To Örebro University

oru.seÖrebro University Publications
Change search
Refine search result
1 - 24 of 24
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Bang Madsen, Kathrine
    et al.
    NCRR - National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark.
    Robakis, Thalia K.
    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Liu, Xiaoqin
    NCRR - National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark.
    Momen, Natalie
    NCRR - National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Dreier, Julie Werenberg
    NCRR - National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark; Department of Clinical Medicine, University of Bergen, Bergen, Norway.
    Kildegaard, Helene
    Hans Christian Andersen's Children's Hospital, Odense University Hospital, Odense, Denmark; Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark, Odense, Denmark.
    Groth, Jane Bjerg
    Department of Otorhinolaryngology and Audiology, Zealand University Hospital, Universty of Copenhagen, Køge, Denmark.
    Newcorn, Jeffrey H.
    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Hove Thomsen, Per
    Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Research Center at the Department for Child- and Adolescent Psychiatry, Aarhus University Hospital, Skejby, Denmark.
    Munk-Olsen, Trine
    NCRR - National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Aarhus, Denmark; Research Unit of Psychiatry, Institute for Clinical Research, University of Southern Denmark, Odense, Denmark.
    Bergink, Veerle
    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands.
    In utero exposure to ADHD medication and long-term offspring outcomes2023In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 28, no 4, p. 1739-1746Article in journal (Refereed)
    Abstract [en]

    Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.

  • 2.
    Borg, J.
    et al.
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Cervenka, S.
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, R
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .
    Matheson, G. J.
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Jönsson, E. G.
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, Psychiatry Section, University of Oslo, Oslo, Norway.
    Lichtenstein, P.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Henningsson, S.
    Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
    Ichimiya, T.
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Stenkrona, P.
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Halldin, C.
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Farde, L.
    Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; AstraZeneca Translational Science Center, Karolinska Institutet, Stockholm, Sweden.
    Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain2016In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 21, no 8, p. 1077-1084Article in journal (Refereed)
    Abstract [en]

    The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [(11)C]raclopride binding to the D2- and D3-dopamine receptor and [(11)C]WAY100635 binding to the serotonin 5-HT1A receptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D2/3 and 5-HT1A receptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D2/3 receptor binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70-0.75) on neocortical 5-HT1A receptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature-nurture interplay, and call for increased efforts to identify not only the genetic but also the environmental factors that influence neurotransmission in health and disease.

  • 3.
    Brander, Gustaf
    et al.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Rosenqvist, Mina A.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Serlachius, Eva
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Fernández de la Cruz, Lorena
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Crowley, James J.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Mataix-Cols, David
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    A population-based family clustering study of tic-related obsessive-compulsive disorder2021In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, no 4, p. 1224-1233Article in journal (Refereed)
    Abstract [en]

    In the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), obsessive-compulsive disorder (OCD) included a new "tic-related" specifier. However, strong evidence supporting tic-related OCD as a distinct subtype of OCD is lacking. This study investigated whether, at the population level, tic-related OCD has a stronger familial load than non-tic-related OCD. From a cohort of individuals born in Sweden between 1967 and 2007 (n = 4,085,367; 1257 with tic-related OCD and 20,975 with non-tic-related OCD), we identified all twins, full siblings, maternal and paternal half siblings, and cousins. Sex- and birth year-adjusted hazard ratios (aHR) were calculated to estimate the risk of OCD in relatives of individuals with OCD with and without comorbid tics, compared with relatives of unaffected individuals. We found that OCD is a familial disorder, regardless of comorbid tic disorder status. However, the risk of OCD in relatives of individuals with tic-related OCD was considerably greater than the risk of OCD in relatives of individuals with non-tic-related OCD (e.g., risk for full siblings: aHR = 10.63 [95% CI, 7.92-14.27] and aHR = 4.52 [95% CI, 4.06-5.02], respectively; p value for the difference < 0.0001). These differences remained when the groups were matched by age at first OCD diagnosis and after various sensitivity analyses. The observed familial patterns of OCD in relation to tics were not seen in relation to other neuropsychiatric comorbidities. Tic-related OCD is a particularly familial subtype of OCD. The results have important implications for ongoing gene-searching efforts.

  • 4.
    Brander, Gustaf
    et al.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Rydell, Mina
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Fernández de la Cruz, Lorena
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul S.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Serlachius, Eva
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Mataix-Cols, David
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 5, p. 1189-1197Article in journal (Refereed)
    Abstract [en]

    Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.

  • 5.
    Brikell, Isabell
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lu, Yi
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Statistical Genetics, Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, Brisbane QLD, Australia.
    Pettersson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Chen, Qi
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Karlsson, Robert
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lahey, Benjamin B.
    Department of Public Health Sciences, University of Chicago, Chicago IL, USA.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Martin, Joanna
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
    The contribution of common genetic risk variants for ADHD to a general factor of childhood psychopathology2020In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 25, no 8, p. 1809-1821Article in journal (Refereed)
    Abstract [en]

    Common genetic risk variants have been implicated in the etiology of clinical attention-deficit/hyperactivity disorder (ADHD) diagnoses and symptoms in the general population. However, given the extensive comorbidity across ADHD and other psychiatric conditions, the extent to which genetic variants associated with ADHD also influence broader psychopathology dimensions remains unclear. The aim of this study was to evaluate the associations between ADHD polygenic risk scores (PRS) and a broad range of childhood psychiatric symptoms, and to quantify the extent to which such associations can be attributed to a general factor of childhood psychopathology. We derived ADHD PRS for 13,457 children aged 9 or 12 from the Child and Adolescent Twin Study in Sweden, using results from an independent meta-analysis of genome-wide association studies of ADHD diagnosis and symptoms. We estimated associations between ADHD PRS, a general psychopathology factor, and several dimensions of neurodevelopmental, externalizing, and internalizing symptoms, using structural equation modeling. Higher ADHD PRS were statistically significantly associated with elevated neurodevelopmental, externalizing, and depressive symptoms (R 2  = 0.26-1.69%), but not with anxiety. After accounting for a general psychopathology factor, on which all symptoms loaded positively (mean loading = 0.50, range = 0.09-0.91), an association with specific hyperactivity/impulsivity remained significant. ADHD PRS explained ~ 1% (p value < 0.0001) of the variance in the general psychopathology factor and ~ 0.50% (p value < 0.0001) in specific hyperactivity/impulsivity. Our results suggest that common genetic risk variants associated with ADHD, and captured by PRS, also influence a general genetic liability towards broad childhood psychopathology in the general population, in addition to a specific association with hyperactivity/impulsivity symptoms.

