Real-world effectiveness of HPV vaccination against cervical neoplasia among birth cohorts ineligible for routine vaccination.

Human papillomavirus (HPV) vaccine effectiveness may differ between settings. Here we present the first real-world effectiveness study of HPV vaccination on high-grade cervical lesions from Norway, among women who received HPV vaccine outside the routine program. We performed an observational study of all Norwegian women born 1975 to 1996 and retrieved individual data from nationwide registries on HPV vaccination status and incidence of histologically verified high-grade cervical neoplasia during 2006 to 2016. We estimated the incidence rate ratio (IRR) and 95% confidence intervals (CI) for vaccination vs no vaccination by Poisson regression stratified by age at vaccination <20 years and ≥20 years. The cohort consisted of 832 732 women, of which 46 381 (5.6%) received at least one dose of HPV vaccine by the end of 2016. The incidence rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) increased with age regardless of vaccination status and was highest at age 25 to 29, at 637/100 000 among unvaccinated women, 487/100 000 among women vaccinated before age 20 and 831/100 000 among women vaccinated at age 20 or older. The adjusted IRR of CIN2+ between vaccinated and unvaccinated women was 0.62 (95% CI: 0.46-0.84) for women vaccinated below age 20, and 1.22 (95% CI: 1.03-1.43) for women vaccinated at age 20 or older. These findings indicate that HPV vaccination among women too old to be eligible for routine HPV vaccination is effective among women who are vaccinated below age 20 but may not have the desired impact among women who are vaccinated at age 20 or older.

Can cognitive inflexibility reduce symptoms of anxiety and depression? Promoting the structural nested mean model in psychotherapy research.

OBJECTIVE: To estimate the causal effect of executive functioning on the remission of depression and anxiety symptoms in an observational dataset from a vocational rehabilitation program. It is also an aim to promote a method from the causal inference literature and to illustrate its value in this setting. METHOD: With longitudinal (four-time points over 13 months) data from four independent sites, we compiled a dataset with 390 participants. At each time point, participants were tested on executive function and self-reported symptoms of anxiety and depression. We used g-estimation to evaluate whether objectively tested cognitive flexibility affected depressive/anxious symptoms and tested for moderation. Multiple imputations were used to handle missing data. RESULTS: The g-estimation showed a strong causal effect of cognitive inflexibility reducing depression and anxiety and modified by education level. In a counterfactual framework, a hypothetical intervention that could lower cognitive flexibility seemed to cause improvement in mental distress at the subsequent time-point (negative sign) for low education. The less flexibility, the larger improvement. For high education, the same but weaker effect was found, with a change in sign, negative during the intervention and positive during follow-up. DISCUSSION: An unexpected and strong effect was found from cognitive inflexibility on symptom improvement. This study demonstrates how to estimate causal psychological effects with standard software in an observational dataset with substantial missing and shows the value of such methods.

Is age of self-harm onset associated with increased frequency of non-suicidal self-injury and suicide attempts in adolescent outpatients?

BACKGROUND: Self-harm in adolescents is an increasing public health concern and an important risk factor for suicide. We aimed to examine how age of self-harm onset in adolescents was associated with frequency of subsequent suicidal and non-suicidal self-harm (NSSI) episodes, and how age of onset and duration of self-harm may influence the frequency of self-harm. METHODS: Data from 103 adolescents with recurrent self-harm recruited from child and adolescent psychiatric outpatient clinics were collected through clinical interviews and self-reports, and analysed with negative binomial and hurdle models. RESULTS: A lower age of self-harm onset and a longer duration of self-harm were both significantly associated with increased frequency of subsequent episodes of NSSI and risk of a first suicide attempt. There was an increase in repeated suicide attempts when the age of onset of self-harm decreased and the duration increased, and dramatically more for long duration of NSSI before first suicide attempt. CONCLUSION: Initiating self-harm behaviour at the youngest age had the highest risk of increased frequency of NSSI and suicide attempts. Longer duration of self-harm behaviour increased this risk. This underlines the importance of early identification of self-harm behaviour in adolescents, and the use of effective interventions.

G-estimation of causal pathways in vocational rehabilitation for adults with psychotic disorders - a secondary analysis of a randomized trial.

BACKGROUND: Vocational rehabilitation (VR) has increasingly become an important intervention targeting poor occupational functioning in schizophrenia. The Norwegian Job Management Program (JUMP), sought to enhance occupational outcomes by augmenting VR with either cognitive behavioral therapy (CBT) techniques aiming to improve psychotic symptoms or cognitive remediation (CR) aiming to improve cognition. CBT is standard treatment in schizophrenia, but recent meta-analyses question the effect of CBT on negative psychotic symptoms. It is of interest to study the causal role of psychotic symptoms and cognitive functioning on occupational functioning. METHODS: Data from the JUMP VR - program, was reanalyzed with a causal inference method to assess the causal effects of reduced symptoms / improved neurocognitive functioning on occupational functioning measured by number of working hours per week. Participants (N = 131) had been randomized to either VR + CBT (N = 68) or VR + CR (N = 63). Large improvements in number of working hours were demonstrated in both intervention groups (nonsignificant group difference). G-estimation was used to assess the strength and nature of the causal effects, adjusted for time-varying confounding and selection - bias from loss to follow-up. RESULTS: Significant causal effects of reduction in each of four dimensions of symptoms and improved neurocognition respectively, on number of working hours were found (separate models). The effect of negative symptoms was the strongest and increased in magnitude during the whole observation period, while the effect of two other symptoms and neurocognition was constant. Adjusted for confounding (including potential feedback), the causal effect of a hypothetical change in negative symptoms equal to the average improvement in the CBT group corresponded to an increase in working hours of 3.2 h per week (95% CI: 1.11, 5.35). CONCLUSION: High performance of g-estimation in a small psychiatric data set with few repeated measures and time-varying confounding and effects, was demonstrated. Augmented vocational rehabilitation showed causal effects of intervention targets with the strongest and increasing effect from negative symptoms on number of working hours. Combination of therapy and activation (indirect and direct approach) might explain improvement in both cognition and negative symptoms, and shed some light on effective ingredients for improved treatment of negative symptoms.

Personal and provider level factors influence participation to cervical cancer screening: A retrospective register-based study of 1.3 million women in Norway.

High coverage is essential for an effective screening programme. Here we present screening barriers and facilitators among 1.3 million women aged 25-69years eligible for screening within the Norwegian Cervical Cancer Screening Program (NCCSP). We defined non-adherence as no screening test in 2008-2012. We divided adherent women into those screened spontaneously, and those who had a smear after receiving a reminder from the NCCSP. Explanatory variables were extracted from several nationwide registers, and modelled by modified Poisson regression. In total, 34% of women were non-adherent. 31% of native Norwegians were non-adherent, compared to 50% of immigrants. Immigrant status was a strong predictor of non-adherence, but the vast majority of non-adherent women were still native Norwegians. Higher non-adherence rates were associated with having a male general practitioner (GP), a foreign GP, a young GP, and distance to the screening site. Being unmarried, having no children, having lower socioeconomic position and region of residence predicted non-adherence and, to a smaller extent, reminded adherence to screening. In contrast, previous experience with cervical abnormalities substantially increased adherence to screening. The population-based screening programme promotes equity by recruiting women who are less likely to participate spontaneously. However, socioeconomic disparities were evident in a country with a nationwide programme and a policy of equal access to health care. Initiatives aimed at removing practical and financial barriers to equitable screening delivery and at reducing the effect of sociodemographic attributes on screening participation are needed.

Contours of a causal feedback mechanism between adaptive personality and psychosocial function in patients with personality disorders: a secondary analysis from a randomized clinical trial.

