Weeks in Pregnancy on Maternal Iodine Status and Infant Neurodevelopment: Mommy's Food, a Randomized-Controlled Trial

Background: Mild-to-moderate iodine deficiency is still present in many countries, particularly in pregnant women. Observational studies suggest that mild-to-moderate iodine deficiency during pregnancy may be associated with impaired thyroid function and child neurodevelopment. Randomized-controlled food trials to increase iodine status are scarce. We assessed the impact of an increased intake of cod during pregnancy on maternal iodine status and infant neurodevelopment. Methods: In this randomized-controlled trial, pregnant women in Bergen, Norway, recruited through Haukeland University Hospital, were randomly assigned (1:1) to an intervention of 200 g of cod twice a week for 16 weeks (gestational week 20–36) or to continue with their standard diet (control group). Randomization was done by lottery. Primary outcome was urinary iodine concentration (UIC) (spot samples from six consecutive days) measured postintervention. Secondary outcome was infant neurodevelopment assessed by the cognitive, language, and motor scales of the Bayley Scales of Infant and Toddler Developmental third edition (Bayley-III) at 11 months of age. In addition, maternal thyroid function was measured (thyrotropin [TSH], free triiodothyronine [fT3], free thyroxine [fT4]) at baseline and postintervention. Results: Between January 2016 until February 2017, 137 women were recruited. Postintervention UIC was higher in the intervention group (n = 61) [median (interquartile range, IQR) 98 (64–145) μg/L], compared with control (n = 61) [median (IQR) 73 (52–120) μg/L] (p = 0.028), also after adjusting for baseline UIC (p = 0.048). Infants of mothers in the intervention group had a lower cognitive composite score on the Bayley-III compared with the control group (p = 0.045). There were no group differences in the Bayley III language- or motor composite scores. Maternal thyroid hormones (TSH, fT3, fT4) did not differ between the groups postintervention. Conclusions: Increased cod intake during pregnancy improved the iodine status in women with mild-to-moderate iodine deficiency, however, did not affect thyroid function. The negative effect on cognition should be followed up to assess whether this is a stable effect over time. More studies are warranted to enable good health advice on iodine nutrition in pregnancy. ClinicalTrials.gov NCT02610959. Registered November 20, 2015.publishedVersio

Effects of cod intake in pregnancy on iodine nutrition and infant development: study protocol for Mommy’s Food - a randomized controlled trial

Background Iodine is a key component of thyroid hormones that are critical for normal development of the brain and nervous system in utero. Recent results indicate that two thirds of pregnant women in Europe have sub-optimal iodine nutrition. In Norway, milk and seafood are the most important dietary iodine sources and contributes to about 80% of the intake. Method Two-armed randomized trial where 137 pregnant women were randomized to either receiving cod twice weekly, or continue with habitual diet for 16 weeks (pregnancy week 20–36). Socioeconomic- and demographic factors, dietary information and biological (urine, blood, and hair) samples are collected pre- and post-intervention, and at six weeks, three-, six-, and eleven months postpartum. Biological samples (urine, blood, and hair) of the infant are collected at six weeks, three-, six-, and eleven months postnatal. Child development is assessed by The Bayley Scale of Infant and Toddler Development, 3rd edition, at eleven months, and by parent report on the Ages and Stages Questionnaire, 3rd edition, and Ages and Stages Questionnaire: Social Emotional at three-, six-, and eleven months. Discussion The Mommy’s Food study will provide knowledge on changes in iodine nutrition when consuming iodine rich fish during pregnancy and contribute to the understanding of the impact of iodine status in pregnancy on infant neurodevelopment.publishedVersio

Higher vitamin B12 levels in neurodevelopmental disorders than in healthy controls and schizophrenia: A comparison among participants between 2 and 53 years

