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  • 1.
    Alaie, Iman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Philipson, Anna
    Orebro Univ, Univ Hlth Care Res Ctr, Fac Med & Hlth, Orebro, Sweden.
    Ssegonja, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social medicine/CHAP.
    Hagberg, Lars
    Orebro Univ, Univ Hlth Care Res Ctr, Fac Med & Hlth, Orebro, Sweden.
    Feldman, Inna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social medicine/CHAP.
    Sampaio, Filipa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social medicine/CHAP.
    Moller, Margareta
    Orebro Univ, Univ Hlth Care Res Ctr, Fac Med & Hlth, Orebro, Sweden.
    Arinell, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Päären, Aivar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    von Knorring, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Olsson, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    von Knorring, Anne-Liis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Bohman, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Jonsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry. Karolinska Inst, Karolinska Inst KIND, Dept Womens & Childrens Hlth, Ctr Neurodev Disorders,Pediat Neuropsychiat Unit, Stockholm, Sweden;Stockholm Cty Council, Stockholm Hlth Care Serv, Ctr Psychiat Res, Stockholm, Sweden.
    Uppsala Longitudinal Adolescent Depression Study (ULADS)2019In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, no 3, article id e024939Article in journal (Refereed)
    Abstract [en]

    Purpose: To present the Uppsala Longitudinal Adolescent Depression Study, initiated in Uppsala, Sweden, in the early 1990s. The initial aim of this epidemiological investigation was to study the prevalence, characteristics and correlates of adolescent depression, and has subsequently expanded to include a broad range of social, economic and health-related long-term outcomes and cost-of-illness analyses.

    Participants: The source population was first-year students (aged 16-17) in upper-secondary schools in Uppsala during 1991-1992, of which 2300 (93%) were screened for depression. Adolescents with positive screening and sex/age-matched peers were invited to a comprehensive assessment. A total of 631 adolescents (78% females) completed this assessment, and 409 subsequently completed a 15year follow-up assessment. At both occasions, extensive information was collected on mental disorders, personality and psychosocial situation. Detailed social, economic and health-related data from 1993 onwards have recently been obtained from the Swedish national registries for 576 of the original participants and an age-matched reference population (N=200 000).

    Findings to date: The adolescent lifetime prevalence of a major depressive episode was estimated to be 11.4%. Recurrence in young adulthood was reported by the majority, with a particularly poor prognosis for those with a persistent depressive disorder or multiple somatic symptoms. Adolescent depression was also associated with an increased risk of other adversities in adulthood, including additional mental health conditions, low educational attainment and problems related to intimate relationships.

    Future plans: Longitudinal studies of adolescent depression are rare and must be responsibly managed and utilised. We therefore intend to follow the cohort continuously by means of registries. Currently, the participants are approaching mid-adulthood. At this stage, we are focusing on the overall long-term burden of adolescent depression. For this purpose, the research group has incorporated expertise in health economics. We would also welcome extended collaboration with researchers managing similar datasets.

  • 2.
    Brenner, Philip
    et al.
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Brandt, Lena
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Li, Gang
    Janssen Res & Dev LLC, Titusville, NJ USA.
    DiBernardo, Allitia
    Janssen Res & Dev LLC, Titusville, NJ USA.
    Bodén, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry. Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Reutfors, Johan
    Karolinska Inst, Dept Med Solna, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Treatment-resistant depression as risk factor for substance use disorders: a nation-wide register-based cohort study2019In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 114, no 7, p. 1274-1282Article in journal (Refereed)
    Abstract [en]

    Background and aims Treatment-resistant depression (TRD) is common among patients with major depressive disorder (MDD). MDD may increase the risk for developing substance use disorders (SUD). The aim of this study was to investigate the risk for developing SUD among patients with TRD compared with other depressed patients.

    Design Observational cohort study.

    Setting Nation-wide governmental health registers in Sweden.

