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  • 1.
    Jederström, Moa
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Agnafors, Sara
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Sodra Alvsborgs Hosp, Sweden.
    Ekegren, Christina L.
    Monash Univ, Australia.
    Fagher, Kristina
    Lund Univ, Sweden.
    Gauffin, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Park, Jennifer
    Univ Gothenburg, Sweden.
    Spreco, Armin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Enheten för folkhälsa.
    Timpka, Toomas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Enheten för folkhälsa.
    A cross-sectional study of anxiety and depression caseness in female competitive figure skaters in Sweden2023In: BMJ OPEN SPORT & EXERCISE MEDICINE, ISSN 2055-7647, Vol. 9, no 1, article id e001491Article in journal (Refereed)
    Abstract [en]

    ObjectivesLittle is known about figure skaters mental health. This study aimed to describe anxiety and depression caseness (defined as a screening condition qualifying for psychiatric examination) in competitive figure skaters and analyse factors associated with such caseness.MethodsA cross-sectional study was performed in April 2019 among all competitive figure skaters in the south-eastern region of Sweden (N=400). The primary outcomes were anxiety caseness, measured using the short-form Spielberger State-Trait Anxiety Inventory and depression caseness, measured using the WHO-5 index. Multivariable logistic regression models were employed to determine the association between anxiety caseness and explanatory factors.ResultsIn total, 36% (n=142) of the invited skaters participated. Only females (n=137), mean age 12.9 (SD 3.0) years) were selected for analysis. Of the participating skaters, 47% displayed anxiety caseness and 10% depression caseness. Overweight body image perception (OR 5.9; 95% CI 2.0 to 17.6; p=0.001) and older age (OR 1.2; 95% CI 1.1 to 1.4; p=0.005) were associated with anxiety caseness. Skaters reporting no caseness were younger than those reporting only anxiety caseness (mean age difference -1.9 years; 95% CI -3.1 to -0.7; p=0.001) or anxiety and depression caseness (OR -3.5 years; 95% CI -5.6 to -1.5 years; p<0.001).ConclusionAnxiety caseness was associated with overweight body image perception and older age in female competitive figure skaters. Older skaters reported generally worse mental health. More research on the mental health of figure skaters is warranted, considering comorbidity and focusing on those needing further assessment and support.

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  • 2.
    Frielingsdorf Lundqvist, Helena
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Center for Refugee Medicine. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health.
    Sarkadi, Anna
    Uppsala universitet.
    Nutley, Sissela
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Alfvén, Tobias
    Karolinska Institutet, Stockholm.
    Wide Gustafsson, Sara
    Lindstrand, Sofia
    Henriksson, Hanna
    Milerad, Josef
    Karolinska Institutet, Stockholm.
    Swartling Peterson, Stefan
    Karolinska Institutet, Stockholm.
    Anpassa digitala medier efter barn, inte tvärtom2023In: Svenska Dagbladet, ISSN 1101-2412Article in journal (Other (popular science, discussion, etc.))
  • 3.
    Otterman, Gabriel
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Nurmatov, Ulugbek
    School of Medicine, Cardiff University, UK.
    Akhlaq, Ather
    Institute of Business Management, Karachi, Pakistan.
    Naughton, Aideen
    National Safeguarding Service, Public Health Wales (NHS), Cardiff, UK.
    Kemp, Alison Mary
    School of Medicine, Cardiff University, Cardiff, UK.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Jud, Andreas
    University Hospital Ulm, Ulm, Germany.
    Vollmer Sandholm, Mary Jo
    Oslo University Hospital, Norway.
    Mora-Theuer, Eva
    Medical University of Vienna, Austria.
    Moultrie, Sarah
    UCSF Benioff Children’s Hospital, Oakland, California, USA.
    Chalumeau, Martin
    Necker-Enfants Malades Hospitals, Paris, France.
    Karst, Wouter A
    GGD Branbant Zuidoost, Eindhoven, Netherlands.
    Greenbaum, Jordan
    International Centre for Missing & Exploited Children, Atlanta, Georgia, USA.
    Appraisal of published guidelines in European countries addressing the clinical care of childhood sexual abuse: protocol for a systematic review2023In: BMJ Open, E-ISSN 2044-6055, Vol. 13, no 4, article id e064008Article, review/survey (Refereed)
    Abstract [en]

    Introduction Childhood sexual abuse (CSA) is a global public health problem with potentially severe health and mental health consequences. Healthcare professionals (HCPs) should be familiar with risk factors and potential indicators of CSA, and able to provide appropriate medical management. The WHO issued global guidelines for the clinical care of children with CSA, based on rigorous review of the evidence base. The current systematic review identifies existing CSA guidelines issued by government agencies and academic societies in the European Region and assesses their quality and clarity to illuminate strengths and identify opportunities for improvement. Methods and analysis This 10-database systematic review will be conducted according to the Centre for Reviews and Dissemination guidelines and will be reported according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Guidance for HCPs regarding CSA, written by a national governmental agency or academic society of HCPs within 34 COST Action 19106 Network Countries (CANC) and published in peer-reviewed or grey literature between January 2012 and November 2022, is eligible for inclusion. Two independent researchers will search the international literature, screen, review and extract data. Included guidelines will be assessed for completeness and clarity, compared with the WHO 2017/2019 guidelines on CSA, and evaluated for consistency between the CANC guidelines. The Appraisal of Guidelines for Research and Evaluation II tool and Grading of Recommendations Assessment, Development and Evaluation methodology will be used to evaluate CANC guidelines. Descriptive statistics will summarise content similarities and differences between the WHO guidelines and national guidelines; data will be summarised using counts, frequencies, proportions and per cent agreement between country-specific guidelines and the WHO 2017/2019 guidelines. Ethics and dissemination There are no individuals or protected health information involved and no safety issues identified. Results will be published in a peer-reviewed medical journal.

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  • 4.
    Korhonen, Laura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Unenge Hällerbäck, Maria
    Örebro universitet, Sweden.
    Fernell, Elisabeth
    Göteborgs universitet, Sweden.
    Lindstrand, Sofia
    Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Widengren, Helka
    Elevhälsan, Solna stad, Sweden.
    Milerad, Josef
    Karolinska institutet, Stockholm, Sweden.
    5 insatser som kan bryta ohälsotrenden hos unga: Förslag från en arbetsgrupp inom Svenska läkaresällskapet2022In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, no 119, article id 22020Article, review/survey (Refereed)
    Abstract [en]

    In their latest survey from 2017/18, the Public Health Agency in Sweden reported an increase in multiple mental health complaints among children and adolescents. The study is part of a collaborative WHO project that started in 1985/86 and collects data every four years.

    With this background, a working group was commissioned by the Swedish Medical Association to identify areas for improvement within the school system and to work out proposals for effective interventions. In this report, we summarize research data on evidence-based knowledge within five areas. How to promote daily physical activity at school to enhance wellbeing and cognitive abilities; how to balance time on the internet; what is known about school-based intervention programs to promote mental health; the need to adapt knowledge requirements in the national curriculum to children’s development and cognitive abilities, and to describe specific risk groups for impaired mental health. Finally, we describe competence-enhancing initiatives and emphasize the need for collaboration between school health, child and adolescent mental health services, pediatrics and the social services.

  • 5.
    Gustafsson, Berit
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    A Multiprofessional and Intersectoral Working Model to Detect and Support Preschool Children With Neurodevelopmental Difficulties (PLUSS Model): Protocol for an Evaluation Study2022In: JMIR Research Protocols, ISSN 1929-0748, E-ISSN 1929-0748, Vol. 11, no 6, article id e34969Article in journal (Refereed)
    Abstract [en]

    Background: Neurodevelopmental difficulties with various emotional and behavioral symptoms increase the risk of mental health problems later in life. Although we know that early detection and interventions are effective, there is a lack of intersectoral, integrative, and evidence-based working models to provide these services for preschool children and their parents. PLUSS (Psykisk hälsa Lärande Utveckling Samverkan kring Små barn; English translation: mental health, learning, development, collaboration around preschool children) is a collaborative “one way in” model involving parents, health care providers, preschools, social services, and researchers. PLUSS provides coordinated services to screen, evaluate, and support toddlers with neurodevelopmental problems. It also offers parental interventions and education for preschool teachers.

    Objective: The model will be studied in a research project that aims to investigate (1) using a quasi-experimental study on longitudinal trajectories of neurodevelopmental difficulties and ability to function among participating preschoolers, (2) user satisfaction, and (3) implementation of the model and its effectiveness. The long-term goal is to provide evidence-based, coordinated services to reduce problems related to neurodevelopmental difficulties among preschool children and promote well-being and functioning in everyday life.

    Methods: The population of interest is children aged 1.5-5 years, whom the child health care nurse refers for further assessment due to suspected neurodevelopmental problems. Data are collected using questionnaires and semistructured interviews. Measures include sociodemographic data, longitudinal data on neurodevelopmental problems, parental well-being and satisfaction, the effectiveness of parental and preschool teacher training and implementation of the model, and fostered multisectoral collaborations. Data will be analyzed with qualitative and quantitative methods.

    Results: The PLUSS model has been approved by the National Ethics Review Board (2019–04839). This study was supported by FUTURUM grants 910161 and 910441. Data collection started in April 2019, with the data collection period planned to end in May 2024.

    Conclusions: PLUSS is an integrative working model with multiprofessional competence and intersectoral collaboration capacity to help preschool children with neurodevelopmental problems and their parents. It will be studied using quasi-experimental cross-sectional and longitudinal study designs. Data will be collected from parents, health care providers, and preschool teachers, and will be analyzed using quantitative and qualitative methods. The study will run in one Swedish county, and generalizability needs to be studied separately. Loss of follow-up could impact the longitudinal analysis.