Author´s accepted manuscript.This is the peer reviewed version of the following article: Hope, S., Nærland, T., Høyland, A. L., Torske, T., Malt, E., Abrahamsen, T. G., Nerhus, M., Wedervang-Resell, K., Lonning, V. L. H., Johannessen, J., Steen, N. E., Agartz, I., Stenberg, N., Hundhausen, T. E., Mørkrid, L. & Andreassen, O. A. (2020). Higher vitamin B12 levels in neurodevelopmental disorders than in healthy controls and schizophrenia : A comparison among participants between 2 and 53 years. The FASEB Journal, 34(6), 8114-8124, which has been published in final form at https://doi.org/10.1096/fj.201900855RRR. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Recent studies suggest that both high and low levels of vitamin B12 (vitB12) may have negative health impacts. We measured VitB12 in patients with the Neurodevelopmental disorders (ND) (n = 222), comprised of Autism Spectrum Disorders, specific Developmental disorders, and Intellectual Disability (aged 2-53 years), schizophrenia (n = 401), and healthy controls (HC) (n = 483). Age-and gender-adjusted vitB12 z-scores were calculated by comparisons with a reference population (n = 76 148). We found higher vitB12 in ND (median 420 pmol/L, mean z-score: 0.30) than in HC (316 pmol/L, z-score: 0.06, P < .01) and schizophrenia (306 pmol/L, z-score: −0.02, P < .001), which was significant after adjusting for age, gender, vitB12 supplement, folate, hemoglobin, leukocytes, liver, and kidney function (P < .02). In ND, 20% (n = 44) had vitB12 above 650 pmol/L, and 1% (n = 3) had below 150 pmol/L (common reference limits). In 6.3% (n = 14) of ND, vitB12 was above 2SD of mean in the age-and gender-adjusted reference population, which was more frequent than in HC (n = 8, 1.6%), OR: 4.0, P = .001. Low vitB12 was equally frequent as in HC, and vitB12 z-scores were equal across the age groups. To conclude, vitB12 was higher in ND than in HC and schizophrenia, suggesting a specific feature of ND, which warrants further studies to investigate the underlying mechanisms.acceptedVersio

Placentation and Expression of Homeobox Genes in Extravillous Trophoblasts in First Trimester Pregnancies

The first part of the thesis comprises a literature review on placental development with focus on trophoblast function and homeobox genes. Homeobox genes belong to a large family of transcription factors that control proliferation, invasion, migration and differentiation. Trophoblast dysfunction is thought to be a major factor in defect placentation and thus important in a number of clinically complicated pregnancies. The second part of the thesis relates to a morphological and immunohistochemical pilot study on remodelled spiral arteries in the placental bed from first trimester pregnancies. Remodelled spiral arteries were identified morphologically in archive curettage tissue material from Ullevål University Hospital in normal and pathological first trimester pregnancies (therapeutic abortions and spontaneous or missed abortions). The remodelled spiral arteries were identified morphologically in routine stained sections and immunohistochemically by means of protein markers to trophoblasts (CK7) and smooth muscle cells (actin). In an immunohistochemical pilot study at Pregnancy Research Centre at the University of Melbourne we tested the quality of two laboratory made antibodies against the proteins coded for by homeobox genes HLX1 and DLX4 on formalin fixed, paraffin embedded archive tissue. The aim was to explore the protein expression of these two important homeobox genes on the archive material from the normal and pathological first trimester pregnancies. Unfortunately, the antibodies were not found suitable for this use. The problems and pitfalls in protein expression studies on tissue material (immunohistochemistry) are discussed

Migration and Vitamin D in psychotic disorders – A cross sectional study of clinical and cognitive correlates