  • 6.
    Bränn, Emma
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Chen, Yufeng
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Song, Huan
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
    László, Krisztina D.
    Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden; Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    D'Onofrio, Brian M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
    Hysaj, Elgeta
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Valdimarsdottir, Unnur A.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
    Lu, Donghao
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bidirectional association between autoimmune disease and perinatal depression: a nationwide study with sibling comparison2024In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Article in journal (Refereed)
    Abstract [en]

    Although major depression, characterized by a pro-inflammatory profile, genetically overlap with autoimmune disease (AD) and the perinatal period involve immune system adaptations and AD symptom alterations, the bidirectional link between perinatal depression (PND) and AD is largely unexplored. Hence, the objective of this study was to investigate the bidirectional association between PND and AD. Using nationwide Swedish population and health registers, we conducted a nested case-control study and a matched cohort study. From 1,347,901 pregnancies during 2001-2013, we included 55,299 incident PND, their unaffected full sisters, and 10 unaffected matched women per PND case. We identified 41 subtypes of AD diagnoses recorded in the registers and compared PND with unaffected population-matched women and full sisters, using multivariable regressions. Women with an AD had a 30% higher risk of subsequent PND (95% CI 1.2-1.5) and women exposed to PND had a 30% higher risk of a subsequent AD (95% CI 1.3-1.4). Comparable associations were found when comparing exposed women with their unaffected sisters (nested case-control OR: 1.3, 95% CI 1.2-1.5, matched cohort HR: 1.3, 95% CI 1.1-1.6), and when studying antepartum and postpartum depression. The bidirectional association was more pronounced among women without psychiatric comorbidities (nested case-control OR: 1.5, 95% CI 1.4-1.6, matched cohort HR: 1.4, 95% CI 1.4-1.5) and strongest for multiple sclerosis (nested case-control OR: 2.0, 95% CI 1.6-2.3, matched cohort HR: 1.8, 95% CI 1.0-3.1). These findings demonstrate a bidirectional association between AD and PND independent of psychiatric comorbidities, suggesting possibly shared biological mechanisms. If future translational science confirms the underlying mechanisms, healthcare providers need to be aware of the increased risk of PND among women with ADs and vice versa.

  • 7.
    Clements, Caitlin C.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
    Karlsson, Robert
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lu, Yi
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Juréus, Anders
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm Health Care Services, Stockholm County Council, Karolinska University Hospital, Huddinge, Sweden.
    Andersson, Evelyn
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm Health Care Services, Stockholm County Council, Karolinska University Hospital, Huddinge, Sweden.
    Boberg, Julia
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm Health Care Services, Stockholm County Council, Karolinska University Hospital, Huddinge, Sweden.
    Pedersen, Nancy L.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bulik, Cynthia M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA; Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
    Nordenskjöld, Axel
    Örebro University, School of Medical Sciences.
    Pålsson, Erik
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Sullivan, Patrick F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
    Landén, Mikael
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy2021In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, no 6, p. 2429-2439Article in journal (Refereed)
    Abstract [en]

    Although large genome-wide association studies (GWAS) of major depressive disorder (MDD) have identified many significant loci, the SNP-based heritability remains notably low, which might be due to etiological heterogeneity in existing samples. Here, we test the utility of targeting the severe end of the MDD spectrum through genome-wide SNP genotyping of 2725 cases who received electroconvulsive therapy (ECT) for a major depressive episode (MDE) and 4035 controls. A subset of cases (n = 1796) met a narrow case definition (MDE occurring in the context of MDD). Standard GWAS quality control procedures and imputation were conducted. SNP heritability and genetic correlations with other traits were estimated using linkage disequilibrium score regression. Results were compared with MDD cases of mild-moderate severity receiving internet-based cognitive behavioral therapy (iCBT) and summary results from the Psychiatric Genomics Consortium (PGC). The SNP-based heritability was estimated at 29-34% (SE: 6%) for the narrow case definition, considerably higher than the 6.5-8.0% estimate in the most recent PGC MDD study. Our severe MDE cases had smaller genetic correlations with neurodevelopmental disorders and neuroticism than PGC MDD cases but higher genetic risk scores for bipolar disorder than iCBT MDD cases. One genome-wide significant locus was identified (rs114583506, P = 5e-8) in an intron of HLA-B in the major histocompatibility locus on chr6. These results indicate that individuals receiving ECT for an MDE have higher burden of common variant risk loci than individuals with mild-moderate MDD. Furthermore, severe MDE shows stronger relations with other severe adult-onset psychiatric disorders but weaker relations with personality and stress-related traits than mild-moderate MDD. These findings suggest a different genetic architecture at the severest end of the spectrum, and support further study of the severest MDD cases as an extreme phenotype approach to understand the etiology of MDD.

