| 1. |
- Henje Blom, Eva, 1962-, et al.
(författare)
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Pro-inflammatory cytokines are elevated in adolescent females with emotional disorders not treated with SSRIs
- 2012
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 136:3, s. 716-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Adults with major depressive disorder (MDD) show elevated levels of IL-6 and TNF-alpha. Studies of adolescents with MDD or anxiety disorders (AD) are few and present conflicting results.METHODS: We studied plasma cytokines in a clinical sample of adolescent females with MDD and/or clinical AD (n=60, mean age 16.8 years), compared to healthy controls (n=44; mean age 16.5 years).RESULTS: The clinical sample showed significantly higher values of IL-2 (Z=-4.09, p>0.0001), IL1-beta (Z=-2.40, p<0.05) and IL-10 (Z=-2.38, p<0.05) as compared to controls. The subgroup of the clinical sample not treated with SSRIs had a significant difference of IL-6 (Z=-2.26, p<0.05) in addition to the difference of IL-2 and IL1-beta, but showed no difference of IL-10 as compared to the controls. SSRI treatment was related to IL-6, explaining 26% of the variance in the clinical sample after controlling for BMI and symptom severity. In the clinical sample, levels of IL-6 and IFN-gamma were positively correlated with self-assessed symptoms of anxiety and/or depression (corr.coeff 0.35 resp 0.40 at p<0.05).LIMITATIONS: The cross-sectional design does not allow for conclusions on causality. The sample sizes were relatively small and a large drop-out in the clinical sample may have influenced the representativity.DISCUSSION: The study suggests that pro-inflammatory cytokines are part of the pathophysiology of emotional disorders in adolescent females and that SSRIs have anti-inflammatory properties. The findings prompt further studies on the specific mechanisms involved and may contribute to the development of more effective treatment and prevention.
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| 2. |
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| 3. |
- Brander, Gustaf, et al.
(författare)
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Association of Perinatal Risk Factors With Obsessive-Compulsive Disorder : A Population-Based Birth Cohort, Sibling Control Study
- 2016
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Ingår i: JAMA psychiatry. - Chicago, USA : American Medical Association. - 2168-6238 .- 2168-622X. ; 73:11, s. 1135-1144
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Perinatal complications may increase the risk of obsessive-compulsive disorder (OCD). Previous reports were based on small, retrospective, specialist clinic-based studies that were unable to rigorously control for unmeasured environmental and genetic confounding.Objective: To prospectively investigate a wide range of potential perinatal risk factors for OCD, controlling for unmeasured factors shared between siblings in the analyses.Design, Setting, and Participants: This population-based birth cohort study included all 2 421 284 children from singleton births in Sweden from January 1, 1973, to December 31, 1996, who were followed up through December 31, 2013. From the 1 403 651 families in the cohort, differentially exposed siblings from the 743 885 families with siblings were evaluated; of these, 11 592 families included clusters of full siblings that were discordant for OCD. Analysis of the data was conducted from January, 26, 2015, to September, 5, 2016.Exposures: Perinatal data were collected from the Swedish Medical Birth Register and included maternal smoking during pregnancy, labor presentation, obstetric delivery, gestational age (for preterm birth), birth weight, birth weight in relation to gestational age, 5-minute Apgar score, and head circumference.Main Outcomes and Measures: Previously validated OCD codes (International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, code F42) in the Swedish National Patient Register.Results: Of 2 421 284 individuals included in the cohort, 17 305 persons were diagnosed with OCD. Of these, 7111 were men (41.1%). The mean (SD) age of individuals at first diagnosis of OCD was 23.4 (6.5) years. An increased risk for OCD remained after controlling for shared familial confounders and measured covariates (including sex, year of birth, maternal and paternal age at birth, and parity), for smoking 10 or more cigarettes per day during pregnancy (hazard ratio [HR], 1.27; 95% CI, 1.02-1.58), breech presentation (HR, 1.35; 95% CI, 1.06-1.71), delivery by cesarean section (HR, 1.17; 95% CI, 1.01-1.34), preterm birth (HR, 1.24; 95% CI, 1.07-1.43), birth weight 1501 to 2500 g (HR, 1.30; 95% CI, 1.05-1.62) and 2501 to 3500 g (HR, 1.08; 95% CI, 1.01-1.16), being large for gestational age (HR, 1.23; 95% CI, 1.05-1.45), and Apgar distress scores at 5 minutes (HR, 1.50; 95% CI, 1.07-2.09). Gestational age and birth weight followed inverse dose-response associations, whereby an increasingly higher risk for OCD was noted in children with a shorter gestational age and lower birth weight. We also observed a dose-response association between the number of perinatal events and increased OCD risk, with HRs ranging from 1.11 (95% CI, 1.07-1.15) for 1 event to 1.51 (95% CI, 1.18-1.94) for 5 or more events.Conclusions and Relevance: A range of perinatal risk factors is associated with a higher risk for OCD independent of shared familial confounders, suggesting that perinatal risk factors may be in the causal pathway to OCD.