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  • 6.
    Mattelin, Erica
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.
    Kristina, Paidar
    Department of Child and Adolescent Psychiatry, Region Halland, Kungsbacka, Sweden.
    Söderlind, Natalie
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Fröberg, Frida
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    A systematic review of studies on resilience and risk and protective factors for health among refugee children in Nordic countries2022In: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165XArticle, review/survey (Refereed)
    Abstract [en]

    The Nordic welfare model is often used as an example for the promotion of health and wellbeing, even in vulnerable groups of children, such as refugees. Nonetheless, there are no published reviews on resilience and/or risk and protective factors for physical and mental health among refugee children living in Nordic countries. In this systematic review, we identified 5181 studies on the topic, screened titles, and abstracts, viewed 632, and finally included 26 studies. These studies described 18 samples with a total of 34,080 individuals ranging in ages 0–18 years. Overall, the studies were of good quality. Nearly all studies assessed adversity. Six studies reported physical health outcomes and all studies mental health outcomes, most often post-traumatic stress disorder and anxiety. None explicitly studied resilience. While we found that age and sex are the most frequently studied  risk- and protective factors, findings are inconclusive, since the direction of the associations was different in the different studies. This systematic review indicates that there is still a need for well-designed and -powered studies using clear definitions of key study concepts to examine health outcomes and resilience among refugee children in Nordic countries.

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  • 7.
    Nelsson, Anna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Johansson, Maria M.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Anmälan om oro att ett barn far illa2022In: Svensk psykiatri, no 3Article in journal (Other academic)
    Abstract [sv]

    Socialtjänsten har en viktig roll för att barn och unga ska kunna växa upp under de trygga förhållanden som de har rätt till. Detta förutsätter att socialtjänsten får kännedom om barn som kan behöva skydd och hjälp i form av en orosanmälan. Man kan även behöva göra polisanmälan vid till exempel allvarliga brott.

  • 8.
    Mattelin, Erica
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Barn på flykt2022In: En förskola för alla - specialpedagigik, inkludering och likvärdighet / [ed] Anneli Nielsen, Mikaela Nyroos, Stockholm: Liber, 2022, p. 149-162Chapter in book (Other academic)
  • 9.
    Berndtsson, Catarina
    et al.
    Göteborgs Stadsmission.
    Sjölandet, Cecilia
    Stiftelsen Allmänna barnhuset.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Eriksson, Maria
    Marie Cederschiöld högskola.
    Frisk, Maria
    Rädda Barnen.
    Barn ska aldrig behöva flytta tillbaka till en våldsam förälder2022In: Göteborgs-Posten, ISSN 1103-9345Article in journal (Other (popular science, discussion, etc.))
  • 10.
    Ringblom, Jenny
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Reg Kalmar Cty, Sweden.
    Proczkowska, Marie
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Wåhlin, Ingrid
    Linnaeus Univ, Sweden; Reg Kalmar Cty, Sweden.
    Experiences of paediatric emergence delirium - from parents and a childs perspective2022In: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 36, no 4, p. 1104-1112Article in journal (Refereed)
    Abstract [en]

    Background Emergence delirium is a complex behaviour of perceptual disturbances that may occur after general anaesthesia in children. These children often exhibit delusions, confusion, restlessness and involuntary physical activity. They cry and are almost impossible to console. Research has mainly focused on comparing different medication agents in the occurrence of and dealing with emergence delirium. However, less is known about parents experiences of emergence delirium during the recovery process, and there is hardly any research concerning the childrens experiences. Aims The primary aim of this study was to describe parents experiences and reflections during their childs emergence delirium behaviour when recovering from anaesthesia. A secondary aim was to describe childrens experiences of having been in this condition. Method A qualitative research approach with thematic analysis was applied. The study was conducted at two county hospitals in southern Sweden. A total of 16 parents and one child were interviewed. Results Watching their child demonstrate emergence delirium made parents feel as if they were encountering an incomprehensible scenario. They experienced fear and insecurity and had feelings of powerlessness and guilt. Information and previous experience turned out to offer relief, and being seen by the healthcare staff when they, in their vulnerability, failed to reach or console their child, gave hope and energy. The child confirmed the unexpected and uncontrolled behaviour described by parents. She clearly remembered being wild and out of control. Conclusion Emergence delirium must be extensively considered in children undergoing general anaesthesia. It is of great importance for healthcare staff to be aware of the parental difficulties it may cause and what is experienced as relieving, such as receiving information and staff members being available, responsive and supportive during the wake-up period.

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  • 11.
    Mattelin, Erica
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Fröberg, Frida
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid.
    Khanolkar, Amal R.
    Karolinska Inst, Sweden; Kings Coll London, England.
    Health and health-related behaviours in refugees and migrants who self-identify as sexual or gender minority – A National population-based study in Sweden2022In: eClinicalMedicine, E-ISSN 2589-5370, Vol. 52Article in journal (Refereed)
    Abstract [en]

    Background To examine health and health-related behaviors in migrant and refugee individuals who identify as sexual or gender minority, and in comparison to their heterosexual peers. Methods The study included 168,952 individuals (aged 16-84 years, males: 45.9%, sexual or gender minorities: 3.1%) who answered the Swedish National Public Health Survey in 2018 and 2020. Participants were grouped into Swedish-and Western-born (White) heterosexual, White sexual- or gender minority, migrant heterosexual, migrant sexual- or gender minority, refugee heterosexual, and refugee sexual- or gender minority. Outcomes included mental health (for example suicidal ideation, wellbeing), general health, risky behaviors (risk alcohol use, risk gambling, and substance use), and experiences of violence. Associations between 1) sexual- or gender -ethnic identities and 2) gender-ethnic identities and all outcomes were analyzed using logistic and linear regression adjusting for sex, age, and educational level. Findings Being a sexual- or gender minority, regardless of ethnic minority status, was associated with worse general health and mental ill-health compared to heterosexual peers including suicidal ideation in refugee sexual- or gender minority individuals (OR 2.42, 95 % CI 1.44-4.08). Ethnic minorities (heterosexual and sexual- or gender minority migrants and refugees) had lower odds of drug and risk alcohol use compared to White heterosexual peers but higher odds of risk gambling (1.88, 1.49-2.37 for refugee heterosexuals). Transgender refugees had high odds for risk gambling (8.62, 1.94-38.40) and exposure to physical violence (7.46, 2.97-18.70). Interpretation In this national population-based study, sexual and gender minority individuals have worse mental and general health regardless of ethnic minority status. We did not find evidence for worse health in sexual- or gender minority refugees in comparison to migrant, and White sexual- or gender minorities and their heterosexual peers. Transgender individuals (White and ethnic minority) experienced significantly higher levels of physical violence. Public health policy should emphasize preventive measures to reduce exposure to violence and discrimination in sexual- and gender minority individuals, increase access and use of mental healthcare services and sensitise healthcare professionals about higher rates of health and related issues faced by sexual- and gender minority individuals including those with multiple minority identities.

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  • 12.
    Högstedt, Erika
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Community Care Department, The Municipality of Norrköping, Norrköping, Sweden.
    Igelström, Kajsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping. Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid.
    Käcker, Pia
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research Division. Linköping University, Faculty of Arts and Sciences.
    Marteinsdottir, Ina
    Department of Medicine and Optometry, Linnaeus University, Kalmar, Sweden.
    Björk, Mathilda
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    ‘It’s like it is designed to keep me stressed’ — Working sustainably with ADHD or autism2022In: Scandinavian Journal of Occupational Therapy, ISSN 1103-8128, E-ISSN 1651-2014, p. 1-12Article in journal (Refereed)
    Abstract [en]

    Background

    Adults with attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) face multiple challenges in obtaining and maintaining employment.

    Aims

    To identify and describe how adults with ADHD or ASD experienced their ability to work and what factors affected their ability to find a sustainable work situation over time.

    Methods

    Individual in-depth interviews were performed with 20 purposively sampled participants with ADHD/ASD. Data were analysed inductively using reflexive thematic analysis.ResultsThree themes were identified, describing (1) one’s own cognitive abilities and challenges, (2) enablement by flexibility and acceptance in the work environment, and (3) accumulated stress that makes the work situation unsustainable over time.

    Conclusions

    Over time, a lack of continuity and predictability of support measures caused great stress and exhaustion, with severe consequences for working life and in life in general. Adaptations needed to be individually tailored and include nonoccupational factors.

    Significance

    The study shows that adults with ADHD/ASD need long-term interventions that flexibly adapt to individual needs, as they vary over time. The findings suggest that occupational therapists and other health care providers, employers, employment services and other involved agencies should pay a greater deal of attention to stability and predictability over time.

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  • 13.
    Gustafsson, Berit
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping. Department of Psychiatry and Rehabilitation, Psychiatric Clinic, Högland Hospital, Region Jönköping County, Jönköping, Sweden.
    Steinwall, Samina
    Department of Child and Adolescent Psychiatry, Division of Psychiatry and Rehabilitation, Region Jönköping County, Jönköping, Sweden.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Multi-professional and multi-agency model PLUSS to facilitate early detection and support of pre-school children with neurodevelopmental difficulties – a model description2022In: BMC Health Services Research, E-ISSN 1472-6963, Vol. 22, no 1, article id 419Article in journal (Refereed)
    Abstract [en]

    Background

    Neurodevelopmental difficulties, such as problems in social inter-relatedness, communication, motor coordination, and attention, are frequent in preschoolers and constitute a risk for later negative consequences. This article describes the development of a multi-professional and multi-agency model, PLUSS, to facilitate care and interventions for preschoolers with neurodevelopmental difficulties.