BACKGROUND: Patients with personality disorders commonly exhibit impairment in psychosocial function that persists over time even with diagnostic remission. Further causal knowledge may help to identify and assess factors with a potential to alleviate this impairment. Psychosocial function is associated with personality functioning which describes personality disorder severity in DSM-5 (section III) and which can reportedly be improved by therapy. METHODS: The reciprocal association between personality functioning and psychosocial function was assessed, in 113 patients with different personality disorders, in a secondary longitudinal analysis of data from a randomized clinical trial, over six years. Personality functioning was represented by three domains of the Severity Indices of Personality Problems: Relational Capacity, Identity Integration, and Self-control. Psychosocial function was measured by Global Assessment of Functioning. The marginal structural model was used for estimation of causal effects of the three personality functioning domains on psychosocial function, and vice versa. The attractiveness of this model lies in the ability to assess an effect of a time - varying exposure on an outcome, while adjusting for time - varying confounding. RESULTS: Strong causal effects were found. A hypothetical intervention to increase Relational Capacity by one standard deviation, both at one and two time-points prior to assessment of psychosocial function, would increase psychosocial function by 3.5 standard deviations (95% CI: 2.0, 4.96). Significant effects of Identity Integration and Self-control on psychosocial function, and from psychosocial function on all three domains of personality functioning, although weaker, were also found. CONCLUSION: This study indicates that persistent impairment in psychosocial function can be addressed through a causal pathway of personality functioning, with interventions of at least 18 months duration.

Vocational rehabilitation for adults with psychotic disorders in a Scandinavian welfare society.

BACKGROUND: This study examined the outcomes of a vocational rehabilitation program (The Job Management Program, JUMP) for persons with psychotic disorders based on close collaboration between health and welfare services. METHODS: Participants (N = 148) with broad schizophrenia spectrum disorders (age 18-65) were recruited from six counties in Norway. Three counties were randomized to vocational rehabilitation augmented with cognitive behaviour therapy (CBT), while the remaining three counties were randomized to vocational rehabilitation augmented with cognitive remediation (CR). This paper compares the vocational activity of the total group of JUMP participants with a treatment as usual group (N = 341), and further examines differences between the two JUMP interventions. Employment status (working/not working) was registered at the time of inclusion and at the end of the intervention period. RESULTS: The total number of JUMP participants in any kind of vocational activity increased from 17 to 77% during the intervention. Of these, 8% had competitive employment, 36% had work placements in ordinary workplaces with social security benefits as their income, and 33% had sheltered work. The total number of working participants in the TAU group increased from 15.5 to 18.2%. The JUMP group showed significant improvements of positive (t = -2.33, p = 0.02) and general (t = -2.75, p = 0.007) symptoms of psychosis. Significant differences between the CBT and CR interventions were not demonstrated. CONCLUSIONS: The study supports existing evidence that the majority of persons with broad schizophrenia spectrum disorders can cope with some kind of work, given that internal and external barriers are reduced. Those who wish to work should be offered vocational rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01139502 . Registered on 6 February 2010.

Employment outcome and predictors of competitive employment at 2-year follow-up of a vocational rehabilitation programme for individuals with schizophrenia in a high-income welfare society.

BACKGROUND: Employment is an important part of recovery for individuals with schizophrenia. The employment rate for this group is as low as 10% in Norway, and major system related barriers to employment are evident. AIMS: This study reports the competitive employment outcome at 2-year follow-up of a vocational rehabilitation study augmented with cognitive remediation (CR) or elements from cognitive behaviour therapy (CBT) for individuals with schizophrenia spectrum disorders. It also investigates if global functioning, self-esteem, and depression at baseline predicts employment outcome, and if change in these variables during the intervention period is associated with employment outcome. METHOD: One hundred and forty-eight participants with schizophrenia spectrum disorders in six Norwegian counties received 10 months vocational rehabilitation augmented with either CBT (n = 84) or CR (n = 64). Both competitive and sheltered workplaces were used. Participants were assessed at baseline, at the end of the intervention period, and at 2-year follow-up. RESULTS: At 2-year follow-up, 21.2% had obtained competitive employment. A further 25.3% had work placements in competitive workplaces. Significant improvements were found in global functioning, self-esteem, and depression during the intervention period, but no significant differences between the two intervention groups. High baseline global functioning and self-esteem, as well as positive change in these variables during the intervention period, were significantly associated with higher competitive employment outcome at 2-year follow-up. CONCLUSION: The results add to existing evidence that competitive employment is attainable for individuals with schizophrenia. High global functioning and self-esteem were strongly associated with competitive employment outcome.

Step-down versus outpatient psychotherapeutic treatment for personality disorders: 6-year follow-up of the Ullevål personality project.

BACKGROUND: Although psychotherapy is considered the treatment of choice for patients with personality disorders (PDs), there is no consensus about the optimal level of care for this group of patients. This study reports the results from the 6-year follow-up of the Ullevål Personality Project (UPP), a randomized clinical trial comparing outpatient individual psychotherapy with a long-term step-down treatment program that included a short-term day hospital treatment followed by combined group and individual psychotherapy. METHODS: The UPP included 113 patients with PDs. Outcome was evaluated after 8 months, 18 months, 3 years and 6 years and was based on a wide range of clinical measures, such as psychosocial functioning, interpersonal problems, symptom severity, and axis I and II diagnoses. RESULTS: At the 6-year follow-up, there were no statistically significant differences in outcome between the treatment groups. Effect sizes ranged from medium to large for all outcome variables in both treatment arms. However, patients in the outpatient group had a marked decline in psychosocial functioning during the period between the 3- and 6-year follow-ups; while psychosocial functioning continued to improve in the step-down group during the same period. This difference between groups was statistically significant. CONCLUSIONS: The findings suggest that both hospital-based long-term step-down treatment and long-term outpatient individual psychotherapy may improve symptoms and psychosocial functioning in poorly functioning PD patients. Social and interpersonal functioning continued to improve in the step-down group during the post-treatment phase, indicating that longer-term changes were stimulated during treatment. TRIAL REGISTRATION: NCT00378248.

Trajectories and Predictors of Change in Emotion Dysregulation and Deliberate Self-Harm Amongst Adolescents with Borderline Features.

BACKGROUND: Deliberate self-harm (DSH) and emotion dysregulation (ED) peaks in adolescence, and is associated with an increased risk of psychopathology, suicide and lower functioning in adulthood. DBT-A has been established as an effective treatment for reducing DSH, however less is known about changes in emotion dysregulation. This study aimed to identify baseline predictors of treatment response in outcome trajectories of DSH and emotion dysregulation. METHODS: Response trajectories of DSH and ED were investigated using Latent Class Analysis on RCT data comparing DBT-A and EUC for 77 adolescents treated for deliberate self-harm and borderline traits. Logistic regression analysis was used to examine baseline predictors. RESULTS: Two-class solutions were selected for both indicators, distinguishing between early and late responders in DSH, and responders and non-responders in ED. Higher levels of depression, shorter DSH histories and not receiving DBT-A predicted less favourable response in DSH, while DBT-A was the only predictor of treatment response in ED. CONCLUSIONS: DBT-A was associated with a significantly faster reduction of deliberate self-harm in the short-term and improved emotion regulation in the long-term.

Patterns of childhood adverse events are associated with clinical characteristics of bipolar disorder.

BACKGROUND: Previous studies in bipolar disorder investigating childhood trauma and clinical presentations of the illness have mainly focused on physical and sexual abuse. Our aim was to explore further the relationship between childhood trauma and disease characteristics in bipolar disorder to determine which clinical characteristics were most strongly associated with childhood trauma total score, as well as subtypes of adverse childhood events, including physical, sexual, emotional abuse and neglect. METHODS: 141 Patients with bipolar disorder were consecutively recruited, and disease history and clinical characteristics were assessed. History of childhood abuse was obtained using the Childhood Trauma Questionnaire (CTQ). Statistical methods used were factor analysis, Poisson and linear regression, and generalized additive modeling (GAM). RESULTS: The factor analysis of CTQ identified three factors: emotional abuse/neglect, sexual abuse and physical abuse. There were significant associations between CTQ total score and earlier onset of illness, reduced level of psychosocial functioning (GAF; Global Assessment of Functioning) and decreased number of hospitalization, which mainly were due to the factor emotional abuse/neglect. Physical abuse was significantly associated with lower GAF scores, and increased number of mood episodes, as well as self-harm. Sexual abuse was significantly associated with increased number of mood episodes. For mood episodes and self-harm the associations were characterized by great variance and fluctuations. CONCLUSIONS: Our results suggest that childhood trauma is associated with a more severe course of bipolar illness. Further, childhood abuse (physical and sexual), as well as emotional abuse and neglect were significantly associated with accelerating staging process of bipolar disorder. By using specific trauma factors (physical abuse, sexual abuse and emotional abuse/neglect) the associations become both more precise, and diverse.

Attention training technique delivered in groups as treatment for anxiety and depression in patients with coronary heart disease: study protocol for a waiting-list randomized controlled trial.

Introduction: Clinically significant symptoms of depression and anxiety in coronary heart disease (CHD) patients are common and associated with adverse outcomes. Psychological treatments have shown limited effectiveness and more effective treatments have been requested. Attention training technique (ATT), a component of metacognitive therapy, can potentially be effective as a stand-alone treatment for anxiety and depression. In an open study, ATT delivered face-to-face in a group format was feasible and potentially effective for improving depression and anxiety symptoms in CHD patients. The next progressive step is to test the effectiveness of ATT in a randomized controlled trial. This paper describes the methodology of this trial. Methods: ATT-CHD is a randomized wait-list (WL) controlled study. Eligible CHD patients from two hospitals with Hospital Anxiety and Depression Scale (HADS)-Anxiety and/or HADS-Depression subscales scores ≥8 will be randomized into ATT (n = 32) or WL control (n = 32). After 6-8 weeks, WL patients will be allocated to ATT. Participants will be evaluated pre-, mid- and post-treatment, and at 6-months follow-up using changes in HADS as primary outcome. Secondary outcomes will be changes in psychiatric disorders, rumination, worry, type D-personality, metacognitions, insomnia, quality of life, and C-Reactive protein (CRP). Discussion: To our knowledge, this will be the first WL-controlled randomized study testing the effectiveness of group-based ATT as treatment of symptoms of anxiety and depression in CHD patients. It will also explore correlations between changes in psychological distress and CRP. A qualitative analysis will reveal patients' experience with ATT including processes that may facilitate or serve as barriers to effectiveness. Recruitment into the study commenced in December 2022. Ethics and dissemination: The Regional Committees for Medical and Health Research Ethics (REK), Norway has granted approval for the study (ID 52002). The trial results will be published in peer-reviewed journals. According to Norwegian legislation, the Norwegian Data Protection Authority, and the Committee of Ethics, we are not allowed to share original study data publicly. Clinical trial registration: ClinicalTrials.gov, identifier NCT05621408 pre-inclusion. There were no significant changes of methods or outcomes after study start.

Combining antidepressants and attention bias modification in primary health care (DEPTREAT): Protocol for a pragmatic randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent psychiatric condition associated with significant disability, mortality and economic burden. A large proportion of MDD patients are treated in primary health care in the local community. Attentional Bias Modification (ABM) training in combination with antidepressants could be an effective treatment. Here we test the hypothesis that adding an ABM procedure to regular treatment with antidepressants in primary health care will result in further improvement of symptoms compared to treatment with antidepressants alone (treatment as usual, TAU) and as compared to an active comparison condition. METHODS: A total of 246 patients with a diagnosis of MDD will be included in this study. The study is a three-armed pragmatic randomized controlled trial comparing the efficacy of ABM as add-on to treatment with antidepressants in primary care (ABM condition) compared to standard antidepressant treatment (TAU condition). In a third group participants will complete the same schedule of intermediate assessments as the ABM condition in addition to TAU, but no ABM, thus controlling for the non-training-specific aspects of the ABM condition (Antidepressant active comparison group). DISCUSSION: The clinical outcome of this study may help develop easily accessible, low-cost treatment of depression in primary health care. Moreover, the study aims to broaden our knowledge of optimal treatment for patients with a MDD by providing adjunct treatment to facilitate recovery and long-term gain.

Is treatment in a day hospital step-down program superior to outpatient individual psychotherapy for patients with personality disorders? 36 months follow-up of a randomized clinical trial comparing different treatment modalities.

Despite increasing interest in the development of effective treatments for patients with PDs, there is still no consensus about the optimal treatment setting for this group of patients. This study reports the 36 months follow-up of the Ullevål Personality Project (UPP) (n=113), a randomized clinical trial comparing two treatment modalities for patients with PDs: an intensive long-term step-down treatment program, consisting of short-term day hospital treatment followed by combined group and individual psychotherapy organized in a hospital setting, with "ordinary" outpatient individual psychotherapy in private practice for patients with moderate to severe PDs. Patients in both treatment groups showed improvements in several clinical measures after 36 months. However, contrary to our expectations, patients in the outpatient treatment setting improved significantly more. Possible explanations for this surprising finding are discussed. The study cannot exclude the possibility that treatment aspects other than differences in modalities could explain some of the differential effectiveness (e.g. differences between therapists).

Avoidant personality disorder and social functioning: A longitudinal, observational study investigating predictors of change in a clinical sample.

Avoidant personality disorder (AvPD) is an understudied, severe disorder. This study includes a clinical sample of AvPD patients (N = 460) treated within specialist mental health services. Social functioning was repeatedly assessed by self-report: Work and Social Adjustment Scale. Personality functioning (self-report), pretreatment occupational activity, civil status/family situation (self-report), and comorbidity; personality and symptom disorders were assessed at baseline. More extensive baseline impairment of social functioning was significantly associated with poorer personality functioning, occupational inactivity, and a larger number of comorbid PD traits and symptom disorders. Poorer personality functioning and greater comorbidity did not impede improvement. More persisting impairment of functioning was associated with living alone. The study confirms major impairments of social functioning in AvPD, strongly related to personality dysfunction. A slow improvement of social functioning was demonstrated. With the exception of the civil status, living alone, improvement was not impeded by baseline severity aspects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Prognostic impact of non-improvement of global longitudinal strain in patients with revascularized acute myocardial infarction.

Global longitudinal strain (GLS) is a more sensitive prognostic factor than left ventricular ejection fraction (LVEF) in various cardiac diseases. Little is known about the clinical impact of GLS changes after acute myocardial infarction (AMI). The present study aimed to explore if non-improvement of GLS after 3 months was associated with higher risk of subsequent composite cardiovascular events (CCVE). Patients with AMI were consecutively included at a secondary care center in Norway between April 2016 and July 2018 within 4 days following percutaneous coronary intervention. Echocardiography was performed at baseline and after 3 months. Patients were categorized with non-improvement (0 to - 100%) or improvement (0 to 100%) in GLS relative to the baseline value. Among 214 patients with mean age 65 (± 10) years and mean LVEF 50% (± 8) at baseline, 50 (23%) had non-improvement (GLS: - 16.0% (± 3.7) to - 14.2% (± 3.6)) and 164 (77%) had improvement (GLS: - 14.0% (± 3.0) to - 16.9% (± 3.0%)). During a mean follow-up of 3.3 years (95% CI 3.2 to 3.4) 77 CCVE occurred in 52 patients. In adjusted Cox regression analyses, baseline GLS was associated with all recurrent CCVE (HR 1.1, 95% CI 1.0 to 1.2, p < 0.001) whereas non-improvement versus improvement over 3 months follow-up was not. Baseline GLS was significantly associated with the number of CCVE in revascularized AMI patients whereas non-improvement of GLS after 3 months was not. Further large-scale studies are needed before repeated GLS measurements may be recommended in clinical practice.Trial registration: Current Research information system in Norway (CRISTIN). Id: 506563.

MINDflex Training for Cognitive Flexibility in Chronic Pain: A Randomized, Controlled Cross-Over Trial.

Impairments in executive functioning are prevalent in chronic pain conditions, with cognitive inflexibility being the most frequently reported. The current randomized, cross-over trial, piloted a computerized cognitive training (CCT) program based on Relational Frame Theory, targeting improvement in cognitive flexibility. At baseline, 73 chronic pain patients completed testing on pre-selected outcomes of executive functioning, alongside IQ measures. When tested three times over the course of 5 months, there was a drop-out rate of 40% at the third time point, leaving 44 patients who had data at all time points. The results showed that there was a substantial learning effect from the MINDFLEX training and a substantial time-dependent improvement on the primary outcomes of increased flexibility, but that this could not be tied to active training. In conclusion, this small study indicated a learning effect as well as improvement on primary outcomes. Based on the current results, a larger trial with improved feasibility of training is warranted.

Cognitive Performance in Early-Onset Schizophrenia and Attention-Deficit/Hyperactivity Disorder: A 25-Year Follow-Up Study.

Early-Onset Schizophrenia (EOS) and Attention Deficit-Hyperactivity Disorder (ADHD) are early- onset neurodevelopmental disorders associated with cognitive deficits. The current study represents the first attempt to compare these groups on a comprehensive cognitive test battery in a longitudinal design over 25 years in order to enhance our knowledge of particular patterns resulting from the interaction between normal maturational processes and different illness processes of these disorders. In the baseline study, 19 adolescents with schizophrenia were compared to 20 adolescents with ADHD and 30 healthy controls (HC), all between 12 and 18 years of age. After 13 years (T2) and after 25 years (T3) they were re-evaluated with the cognitive test battery. A cognitive Composite Score was used in a linear mixed model. The EOS group had a significant cognitive stagnation or deterioration from T1 to T2 compared to HC. However, the EOS group had the most positive change from T2 to T3, supporting a stable level of cognitive performance over the 25 year span. The ADHD group improved or had similar development as the HC group from T1 to T2. They continued to improve significantly compared to the HC group from T2 to T3. Individuals in the EOS group performed more impaired on the cognitive composite score compared to the HC group and the ADHD group at all three time points. Results might indicate a neurodevelopmental pathway of EOS with subnormal cognitive development specific in adolescence. In comparison, the ADHD group had a more consistent cognitive maturation supporting a maturational delay hypothesis of ADHD.

The Influence of Persistent Organic Pollutants on Thyroidal, Reproductive and Adrenal Hormones After Bariatric Surgery.

INTRODUCTION: Persistent organic pollutants (POPs) including organochlorine pesticides, polychlorinated biphenyls (PCBs), and per- and polyfluoroalkylated substances (PFASs) are suspected endocrine disruptors. AIM: To evaluate the associations between POPs and thyroidal, reproductive, and adrenal hormones in a study population treated with bariatric surgery. METHODS: Blood samples from a cohort of 63 participants before and 1 year after bariatric surgery were analyzed for 16 lipophilic POPs, 17 PFASs, and thyroidal, reproductive, and adrenal hormones. Participants reporting relevant medical conditions or interfering medication were excluded, and plausible confounders were corrected for in multiple regression analyses. RESULTS: Free thyroxine (fT4) showed a significant decrease from preoperative to postoperative follow-up, and regression analyses demonstrated that p,p'-dichlorodiphenyldichloroethylene (p,p-DDE) was inversely associated with the ratio free triiodothyronine/free thyroxine (fT3/fT4). Testosterone concentrations in male participants increased significantly in the study period, and sex hormone-binding globulin (SHBG) increased in both gender. Regression analyses showed positive associations between increased levels of lipophilic POPs and the raised postoperative testosterone and SHBG concentrations in males. For females, an inverse association between the sum perfluoroalkyl carboxylic acids (ΣPFCA) and SHBG was seen. Regression analyses of postoperative serum cortisol concentrations on changes in hexachlorobenzene (HCB) showed a non-significant inverse association. CONCLUSION: The results suggest that POPs may have an influence on the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-gonadal (HPG) axes after bariatric surgery. Because of small sample sizes and discrepancy in the sampling time points pre- and postoperatively, the observed hormonal impacts of POPs must be interpreted as associative and not causative. Further studies are needed to confirm the findings.