    Participants All patients aged 18-69 years with an MDD diagnosis in specialized health care who had received at least one antidepressant prescription during 2006-14 were identified. Patients with at least three treatment trials within a single depressive episode were classified with TRD.

    Measurements Patients with TRD were compared with the whole MDD cohort regarding risk for obtaining a SUD diagnosis or medication using survival analyses adjusted for socio-demographics and comorbidities.

    Findings Of 121 669 MDD patients, 13% were classified with TRD. Among the patients without any history of SUD, patients with TRD had a risk increase for any SUD both ≤ 1 and > 1 year after antidepressant initiation [> 1 year hazard ratio (HR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Risks were elevated for the subcategories of opioid (HR = 1.9, 95% CI = 1.4-2.5) and sedative SUD (HR = 2.7, 95% CI = 2.2-3.2). Patients with a history of SUD had a risk increase for any SUD ≤ 1 year after start of treatment (HR = 1.2, 95% CI = 1.1-1.4), and both ≤ 1 year and > 1 year for sedative (> 1 year HR = 2.0, 95% CI = 1.3-3.0) and multiple substance SUD (HR = 1.9, 95% CI = 1.4-2.5).

    Conclusions Patients with treatment-resistant depression may be at greater risk for substance use disorders compared with other patients with major depressive disorder. Patterns may differ for patients with and without a history of substance use disorders, and for different categories of substance use disorder.

  • 3. Lööf, Måns
    et al.
    Meyer, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Isaksson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    SKILLS – A PSYCHOEDUCATIONAL GROUP PROGRAM FOR ADOLESCENTS WITH ADHD2018In: Journal of the American Academy of Child and Adolescent Psychiatry, 2018, Vol. 57Conference paper (Refereed)
  • 4.
    Szalisznyo, Krisztina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry. Hungarian Acad Sci Budapest, Computat Neurosci Grp, Wigner Res Inst, Budapest, Hungary.
    Silverstein, David
    KTH Royal Inst Technol, Dept Computat Sci & Technol, Stockholm, Sweden.
    Tóth, János
    Budapest Univ Technol & Econ, Dept Math Anal, Budapest, Hungary.
    Neural dynamics in co-morbid schizophrenia and OCD: A computational approach2019In: Journal of Theoretical Biology, ISSN 0022-5193, E-ISSN 1095-8541, Vol. 473, p. 80-94Article in journal (Refereed)
    Abstract [en]

    The co-morbidity of obsessive-compulsive disorder (OCD) and schizophrenia is higher than what would be expected by chance and the common underlying neuropathophysiology is not well understood. Repetitive stereotypes and routines can be caused by perseverative thoughts and motor sequences in both of these disorders. We extended a previously published computational model to investigate cortico-striatal network dynamics. Given the considerable overlap in symptom phenomenology and the high degree of co-morbidity between OCD and schizophrenia, we examined the dynamical consequences of functional connectivity variations in the overlapping network. This was achieved by focusing on the emergence of network oscillatory activity and examining parameter sensitivity. Opposing activity levels are present in orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) in schizophrenia and OCD. We found that with over-compensation of the primary pathology, emergence of the other disorder can occur. The oscillatory behavior is delicately modulated by connections between the OFC/ACC to the ventral and dorsal striatum and by the coupling between the ACC and dorsolateral prefrontal cortex (DLPFC). Modulation on cortical self-inhibition (e.g. serotonin reuptake inhibitor treatment) together with dopaminergic input to the striatum (e.g. anti-dopaminergic medication) has non-trivial complex effects on the network oscillatory behavior, with an optimal modulatory window. Additionally, there are several disruption mechanisms and compensatory processes in the cortico-striato-thalamic network which may contribute to the underlying neuropathophysiology and clinical heterogeneity in schizo-obsessive spectrum disorders. Our mechanistic model predicts that dynamic over-compensation of the primarily occuring neuropathophysiology can lead to the secondary co-morbid disease.

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