    Methods

    The PLUSS model was developed for children aged 1.5–5 years with a need for a further assessment of neurodevelopmental symptoms. The model is evaluated using a quasi-experimental study design along with qualitative interviews that study preschool teacher, and parent experiences of PLUSS. Outcomes of interest are a) implementation, b) effectiveness related to processes and multi-agency collaboration, c) capacity building among professionals, d) child-related outcomes with a longitudinal follow-up as well as d) parental wellbeing and satisfaction.

    Results

    The model was launched in 2019 and so far, approximately 130 children have been assessed. Results from a pilot study with 62 children (27–72 months; boys: girls 2.65:1) show that the total mean SDQ score in parental rating was 15 ± 6 and in preschool teacher ratings 14 ± 7, exceeding the Swedish cut-off of 12. 54 parents have participated in parental training and rate high levels of satisfaction (mean score 4.5, max 5.0). In addition, 74 pre-school professionals have been trained in early signs of neurodevelopmental difficulties to facilitate early detection. Feedback from participants indicates high satisfaction with educational activities (mean score 4.2, max 5.0 = very satisfied).

    Conclusions

    The pilot study shows that the screening procedure can detect children with clinically significant problems. In addition, participant satisfaction is high in parent- and preschool teacher training. The longitudinal study approach enables both child follow-up and evaluation of interventions provided by the working model.

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  • 14.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Nationellt kunskapscentrum Barnafrid – resurs för yrkesverksamma som möter utsatta barn2022In: Barnläkaren, no 4Article in journal (Other (popular science, discussion, etc.))
  • 15.
    Lundqvist, Carolina
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Jederström, Moa
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Timpka, Toomas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Enheten för folkhälsa.
    Nuances in key constructs need attention in research on mental health and psychiatric disorders in sports medicine2022In: BMJ Open Sport & Exercise Medicine, E-ISSN 2055-7647, Vol. 8, no 3, article id e001414Article in journal (Other academic)
    Abstract [en]

    The WHO1 defines mental health as ‘a state of well-being in which an individual realises his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully and is able to make a contribution to his or her community’ (p. 12). According to this definition, mental health is more than a lack of symptoms of mental ill-being or disorders. Variations in mood and perception of symptoms, also with aversive valence, may occur during regular participation in competitive sports. This editorial discusses the importance of acknowledging nuances in studies of mental health and psychiatric disorders in sports medicine and calls for a deepened understanding of ‘mental health’ and how various mental health symptoms and disorders are reported.

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  • 16.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Research and practice should also focus on the untapped benefits of screen time2022In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 111, no 1, p. 184-184Article in journal (Other academic)
    Abstract [en]

    n/a

  • 17.
    Korhonen, Laura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Münger, Ann-Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Våld mot barn – aktuellt kunskapsläge och tips på vidare kompetensutveckling2022Other (Other (popular science, discussion, etc.))
  • 18.
    Korhonen, Laura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Münger, Ann-Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Våld mot barn – aktuellt kunskapsläge och tips på vidare kompetensutveckling2022In: Tidningen SkolhälsanArticle in journal (Other academic)
  • 19.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Barnkonventionen, ett rättesnöre att förebygga utsatthet under pandemin och framöver2021In: Barnläkaren, ISSN 1651-0534, Vol. 3, p. 20-21Article in journal (Other academic)
  • 20.
    Jederström, Moa
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Agnafors, Sara
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences.
    Ekegren, Christina
    Monash Univ, Australia.
    Fagher, Kristina
    Lund Univ, Sweden.
    Gauffin, Håkan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Park, Jennifer
    Univ Gothenburg, Sweden.
    Spreco, Armin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Enheten för folkhälsa.
    Timpka, Toomas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Society and Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Enheten för folkhälsa.
    Determinants of Sports Injury in Young Female Swedish Competitive Figure Skaters2021In: Frontiers in Sports and Active Living, E-ISSN 2624-9367, Vol. 3, article id 686019Article in journal (Refereed)
    Abstract [en]

    Introduction: Although figure skating attracts several hundred thousand participants worldwide, there is little knowledge about physical health and sports injuries among young skaters. The present study aimed to describe the health status of a geographically defined Swedish population of licensed competitive figure skaters and to examine injury determinants. Methods: All licensed competitive skaters in the southeastern region of Sweden were in April 2019 invited to participate in a cross-sectional study using an online questionnaire. Multiple binary logistic regression was used for the examination of injury determinants. The primary outcome measure was the 1-year prevalence of a severe sports injury episode (time loss >21 days). The secondary outcome measure was the point prevalence of an ongoing injury. The determinants analyzed were age, skating level, relative energy deficiency indicators, and training habits. Results: In total, 142 (36%) skaters participated, 137 (96%) girls [mean (SD) age: 12.9 (SD 3.0) years]. Participating boys (n = 5) were excluded from further analysis. The 1-year prevalence of a severe sports injury episode was 31%. The most common injury locations for these injuries were the knee (25%), ankle (20%), and hip/groin (15%). In the multiple model, having sustained a severe injury episode was associated with older age (OR 1.2, 95% CI 1.1-1.4; p = 0.002) and an increased number of skipped meals per week (OR 1.1, 95% CI 1.0-1.3; p = 0.014). The point prevalence of an ongoing injury episode was 19%. The most common locations were the knee (24%), ankle (24%), and foot (24%). Having an ongoing injury episode was associated with older age (OR 1.4, 95% CI 1.2-1.7; p < 0.001) and an increased number of skipped meals per week (OR 1.1, 95% CI 1.0-1.3; p = 0.049). Conclusion: One-third of young female Swedish competitive figure skaters had sustained a severe injury episode during the past year, and a fifth reported an ongoing episode. Older age and an increased number of skipped meals per week were associated with a sports injury episode. Long-term monotonous physical loads with increasing intensity and insufficient energy intake appear to predispose for injury in young female figure skaters. Further examination of injury determinants among competitive figure skaters is highly warranted.

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  • 21.
    Münger, Ann-Charlotte
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Lindberg, Jens
    Socialt arbete, Umeå universitet, Umeå, Sweden.
    Fröberg, Frida
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Erfarenheter av pedagogiska utmaningar vid genomförandet av examensmålet våld mot barn på landets lärosäten2021In: Socialmedicinsk Tidskrift, ISSN 0037-833X, Vol. 98, no 4, p. 661-670Article in journal (Refereed)
    Abstract [sv]

    Artikelns syftar till att undersöka hur examensmålet fokus på barns våldsutsatthet tolkas och implementeras i professionsutbildningar. Det empiriska materialetutgår från en högskolepedagogisk kurs som Barnafrid, Linköpings universitethar genomfört på uppdrag av JÄMY samt två fallbeskrivningarResultat visar på pedagogiska och didaktiska utmaningar som dels handlar omhur ett nytt examensmål ska kunna integreras i fulltecknade utbildningsplaner,dels om hur examensmålet innehåll ska tolkas. I examensmålet finns en hierarkisk ordning där olika våldsformer exempelvis våld mot barn är underordnatmäns våld mot kvinnor. Det krävs därför prioriteringar av vilket våld och målgrupp som ska ingå i undervisningen. Om blivande professioner redan i sinutbildning får uppfattningen att olika former av våld kan särskiljas och vägasmot varandra kan det ge en endimensionell och förenklad syn på våldsutsatthet.

  • 22. Milerad, Josef
    et al.
    Runeson, Bo
    Karolinska Institutet, Stockholm, Sweden.
    Alvén, Tobias
    Karolinska Institutet, Stockholm, Sweden.
    Cernerud, Lars
    Fernell, Elisabeth
    Göteborgs universitet, Gothenburg, Sweden.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Leissner, Margareta
    Lindstrand, Sofia
    Region Östergötland.
    Norlander, Ylva
    Unänge Hallerbäck, Maria
    Örebro universitet, Örebro, Sweden.
    Widengren, Helka
    Fem förslag för att minska psykisk ohälsa hos unga2021In: Dagens Nyheter, no 20 maj, p. 1Article in journal (Other (popular science, discussion, etc.))
  • 23.
    Uotila, Jaakko
    et al.
    Department of Child Psychiatry, University of Turku, Turku, Finland.
    David, Gyllenberg
    Department of Child Psychiatry, University of Turku, Turku, Finland; Department of Adolescent Psychiatry, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland Finnish; Institute of Health and Welfare, Helsinki, Finland.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Hinkka-Yli-Salomäki, Susanna
    Department of Child Psychiatry, University of Turku, Turku, Finland.
    Emmi, Heinonen
    Department of Child Psychiatry, University of Turku, Turku, Finland.
    Chudal, Roshan
    Department of Child Psychiatry, University of Turku, Turku, Finland.
    Mika, Gissler
    Department of Child Psychiatry, University of Turku, Turku, Finland; Finnish Institute of Health and Welfare, Helsinki, Finland; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Andre, Sourander
    Department of Child Psychiatry, University of Turku, Turku, Finland.
    Incidence and comorbidities of disruptive behavior disorders diagnosed in Finnish specialist psychiatric services2021In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 56, no 11, p. 2063-2072Article in journal (Refereed)
    Abstract [en]

    Purpose: Disruptive behavior disorders (DBD), including oppositional defiant disorder (ODD) and conduct disorder (CD), are some of the most common psychiatric conditions in childhood. Despite this, there has been limited research on DBDs. We examined the incidence, comorbidity and gender differences of DBDs diagnosed by specialist services.