  • 8.
    Cortese, Samuele
    et al.
    Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York City, NY, USA; Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.
    Song, Minjin
    Yonsei University College of Medicine, Seoul, South Korea.
    Farhat, Luis C.
    Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
    Yon, Dong Keon
    Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea.
    Lee, Seung Won
    Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, South Korea.
    Kim, Min Seo
    Department of digital health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea.
    Park, Seoyeon
    Yonsei University College of Medicine, Seoul, South Korea.
    Oh, Jae Won
    Department of Psychiatry, Yongin Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
    Lee, San
    Department of Psychiatry, Yongin Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Psychiatry and Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
    Cheon, Keun-Ah
    Division of Child and Adolescent Psychiatry, Department of Psychiatry, Severance Hospital, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Korea.
    Smith, Lee
    Centre for Health, Performance, and Wellbeing, Anglia Ruskin University, Cambridge, UK.
    Gosling, Corentin J.
    Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; DysCo Lab, Department of Psychology, Université Paris Nanterre, Nanterre, France; Laboratoire de Psychopathologie et Processus de Santé, Université de Paris, Boulogne-Billancourt, France.
    Polanczyk, Guilherme V.
    Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Rohde, Luis A.
    ADHD Outpatient Program & Developmental Psychiatry Program, Hospital de Clinica de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; UNIEDUK, National Institute of Developmental Psychiatry, São Paulo, Brazil.
    Faraone, Stephen V.
    Department of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
    Koyanagi, Ai
    Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, ISCIII, Barcelona, Spain; ICREA, Pg. Lluis Companys, Barcelona, Spain.
    Dragioti, Elena
    Pain and Rehabilitation Centre, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Research Laboratory Psychology of Patients, Families and Health Professionals, Department of Nursing, School of Health Sciences, University of Ioannina, Ioannina, Greece.
    Radua, Joaquim
    Institut d'Investigacions Biomediques August Pi i Sunyer, CIBERSAM, Instituto de Salud Carlos III, University of Barcelona, Barcelona, Spain.
    Carvalho, Andre F.
    IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, Australia.
    Il Shin, Jae
    Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea; Severance Underwood Meta-research Center, Institute of Convergence Science, Yonsei University, Seoul, Republic of Korea.
    Solmi, Marco
    Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Department of Psychiatry, University of Ottawa, Ottawa, ON, Canada; Department of Mental Health, The Ottawa Hospital, Ottawa, ON, Canada; School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; Ottawa Hospital Research Institute (OHRI), Clinical Epidemiology Program, University of Ottawa, Ottawa, ON, Canada; Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany.
    Incidence, prevalence, and global burden of ADHD from 1990 to 2019 across 204 countries: data, with critical re-analysis, from the Global Burden of Disease study2023In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578Article in journal (Refereed)
    Abstract [en]

    Data on incidence, prevalence and burden of ADHD are crucial for clinicians, patients, and stakeholders. We present the incidence, prevalence, and burden of ADHD globally and across countries from 1990 to 2019 from the Global Burden of Disease (GBD) study. We also: (1) calculated the ADHD prevalence based on data actually collected as opposed to the prevalence estimated by the GBD with data imputation for countries without prevalence data; (2) discussed the GBD estimated ADHD burden in the light of recent meta-analytic evidence on ADHD-related mortality. In 2019, GBD estimated global age-standardized incidence and prevalence of ADHD across the lifespan at 0.061% (95%UI = 0.040-0.087) and 1.13% (95%UI = 0.831-1.494), respectively. ADHD accounted for 0.8% of the global mental disorder DALYs, with mortality set at zero by the GBD. From 1990 to 2019 there was a decrease of -8.75% in the global age-standardized prevalence and of -4.77% in the global age-standardized incidence. The largest increase in incidence, prevalence, and burden from 1990 to 2019 was observed in the USA; the largest decrease occurred in Finland. Incidence, prevalence, and DALYs remained approximately 2.5 times higher in males than females from 1990 to 2019. Incidence peaked at age 5-9 years, and prevalence and DALYs at age 10-14 years. Our re-analysis of data prior to 2013 showed a prevalence in children/adolescents two-fold higher (5.41%, 95% CI: 4.67-6.15%) compared to the corresponding GBD estimated prevalence (2.68%, 1.83-3.72%), with no significant differences between low- and middle- and high-income countries. We also found meta-analytic evidence of significantly increased ADHD-related mortality due to unnatural causes. While it provides the most detailed evidence on temporal trends, as well as on geographic and sex variations in incidence, prevalence, and burden of ADHD, the GBD may have underestimated the ADHD prevalence and burden. Given the influence of the GBD on research and policies, methodological issues should be addressed in its future editions.

  • 9.
    Faraone, Stephen V.
    et al.
    Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Genetics of attention deficit hyperactivity disorder2019In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 24, no 4, p. 562-575Article, review/survey (Refereed)
    Abstract [en]

    Decades of research show that genes play an vital role in the etiology of attention deficit hyperactivity disorder (ADHD) and its comorbidity with other disorders. Family, twin, and adoption studies show that ADHD runs in families. ADHD's high heritability of 74% motivated the search for ADHD susceptibility genes. Genetic linkage studies show that the effects of DNA risk variants on ADHD must, individually, be very small. Genome-wide association studies (GWAS) have implicated several genetic loci at the genome-wide level of statistical significance. These studies also show that about a third of ADHD's heritability is due to a polygenic component comprising many common variants each having small effects. From studies of copy number variants we have also learned that the rare insertions or deletions account for part of ADHD's heritability. These findings have implicated new biological pathways that may eventually have implications for treatment development.

