-SADS-PL) into an in-patient adolescent clinical setting. METHODS: Participants were all adolescents admitted through the years 2001-2004 (N = 333 admissions, age 12-17 years). The authors reviewed the charts of the previous three years of consecutive admissions, patients being evaluated using routine psychiatric evaluation, before the Kiddie-SADS-PL was introduced. They then reviewed the charts of all consecutive admissions during the next twelve months, patients being evaluated by adding the instrument to routine practice. RESULTS: The rates of several main diagnostic categories (depressive, anxiety, bipolar and disruptive disorders) increased considerably, suggesting that those disorders were likely underreported when using non-structured routine assessment procedures. The rate of co-morbidity increased markedly as the number of diagnoses assigned to each patient increased. CONCLUSION: The major differences in diagnostic assignment rates provide arguments for the utility of diagnostic interviews in inpatient clinical settings but need further research, especially on factors that affect clinical diagnostic assignment in "real world" settings.