    Method: This was a nationwide register study of 570,815 children and adolescents born in 1996-2005. The 7050 individuals diagnosed with DBD by specialist healthcare services were matched to 26,804 controls.

    Results: By the age of 15, the cumulative incidence of diagnosed DBDs was 3.5% for boys and 1.4% for girls. The yearly incidence rate increased for girls after 13 years of age, while the incidence for boys was relatively stable between 8 and 15 years of age. When we compared subjects born between 1996-1998 and 1999-2001, we found that by the age of 12, the cumulative incidence per 100 people had increased from 0.56 to 0.68 among girls and from 2.3 to 2.6 among boys. This indicated a minor increase in treated incidence. The parents of children diagnosed with DBDs had lower educational levels than the parents of controls. Children with DBD were also more likely to have been diagnosed with other psychiatric disorders.

    Conclusion: Although DBDs were 3.5 times more common among boys during the whole follow-up period, the yearly incidence during adolescence was fairly similar between boys and girls. DBD existed alongside various psychiatric disorders at a relatively young age and only a minor increase in treated incidence was found during childhood.Keywords: Co-morbidity; Conduct disorder; Disruptive behavior disorder; Oppositional defiant disorder; Register-based study.

  • 24.
    Milerad, Josef
    et al.
    Svenska skolläkarföreningen.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Kraftsamling för ungas psykiska hälsa - Kunskapssammanfattning och förslag till interventioner från Svenska Läkarsällskapet arbetsgrupp2021In: Tidskriften för Svensk psykiatri, Vol. 3, p. 52-54Article in journal (Other academic)
  • 25.
    Milerad, Josef
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Runeson, Bo
    Karolinska Institutet, Stockholm, Sweden.
    Fernell, Elisabeth
    Widengren, Helka
    Cernerud, Lars
    Göteborgs universitet.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Leissner, Margareta
    Unänge Hallerbäck, Maria
    Örebro universitet.
    Lindstrand, Sofia
    Region Östergötland.
    Norlander, Ylva
    Kraftsamling för ungas psykiska hälsa: Kunskapssammanfattning och förslag till interventioner från Svenska Läkarsällskapet arbetsgrupp 20212021Report (Other academic)
    Abstract [sv]

    Utvecklingen från mitten av 1960-talet och framåt har kännetecknats av ökad materiell levnadsstandard, stärkt rättskydd för barn, minskande somatisk ohälsa, och en kraftigt sjunkande barnadödlighet. Denna positiva utveckling i Sverige och andra höginkomstländer har inte lett till en minskning av psykiska symptom hos unga. Att barn rapporterar mer stress och psykiska symptom trots bättre levnadsförhållanden, ”välfärdsparadoxen”, har varit tydligt i Sverige. Utgångspunkten för denna översikthar varit att lyfta fram vilka livsstils- och omgivningsfaktorer som har visat sig kunna bromsa eller vända denna utveckling.

    Folkhälsomyndighetens undersökning “Skolbarns hälsovanor”, och liknande rapporter från WHO, Unicef samt USA:s och Kanadas folkhälsomyndigheter har påtalat tydliga samband mellan psykiska symptom hos unga i skolåldern och fysisk inaktivitet. Låg fysisk aktivitet har i sin tur ofta ett samband med att tid på digitala medier tar utrymme från sömn och hälsofrämjande aktiviteter. Det finns även belägg för att program som stärker ungas förmåga att hantera känslor, sociala relationer och fatta ansvarsfulla beslutleder till bättre skolresultat, anpassning till vuxenlivet och bidrar till bättre psykisk hälsa. Ett omfattandekunskapsunderlag talar för att skolan har en central roll när det gäller att främja psykisk hälsa. Samma gäller vikten av tidiga insatser till unga med individuella svårigheter eller problem som beror på ogynnsamma eller socialt belastade uppväxtmiljöer.

    Utifrån publicerade samband mellan psykiska symptom och livsstil eller livsomständigheter föreslår Svenska Läkarsällskapets arbetsgrupp fem konkreta interventioner där vi ser skolan som en viktig arena där man når alla unga i skolåldern.

    5 konkreta interventioner för förbättrad psykisk hälsa bland barn och unga:

    1. Regelbunden strukturerad fysisk aktivitet – gärna i anslutning till skoltid.
    2. Hjälpa unga att nå en balans mellan tid ägnad åt digitala medier och hälsofrämjande aktiviteter.
    3. “Livskunskapsprogram” som hjälp till ungdomar att stärka självkänslan, hantera stress och skapa positiva förändringar.
    4. Främja psykisk hälsa i skolmiljön genom att anpassa kunskaps- och betygskrav till ungas utveckling och förutsättningar.
    5. Satsa på program för tidig upptäckt och stöd till unga med ökad risk för sämre psykisk hälsa.

    För att kunna genomföra dessa insatser krävs ett nära samarbete mellan alla som verkar för ungas hälsa; professioner inom hälso- och sjukvård, elevhälsa, socialtjänst men även föräldra- och elevorganisationer. När det gäller samhällsfunktioner som hälso- och sjukvård, skola och socialtjänst behöver man undanröja organisatoriska hinder för samverkan. Olika huvudmän för samhällsfunktioner har skilda ansvarsområden och ibland olika syn på sitt uppdrag. Vi vill även understryka vikten av fler kontaktytor mellan akademisk forskning som utvärderar hälsofrämjande program och verksamheter som ska tillämpa dessa.

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  • 26.
    Mattelin, Erica
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Khanolkar, Amal R.
    UCL, England; Karolinska Inst, Sweden.
    Fröberg, Frida
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Jonsson, Linda
    Ersta Skondal Bracke Univ Coll, Sweden.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    "Long journey to shelter": a study protocol: a prospective longitudinal analysis of mental health and its determinants, exposure to violence and subjective experiences of the migration process among adolescent and young adult migrants in Sweden2021In: BMJ Open, E-ISSN 2044-6055, Vol. 11, no 9, article id e043822Article in journal (Refereed)
    Abstract [en]

    Introduction According to the UN Refugee Agency (UNHCR), around 40% of the 79.5 million forcibly displaced persons in the end of the year 2019 were children. Exposure to violence and mental health problems such as posttraumatic stress disorder are frequently reported among migrant children, but there is a knowledge gap in our understanding of the complex longitudinal interplay between individual, social and societal risk and resilience factors that impact mental health and well-being, quality of life and ability to function and adapt. There is also an urgent societal need to facilitate interdisciplinary and intersectoral collaborative efforts to develop effective methods to prevent, detect and respond to the needs of the migrants. This project will study adolescent and young adult migrants in Sweden using multiple methods such as quantitative analysis of data from a prospective cohort study and qualitative analysis of data gathered from teller-focused interviews. The aim is to understand how different factors impact mental health and integration into the Swedish society. Furthermore, individual experiences related to the migration process and exposure to violence will be studied in detail. Methods and analysis Study participants will include 490 migrants aged 12-25 years recruited through social services, healthcare, social media and the civil society. A subsample of adolescents (n=160) will be re-interviewed after 1 year. Data are collected using structured and semi-structured interviews along with saliva and hair sampling. Measures include sociodemographic data, longitudinal data on mental health and its determinants, including genotypes and stress-hormone levels, access to healthcare and the process of migration, including settlement in Sweden. Ethics and dissemination The Regional Ethics Board of Linkoping (2018/292-31 and 2018/504-32) and the National Ethics Board (2019-05473,2020-00949 and 2021-03001) have approved the study. Results will be made available to participants, their caregivers, professionals working with migrants, researchers and the funders.

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  • 27.
    Vanaveski, Taavi
    et al.
    Univ Helsinki, Finland; Minerva Fdn, Finland; Univ Tartu, Estonia; Quretec Ltd, Estonia.
    Molchanova, Svetlana
    Univ Helsinki, Finland.
    Duc Pham, Dan
    Univ Helsinki, Finland; Minerva Fdn, Finland.
    Schafer, Annika
    Univ Helsinki, Finland; Minerva Fdn, Finland.
    Pajanoja, Ceren
    Univ Helsinki, Finland; Minerva Fdn, Finland.
    Narvik, Jane
    Univ Tartu, Estonia; Quretec Ltd, Estonia.
    Srinivasan, Vignesh
    Univ Helsinki, Finland; Minerva Fdn, Finland.
    Urb, Mari
    Protobios LCC, Estonia.
    Koivisto, Maria
    Univ Helsinki, Finland; Minerva Fdn, Finland.
    Vasar, Eero
    Univ Tartu, Estonia.
    Timmusk, Tonis
    Protobios LCC, Estonia; Tallinn Univ Technol, Estonia.
    Minkeviciene, Rimante
    Minerva Fdn, Finland.
    Eriksson, Ove
    Univ Helsinki, Finland.
    Lalowski, Maciej
    Univ Helsinki, Finland; Univ Helsinki, Finland; Polish Acad Sci, Poland.
    Taira, Tomi
    Univ Helsinki, Finland.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Voikar, Vootele
    Univ Helsinki, Finland.
    Lindholm, Dan
    Univ Helsinki, Finland; Minerva Fdn, Finland.
    PGC-1 alpha Signaling Increases GABA(A) Receptor Subunit alpha 2 Expression, GABAergic Neurotransmission and Anxiety-Like Behavior in Mice2021In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 14, article id 588230Article in journal (Refereed)
    Abstract [en]

    Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1 alpha expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of gamma-aminobutyric acid (GABA) type A receptor-alpha 2 subunit (GABAR alpha 2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1 alpha in neurons. Along with this, GABAR alpha 2 expression was enhanced in the hippocampus of the PGC-1 alpha Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABAR alpha 2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1 alpha Tg mice compared with controls. To study whether drugs acting on PPAR gamma can affect GABAR alpha 2, we employed pioglitazone that elevated GABAR alpha 2 expression in primary cultured neurons. Similar results were obtained using the specific PPAR gamma agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1 alpha regulates GABAR alpha 2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABAR alpha 2 expression via the PPAR gamma/PGC-1 alpha system.