  • 10.
    Fernández de la Cruz, Lorena
    et al.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Rydell, Mina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Runeson, Bo Sigurd
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Department of Psychological and Brain Sciences, Indiana University, Bloomington IN, USA.
    Brander, Gustaf
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul S.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Mataix-Cols, David
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Suicide in obsessive-compulsive disorder: a population-based study of 36 788 Swedish patients2017In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 22, no 11, p. 1626-1632Article in journal (Refereed)
    Abstract [en]

    The risk of death by suicide in individuals with obsessive-compulsive disorder (OCD) is largely unknown. Previous studies have been small and methodologically flawed. We analyzed data from the Swedish national registers to estimate the risk of suicide in OCD and identify the risk and protective factors associated with suicidal behavior in this group. We used a matched case-cohort design to estimate the risk of deaths by suicide and attempted suicide in individuals diagnosed with OCD, compared with matched general population controls (1:10). Cox regression models were used to study predictors of suicidal behavior. We identified 36 788 OCD patients in the Swedish National Patient Register between 1969 and 2013. Of these, 545 had died by suicide and 4297 had attempted suicide. In unadjusted models, individuals with OCD had an increased risk of both dying by suicide (odds ratio (OR)=9.83 (95% confidence interval (CI), 8.72-11.08)) and attempting suicide (OR=5.45 (95% CI, 5.24-5.67)), compared with matched controls. After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial for both death by suicide and attempted suicide. Within the OCD cohort, a previous suicide attempt was the strongest predictor of death by suicide. Having a comorbid personality or substance use disorder also increased the risk of suicide. Being a woman, higher parental education and having a comorbid anxiety disorder were protective factors. We conclude that patients with OCD are at a substantial risk of suicide. Importantly, this risk remains substantial after adjusting for psychiatric comorbidities. Suicide risk should be carefully monitored in patients with OCD.

  • 11.
    Garcia-Argibay, Miguel
    et al.
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. miguel.garcia-argibay@oru.se.
    Zhang-James, Yanli
    Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
    Cortese, Samuele
    School of Psychology, University of Southampton, Southampton, UK; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK; Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York City, New York, NY, USA; Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Faraone, Stephen V.
    Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA.
    Predicting childhood and adolescent attention-deficit/hyperactivity disorder onset: a nationwide deep learning approach2023In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 28, no 3, p. 1232-1239Article in journal (Refereed)
    Abstract [en]

    Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder with a high degree of psychiatric and physical comorbidity, which complicates its diagnosis in childhood and adolescence. We analyzed registry data from 238,696 persons born and living in Sweden between 1995 and 1999. Several machine learning techniques were used to assess the ability of registry data to inform the diagnosis of ADHD in childhood and adolescence: logistic regression, random Forest, gradient boosting, XGBoost, penalized logistic regression, deep neural network (DNN), and ensemble models. The best fitting model was the DNN, achieving an area under the receiver operating characteristic curve of 0.75, 95% CI (0.74-0.76) and balanced accuracy of 0.69. At the 0.45 probability threshold, sensitivity was 71.66% and specificity was 65.0%. There was an overall agreement in the feature importance among all models (τ > .5). The top 5 features contributing to classification were having a parent with criminal convictions, male sex, having a relative with ADHD, number of academic subjects failed, and speech/learning disabilities. A DNN model predicting childhood and adolescent ADHD trained exclusively on Swedish register data achieved good discrimination. If replicated and validated in an external sample, and proven to be cost-effective, this model could be used to alert clinicians to individuals who ought to be screened for ADHD and to aid clinicians' decision-making with the goal of decreasing misdiagnoses. Further research is needed to validate results in different populations and to incorporate new predictors.

  • 12.
    Ghirardi, L.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Brikell, I.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, R.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Freitag, C. M.
    Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
    Franke, B.
    Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
    Asherson, P.
    MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
    Lichtenstein, P.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    The familial co-aggregation of ASD and ADHD: a register-based cohort study2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 2, p. 257-262Article in journal (Refereed)
    Abstract [en]

    Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD. We studied 1 899 654 individuals born in Sweden between 1987 and 2006. Logistic regression was used to estimate the association between clinically ascertained ASD and ADHD in individuals and in families. Stratified estimates were obtained for ASD with (low-functioning) and without (high-functioning) intellectual disability. Individuals with ASD were at higher risk of having ADHD compared with individuals who did not have ASD (odds ratio (OR)=22.33, 95% confidence interval (CI): 21.77-22.92). The association was stronger for high-functioning than for low-functioning ASD. Relatives of individuals with ASD were at higher risk of ADHD compared with relatives of individuals without ASD. The association was stronger in monozygotic twins (OR=17.77, 95% CI: 9.80-32.22) than in dizygotic twins (OR=4.33, 95% CI: 3.21-5.85) and full siblings (OR=4.59, 95% CI: 4.39-4.80). Individuals with ASD and their relatives are at increased risk of ADHD. The pattern of association across different types of relatives supports the existence of genetic overlap between clinically ascertained ASD and ADHD, suggesting that genomic studies might have underestimated this overlap.

  • 13.
    Kowalec, Kaarina
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada.
    Lu, Yi
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sariaslan, Amir
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Song, Jie
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ploner, Alexander
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Dalman, Christina
    Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
    Hultman, Christina M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sullivan, Patrick F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
    Increased schizophrenia family history burden and reduced premorbid IQ in treatment-resistant schizophrenia: a Swedish National Register and Genomic Study2021In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, p. 4487-4495Article in journal (Refereed)
    Abstract [en]

    A high proportion of those with schizophrenia experience treatment non-response, placing them at higher risk for mortality and suicide attempts, compared to treatment responders. The clinical, social, and economic burden of treatment-resistant schizophrenia (TRS) are substantial. Previous genomic and epidemiological studies of TRS were often limited by sample size or lack of comprehensive genomic data. We aimed to systematically understand the clinical, demographic, and genomic correlates of TRS using epidemiological and genetic epidemiological modelling in a Swedish national population sample (n = 24,706) and then in a subgroup with common variant genetic risk scores, rare copy-number variant burden, and rare exonic burden (n = 4936). Population-based analyses identified increasing schizophrenia family history to be significantly associated with TRS (highest quartile of familial burden vs. lowest: adjusted odds ratio (aOR): 1.31, P = 4.8 × 10-8). In males, a decrease of premorbid IQ of one standard deviation was significantly associated with greater risk of TRS (minimal aOR: 0.94, P = 0.002). In a subset of cases with extensive genomic data, we found no significant association between the genetic risk scores of four psychiatric disorders and two cognitive traits with TRS (schizophrenia genetic risk score: aOR = 1.07, P = 0.067). The association between copy number variant and rare variant burden measures and TRS did not reach the pre-defined statistical significance threshold (all P ≥ 0.005). In conclusion, direct measures of genomic risk were not associated with TRS; however, premorbid IQ in males and schizophrenia family history were significantly correlated with TRS and points to new insights into the architecture of TRS.