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| 4. |
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| 5. |
- Brander, Gustaf, et al.
(författare)
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Perinatal risk factors in Tourette's and chronic tic disorders : a total population sibling comparison study
- 2018
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 23:5, s. 1189-1197
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Butwicka, Agnieszka, et al.
(författare)
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Association of Childhood-Onset Inflammatory Bowel Disease With Risk of Psychiatric Disorders and Suicide Attempt
- 2019
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Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 173:10, s. 969-978
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Inflammatory bowel disease (IBD) has been associated with psychiatric morbidity in adults, although previous studies have not accounted for familial confounding. In children, IBD has an even more severe course, but the association between childhood-onset IBD and psychiatric morbidity remains unclear.Objective: To examine the risk of psychiatric morbidity in individuals with childhood-onset IBD, controlling for potential confounding shared between siblings.Design, Setting, and Participants: A population-based cohort study was conducted using data from the Swedish national health care and population registers of all children younger than 18 years born from 1973 to 2013. The study included 6464 individuals with a diagnosis of childhood-onset IBD (3228 with ulcerative colitis, 2536 with Crohn disease, and 700 with IBD unclassified) who were compared with 323 200 matched reference individuals from the general population and 6999 siblings of patients with IBD. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% CIs. Statistical analysis was performed from January 1, 1973, to December 1, 2013.Main Outcomes and Measures: The primary outcome was any psychiatric disorder and suicide attempt. Secondary outcomes were the following specific psychiatric disorders: psychotic, mood, anxiety, eating, personality, and behavioral disorders; substance misuse; attention-deficit/hyperactivity disorder; autism spectrum disorders; and intellectual disability.Results: The study included 6464 individuals with a diagnosis of childhood-onset IBD (2831 girls and 3633 boys; mean [SD] age at diagnosis of IBD, 13 [4] years). During a median follow-up time of 9 years, 1117 individuals with IBD (17.3%) received a diagnosis of any psychiatric disorder (incidence rate, 17.1 per 1000 person-years), compared with 38 044 of 323 200 individuals (11.8%) in the general population (incidence rate, 11.2 per 1000 person-years), corresponding to an HR of 1.6 (95% CI, 1.5-1.7), equaling 1 extra case of any psychiatric disorder per 170 person-years. Inflammatory bowel disease was significantly associated with suicide attempt (HR, 1.4; 95% CI, 1.2-1.7) as well as mood disorders (HR, 1.6; 95% CI, 1.4-1.7), anxiety disorders (HR, 1.9; 95% CI, 1.7-2.0) eating disorders (HR, 1.6; 95% CI, 1.3-2.0), personality disorders (HR, 1.4; 95% CI, 1.1-1.8), attention-deficit/hyperactivity disorder (HR, 1.2; 95% CI, 1.1-1.4), and autism spectrum disorders (HR, 1.4; 95% CI, 1.1-1.7) Results were similar for boys and girls. Hazard ratios for any psychiatric disorder were highest in the first year of follow-up but remained statistically significant after more than 5 years. Psychiatric disorders were particularly common for patients with very early-onset IBD (<6 years) and for patients with a parental psychiatric history. Results were largely confirmed by sibling comparison, with similar estimates noted for any psychiatric disorder (HR, 1.6; 95% CI, 1.5-1.8) and suicide attempt (HR, 1.7; 95% CI, 1.2-2.3).Conclusions and Relevance: Overall, childhood-onset IBD was associated with psychiatric morbidity, confirmed by between-sibling results. Particularly concerning is the increased risk of suicide attempt, suggesting that long-term psychological support be considered for patients with childhood-onset IBD.
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| 7. |
- Andren, Per, et al.