Migration is a major environmental risk factor associated with schizophrenia and other psychotic disorders. Furthermore, people with migration background may have specific challenges due to their migration background or ethnic background influencing clinical correlates in established disease. An observed high prevalence of vitamin D deficiency in ethnic minorities in Northern European countries has generated hypotheses around the role of vitamin D in psychotic disorders. In this thesis we investigated the influence of migration, ethnicity and vitamin D levels in early phases of psychotic disorders and later in the course of illness. As vitamin D is found to have receptors widespread in the human brain and has been linked to the pathogenesis of core features in psychotic disorders, we wanted to explore the potential clinical relevance of vitamin D. Thus, investigating how vitamin D levels relate to specific symptom profiles and cognitive functioning. We conducted four cross-sectional studies in large clinical samples of patients with a DSM-IV diagnosis of a psychotic disorder from the public health care system in Norway. In two of the studies we also included healthy controls from the same catchment area as the patients. In the first study we investigated the associations between having migration background or ethnic minority status and duration of untreated psychosis. In the second, we explored the vitamin D levels in a first episode sample compared to a sample with longer duration of illness and a matched control group. In the third and fourth study we investigated the associations between vitamin D levels and symptom profiles in patients, and the associations between vitamin D deficiency and cognitive function in patients and in controls. Our main results are that migration after the age of six was significantly associated with prolonged duration of untreated psychosis while ethnic minority status only had a trend level significance for the same. Furthermore being an ethnic minority with ancestry from Asia, Africa or Latin-America, had a significant impact on vitamin D levels. Ethnic minorities had lower vitamin D levels than the majority population across groups; we found significantly lower levels both in first episode psychosis, in a sample of patients with a longer duration of illness, as well as in controls. However, we did not find any significant differences in vitamin D levels between patients and healthy controls, after controlling for ethnic minority status, as opposed to previous studies. Secondly we found that low vitamin D levels were associated with more severe negative and depressive symptomatology when controlling for a variety of potential confounding variables. Furthermore, a vitamin D level below a critical threshold, defined as vitamin D deficiency, was associated with cognitive functioning in terms of impaired processing speed and impaired verbal fluency, also after adjusting for patient versus control status and other potential confounders. In patients the associations between vitamin D deficiency and cognition were partly mediated by negative symptoms. The severity of the problems related to negative and depressive symptoms and cognitive impairments for patients with psychotic disorders indicate that these aspects are of clinical relevance. Negative symptoms and cognitive impairments have large impact on function and outcome both in the early phases of the disease and in a long term perspective and depressive symptoms are associated with reduced quality of life and impaired long term prognosis. Our studies demonstrated that migration and ethnic minority status provide specific challenges related to duration of untreated psychosis and vitamin D levels. The current findings in a health care based sample may suggest that further emphasis on the specific challenges of this population is needed. People experiencing migration and/or are ethnic minorities represent a vulnerable population both related to severity of severe mental illness related to prolonged duration of untreated psychosis, as well as vitamin D- derived somatic health problems. Our studies are cross-sectional and do not allow us to conclude about the directions of the associations. Our findings however provide support for initiating a randomized controlled trial to evaluate whether vitamin D substitution in individuals with low vitamin D levels has beneficial effect on either negative symptoms, cognitive impairments or depressive symptoms, as an adjuvant treatment strategy

The Influence of Mental Health Literacy, Migration, and Education on the Duration of Untreated Psychosis

Background: Duration of untreated psychosis (DUP) is associated with outcome in psychotic disorders and influenced by contextual factors such as immigration. Here we aimed to investigate the effect of mental health literacy (MHL) on duration of untreated psychosis considering the influence of migration and education. Methods: A total of 269 participants who received their first adequate medical treatment for a psychotic disorder within the current or past year were included to the Thematically Organized Psychosis study in Oslo, Norway. Sociodemographic and clinical information was collected through systematic interviews. MHL was measured as “recognition of psychotic symptoms” and assessed by “The Attitudes and Beliefs about Mental Health Problems” schizophrenia version. Influence of education, migration and MHL on DUP was analyzed with hierarchical block-wise multiple regression analysis. Results: Recognition of psychotic symptoms explained a small but unique variance (2.3%) in DUP after the effects of other important predictors were controlled for. Longer DUP was also associated with less education, lower premorbid social, and academic functioning, a diagnosis within schizophrenia spectrum disorder, and earlier age of onset. The model explained 26% of variance in DUP. Migration after the age of six and length of education were associated with MHL but did not have a significant interaction with MHL in predicting DUP. Conclusions: MHL, measured as recognition of psychotic symptoms, has a small but significant independent effect on DUP. The effect of MHL was larger than years of education and migration history, and did not interact with either, in predicting DUP. This suggests that MHL is an independent factor in prevention strategies for early psychosis