  • 14.
    Kuja-Halkola, Ralf
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lind Juto, Kristina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Skoglund, Charlotte
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Rück, Christian
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Mataix-Cols, David
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Pérez-Vigil, Ana
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Larsson, Johan
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Hellner, Clara
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Långström, Niklas
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Petrovic, Predrag
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Do borderline personality disorder and attention-deficit/hyperactivity disorder co-aggregate in families?: A population-based study of 2 million Swedes2021In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, no 1, p. 341-349Article in journal (Refereed)
    Abstract [en]

    Large-scale family studies on the co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of clinically ascertained ADHD and BPD diagnoses using the entire Swedish population. In a register-based cohort design we included individuals born in Sweden 1979-2001, and identified their diagnoses during 1997-2013; in total, 2,113,902 individuals were included in the analyses. We obtained clinical diagnoses of ADHD and BPD from inpatient and outpatient care. Individuals with an ADHD diagnosis had an adjusted (for birth year, sex, and birth order) odds ratio (aOR) of 19.4 (95% confidence interval [95% CI] = 18.6-20.4) of also having a BPD diagnosis, compared to individuals not diagnosed with ADHD. Having a sibling with ADHD also increased the risk for BPD (monozygotic twins, aOR = 11.2, 95% CI = 3.0-42.2; full siblings, aOR = 2.8, 95% CI = 2.6-3.1; maternal half-siblings, aOR = 1.4, 95% CI = 1.2-1.7; paternal half-siblings, aOR = 1.5, 95% CI = 1.3-1.7). Cousins also had an increased risk. The strength of the association between ADHD and BPD was similar in females and males, and full siblings showed similar increased risks regardless of sex. Among both males and females, ADHD and BPD co-occur within individuals and co-aggregate in relatives; the pattern suggests shared genetic factors and no robust evidence for etiologic sex differences was found. Clinicians should be aware of increased risks for BPD in individuals with ADHD and their relatives, and vice versa.

  • 15.
    Leung, Edison
    et al.
    McGovern Medical School, The University of Texas Health Science Center at Houston, Houston TX, USA; Depression Research Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston TX, USA.
    Lau, Ethan W.
    McGovern Medical School, The University of Texas Health Science Center at Houston, Houston TX, USA.
    Liang, Andi
    McGovern Medical School, The University of Texas Health Science Center at Houston, Houston TX, USA.
    de Dios, Constanza
    Depression Research Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston TX, USA.
    Suchting, Robert
    Depression Research Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston TX, USA.
    Östlundh, Linda
    The National Medical Library, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
    Masdeu, Joseph C.
    Houston Methodist Neurological Institute, Houston TX, USA; Weill Cornell Medicine, New York NY, USA.
    Fujita, Masahiro
    Weill Cornell Medicine, New York NY, USA; PET Core Facility, Houston Methodist Research Insitute, Houston TX, USA.
    Sanches, Marsal
    McGovern Medical School, The University of Texas Health Science Center at Houston, Houston TX, USA; Depression Research Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston TX, USA.
    Soares, Jair C.
    McGovern Medical School, The University of Texas Health Science Center at Houston, Houston TX, USA; Depression Research Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston TX, USA.
    Selvaraj, Sudhakar
    McGovern Medical School, The University of Texas Health Science Center at Houston, Houston TX, USA; Depression Research Program, Faillace Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston TX, USA.
    Alterations in brain synaptic proteins and mRNAs in mood disorders: a systematic review and meta-analysis of postmortem brain studies2022In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 27, no 3, p. 1362-1372Article, review/survey (Refereed)
    Abstract [en]

    The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and dysregulation. There are multiple synaptic proteins but three synaptic proteins, namely SNAP-25, PSD-95, and synaptophysin, have been widely studied for their role in synaptic function in human brain postmortem studies in BD and MDD. These studies have yielded contradictory results, possibly due to the small sample size and sourcing material from different cortical regions of the brain. We performed a systematic review and meta-analysis to understand the role of these three synaptic proteins and other synaptic proteins, messenger RNA (mRNA) and their regional localizations in BD and MDD. A systematic literature search was conducted and the review is reported in accordance with the MOOSE Guidelines. Meta-analysis was performed to compare synaptic marker levels between BD/MDD groups and controls separately. 1811 papers were identified in the literature search and screened against the preset inclusion and exclusion criteria. A total of 72 studies were screened in the full text, of which 47 were identified as eligible to be included in the systematic review. 24 of these 47 papers were included in the meta-analysis. The meta-analysis indicated that SNAP-25 protein levels were significantly lower in BD. On average, PSD-95 mRNA levels were lower in BD, and protein levels of SNAP-25, PSD-95, and syntaxin were lower in MDD. Localization analysis showed decreased levels of PSD-95 protein in the frontal cortex. We found specific alterations in synaptic proteins and RNAs in both BD and MDD. The review was prospectively registered online in PROSPERO international prospective register of systematic reviews, registration no. CRD42020196932.

  • 16.
    Li, Yuchen
    et al.
    Mental Health Center, West China Hospital of Sichuan University, Chengdu, China; West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sjölander, Arvid
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Song, Huan
    West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China; Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
    Cnattingius, Sven
    Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Fang, Fang
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Yang, Qian
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    de la Cruz, Lorena Fernández
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Mataix-Cols, David
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
    Brander, Gustaf
    Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
    Li, Jiong
    Department of Clinical Medicine-Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark.
    Zhang, Wei
    Mental Health Center, West China Hospital of Sichuan University, Chengdu, China; West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
    Fall, Katja
    Örebro University, School of Medical Sciences. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
    D'Onofrio, Brian M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Valdimarsdottir, Unnur A.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 4Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland; 3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA.
    Lu, Donghao
    West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 3Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA.
    Associations of parental and perinatal factors with subsequent risk of stress-related disorders: a nationwide cohort study with sibling comparison2022In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 27, p. 1712-1719Article in journal (Refereed)
    Abstract [en]

    Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973-2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity >= 4, mothers with BMI >= 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32-36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.12] and sibling analyses (HR 1.10, 95% CI 1.02-1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.