(författare)
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Efficacy and cost-effectiveness of therapist-guided internet-delivered behaviour therapy for children and adolescents with Tourette syndrome : study protocol for a single-blind randomised controlled trial
- 2021
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Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Treatment guidelines recommend behaviour therapy (BT) for patients with Tourette syndrome (TS) and chronic tic disorder (CTD). However, BT is rarely accessible due to limited availability of trained therapists and long travel distances to specialist clinics. Internet-delivered BT has the potential of overcoming these barriers through remote delivery of treatment with minimal therapist support. In the current protocol, we outline the design and methods of a randomised controlled trial (RCT) evaluating an internet-delivered BT programme referred to as BIP TIC. The trial's primary objective is to determine the clinical efficacy of BIP TIC for reducing tic severity in young people with TS/CTD, compared with an active control intervention. Secondary objectives are to investigate the 12-month durability of the treatment effects and to perform a health economic evaluation of the intervention.Methods: In this single-blind superiority RCT, 220 participants (9-17 years) with TS/CTD throughout Sweden will be randomised to 10-12 weeks of either therapist-supported internet-delivered BT based on exposure with response prevention (BIP TIC) or therapist-supported internet-delivered education. Data will be collected at baseline, 3 and 5 weeks into the treatment, at post-treatment, and 3, 6, and 12 months post-treatment. The primary endpoint is the 3-month follow-up. The primary outcome is tic severity as measured by the Yale Global Tic Severity Scale - Total Tic Severity Score. Treatment response is operationalised as scores of "Very much improved" or "Much improved" on the Clinical Global Impression - Improvement scale, administered at the primary endpoint. Outcome assessors will be blind to treatment condition at all assessment points. A health economic evaluation of BIP TIC will be performed, both in the short term (primary endpoint) and the long term (12-month follow-up). There are no planned interim analyses.Discussion: Participant recruitment started on 26 April 2019 and finished on 9 April 2021. The total number of included participants was 221. The final participant is expected to reach the primary endpoint in September 2021 and the 12-month follow-up in June 2022. Data analysis for the primary objective will commence after the last participant reaches the primary endpoint.
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| 8. |
- Andrén, Per, et al.
(författare)
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Evaluating care pathways for pediatric anxiety disorders: Study protocol for a pilot randomized controlled trial of stepped care vs stratified care.
- 2023
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Konferensbidrag (refereegranskat)abstract
- Introduction: Anxiety disorders are common and debilitating in children and adolescents. Cognitive behavioral therapy (CBT), delivered both in-person and by the internet (ICBT), is efficacious, but access for young individuals is limited and it remains unclear how to structure the care pathway to maximize benefit.Methods: To inform a fully powered randomized controlled trial (RCT), a pilot RCT will be conducted where 50 youth with anxiety disorders are randomized to one out of two care pathways: stepped care or stratified care. Both pathways consist of up to two courses (A and B) of evidence-based treatment (12 weeks of either ICBT or in-person CBT). The two treatments share the same basic components (e.g., psychoeducation, exposure) but differ in their format of delivery, with in-person CBT enabling higher personalization and therapist-involvement, but to a higher cost. In stepped care, all participants are offered ICBT in course A and treatment non-responders are offered in-person CBT in course B. In stratified care, those with the highest risk of treatment non-response are offered in-person CBT in course A (~50%), while the other half are offered ICBT. As in stepped care, non-responders in stratified care are offered in-person CBT in course B. The primary endpoint is the outcome assessment after course B. The objectives of the pilot are to examine the feasibility, acceptability, and safety of the study procedures.Time plan: Recruitment for the study will begin in August 2023 and the final participant is expected to reach the primary endpoint in August 2024.
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| 9. |
- Andrén, Per, et al.
(författare)
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Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome : 12-Month Follow-Up of a Randomized Clinical Trial
- 2024
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain.OBJECTIVE: To investigate the long-term efficacy and cost-effectiveness of therapist-supported, internet-delivered exposure and response prevention (ERP) vs psychoeducation for youths with TS or CTD.DESIGN, SETTING, AND PARTICIPANTS: This 12-month controlled follow-up of a parallel group, superiority randomized clinical trial was conducted at a research clinic in Stockholm, Sweden, with nationwide recruitment. In total, 221 participants aged 9 to 17 years with TS or CTD were enrolled between April 26, 2019, and April 9, 2021, of whom 208 (94%) provided 12-month follow-up data. Final follow-up data were collected on June 29, 2022. Outcome assessors were masked to treatment allocation throughout the study.INTERVENTIONS: A total of 111 participants were originally randomly allocated to 10 weeks of therapist-supported, internet-delivered ERP and 110 participants to