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  • 28.
    Magnusson, Mikaela
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Göteborgs universitet, Gothenburg, Sweden.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Sanningens roll i utredningar om brott mot barn2021In: Tidskriften för svensk psykiatri, ISSN 1653-8579, no 2, p. 19-21Article in journal (Other academic)
  • 29.
    Törnquist, Kid
    et al.
    Minerva Foundation Institute for Medical Research, Helsinki, Finland; Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.
    Asghar, Yasin
    Minerva Foundation Institute for Medical Research, Helsinki, Finland.
    Srinivasan, Vingesh
    Minerva Foundation Institute for Medical Research, Helsinki, Finland; Medicum, Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Lindholm, Dan
    Minerva Foundation Institute for Medical Research, Helsinki, Finland; Medicum, Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
    Sphingolipids as modulators of SARS-CoV-2 infection2021In: Frontiers in Cell and Developmental Biology, E-ISSN 2296-634X, Vol. 9, article id 689854Article, review/survey (Refereed)
    Abstract [en]

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic with severe consequences for afflicted individuals and the society as a whole. The biology and infectivity of the virus has been intensively studied in order to gain a better understanding of the molecular basis of virus-host cell interactions during infection. It is known that SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) via its spike protein. Priming of the virus by specific proteases leads to viral entry via endocytosis and to the subsequent steps in the life cycle of SARS-CoV-2. Sphingosine and ceramide belong to the sphingolipid family and are abundantly present in cell membranes. These lipids were recently shown to interfere with the uptake of virus particles of SARS-CoV-2 into epithelial cell lines and primary human nasal cells in culture. The mechanisms of action were partly different, as sphingosine blocked, whilst ceramide facilitated viral entry. Acid sphingomyelinase (ASM) is vital for the generation of ceramide and functional inhibition of ASM by drugs like amitriptyline reduced SARS-CoV-2 entry into the epithelial cells. Recent data indicates that serum level of sphingosine-1-phosphate (S1P) is a prognostic factor for COVID-2 severity. Further, stimulation of sphingosine-1-phosphate receptor 1 (S1PR1) might also constrain the hyper-inflammatory conditions linked to SARS-CoV-2. Here, we review recent exciting findings regarding sphingolipids in the uptake of SARS-CoV-2 and in the course of COVID-19 disease. More studies are required on the mechanisms of action and the potential use of antidepressant drugs and sphingolipid modifiers in SARS-CoV-2 infections and in the treatment of the more serious and fatal consequences of the disease.

     

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  • 30.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    The good, the bad and the ugly of children´s screen time during the COVID-19 pandemic2021In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 110, no 10, p. 2671-2672Article in journal (Refereed)
  • 31.
    Korhonen, Laura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Mattelin, Erica
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Barn kan bli en riskgrupp under COVID-19-pandemin2020Other (Other (popular science, discussion, etc.))
  • 32.
    Schillaci, Maria
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Barnafrid - basprogram våld mot barn2020In: Barnbladet, ISSN 0349-1994, no 5, p. 16-17Article in journal (Other (popular science, discussion, etc.))
  • 33.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Barnafrid sprider kunskap om våld mot barn2020In: Barntandläkarbladet, ISSN 2001-9483, no 2, p. 16-18Article in journal (Other (popular science, discussion, etc.))
  • 34.
    Mattelin, Erica
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Child safeguarding – principer för att att driva verksamheter på ett barnsäkert sätt2020Other (Other (popular science, discussion, etc.))
  • 35.
    Korhonen, Laura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Mattelin, Erica
    Linköping University, Department of Biomedical and Clinical Sciences, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences.
    Har våld mot barn ökat i Sverige under COVID-19-pandemin?2020Other (Other (popular science, discussion, etc.))
  • 36.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Låt barnkonventionen bli vägledande i Covid-19 pandemin.2020Other (Other (popular science, discussion, etc.))
  • 37.
    Srinivasan, Vignesh
    et al.
    Univ Helsinki, Finland; Biomedicum Helsinki 2U, Finland.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Psykiatricentrum, Department of Child and Adolescent Psychiatry in Linköping.
    Lindholm, Dan
    Univ Helsinki, Finland; Biomedicum Helsinki 2U, Finland.
    The Unfolded Protein Response and Autophagy as Drug Targets in Neuropsychiatric Disorders2020In: Frontiers in Cellular Neuroscience, E-ISSN 1662-5102, Vol. 14, article id 554548Article, review/survey (Refereed)
    Abstract [en]

    Neurons are polarized in structure with a cytoplasmic compartment extending into dendrites and a long axon that terminates at the synapse. The high level of compartmentalization imposes specific challenges for protein quality control in neurons making them vulnerable to disturbances that may lead to neurological dysfunctions including neuropsychiatric diseases. Synapse and dendrites undergo structural modulations regulated by neuronal activity involve key proteins requiring strict control of their turnover rates and degradation pathways. Recent advances in the study of the unfolded protein response (UPR) and autophagy processes have brought novel insights into the specific roles of these processes in neuronal physiology and synaptic signaling. In this review, we highlight recent data and concepts about UPR and autophagy in neuropsychiatric disorders and synaptic plasticity including a brief outline of possible therapeutic approaches to influence UPR and autophagy signaling in these diseases.

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  • 38.
    Korhonen, Laura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Jonsson, Linda
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Delrapport - uppdrag om att stärka barnahusens kompetens om hedersrelaterat våld och förtryck (S2018/03927/JÄM)2019Report (Other (popular science, discussion, etc.))
    Abstract [sv]

    Den 28 juni 2018 gav regeringen Linköpings universitet/Barnafrid, i uppdrag att stärka Barnahusens kompetens om hedersrelaterat våld och förtryck. Inom ramen för uppdraget ska Linköpings universitet även samla in och sprida erfarenheter från Barnahusverksamheternas utredningsarbete. Detta i syfte att säkerställa kvaliteten och ett likvärdigt bemötande av flickor och pojkar som är utsatta för hedersrelaterad brottlighet.

    I uppdraget ska synpunkter inhämtas från Länsstyrelsen i Östergötlands län, Jämställdhetsmyndigheten, Barnombudsmannen, Socialstyrelsen, Polismyndigheten, Åklagarmyndigheten och Rättsmedicinalverket.

    Under perioden 8/2018 - 4/2019 har samtliga 32 Barnahus besökts och vi har samlat in material kring aktuellt kunskapsläge och utredningsförfarande av fall där hedersbrottlighet misstänks. Det har återkommande lyfts att Barnahusen möter få ärenden med barn som är utsatta för brott inom ramen för en hederskultur, samt att dessa ärenden generellt upplevs som komplicerade. Det framkom också att den tillgång till konsultation som erbjuds av bland andra Länstyrelsen i Östergötland och resurscentrum ORIGO är viktig och uppskattas. Barnahusens personal anger att de behöver lära sig att uppmärksamma signaler kring heder samt att de har behov av att få praktiska verktyg som stöd för utredningsarbetet. Det beskrevs också att det finns ett utbildningsbehov bland personal i skolor och på BVC för att öka benägenheten för en socialtjänstanmälan vid misstänkta fall av hedersrelaterat våld.

    En delredovisning ska lämnas till regeringskansliet (Socialdepartementet) senast den 30 april 2019, vilket härmed sker i denna rapport.

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  • 39.
    Korhonen, Laura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Jonsson, Linda
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Larsson, Anneli
    Institutionen för kriminologi och polisiärt arbete, Linnéuniversitetet, Sverige.
    Kinden, Hanna
    Linköping University.
    Landberg, Åsa
    Stiftelsen Allmänna Barnhuset, Sverige.
    Svedin, Carl Göran
    Linköping University, Department of Clinical and Experimental Medicine, Barnafrid. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Gustafsson, Per A.
    Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Slutrapport. Utvärdering av Barnahus: S2018/00212/FST2019Report (Other academic)
    Abstract [sv]

    I januari 2018 gav regeringen Barnafrid, nationellt centrum för kunskap om våld mot barn, vid Linköpings universitet, i uppdrag att att utvärdera barnahusverksamheterna i Sverige. I uppdraget (Uppdrag angående utvärdering av barnahus S2018/00212/FST) skriver Socialdepartementet att det är angeläget att den samverkan som sker inom barnahus uppfyller de kriterier som finns för vad som ska känneteckna verksamheterna samt att de nationella riktlinjerna är ändamålsenliga (Rikspolisstyrelsen, 2009). I uppdraget önskades identifiering av goda exempel och eventuella brister i syfte att främja ett kvalitativt och likvärdigt bemötande för brottsutsatta barn. I uppdraget anges vidare att ”en utvärdering belyser kvalitet, behovsuppfyllnad, eventuella skillnader och de konsekvenser sådana skillnader kan få för de barn som utgör målgruppen och kan på så sätt utgöra ett viktigt underlag för berörda myndigheter.” I uppdraget ingår inte att lämna åtgärdsförslag.

    Inom ramen för utvärderingen besöktes 32 barnahus under september 2018 – februari 2019. Vid varje Barnahus genomfördes gruppintervjuer med Barnahusens samverkansparter och samordnare utifrån en intervjuguide. Intervjuerna har analyserats tematiskt utifrån befintliga nationella riktlinjer och kriterier. Då Barnahusen saknar heltäckande statistik för sina verksamheter baseras utvärderingens resultat på egenrapporterad praxis, med andra ord det samverkansparterna och samordnarna själva uppgav att de gör. Därtill inkom Barnahusen med skriftligt material (aktuella samverkansavtal, lokala riktlinjer och rutiner, verksamhetsberättelser, informationsmaterial med mera) och ledamöter i styrgrupper eller motsvarande ombads besvara en enkät med frågor om det egna Barnahuset.

    I utvärderingen konstateras att det finns många välfungerande barnahus men att det förekommer regionala skillnader i Barnahusens organisation och verksamhet. 68 kommuner, främst i Norra Sverige, Jämtland, Halland och sydöstra delar av Sverige, står utanför Barnahusverksamheten.

    De främsta brister som lyfts fram av de intervjuade gäller otydligheter i de nationella riktlinjerna (tex. sekretess och den särskilda företrädarens kompetens och roll) samt tillgång till rättsmedicinsk, barnmedicinsk och barn- och ungdomspsykiatrisk kompetens. Det finns beredskap att ge krisstöd till barnet och hens föräldrar, ibland även till trygghetspersonen, efter barnförhör. Uppgifter om i vilken omfattning krisstöd/ behandling erbjuds saknas i denna utvärdering. Det efterfrågas nationell styrning, översikt av de nationella riktlinjerna i samråd med alla Barnahusens samverkansparter, statistik och certifiering av barnahusen. Det finns även behov av att se över målgruppsdefinitionen och att alla Barnahus arbetar utifrån dessa. Utredningen fann brister särskilt då det gällde barn som som bevittnat våld, internetbrott och i vissa fall hedersrelaterat våld.

    Ur ett barnperspektiv medför de konstaterade regionala skillnaderna en risk för ett icke likvärdigt bemötande, stöd och skydd. Detta kan yttra sig i form av olikheter bland annat gällande definition av målgrupper för Barnahusen, krisstöd och bedömning av vårdbehov, tillgång till barnmedicinsk och barn- och ungdomspsykiatrisk vård, möjlighet att erbjuda frivilliga hälsokontroller samt att tillgodose syskons behov av stöd och behandling. Läget ter sig problematisk för åldersgruppen 15-18 åringar, som nödvändigtvis inte kommer i kontakt med Barnahus.

    Sammanfattningsvis kan man konstatera att det har sedan 2013 tillkommit ytterligare ett antal Barnahus samtidigt som de grundläggande problemen som belysts i de tidigare utredningarna kvarstår. Det finns dock utrymme för förbättringar då det gäller det multiprofessionella teamarbetet och det tvärsektionella samarbetet, men de stora utmaningarna finns då det gäller behovet av en enhetlig nationell styrning som slår fast att barn som misstänks vara utsatta för brott ska utredas i en barnvänlig miljö där brörda myndigheter samlas och samverkar under ett tak, och där brottsutredning, skydd, samt fysisk och psykisk hälsa beaktas. Vidare saknas en nationell samordning av verksamheten i Barnahus. Befintlig sekretesslagstiftning försvårar samverkan och gör det svårt för Barnahusen att leva upp till de nationella kriterierna. Lagstiftningen förhindrar även gemensam statistikföring och försvårar därmed uppföljning och planering av verksamheten i Barnahus.

    Genomförandet av uppdraget har skett i dialog med Polismyndigheten, Åklagarmyndigheten, Socialstyrelsen och Rättsmedicinalverket.

    Uppdraget ska slutredovisas senast den 31 mars 2019, vilket görs härmed i denna rapport.

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  • 40.
    Do, Hai Thi
    et al.
    Department of Biochemistry and Developmental Biology, Medical Faculty, Medicum, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
    Bruelle, Celine
    Department of Biochemistry and Developmental Biology, Medical Faculty, Medicum, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
    Pham, Dan Duc
    Department of Biochemistry and Developmental Biology, Medical Faculty, Medicum, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
    Jauhiainen, Matti
    Genomics and Biomarkers Unit, National Institute for Health and Welfare, Helsinki, Finland.
    Eriksson, Ove
    Minerva Foundation Institute for Medical Research, Helsinki, Finland.
    Korhonen, Laura T.
    Minerva Foundation Institute for Medical Research, Helsinki, Finland; Division of Child Psychiatry, Helsinki University Central Hospital, Helsinki, Finland.
    Lindholm, Dan
    Department of Biochemistry and Developmental Biology, Medical Faculty, Medicum, University of Helsinki, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
    Nerve growth factor (NGF) and pro-NGF increase low-density lipoprotein (LDL) receptors in neuronal cells partly by different mechanisms: role of LDL in neurite outgrowth2016In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 136, no 2, p. 306-315Article in journal (Refereed)
    Abstract [en]

    Low-density lipoprotein receptors (LDLRs) mediate the uptake of lipoprotein particles into cells, as studied mainly in peripheral tissues. Here, we show that nerve growth factor (NGF) increases LDLR levels in PC6.3 cells and in cultured septal neurons from embryonic rat brain. Study of the mechanisms showed that NGF enhanced transcription of the LDLR gene, acting mainly via Tropomyosin receptor kinase A receptors. Simvastatin, a cholesterol-lowering drug, also increased the LDLR expression in PC6.3 cells. In addition, pro-NGF and pro-brain-derived neurotrophic factor, acting via the p75 neurotrophin receptor (p75NTR) also increased LDLRs. We further observed that Myosin Regulatory Light Chain-Interacting Protein/Inducible Degrader of the LDLR (Mylip/Idol) was down-regulated by pro-NGF, whereas the other LDLR regulator, proprotein convertase subtilisin kexin 9 (PCSK9) was not significantly changed. On the functional side, NGF and pro-NGF increased lipoprotein uptake by neuronal cells as shown using diacetyl-labeled LDL. The addition of serum-derived lipoprotein particles in conjunction with NGF or simvastatin enhanced neurite outgrowth. Collectively, these results show that NGF and simvastatin are able to stimulate lipoprotein uptake by neurons with a positive effect on neurite outgrowth. Increases in LDLRs and lipoprotein particles in neurons could play a functional role during brain development, in neuroregeneration and after brain injuries.

  • 41.
    Lindholm, Dan
    et al.
    Helsingfors universitet.
    Mäkela, Johanna
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Helsingfors universitet.
    PACAP and Neural Progenitor cells2016In: Pituitary Adenylate Cyclase Activating Peptide-PACAP / [ed] Reglodi D and Tamas A, Springer-Verlag New York, 2016, p. 53-63Chapter in book (Refereed)
    Abstract [en]

    PACAP is a neuropeptide with a multitude of functions on different cell types and organs including brain tissue. PACAP is relatively highly expressed in embryonic brain indicating a role in neuronal development. Particularly PACAP is expressed in the subventricular zone of lateral ventricles and in the dentate gyrus of hippocampus harboring the neural stem/progenitor cells (NPCs) that give rise to new neurons and glial cells in the developing brain. PACAP is known to stimulate the PACAP-1 receptors (PAC1R) that are expressed by the progenitor and other cells in the brain. Here we will shortly discuss the current view about the role of PACAP in NPCs and how PACAP affects cell proliferation, differentiation, specification, migration and survival of these cells as have been studied mainly in rodent brain. Available data suggests that PACAP acts in concert with other peptides, growth factors and other signaling molecules in governing the behavior of the NPCs both during development and in the adult brain. A better understanding about the action of PACAP in stem cells and its interactions with other factors will be helpful for the potential use of PACAP in treatment of different brain disorders and for understanding of neural repair mechanisms.

  • 42.
    Makela, Johanna
    et al.
    Univ Helsinki, Dept Biochem & Dev Biol, Medicum, Fac Med, POB 63, FIN-00014 Helsinki, Finland.;Biomedicum Helsinki 2U, Minerva Fdn Inst Med Res, Tukholmankatu 8, FIN-00290 Helsinki, Finland..
    Tselykh, Timofey V.
    Univ Helsinki, Dept Biochem & Dev Biol, Medicum, Fac Med, POB 63, FIN-00014 Helsinki, Finland.;Biomedicum Helsinki 2U, Minerva Fdn Inst Med Res, Tukholmankatu 8, FIN-00290 Helsinki, Finland..
    Kukkonen, Jyrki P.
    Univ Helsinki, Unit Biochem & Cell Biol, Dept Vet Biosci, POB 66, FIN-00014 Helsinki, Finland..
    Eriksson, Ove
    Biomedicum Helsinki 2U, Minerva Fdn Inst Med Res, Tukholmankatu 8, FIN-00290 Helsinki, Finland..
    Korhonen, Laura T.
    Biomedicum Helsinki 2U, Minerva Fdn Inst Med Res, Tukholmankatu 8, FIN-00290 Helsinki, Finland.;Univ Helsinki, Cent Hosp, Div Child Psychiat, Clinicum, FIN-00014 Helsinki, Finland..
    Lindholm, Dan
    Univ Helsinki, Dept Biochem & Dev Biol, Medicum, Fac Med, POB 63, FIN-00014 Helsinki, Finland.;Biomedicum Helsinki 2U, Minerva Fdn Inst Med Res, Tukholmankatu 8, FIN-00290 Helsinki, Finland..
    Peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist is neuroprotective and stimulates PGC-1 alpha expression and CREB phosphorylation in human dopaminergic neurons2016In: Neuropharmacology, ISSN 0028-3908, E-ISSN 1873-7064, Vol. 102, p. 266-275Article in journal (Refereed)
    Abstract [en]

    Mitochondrial dysfunction has been linked to several neurodegenerative diseases such as Parkinson's disease (PD). Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) is a master gene for mitochondrial biogenesis and has been shown to be neuroprotective in models of PD. In this work we have studied the mechanisms by which peroxisome proliferator-activated receptor-gamma (PPAR gamma) selective agonist N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino)ethyl]-L-tyrosine hydrate (GW1929) acts on human dopaminergic neurons in culture. Data showed that GW1929 increased the viability of human dopaminergic neurons and protected them against oxidative stress induced by H2O2 and the mitochondrial toxin Rotenone. The enhanced resilience of the neurons was attributed to increased levels of mitochondrial antioxidants and of PGC-1 alpha. GW1929 treatment further increased cell respiration, mitochondrial biogenesis and sirtuin-1 (SIRT1) expression in the human dopaminergic neurons. Phosphorylation of cAMP responsive element-binding protein (CREB) was also robustly increased in GW1929-treated cells. Together these results show that the PPAR gamma agonist GW1929 influences CREB signaling and PGC-1 alpha activities in the human dopaminergic neurons contributing to an increased cell viability. This supports the view that drugs acting on the PPAR gamma-PGC-1 alpha signaling in neurons may have beneficial effects in PD and possible also in other brain disorders. (c) 2015 Elsevier Ltd. All rights reserved.

  • 43.
    Korhonen, Laura
    et al.
    Department of Neuroscience, Neurobiology, Uppsala University, BMC, Box 587, S-751 23 Uppsala, Sweden.
    Belluardo, Natale
    Department of Experimental Medicine, Section of Human Physiology, Faculty of Medicine, University of Palermo, Palermo, Italy.
    Mudo, Giuseppa
    Department of Experimental Medicine, Section of Human Physiology, Faculty of Medicine, University of Palermo, Palermo, Italy.
    Lindholm, Dan
    Department of Neuroscience, Neurobiology, Uppsala University, BMC, Box 587, S-751 23 Uppsala, Sweden.
    Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain2003In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 18, no 5, p. 1121-1134Article in journal (Refereed)
    Abstract [en]

    Kainic acid induces excitotoxicity and nerve cell degeneration in vulnerable regions of rat brain, most markedly in hippocampus and amygdala. Part of the cell death following kainic acid is apoptotic as shown by caspase 3 activation and chromatin condensation. Here we have studied the regulation of pro- and anti-apoptotic proteins belonging to the Bcl-2 family in rat hippocampus and amygdala by kainic acid in relationship to ensuing neuronal death. The pro-apoptotic protein Bax was up-regulated in hippocampus 6 h after kainic acid administration. The increase in Bax was followed by the appearance of TdT-mediated dUTP nick end label ling-positive cells which were prominent at 24 h. Immunohistochemistry for active Bax revealed a punctated labelling of neurons in the CA3 and hilar regions of hippocampus as well as in amygdala. Double staining for NeuN, a marker for nerve cells, and TdT-mediated dUTP nick end labelling showed that mainly neurons undergo degeneration after kainic acid treatment. In contrast to Bax, the pro-apoptotic BH3-only Bcl-2 proteins Bim and Harakiri/DP5 were down-regulated by kainic acid. This was also observed for the anti-apoptotic proteins Bcl-x and Bcl-w. Immunoreactive Bcl-2 was up-regulated in hippocampus after kainic acid together with an increase in the phosphorylation of serine-87 in Bcl-2, suggesting a post-transcriptional modification of the protein. This was confirmed using immunoprecipitation of total Bcl-2 from hippocampus and amygdala which revealed an increase in serine-87 phospho-Bcl-2 after kainic acid. Inhibition of the c-jun N-terminal protein kinase pathway reduced both serine-87 phosphorylation and cell death after kainic acid. This indicates an important role of Bcl-2 phosphorylation in controlling neuronal death after kainic acid. In contrast to the situation in trophic factor-deprived neurons, no up-regulation of Bim or Harakiri/DP5 proteins occurred after kainic acid, suggesting alternative pathways for regulation of cell death in excitotoxicity The results indicate that not only the relative levels of Bcl-2 family proteins but also conformation changes and post-translational modifications contribute to neuronal death following kainic acid.

  • 44.
    Hansson, Oskar
    et al.
    Section for Neuronal Survival, Wallenberg Neuroscience Center, Department of Physiological Sciences, Lund University, Lund, Sweden.
    Castilho, Roger F.
    Department of Clinical Pathology, School of Medical Sciences, State University of Campinas, Campinas, Brazil.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping. Department of Neuroscience, Neurobiology, Uppsala University, Uppsala, Sweden.
    Lindholm, Dan
    Department of Neuroscience, Neurobiology, Uppsala University, Uppsala, Sweden.
    Bates, Gillian P.
    Medical and Molecular Genetics, GKT School of Medicine, London, UK.
    Brundin, Patrik
    Section for Neuronal Survival, Wallenberg Neuroscience Center, Department of Physiological Sciences, Lund University, Lund, Sweden.
    Partial resistance to malonate-induced striatal cell death in transgenic mouse models of Huntington's disease is dependent on age and CAG repeat length2001In: Journal of Neurochemistry, ISSN 0022-3042, E-ISSN 1471-4159, Vol. 78, no 4, p. 694-703Article in journal (Refereed)
    Abstract [en]

    Transgenic, Huntington's disease (HD) mice, expressing exon I of the HD gene with an expanded CAG repeat, are totally resistant to striatal, lesion induced by excessive NMDA receptor activation. We now show that striatal lesions induced by the mitochondrial toxin malonate are reduced by 70-80% in transgenic HD mice compared with wild-type littermate controls. This occurred in 6- and 12-week-old HID mice with 150 CAG repeats (line R6/2) and in 18-week-old, but not 6-week-old, HID mice with 115 CAG repeats (line R6/1). Therefore, we show for the first time that the resistance to neurotoxin in transgenic HD mice is dependent on both the CAG repeat length and the age of the mice. Importantly, most HD patients develop symptoms in adulthood and exhibit an inverse relationship between GAG repeat length and age of onset. Transgenic mice expressing a normal CAG repeat (18 CAG) were not resistant to malonate. Although endogenous glutamate release has been implicated in malonate-induced cell death, glutamate release from striatal synaptosomes was not decreased in HID mice. Malonate-induced striatal cell death was reduced by 50-60% in wild-type mice when they were treated with either the NMDA receptor antagonist MK-801 or the caspase inhibitor zVAD-fmk. These two compounds did not reduce lesion size in transgenic R6/1 mice. This might suggest that NMDA receptor- and caspase-mediated cell death pathways are inhibited and that the limited malonate-induced cell death still occurring in HID mice is independent of these pathways. There were no changes in striatal levels of the two anti cell death proteins Bcl-X-L and X-linked Inhibitor of apoptosis protein (XIAP), before or after the lesion in transgenic HD mice. We propose that mutant huntingtin causes a sublethal grade of metabolic stress which is CAG repeat length-dependent and results in up-regulation over time of cellular defense mechanisms against impaired energy metabolism and excitotoxicity.

  • 45.
    Korhonen, Laura
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping. Department of Neuroscience, Neurobiology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
    Belluardo, Natale
    Institute of Human Physiology, Faculty of Medicine, University of Palermo, Palermo, Italy.
    Lindholm, Dan
    Department of Neuroscience, Neurobiology, Biomedical Centre, Uppsala University, Uppsala, Sweden.
    Regulation of X-chromosome-linked inhibitor of apoptosis protein in kainic acid-induced neuronal death in the rat hippocampus2001In: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 17, no 2, p. 364-372Article in journal (Refereed)
    Abstract [en]

    XIAP (X-chromosome-linked inhibitor of apoptosis protein) is an antiapoptotic protein which inhibits the activity of caspases and suppresses cell death. However, little is known about the presence and function of XIAP in the nervous system. Here we report that XIAP mRNA is expressed in developing and adult rat brain. Using a specific antibody, we observed XIAP-immunoreactive cells in different brain regions, among others, in the hippocampus and cerebral cortex. Kainic acid, which induces delayed cell death of specific neurons, increased the levels of XIAP in the CA3 region of hippocampus. XIAP was, however, largely absent in cells undergoing cell death, as shown by TUNEL labeling and staining for active caspase-3. In cultured hippocampal neurons, XIAP was initially upregulated by kainic acid and then degraded in a process blocked by the caspase-3 inhibitor DEVD. Similarly, recombinant XIAP is cleaved by active caspase-3 in vitro. The results show that there is biphasic regulation of XIAP in the hippocampus following kainic acid and that XIAP becomes a target for caspase-3 activated during cell death in the hippocampus. The degradation of XIAP by kainic acid contributes to neuronal cell death observed in vulnerable neurons of the hippocampus after caspase activation.

  • 46.
    Korhonen, Laura
    et al.
    Uppsala University, Uppsala, Sweden.
    Sjoholm, Ulrika
    Uppsala University, Uppsala, Sweden.
    Takei, Nobuyuki
    Uppsala University, Uppsala, Sweden.
    Kern, Michael A.
    Uppsala University, Uppsala, Sweden; University of Köln, Köln, Germany.
    Schirmacher, Peter
    University of Köln, Köln, Germany.
    Castren, Eero
    University of Kuopio. Kuopio, Finland.
    Lindholm, Dan
    Uppsala University, Uppsala, Sweden.
    Expression of c-Met in developing rat hippocampus: evidence for HGF as a neurotrophic factor for calbindin D-expressing neurons2000In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 12, no 10, p. 3453-3461Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor-scatter factor (HGF) is expressed in different parts of the nervous system, and has been shown to exhibit neurotrophic activity. Here we show that c-Met, the receptor for HGF, is expressed in developing rat hippocampus, with the highest levels during the first postnatal weeks. To study the function of HGF, hippocampal neurons were prepared from embryonic rats and treated with different HGF concentrations. In these cultures, HGF increased the number of neurons expressing the 28-kDa calcium-binding protein (calbindin D) in a dose-dependent manner. The effect of HGF was larger than that observed with either brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3), and cotreatment of the cultures with HGF and the neurotrophins was additive with respect to calbindin D neurons. Besides affecting the number of neurons, HGF significantly increased the degree of sprouting of calbindin D-positive neurons, suggesting an influence on neuronal maturation. BDNF and NT-3 stimulated neurite outgrowth of calbindin D neurons to a much smaller degree. In contrast to calbindin D neurons, HGF did not significantly increase the number of neurons immunoreactive with the neurotransmitter gamma-aminobutyric acid (GABA) in the hippocampal cultures. Immunohistochemical studies showed that c-Met-, calbindin D- and HGF-immunoreactive cells are all present in the dentate gyrus and partly colocalize within neurons. These results show that HGF acts on calbindin D-containing hippocampal neurons and increases their neurite outgrowth, suggesting that HGF plays an important role for the maturation and function of these neurons in the hippocampus.

  • 47.
    Peltola, J
    et al.
    Department of Neurology, Tampere University Hospital, Tampere, Finland; Medical School, University of Tampere, Tampere, Finland.
    Palmio, J
    Department of Neurology, Tampere University Hospital, Tampere, Finland.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping.
    Suhonen, J
    Department of Neurology, Tampere University Hospital, Tampere, Finland.
    Miettinen, A
    Department of Clinical Microbiology, Tampere University Hospital, Tampere, Finland.
    Hurme, M
    Medical School, University of Tampere, Tampere, Finland.
    Lindholm, D
    Department of Neuroscience, Uppsala university, Uppsala, Sweden.
    Keranen, T
    Department of Neurology, Tampere University Hospital, Tampere, Finland.
    Interleukin-6 and Interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic-clonic seizures2000In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 41, no 3, p. 205-211Article in journal (Refereed)
    Abstract [en]

    We have previously reported increased concentrations of interleukin (IL)-6 in CSF from patients with tonic-clonic seizures, where increased cytokine production most likely is a consequence of neuronal epileptic activity associated with seizures. The biological effects of IL-6 are mediated by other cytokines, which are studied here in addition to IL-6. The purpose of this study was to analyze levels of soluble cytokines from plasma and CSF from patients with newly developed tonic-clonic seizures. The concentrations of IL-6, IL-1 receptor antagonist (IL-1RA), IL-1 beta, tumor necrosis factor (TNF alpha) and nerve growth factor (NGF) were measured from plasma and CSF from 22 patients with newly developed tonic-clonic seizures within 24 h from the seizure and 18 controls. The mean concentrations of IL-6 were significantly increased in CSF (P < 0.001) and plasma (P < 0.01) after tonic-clonic seizures, there was some indication of increased concentrations of IL-IRA and no significant change in NGF, IL-1 beta or TNF alpha. Our study shows that cytokine network is activated in patients after recent tonic-clonic seizures. We provide evidence of intrathecal production of IL-6 associated with electrical seizure activity. (C) 2000 Elsevier Science B.V. All rights reserved.

  • 48.
    Mercer, Eric A
    et al.
    Uppsala University, Uppsala, Sweden.
    Korhonen, Laura
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Child and Adolescent Psychiatry in Linköping. Uppsala University, Uppsala, Sweden.
    Skoglosa, Ylva
    Uppsala University, Uppsala, Sweden.
    Olsson, Per‐Anders
    Uppsala University, Uppsala, Sweden.
    Kukkonen, Jyrki P
    Uppsala University, Uppsala, Sweden.
    Lindholm, Dan
    Uppsala University, Uppsala, Sweden.
    NAIP interacts with hippocalcin and protects neurons against calcium-induced cell death through caspase-3-dependent and -independent pathways2000In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 19, no 14, p. 3597-3607Article in journal (Refereed)
    Abstract [en]

    Inhibitor-of-apoptosis proteins (IAPs), including neuronal apoptosis inhibitory protein (NAIP), inhibit cell death. Other IAPs inhibit key caspase proteases which effect cell death, but the mechanism by which NAIP acts is unknown. Here we report that NAIP, through its third baculovirus inhibitory repeat domain (BIR3), binds the neuron-restricted calcium-binding protein, hippocalcin, in an interaction promoted by calcium. In neuronal cell lines NSC-34 and Neuro-2a, over-expression of the BIR domains of NAIP (NAIP-BIR1-3) counteracted the calcium-induced cell death induced by ionomycin and thapsigargin. This protective capacity was significantly enhanced when NAIP-BIR1-3 was co-expressed with hippocalcin. Over-expression of the BIR3 domain or hippocalcin alone did not substantially enhance cell survival, but co-expression greatly increased their protective effects. These data suggest synergy between NAIP and hippocalcin in facilitating neuronal survival against calcium-induced death stimuli mediated through the BIR3 domain. Analysis of caspase activity after thapsigargin treatment revealed that caspase-3 is activated in NSC-34, but not Neuro-2a, cells, Thus NAIP, in conjunction with hippocalcin, can protect neurons against calcium-induced cell death in caspase-3-activated and non-activated pathways.

  • 49.
    Olsson, Per-Anders
    et al.
    Uppsala University, Uppsala, Sweden.
    Bornhauser, Beat C.
    Uppsala University, Uppsala, Sweden.
    Korhonen, Laura
    Uppsala University, Uppsala, Sweden.
    Lindholm, Dan
    Uppsala University, Uppsala, Sweden.
    Neuronal expression of the ERM-like protein MIR in rat brain and its localization to human chromosome 62000In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 279, no 3, p. 879-883Article in journal (Refereed)
    Abstract [en]

    The ERM proteins, ezrin, radixin, and moesin, regulate cell motility by linking cortical F-actin to the plasma membrane in different cell types. Myosin regulatory light chain interacting protein (MIR) is a recently cloned ERM-like protein which was shown to be involved in neurite outgrowth. Here we have studied the occurrence and expression of MIR in rats during brain development. As Shown using Western blotting, MIR is present in different regions both in developing and adult brain, Immunohistochemistry and double labelling studies showed that MIR is localized especially to neurons in hippocampus and cerebellum. A search using the gene bank showed that the MIR gene localised to human chromosome 6 in the interval 6p22.3-23, the loss of which is characterized by mental retardation and different malformations in man. The presence of MIR in brain neurons during development together with its known effects on neurite outgrowth suggest an important function of the protein in the regulation of nerve cell motility and cytoskeletal interactions. (C) 2000 Academic Press.

  • 50.
    Takei, Nobuyuki
    et al.
    University of Uppsala, Uppsala, Sweden.
    Torres, Eduardo
    University of Cambridge, UK.
    Yuhara, Aki
    Osaka University, Japan.
    Jongsma, H
    University of Uppsala, Uppsala, Sweden.
    Otto, Christiane
    German Cancer Research Center, Heidelberg, Germany.
    Korhonen, Laura
    University of Uppsala, Uppsala, Sweden.
    Abiru, Yasuhiro
    Institute for Protein Research, Osaka University, Japan.
    Skoglösa, Ylva
    University of Uppsala, Uppsala, Sweden.
    Schutz, Günther
    German Cancer Research Center, Heidelberg, Germany.
    Hatanaka, Hiroshi
    Institute for Protein Research, Osaka University, Japan.
    Sofroniew, Michael V.
    University of Cambridge, UK.
    Lindholm, Dan
    University of Uppsala, Uppsala, Sweden.
    Pituitary adenylate cyclase-activating polypeptide promotes the survival of basal forebrain cholinergic neurons in vitro and in vivo: comparison with effects of nerve growth factor2000In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 12, no 7, p. 2273-2280Article in journal (Refereed)
    Abstract [en]

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the vasointestinal polypeptide gene family for which neurotrophic activity has been postulated. PACAP mRNA is expressed in the developing and adult hippocampus, which is the principal target region of septal cholinergic neurons. We therefore studied the effects of PACAP on septal cholinergic neurons. In primary cultures from septum of embryonic and postnatal rats, PACAP increased the number of neurons immunohistochemically stained for the low-affinity nerve growth factor (NGF) receptor p75 and for the enzyme choline acetyltransferase (ChAT). PACAP also caused a corresponding increase in ChAT activity. In comparison, NGF had a greater effect than PACAP on the number of p75- and ChAT-positive neurons in these cultures. In vivo, following fimbria fornix transection, the number of immunohistochemically stained septal cholinergic neurons fell significantly to 18% in rats given continuous intracerebroventricular infusion of vehicle, whereas in rats given NGF the number of these neurons did not differ significantly from unoperated controls. In PACAP-treated rats the number was 48% of unoperated values, which represented a significant increase compared with vehicle-treated rats and a significant decrease compared with NGF-treated rats or unoperated controls. Double-staining experiments revealed that most ChAT-positive neurons in rat medial septum also express PACAP receptor 1. Together the results show that PACAP promotes the survival of septal cholinergic neurons in vitro, and after injury in vivo, suggesting that PACAP acts as a neurotrophic factor influencing the development and maintenance of these neurons.

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