Matchbox : bacheloroppgave i IT og informasjonssystemer

Denne rapporten beskriver bachelorprosjektet og utviklingen av en nettportal på oppdrag fra Matchbox Ringerike og NorIT. Rapporten er en prosjektoppgave i faget BOP3000 og er en del av studiet IT og informasjonssystemer ved Universitetet i Sørøst-Norge. Vi har vært fire studenter på gruppa, men på grunn av prosjektets omfang har vi også samarbeidet med en annen bachelorgruppe om prosjektet. Matchbox Ringerike er et kommunalt prosjekt som har som mål å få arbeidsledige unge mennesker ut i jobb eller skole. Matchbox ønsket seg et system hvor de kan kommunisere med brukerne sine, legge inn avtaler for brukerne og gi brukerne informasjonen de trenger. Målet vi satte oss med dette prosjektet var å lage en brukervennlig nettportal som oppdragsgiver var fornøyd med. I prosjektet har vi brukt Scrum som utviklingsmetode. Rapporten beskriver systemutviklingsprosjektet med start januar 2021 til mai 2021. I rapporten redegjør vi først for bakgrunnen for prosjektet med problemstilling. Vi beskriver bakgrunnslitteraturen for prosjektet. Deretter beskriver vi hvordan prosjektet er gjennomført og begrunner hvilke valg vi har tatt. Til slutt drøfter vi utfordringer vi har møtt og hva vi har lært av prosjektet. Vi har hatt mange små og store utfordringer underveis i prosjektet. De største utfordringene våre har vært å lære seg nye programmeringsverktøy React-Bootstrap og Node.js/Express, samarbeid/kommunikasjon og tekniske vansker i form av hosting og databasetilkobling i ulike skytjenester. I løpet av prosjektet har vi lært mye om hvordan man planlegger, og gjennomfører et systemutviklingsprosjekt. Spesielt vil vi trekke fram at vi har lært om viktigheten av god kommunikasjon og et godt samarbeid med alle parter i et slikt prosjekt

Childhood trauma mediates the association between ethnic minority status and more severe hallucinations in psychotic disorder

Background Ethnic minority status and childhood trauma are established risk factors for psychotic disorders. Both are found to be associated with increased level of positive symptoms, in particular auditory hallucinations. Our main aim was to investigate the experience and effect of childhood trauma in patients with psychosis from ethnic minorities, hypothesizing that they would report more childhood trauma than the majority and that this would be associated with more current and lifetime hallucinations. Method In this cross-sectional study we included 454 patients with a SCID-I DSM-IV diagnosis of non-affective or affective psychotic disorder. Current hallucinations were measured with the Positive and Negative Syndrome Scale (P3; Hallucinatory Behaviour). Lifetime hallucinations were assessed with the SCID-I items: auditory hallucinations, voices commenting and two or more voices conversing. Childhood trauma was assessed with the Childhood Trauma Questionnaire, self-report version. Results Patients from ethnic minority groups (n = 69) reported significantly more childhood trauma, specifically physical abuse/neglect, and sexual abuse. They had significantly more current hallucinatory behaviour and lifetime symptoms of hearing two or more voices conversing. Regression analyses revealed that the presence of childhood trauma mediated the association between ethnic minorities and hallucinations. Conclusions More childhood trauma in ethnic minorities with psychosis may partially explain findings of more positive symptoms, especially hallucinations, in this group. The association between childhood trauma and these first-rank symptoms may in part explain this group's higher risk of being diagnosed with a schizophrenia-spectrum diagnosis. The findings show the importance of childhood trauma in symptom development in psychosis. Copyright © Cambridge University Press 201

Clinical and socio-cultural insight in immigrants in their first episode of psychosis

Aim: Lack of insight into illness is frequent in psychotic disorders and seen as part of their primary pathology. The recognition of symptoms as psychotic, and beliefs about treatment alternatives, is also influenced by socio-cultural factors. Here we examined clinical insight into illness and beliefs about psychosis in immigrants in their first episode of psychosis compared to a reference group. Methods: 277 first episode psychosis participants were recruited to this cross-sectional study; 40 first- and 40 second-generation immigrants from Europe, Americas and Oceania (n=37), Asia including Turkey (n=28), or Africa (n=15). The Birchwood Insight Scale was used to measure clinical insight and “The Attitudes and Beliefs about Mental Health Problems”, schizophrenia version to assess socio-cultural beliefs. Results: Immigrants did not differ from the reference sample in clinical insight. After controlling for education level first generation immigrants were less likely to recognize psychotic symptoms (OR 2.9; Wald = 8.977, df 1, p =.003) and viewed hospitalization (OR 5.2; Wald = 20.388, df 1, p =.001) and treatment by a psychiatrist (OR 4.9; Wald = 6.609, df 1, p =.01)) as less beneficial than the reference group. Immigrants from Asia held more alternative explanations (OR 0.3; Wald = 6.567, df 1, p=.010). There were significantly stronger associations between clinical insight and socio-cultural beliefs in the reference group. Conclusions: Socio-cultural beliefs about psychosis in immigrants in first episode psychosis calls for more tailored information to this group, and emphasize the importance of treatment interventions involving both a cultural and personal perspective of insight