therapist-supported, internet-delivered psychoeducation.MAIN OUTCOMES AND MEASURES: The primary outcome was within-group change in tic severity, measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS), from the 3-month follow-up to the 12-month follow-up. Treatment response was defined as 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement scale. Analyses were intention-to-treat and followed the plan prespecified in the published study protocol. A health economic evaluation was performed from 3 perspectives: health care organization (including direct costs for treatment provided in the study), health care sector (additionally including health care resource use outside of the study), and societal (additionally including costs beyond health care [eg, parent's absenteeism from work]).RESULTS: In total, 221 participants were recruited (mean [SD] age, 12.1 [2.3] years; 152 [69%] male). According to the YGTSS-TTSS, there were no statistically significant changes in tic severity from the 3-month to the 12-month follow-up in either group (ERP coefficient, -0.52 [95% CI, -1.26 to 0.21]; P = .16; psychoeducation coefficient, 0.00 [95% CI, -0.78 to 0.78]; P > .99). A secondary analysis including all assessment points (baseline to 12-month follow-up) showed no statistically significant between-group difference in tic severity from baseline to the 12-month follow-up (coefficient, -0.38 [95% CI, -1.11 to 0.35]; P = .30). Treatment response rates were similar in both groups (55% in ERP and 50% in psychoeducation; odds ratio, 1.25 [95% CI, 0.73-2.16]; P = .42) at the 12-month follow-up. The health economic evaluation showed that, from a health care sector perspective, ERP produced more quality-adjusted life years (0.01 [95% CI, -0.01 to 0.03]) and lower costs (adjusted mean difference -$84.48 [95% CI, -$440.20 to $977.60]) than psychoeducation at the 12-month follow-up. From the health care organization and societal perspectives, ERP produced more quality-adjusted life years at higher costs, with 65% to 78% probability of ERP being cost-effective compared with psychoeducation when using a willingness-to-pay threshold of US $79 000.CONCLUSIONS AND RELEVANCE: There were no statistically significant changes in tic severity from the 3-month through to the 12-month follow-up in either group. The ERP intervention was not superior to psychoeducation at any time point. While ERP was not superior to psychoeducation alone in reducing tic severity at the end of the follow-up period, ERP is recommended for clinical implementation due to its likely cost-effectiveness and support from previous literature.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03916055.
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| 10. |
- Andrén, Per, et al.
(författare)
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Therapist-Supported Internet-Delivered Exposure and Response Prevention for Children and Adolescents with Tourette Syndrome : A Randomized Clinical Trial
- 2022
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The availability of behavior therapy for individuals with Tourette syndrome (TS) and chronic tic disorder (CTD) is limited.OBJECTIVE: To determine the efficacy and cost-effectiveness of internet-delivered exposure and response prevention (ERP) for children and adolescents with TS or CTD.DESIGN, SETTING, AND PARTICIPANTS: This single-masked, parallel group, superiority randomized clinical trial with nationwide recruitment was conducted at a research clinic in Stockholm, Sweden. Out of 615 individuals assessed for eligibility, 221 participants meeting diagnostic criteria for TS or CTD and aged 9 to 17 years were included in the study. Enrollment began in April 2019 and ended in April 2021. Data were analyzed between October 2021 and March 2022.INTERVENTIONS: Participants were randomized to 10 weeks of therapist-supported internet-delivered ERP for tics (111 participants) or to therapist-supported internet-delivered education for tics (comparator group, 110 participants).MAIN OUTCOMES AND MEASURES: The primary outcome was change in tic severity from baseline to the 3-month follow-up as measured by the Total Tic Severity Score of the Yale Global Tic Severity Scale (YGTSS-TTSS). YGTSS-TTSS assessors were masked to treatment allocation. Treatment response was operationalized as a score of 1 ("Very much improved") or 2 ("Much improved") on the Clinical Global Impression-Improvement scale.RESULTS: Data loss was minimal, with 216 of 221 participants (97.7%) providing primary outcome data. Among randomized participants (152 [68.8%] boys; mean [SD] age, 12.1 [2.3] years), tic severity improved significantly, with a mean reduction of 6.08 points on the YGTSS-TTSS in the ERP group (mean [SD] at baseline, 22.25 [5.60]; at 3-month follow-up, 16.17 [6.82]) and 5.29 in the comparator (mean [SD] at baseline, 23.01 [5.92]; at 3-month follow-up, 17.72 [7.11]). Intention-to-treat analyses showed that the 2 groups improved similarly over time (interaction effect, -0.53; 95% CI, -1.28 to 0.22; P = .17). Significantly more participants were classified as treatment responders in the ERP group (51 of 108 [47.2%]) than in the comparator group (31 of 108 [28.7%]) at the 3-month follow-up (odds ratio, 2.22; 95% CI, 1.27 to 3.90). ERP resulted in more treatment responders at little additional cost compared with structured education. The incremental cost per quality-adjusted life-year gained was below the Swedish willingness-to-pay threshold, at which ERP had a 66% to 76% probability of being cost-effective.CONCLUSIONS AND RELEVANCE: Both interventions were associated with clinically meaningful improvements in tic severity, but ERP led to higher response rates at little additional cost.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03916055.
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