  • 17.
    Mataix-Cols, D.
    et al.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Frans, E.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Pérez-Vigil, A.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Kuja-Halkola, R.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Gromark, C.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Isomura, K.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Fernández de la Cruz, L.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Serlachius, E.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Leckman, J. F.
    Child Study Center, Yale University School of Medicine, New Haven CT, USA.
    Crowley, J. J.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Departments of Genetics and Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill NC, USA.
    Rück, C.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Almqvist, C.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Lichtenstein, P.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    A total-population multigenerational family clustering study of autoimmune diseases in obsessive-compulsive disorder and Tourette's/chronic tic disorders2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, no 7, p. 1652-1658Article in journal (Refereed)
    Abstract [en]

    The association between obsessive-compulsive disorder (OCD) and Tourette's/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013. The risk of 40 ADs was evaluated in individuals with OCD, individuals with TD/CTD and their first- (siblings, mothers, fathers), second- (half siblings) and third-degree (cousins) relatives, compared with population controls. Individuals with OCD and TD/CTD had increased comorbidity with any AD (43% and 36%, respectively) and many individual ADs. The risk of any AD and several individual ADs was consistently higher among first-degree relatives than among second- and third-degree relatives of OCD and TD/CTD probands. The risk of ADs was very similar in mothers, fathers and siblings of OCD probands, whereas it tended to be higher in mothers and fathers of TD/CTD probands (compared with siblings). The results suggest a familial link between ADs in general (that is, not limited to Streptococcus-related conditions) and both OCD and TD/CTD. Additional mother-specific factors, such as the placental transmission of antibodies, cannot be fully ruled out, particularly in TD/CTD.

  • 18.
    Neumann, Alexander
    et al.
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Küçükali, Fahri
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Bos, Isabelle
    Netherlands Institute for Health Services Research, Utrecht, the Netherlands.
    Vos, Stephanie J. B.
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands.
    Engelborghs, Sebastiaan
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Universitair Ziekenhuis Brussel (UZ Brussel) and Center for Neurosciences (C4N), Vrije Universiteit Brussel (VUB), Brussels, Belgium .
    De Pooter, Tim
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium .
    Joris, Geert
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium .
    De Rijk, Peter
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
    De Roeck, Ellen
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium.
    Tsolaki, Magda
    1st Department of Neurology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Makedonia, Thessaloniki, Greece.
    Verhey, Frans
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands; Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Martinez-Lage, Pablo
    Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Tainta, Mikel
    Center for Research and Advanced Therapies, CITA-Alzheimer Foundation, San Sebastian, Spain.
    Frisoni, Giovanni
    Department of Psychiatry, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland; RCCS Instituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
    Blin, Oliver
    Clinical Pharmacology & Pharmacovigilance Department, Marseille University Hospital, Marseille, France.
    Richardson, Jill
    Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevanage, UK.
    Bordet, Régis
    Neuroscience & Cognition, CHU de Lille, University of Lille, Inserm, France.
    Scheltens, Philip
    Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands.
    Popp, Julius
    Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich, Zürich, Switzerland; Old Age Psychiatry, Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Peyratout, Gwendoline
    Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland.
    Johannsen, Peter
    Clinical Drug Development, Novo Nordisk, Copenhagen, Denmark.
    Frölich, Lutz
    Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
    Vandenberghe, Rik
    Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven, Leuven, Belgium.
    Freund-Levi, Yvonne
    Örebro University, School of Medical Sciences. Center for Alzheimer Research, Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society Karolinska Institute Stockholm Sweden, Stockholm, Sweden.
    Streffer, Johannes
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Lovestone, Simon
    Department of Psychiatry, University of Oxford, Oxford, UK; Janssen Medical Ltd, High Wycombe, UK.
    Legido-Quigley, Cristina
    Steno Diabetes Center, Copenhagen, Denmark; Institute of Pharmaceutical Sciences, King's College London, London, UK.
    Ten Kate, Mara
    Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands; Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
    Barkhof, Frederik
    Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands; Institutes of Neurology and Healthcare Engineering, University College London, London, UK.
    Strazisar, Mojca
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neuromics Support Facility, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; UK Dementia Research Institute, University College London, London, UK; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
    Bertram, Lars
    Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany; Centre for Lifespan Changes in Brain and Cognition, University of Oslo, Oslo, Norway.
    Visser, Pieter Jelle
    Alzheimer Centrum Limburg, Maastricht University, Maastricht, the Netherlands; Alzheimer Center and Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands .
    van Broeckhoven, Christine
    Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; Neurodegenerative Brain Diseases Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
    Sleegers, Kristel
    Complex Genetics of Alzheimer's Disease Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
    Rare variants in IFFO1, DTNB, NLRC3 and SLC22A10 associate with Alzheimer's disease CSF profile of neuronal injury and inflammation2022In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 27, no 4, p. 1990-1999Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease (AD) biomarkers represent several neurodegenerative processes, such as synaptic dysfunction, neuronal inflammation and injury, as well as amyloid pathology. We performed an exome-wide rare variant analysis of six AD biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and Neurogranin) to discover genes associated with these markers. Genetic and biomarker information was available for 480 participants from two studies: EMIF-AD and ADNI. We applied a principal component (PC) analysis to derive biomarkers combinations, which represent statistically independent biological processes. We then tested whether rare variants in 9576 protein-coding genes associate with these PCs using a Meta-SKAT test. We also tested whether the PCs are intermediary to gene effects on AD symptoms with a SMUT test. One PC loaded on NfL and YKL-40, indicators of neuronal injury and inflammation. Four genes were associated with this PC: IFFO1, DTNB, NLRC3, and SLC22A10. Mediation tests suggest, that these genes also affect dementia symptoms via inflammation/injury. We also observed an association between a PC loading on Neurogranin, a marker for synaptic functioning, with GABBR2 and CASZ1, but no mediation effects. The results suggest that rare variants in IFFO1, DTNB, NLRC3, and SLC22A10 heighten susceptibility to neuronal injury and inflammation, potentially by altering cytoskeleton structure and immune activity disinhibition, resulting in an elevated dementia risk. GABBR2 and CASZ1 were associated with synaptic functioning, but mediation analyses suggest that the effect of these two genes on synaptic functioning is not consequential for AD development.

  • 19.
    Pettersson, E.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, P.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden .
    Common psychiatric disorders share the same genetic origin: a multivariate sibling study of the Swedish population2016In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 21, no 5, p. 717-721Article in journal (Refereed)
    Abstract [en]

    Recent studies have shown that different mental-health problems appear to be partly influenced by the same set of genes, which can be summarized by a general genetic factor. To date, such studies have relied on surveys of community-based samples, which could introduce potential biases. The goal of this study was to examine whether a general genetic factor would still emerge when based on a different ascertainment method with different biases from previous studies. We targeted all adults in Sweden (n=3 475 112) using national registers and identified those who had received one or more psychiatric diagnoses after seeking or being forced into mental health care. In order to examine the genetic versus environmental etiology of the general factor, we examined whether participants' full- or half-siblings had also received diagnoses. We focused on eight major psychiatric disorders based on the International Classification of Diseases, including schizophrenia, schizoaffective disorder, bipolar disorder, depression, anxiety, attention-deficit/hyperactivity disorder, alcohol use disorder and drug abuse. In addition, we included convictions of violent crimes. Multivariate analyses demonstrated that a general genetic factor influenced all disorders and convictions of violent crimes, accounting for between 10% (attention-deficit/hyperactivity disorder) and 36% (drug abuse) of the variance of the conditions. Thus, a general genetic factor of psychopathology emerges when based on both surveys as well as national registers, indicating that a set of pleiotropic genes influence a variety of psychiatric disorders.

  • 20.
    Ronald, A.
    et al.
    Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck, University of London, London, UK.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, and Center of Neurodevelopmental Disorders, Karolinska Institutet, Stockholm, Sweden.
    Anckarsäter, H.
    Forensic Psychiatry, Institute of Neuroscience and Physiology, Sahlgren’s Academy, University of Gothenburg, Gothenburg, Sweden.
    Lichtenstein, P.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    A twin study of autism symptoms in Sweden2011In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 16, no 10, p. 1039-1047Article in journal (Refereed)
    Abstract [en]

    This study aimed to identify empirically the number of factors underlying autism symptoms-social impairments, communication impairments, and restricted repetitive behaviors and interests-when assessed in a general population sample. It also investigated to what extent these autism symptoms are caused by the same or different genetic and environmental influences. Autistic symptoms were assessed in a population-based twin cohort of >12,000 (9- and 12-year-old) children by parental interviews. Confirmatory factor analyses, principal component analyses and multivariate structural equation model fitting were carried out. A multiple factor solution was suggested, with nearly all analyses pointing to a three-factor model for both boys and girls and at both ages. A common pathway twin model fit the data best, which showed that there were some underlying common genetic and environmental influences across the different autism dimensions, but also significant specific genetic effects on each symptom type. These results suggest that the autism triad consists of three partly independent dimensions when assessed in the general population, and that these different autism symptoms, to a considerable extent, have partly separate genetic influences. These findings may explain the large number of children who do not meet current criteria for autism but who show some autism symptoms. Molecular genetic research may benefit from taking a symptom-specific approach to finding genes associated with autism.

  • 21.
    Sariaslan, A.
    et al.
    Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fazel, S.
    Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
    Genetic and environmental determinants of violence risk in psychotic disorders: a multivariate quantitative genetic study of 1.8 million Swedish twins and siblings2016In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 21, no 9, p. 1251-1256Article in journal (Refereed)
    Abstract [en]

    Patients diagnosed with psychotic disorders (for example, schizophrenia and bipolar disorder) have elevated risks of committing violent acts, particularly if they are comorbid with substance misuse. Despite recent insights from quantitative and molecular genetic studies demonstrating considerable pleiotropy in the genetic architecture of these phenotypes, there is currently a lack of large-scale studies that have specifically examined the aetiological links between psychotic disorders and violence. Using a sample of all Swedish individuals born between 1958 and 1989 (n=3 332 101), we identified a total of 923 259 twin-sibling pairs. Patients were identified using the National Patient Register using validated algorithms based on International Classification of Diseases (ICD) 8-10. Univariate quantitative genetic models revealed that all phenotypes (schizophrenia, bipolar disorder, substance misuse, and violent crime) were highly heritable (h(2)=53-71%). Multivariate models further revealed that schizophrenia was a stronger predictor of violence (r=0.32; 95% confidence interval: 0.30-0.33) than bipolar disorder (r=0.23; 0.21-0.25), and large proportions (51-67%) of these phenotypic correlations were explained by genetic factors shared between each disorder, substance misuse, and violence. Importantly, we found that genetic influences that were unrelated to substance misuse explained approximately a fifth (21%; 20-22%) of the correlation with violent criminality in bipolar disorder but none of the same correlation in schizophrenia (Pbipolar disorder<0.001; Pschizophrenia=0.55). These findings highlight the problems of not disentangling common and unique sources of covariance across genetically similar phenotypes as the latter sources may include aetiologically important clues. Clinically, these findings underline the importance of assessing risk of different phenotypes together and integrating interventions for psychiatric disorders, substance misuse, and violence.

  • 22.
    Sidorchuk, Anna
    et al.
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Runeson, Bo
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, S:t Görans Hospital, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Rück, Christian
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychological and Brain Science, Indiana University, Bloomington, IN, USA.
    Mataix-Cols, David
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Fernández de la Cruz, Lorena
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Genetic and environmental sources of familial coaggregation of obsessive-compulsive disorder and suicidal behavior: a population-based birth cohort and family study2021In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, no 3, p. 974-985Article in journal (Refereed)
    Abstract [en]

    Obsessive-compulsive disorder (OCD) is associated with high risk of suicide. It is yet unknown whether OCD and suicidal behaviors coaggregate in families and, if so, what are the mechanisms underlying this coaggregation. In a population-based birth cohort and family study, we linked individuals born in Sweden in 1967-2003 (n = 3,594,181) to their parents, siblings, and cousins, and collected register-based diagnoses of OCD, suicide attempts, and deaths by suicide and followed them until December 31, 2013. We also applied quantitative genetic modeling to estimate the contribution of genetic and environmental factors to the familial coaggregation of OCD and suicidal behavior. An elevated risk of suicide attempts was observed across all relatives of individuals with OCD, increasing proportionally to the degree of genetic relatedness, with odds ratios (OR) ranging from 1.56 (95% confidence interval (CI) 1.49-1.63) in parents to 1.11 (95% CI 1.07-1.16) in cousins. The risk of death by suicide also increased alongside narrowing genetic distance, but was only significant in parents (OR 1.55; 95% CI 1.40-1.72) and full siblings (OR 1.80; 95% CI 1.43-2.26) of individuals with OCD. Familial coaggregation of OCD and suicide attempts was explained by additive genetic factors (60.7%) and non-shared environment (40.4%), with negligible contribution of shared environment. Similarly, familial coaggregation with death by suicide was attributed to additive genetics (65.8%) and nonshared environment (34.2%). Collectively, these observations indicate that OCD and suicidal behaviors coaggregate in families largely due to genetic factors. The contribution of unique environment is also considerable, providing opportunities to target high-risk groups for prevention and treatment.

  • 23.
    Tate, Ashley E.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Sahlin, Hanna
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Liu, Shengxin
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Lu, Yi
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Lundström, Sebastian
    Centre for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Gothenburg, Sweden; Gillberg Neuropsychiatry Centre, University of Gothenburg, Gothenburg, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Borderline personality disorder: associations with psychiatric disorders, somatic illnesses, trauma, and adverse behaviors2022In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 27, no 5, p. 2514-2521Article in journal (Refereed)
    Abstract [en]

    In one of the largest, most comprehensive studies on borderline personality disorder (BPD) to date, this article places into context associations between this diagnosis and (1) 16 different psychiatric disorders, (2) eight somatic illnesses, and (3) six trauma and adverse behaviors, e.g., violent crime victimization and self-harm. Second, it examines the sex differences in individuals with BPD and their siblings. A total of 1,969,839 Swedish individuals were identified from national registers. Cumulative incidence with 95% confidence intervals (CI) was evaluated after 5 years of follow-up from BPD diagnosis and compared with a matched cohort. Associations were estimated as hazard ratios (HR) with 95% CIs from Cox regression. 12,175 individuals were diagnosed with BPD (85.3% female). Individuals diagnosed with BPD had higher cumulative incidences and HRs for nearly all analyzed indicators, especially psychiatric disorders. Anxiety disorders were most common (cumulative incidence 95% CI 33.13% [31.48-34.73]). Other notable findings from Cox regressions include psychotic disorders (HR 95% CI 24.48 [23.14-25.90]), epilepsy (3.38 [3.08-3.70]), violent crime victimization (7.65 [7.25-8.06]), and self-harm (17.72 [17.27-18.19]). HRs in males and females with BPD had overlapping CIs for nearly all indicators. This indicates that a BPD diagnosis is a marker of vulnerability for negative events and poor physical and mental health similarly for both males and females. Having a sibling with BPD was associated with an increased risk for psychiatric disorders, trauma, and adverse behaviors but not somatic disorders. Clinical implications include the need for increased support for patients with BPD navigating the health care system.

  • 24.
    Zhang, Ruyue
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsen, Janne Tidselbak
    National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; Centre for Integrated Register-based Research at Aarhus University (CIRRAU), Aarhus, Denmark.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Thornton, Laura
    Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
    Yao, Shuyang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Petersen, Liselotte Vogdrup
    National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
    Bulik, Cynthia M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
    Bergen, Sarah E.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Familial co-aggregation of schizophrenia and eating disorders in Sweden and Denmark2021In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, no 9, p. 5389-5397Article in journal (Refereed)
    Abstract [en]

    Eating disorders and schizophrenia are both moderately to highly heritable and share significant genetic risk despite distinct diagnostic criteria. Large-scale family studies on the co-aggregation of these disorders are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of these disorders within the entire Swedish and Danish population. The proband cohort consisted of individuals born in Sweden (1977-2003) and Denmark (1984-2006) and still residing in their respective country at age six (NSweden = 2,535,191, NDenmark = 1,382,367). Probands were linked to their biological parents, siblings, grandparents, uncles/aunts, and cousins. Diagnoses for anorexia nervosa (AN) and other eating disorders (OED: bulimia nervosa, binge-eating disorder, and eating disorder not otherwise specified) for probands and schizophrenia diagnoses for both probands and relatives were obtained. The likelihood of having schizophrenia in those with AN or OED and their relatives was compared with individuals without eating disorder diagnoses and their relatives. Probands with AN or OED were more likely to have schizophrenia than probands without these disorders. All relatives of probands with AN or OED (except parents and uncles/aunts of probands with AN) were at increased risk of schizophrenia. In general, the magnitude of odds ratios attenuated with decreasing genetic relatedness. These results suggest familial liability contributes to the association between eating disorders and schizophrenia. Clinicians should be mindful of this comorbid and co-aggregation pattern as it may influence case conceptualization and treatment decisions.

1 - 24 of 24
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf