Morbidity and mortality among children, adolescents, and young adults with cancer over six decades: a Swedish population-based cohort study (the Rebuc study).

Background: Despite progress in managing cancer in children, adolescents, and young adults (CAYAs), persistent complications may impact their quality of life. This study covers the morbidity and mortality, among CAYAs, with the aim to investigate the influence of socioeconomic factors on outcomes. Methods: This retrospective matched cohort study included the entire Swedish population of individuals under 25 with cancer 1958-2021. The population was identified from the Cancer Register, and controls were paired 1:5 based on age, sex, and residence. Multiple registers provided data on morbidity, mortality, and demographics. Findings: This survey covering 63 years, identified 65,173 CAYAs and matched controls, a total of 378,108 individuals (74% females). CAYAs exhibited a 3.04-times higher risk for subsequent cancer (Odds ratio (OR) 95% confidence interval (CI) 2.92-3.17, p < 0.0001), a 1.23-times higher risk for cardiovascular disease (OR 95% CI 1.20-1.26, p < 0.0001), and a 1.41-times higher risk for external affliction (OR 95% CI 1.34-1.49, p < 0.0001). CAYAs had a higher mortality hazard, and after adjusting for socioeconomic factors, males, individuals born outside Europe, and those with greater sick-leave had a higher association with mortality, while education and marriage showed a beneficial association. Interpretation: The Rebuc study, showed an increased risk for serious complications among young cancer patients in Sweden. Patient-specific variables, demographics, and socioeconomic factors influenced mortality. These results underscore the impact of cancer on the health and lifespan of young individuals and the necessity for further research to address socioeconomic disparities in cancer care. Funding: Grants from the Medical Research Council of Southeast Sweden (FORSS), ALF Grants, Region Ostergotland, and The Swedish Childhood Cancer Fund.

The protective effects of Swedish COVID-19 pandemic strategies on adolescents' mental health: a longitudinal cohort study.

AIM: The aim of this study was to investigate a cohort of Swedish eighth graders' mental health and experiences during the COVID-19 pandemic. METHODS: Participants were 157 eighth graders recruited in junior high schools during 2020 who completed a depression questionnaire and a survey about their psychosocial health in relation to the COVID-19 pandemic, alongside a follow-up assessment in 2021. Analyses were conducted using latent change score and cross-lagged models. RESULTS: Participants' depressive symptoms did not substantially increase during the COVID-19 pandemic. The level of depressive symptoms in 2020 was significantly associated with participants' perceptions of the pandemic in 2020 and spring 2021. Participants with higher depression scores reported worse experiences of the pandemic. CONCLUSIONS: The stable level of depressive symptoms among this cohort of eighth graders suggested that keeping schools open during a nationwide lockdown could mitigate some mental health consequences. Adolescents in this study with higher self-assessed depressive symptoms were more likely to experience increased depression after 6 months and had worse experiences during the pandemic than others. This suggests that the pandemic may not immediately affect mental well-being, but those at risk may be affected over time.

Epigenetic modifications appear in the human placenta following anxiety and depression during pregnancy.

INTRODUCTION: The future health of the offspring can be influenced by longstanding maternal anxiety and depression disorders during pregnancy. The present study aimed to explore the effect of psychiatric disorders during pregnancy on placental epigenetics. METHODS: We measured DNA methylation patterns in term-placentas of women either suffering longstanding anxiety and depression symptoms (Index group, with overt symptoms), or a healthy population (Control, none/only mild symptoms). Whole genome DNA methylation profiling was performed using the TruSeq® Methyl Capture EPIC Library Prep Kit (Illumina, San Diego, CA, USA) for library preparation and NGS technology for genomic DNA sequencing. RESULTS: The results of high-throughput DNA methylation analysis revealed that the Index group had differential DNA methylation at epigenome-wide significance (p < 0.05) in 226 genes in the placenta. Targeted enrichment analyses identified hypermethylation of genes associated with psychiatric disorders (BRINP1, PUM1), and ion homeostasis (COMMD1), among others. The ECM (extracellular matrix)-receptor interaction pathway was significantly dysregulated in the Index group compared to the Control. In addition, DNA methylation/mRNA integration analyses revealed that four genes with key roles in neurodevelopment and other important processes (EPB41L4B, BMPR2, KLHL18, and UBAP2) were dysregulated at both, DNA methylation and transcriptome levels in the Index group compared to Control. DISCUSSION: The presented results increase our understanding of how maternal psychiatric disorders may affect the newborn through placental differential epigenome, suggesting DNA methylation status as a biomarker when aiming to design new preventive techniques and interventions.

'It's like it is designed to keep me stressed'-Working sustainably with ADHD or autism.

BACKGROUND: Adults with attention deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) face multiple challenges in obtaining and maintaining employment. AIMS: To identify and describe how adults with ADHD or ASD experienced their ability to work and what factors affected their ability to find a sustainable work situation over time. METHODS: Individual in-depth interviews were performed with 20 purposively sampled participants with ADHD/ASD. Data were analysed inductively using reflexive thematic analysis. RESULTS: Three themes were identified, describing (1) one's own cognitive abilities and challenges, (2) enablement by flexibility and acceptance in the work environment, and (3) accumulated stress that makes the work situation unsustainable over time. CONCLUSIONS: Over time, a lack of continuity and predictability of support measures caused great stress and exhaustion, with severe consequences for working life and in life in general. Adaptations needed to be individually tailored and include nonoccupational factors. SIGNIFICANCE: The study shows that adults with ADHD/ASD need long-term interventions that flexibly adapt to individual needs, as they vary over time. The findings suggest that occupational therapists and other health care providers, employers, employment services and other involved agencies should pay a greater deal of attention to stability and predictability over time.

Predictors of problems reported on the EQ-5D-3L dimensions among people with impaired vision in northern Portugal.

BACKGROUND: The EQ-5D index often fails to detect the effect of ophthalmic diseases and sight loss. Investigating predictors of individual EQ-5D health dimensions might reveal the underlying reasons. The aim of this study was to investigate predictors of health dimension ratings obtained with the EQ-5D-3L from participants with impaired vision representing a spectrum of eye diseases. METHODS: Observational cross-sectional study with participants recruited at four public hospitals in Portugal. Outpatients with visual acuity of 0.30 logMAR(6/12) or worse in the better-seeing eye were invited to participate. Participants completed two instruments: the EQ-5D-3L (measures participants' perceived health-related quality-of-life) and the Massof Activity Inventory (measures visual ability-ability to perform vision-related activities). This study used logistic regression models to identify factors associated with responses to the EQ-5D-3L. RESULTS: The study included 492 participants, mean age 63.4 years (range = 18-93), 50% females. The most common diagnosis was diabetic retinopathy (37%). The mean visual acuity in the better seeing eye was 0.65 logMAR (SD = 0.48) and the mean visual ability was 0.62 logits (SD = 2.04), the correlation between the two was r = - 0.511 (p < 0.001). Mobility and self-care were the health dimensions with the fewest problems (1% reported extreme problems), anxiety and depression the dimension with the most problems (24% reported extreme problems). ROC curve analysis showed that the EQ-5D index was a poor predictor of cases of vision impairment whilst visual ability given was a good predictor of cases of vision impairment. Visual ability was an independent predictor of the response for all dimensions, higher ability was always associated with a reduced odds of reporting problems. The odds of reporting problems were increased for females in 3 out of 5 dimensions. Comorbidities, visual acuity and age-category were predictors of the odds of reporting problems for one dimension each. CONCLUSIONS: The odds of reporting problems for the five health dimensions of the EQ-5D-3L were strongly influenced by the ability to perform vision-related activities (visual ability). The EQ-5D index showed poor performance at detecting vision impairment. These findings are informative and relevant for the clinic and for research evaluating the impact of eye diseases and disease treatments in ophthalmology.

Prenatal stress, anxiety and depression alter transcripts, proteins and pathways associated with immune responses at the maternal-fetal interface†.

During pregnancy, the immune system is modified to allow developmental tolerance of the semi-allogeneic fetus and placenta to term. Pregnant women suffering from stress, anxiety, and depression show dysfunctions of their immune system that may be responsible for fetal and/or newborn disorders, provided that placental gene regulation is compromised. The present study explored the effects of maternal chronic self-perceived stress, anxiety, and depression during pregnancy on the expression of immune-related genes and pathways in term placenta. Pregnancies were clinically monitored with the Beck Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 divided patients into two groups: Index group (>10, n = 11) and a Control group (<10, n = 11), whose placentae were sampled at delivery. The placental samples were subjected to RNA-Sequencing, demonstrating that stress, anxiety, and depression during pregnancy induced a major downregulation of placental transcripts related to immune processes such as T-cell regulation, interleukin and cytokine signaling, or innate immune responses. Expression differences of main immune-related genes, such as CD46, CD15, CD8α & ß ILR7α, and CCR4 among others, were found in the Index group (P < 0.05). Moreover, the key immune-like pathway involved in humoral and cellular immunity named "Primary immunodeficiency" was significantly downregulated in the Index group compared with Controls. Our results show that mechanisms ruling immune system functions are compromised at the maternal-fetal interface following self-perceived depressive symptoms and anxiety during pregnancy. These findings may help unveil mechanisms ruling the impact of maternal psychiatric symptoms and lead to new prevention/intervention strategies in complicated pregnancies.

Is the Thoughts and Health programme feasible in the context of Swedish schools? A quasi-experimental controlled trial study protocol.

INTRODUCTION: Clinical depression is a substantial problem among adolescents, increasing significantly at about age 15 years. It causes impairment in social, academic and familial relationships, as well as ongoing cognitive and emotional difficulties for the individual. A study in Iceland demonstrated that a cognitive-behavioural, developmentally based intervention programme, 'Thoughts and Health', prevented initial episodes of depression and/or dysthymia (DYS) (major depressive disorder/DYS) in adolescents for up to 12 months following completion of the programme. We would like to test the feasibility of implementing the Icelandic method in a Swedish context and to evaluate the long-term effects of such a programme. METHODS AND ANALYSIS: A quasi-experimental controlled design, combined with qualitative and quantitative methods, will be used to address the research questions.In this study, 617 children aged ~14 years will be screened for depression, and those "at risk" for development of clinical depression will be offered a 12 week course, 'Thoughts and Health'. This course aims to prevent first depression in adolescents. A comparable group of children will function as controls.Depending on the type of variable, baseline comparisons between the two groups of relevant initial measures will be evaluated with t-tests or χ2 analyses. The effects of the programme on the development of clinical levels of depression will be evaluated using the follow-up data of 6, 12 and 18 months. Index parental depression at baseline will be tested as a moderator in the evaluation of the effects of the prevention programme. ETHICS AND DISSEMINATION: This study is approved by the Swedish Ethical Review Board (reference number 2019-03347) in Gothenburg.We plan to disseminate the knowledge gained from this study by publishing our results in peer-reviewed scientific journals and other scholarly outlets. TRIAL REGISTRATION NUMBER: NCT04128644; Pre-results.

Expression of Stress-Mediating Genes is Increased in Term Placentas of Women with Chronic Self-Perceived Anxiety and Depression.

Anxiety, chronical stress, and depression during pregnancy are considered to affect the offspring, presumably through placental dysregulation. We have studied the term placentae of pregnancies clinically monitored with the Beck's Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 classed patients into an Index group (>10, n = 23) and a Control group (<10, n = 23). Cortisol concentrations in hair (HCC) were periodically monitored throughout pregnancy and delivery. Expression differences of main glucocorticoid pathway genes, i.e., corticotropin-releasing hormone (CRH), 11ß-hydroxysteroid dehydrogenase (HSD11B2), glucocorticoid receptor (NR3C1), as well as other key stress biomarkers (Arginine Vasopressin, AVP and O-GlcNAc transferase, OGT) were explored in medial placentae using real-time qPCR and Western blotting. Moreover, gene expression changes were considered for their association with HCC, offspring, gender, and birthweight. A significant dysregulation of gene expression for CRH, AVP, and HSD11B2 genes was seen in the Index group, compared to controls, while OGT and NR3C1 expression remained similar between groups. Placental gene expression of the stress-modulating enzyme 11ß-hydroxysteroid dehydrogenase (HSD11B2) was related to both hair cortisol levels (Rho = 0.54; p < 0.01) and the sex of the newborn in pregnancies perceived as stressful (Index, p < 0.05). Gene expression of CRH correlated with both AVP (Rho = 0.79; p < 0.001) and HSD11B2 (Rho = 0.45; p < 0.03), and also between AVP with both HSD11B2 (Rho = 0.6; p < 0.005) and NR3C1 (Rho = 0.56; p < 0.03) in the Control group but not in the Index group; suggesting a possible loss of interaction in the mechanisms of action of these genes under stress circumstances during pregnancy.

Psychiatric symptoms among patients with acute abdominal pain.

Background: Abdominal pain is a common cause of visits to emergency facilities. It is related to psychiatric disorders in primary care, but it is unclear if this also holds in emergency departments.Objective: Is to explore potential differences between diagnostic groups in patients with acute abdominal pain in an emergency ward regarding concurrent somatic-and psychiatric symptoms, 'Length of stay' (LOS) and perceived health.Method: The patients (N = 137) were divided into three groups; organic dyspepsia, specific abdominal diagnoses, and non-specific abdominal pain. The Prime-MD results for extra gastrointestinal symptoms (outside the gastrointestinal tract), psychiatric symptoms, frequency of symptoms, self-reported health, and LOS within the month before admittance were compared between the diagnostic groups.Results: There was a significant positive correlation between the number of physical extra gastrointestinal and psychiatric symptoms (p < .001), especially regarding anxiety (p < .001) and depression (p = .002). Patients with organic dyspepsia reported significantly more total (p = .016), extragastrointestinal (p = .026) (chest pain; p = .017, dizziness; p = .004, palpitations; p = .005, insomnia; p = .005 and worries; p = .001), and summarized anxiety and depression symptoms (p = .001-0.002) besides poorer general health (p < .001) compared to other abdominal conditions. Also, organic dyspepsia patients needed longer hospital stay than the non-specific abdominal group (p = .002) but similar to the specific abdominal disorders group.Conclusion: Organic dyspepsia is accompanied by more co-occurring physical, anxiety and depression symptoms as well as poorer perceived health than other abdominal pain conditions and comparably increased LOS. This suggests that psychiatric consultations might be beneficial for diagnosing and treating psychiatric comorbidity in emergency care.

Higher- and lower-order personality traits and cluster subtypes in social anxiety disorder.

Social anxiety disorder (SAD) can come in different forms, presenting problems for diagnostic classification. Here, we examined personality traits in a large sample of patients (N = 265) diagnosed with SAD in comparison to healthy controls (N = 164) by use of the Revised NEO Personality Inventory (NEO-PI-R) and Karolinska Scales of Personality (KSP). In addition, we identified subtypes of SAD based on cluster analysis of the NEO-PI-R Big Five personality dimensions. Significant group differences in personality traits between patients and controls were noted on all Big Five dimensions except agreeableness. Group differences were further noted on most lower-order facets of NEO-PI-R, and nearly all KSP variables. A logistic regression analysis showed, however, that only neuroticism and extraversion remained significant independent predictors of patient/control group when controlling for the effects of the other Big Five dimensions. Also, only neuroticism and extraversion yielded large effect sizes when SAD patients were compared to Swedish normative data for the NEO-PI-R. A two-step cluster analysis resulted in three separate clusters labelled Prototypical (33%), Introvert-Conscientious (29%), and Instable-Open (38%) SAD. Individuals in the Prototypical cluster deviated most on the Big Five dimensions and they were at the most severe end in profile analyses of social anxiety, self-rated fear during public speaking, trait anxiety, and anxiety-related KSP variables. While additional studies are needed to determine if personality subtypes in SAD differ in etiological and treatment-related factors, the present results demonstrate considerable personality heterogeneity in socially anxious individuals, further underscoring that SAD is a multidimensional disorder.

Impact of personality on adherence to and beliefs about ADHD medication, and perceptions of ADHD in adolescents.

BACKGROUND: Adherence to attention deficit hyperactivity disorder (ADHD) medication can prevent serious consequences, possibly with lifelong effects. Numerous factors have been observed that influence adherent behaviour, but the impact of personality traits has been inadequately explored. The purpose of this study was to explore the associations between personality traits and adherence to ADHD medication, beliefs about the medication, and perceptions of ADHD. METHOD: Adolescents (n = 99) on ADHD medication were administered: Health-Relevant Personality Traits Five-Factor Inventory, Medication Adherence Report Scale, Beliefs about Medicines Specific and Brief Illness Perceptions Questionnaires. RESULTS: The personality trait Antagonism correlated with adherence behaviour (r = - 0.198, p = 0.005) and perceived personal control of ADHD (r = - 0.269, p = 0.007). Negative Affectivity correlated with beliefs regarding necessity (r = 0.319, p = 0.001), concerns (r = 0.344, p = 0.001), and experienced side effects of medication (r = 0.495, p = 0.001), alongside perceptions regarding duration (r = 0.272, p = 0.007), identity (r = 0.388, p < 0.001), being emotionally affected (r = 0.374, p < 0.01), personal control (r = - 0.287, p = 0.004) and concerns about ADHD (r = 0.465, p < 0.001). Impulsivity correlated with perceived consequences (r = - 0.226, p = 0.0255) and personal control of ADHD (r = - 0.379, p < 0.001). Hedonic Capacity correlated with concerns about medication (r = - 0.218, p = 0.0316) and perceived identification with ADHD (r = - 0.203, p = 0.045). CONCLUSION: Personality traits are related to adherence, beliefs about ADHD medicines and perceptions of ADHD. Antagonism is associated with adherence, especially intentional non-adherence, while Negative Affectivity correlates with numerous perceptions of ADHD and beliefs about medications. Personality assessments could be useful in the care and treatment of adolescents with ADHD.

Reliability and validation of Swedish translation of Beliefs about Medication Specific (BMQ-Specific) and Brief Illness Perception Questionnaire (B-IPQ) for use in adolescents with attention-deficit hyperactivity disorder.

Objectives: The purpose of this study was to assess the reliability and validity of Swedish translations of the Beliefs about Medicines Questionnaire-Specific (BMQ-Specific) and Brief Illness Perception Questionnaire (B-IPQ) for use in adolescents with ADHD.Methods: Forward and backward translations of the BMQ-Specific and B-IPQ scales to Swedish were conducted and reviewed by adolescents with ADHD and professionals. The validity and reliability of both questionnaires were investigated in a cross-sectional study of 101 adolescents (13-17 years) on a long-term prescription of ADHD medication recruited from two child and adolescent psychiatric outpatient clinics in Sweden.Results: Regarding the BMQ-Specific, principal component analysis (PCA) loadings confirmed the previously defined components of Specific-Necessity and Specific-Concern. The PCA for B-IPQ revealed two components, the first one, B-IPQ Consequences, captured questions regarding perceptions of the implication of having ADHD (items 1, 2, 5, 6 and 8) and the second one, B-IPQ-Control, the perceptions of the capability to manage the ADHD disorder (items 3, 4 and 7). The Cronbach alpha coefficients for BMQ-Specific-Necessity scale was α = 0.80, for BMQ-Specific-Concern scale α = 0.75, B-IPQ Consequences α = 0.74 and for B-IPQ-Control α = 0.44.Conclusions: The present results prove the Swedish translation of BMQ-Specific and B-IPQ to be valid and reliable for utilization in adolescents with ADHD. The PCA confirmed the original components for BMQ-Specific and the recent findings of two main B-IPQ components describing emotional and cognitive implications versus the capability for self-care maintenance of ADHD.

Comorbidity of Adult ADHD and Its Subtypes With Substance Use Disorder in a Large Population-Based Epidemiological Study.

Objective: The objective of the study is to explore the role and possible substance preference in ADHD and subtypes in substance use disorder (SUD). Method: Using self-report data on ADHD Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) symptoms and SUD (alcohol, illicit drugs, and nicotine) in 18,167 Swedish twins, aged 20 to 45 years, we obtained odds ratios (OR) from mixed effect logistic regression, controlling for age, sex, education, and nonindependence of twin data. Results: Increased ADHD symptoms were significantly associated with increased odds for all SUD. ORs ranged between 1.33 for regular nicotine (95% confidence interval [CI] = [1.12, 1.59]); 2.54 for multiple drug use (95% CI = [2.00, 3.23]), and 3.58 for alcohol dependence (95% CI = [2.86, 4.49]). Conclusion: ADHD symptoms and subtypes in the population are associated with increased risks for all SUD outcomes, with no difference between ADHD subtypes, no substance preference, and no sex differences for the comorbidity. Clinicians need to consider ADHD evaluation and treatment as part of management of SUD in adults.

Temperament and character in patients with acute abdominal pain.

BACKGROUND: Several conditions presenting with abdominal pain are associated with specific personality factors although it is unclear if this is true also in emergency clinic settings. OBJECTIVE: To study personality factors among patients with acute abdominal pain in an emergency ward. METHODS: Consecutive patients (N = 165) with abdominal symptoms at an emergency clinic were administrated the Temperament and Character Inventory (TCI). Three main groups were identified; specific abdominal diagnoses, (N = 77), non-specific abdominal pain, (N = 67) and organic dyspepsia (N = 21). TCI results were compared between clinical groups and a control group (N = 122). RESULTS: As compared to individuals with specific abdominal diagnoses and controls, those with organic dyspepsia were significantly more anxious (harm avoidance), (p = 0.003), and had lower ability to cooperate (cooperativeness) (p = 0.048 and p = 0.004 respectively). They were also significantly more unpretentious (self-transcendence) compared to individuals with specific abdominal diagnoses (p = 0.048), non-specific abdominal pain (p = 0.012) and controls (p = 0.004) and evidenced less mature character (sum of self-directedness and cooperativeness) compared to those with specific abdominal diagnoses and controls (p = 0.003). CONCLUSION: Individuals seeking care at an emergency clinic with organic dyspepsia showed a distinguishable pattern of personality features that distinguished them from the other comparison groups. Therefore an evaluation of personality factors may add a new dimension to the diagnostic investigation in the emergency care of abdominal pain and contribute to the optimization of the treatment of organic dyspepsia.

A systematic review including meta-analysis of work environment and burnout symptoms.

BACKGROUND: Practitioners and decision makers in the medical and insurance systems need knowledge on the relationship between work exposures and burnout. Many burnout studies - original as well as reviews - restricted their analyses to emotional exhaustion or did not report results on cynicism, personal accomplishment or global burnout. To meet this need we carried out this review and meta-analyses with the aim to provide systematically graded evidence for associations between working conditions and near-future development of burnout symptoms. METHODS: A wide range of work exposure factors was screened. Inclusion criteria were: 1) Study performed in Europe, North America, Australia and New Zealand 1990-2013. 2) Prospective or comparable case control design. 3) Assessments of exposure (work) and outcome at baseline and at least once again during follow up 1-5 years later. Twenty-five articles met the predefined relevance and quality criteria. The GRADE-system with its 4-grade evidence scale was used. RESULTS: Most of the 25 studies focused emotional exhaustion, fewer cynicism and still fewer personal accomplishment. Moderately strong evidence (grade 3) was concluded for the association between job control and reduced emotional exhaustion and between low workplace support and increased emotional exhaustion. Limited evidence (grade 2) was found for the associations between workplace justice, demands, high work load, low reward, low supervisor support, low co-worker support, job insecurity and change in emotional exhaustion. Cynicism was associated with most of these work factors. Reduced personal accomplishment was only associated with low reward. There were few prospective studies with sufficient quality on adverse chemical, biological and physical factors and burnout. CONCLUSION: While high levels of job support and workplace justice were protective for emotional exhaustion, high demands, low job control, high work load, low reward and job insecurity increased the risk for developing exhaustion. Our approach with a wide range of work exposure factors analysed in relation to the separate dimensions of burnout expanded the knowledge of associations, evidence as well as research needs. The potential of organizational interventions is illustrated by the findings that burnout symptoms are strongly influenced by structural factors such as job demands, support and the possibility to exert control.

Beliefs regarding medication and side effects influence treatment adherence in adolescents with attention deficit hyperactivity disorder.

Adherence to attention deficit hyperactivity disorder (ADHD) treatment is important because, when untreated, it may have serious consequences with lifelong effects. In the case of adolescents on long-term medicine prescription, more knowledge is needed regarding adherence and factors influencing adherence, which was the purpose of this study. Adolescents (n = 101) on ADHD medication ≥6 months were administrated questionnaires at a monitoring appointment: Medication Adherence Report Scale (MARS), beliefs about medicines (BMQ) and the Brief Illness Perception Questionnaire (B-IPQ). Adherence was high, the mean value was 88% of the maximum MARS score, and correlated positively with the "BMQ-necessity-concerns differential" but negatively with "BMQ-concerns" and "BMQ-side effects". Adolescents with more belief in the necessity of the medication, less concerns and less experience of side effects tended to be more adherent to medication prescription ("intentional non-adherence"), while "unintentional non-adherence" (forgetfulness) was associated with how much they perceived that their ADHD affected their lives. In a multiple regression model, the variance of MARS total (R 2 = 0.21) and "intentional non-adherence" (R 2 = 0.24) was explained by the "BMQ-necessity-concern differential" and "BMQ-experienced side effects". The variance of "unintentional non-adherence" (R 2 = 0.12) was explained by the "BMQ-necessity-concern differential" and "B-IPQ-consequences of ADHD". In conclusion, adolescents on long-term medication reported good adherence, mainly influenced by more beliefs in the necessity versus concerns of the medications, less experienced side effects and more perceived consequences of ADHD. BMQ could be useful to identify risks of low adherence, which should be counteracted by partially gender-specific interventions.

Women with Premenstrual Dysphoria Lack the Seemingly Normal Premenstrual Right-Sided Relative Dominance of 5-HTP-Derived Serotonergic Activity in the Dorsolateral Prefrontal Cortices - A Possible Cause of Disabling Mood Symptoms.

STUDY OBJECTIVE: To investigate potential quantitative and qualitative differences in brain serotonergic activity between women with Premenstrual Dysphoria (PMD) and asymptomatic controls. BACKGROUND: Serotonin-augmenting drugs alleviate premenstrual mood symptoms in the majority of women with PMD while serotonin-depleting diets worsen PMD symptoms, both indicating intrinsic differences in brain serotonergic activity in women with PMD compared to asymptomatic women. METHODS: Positron-emission tomography with the immediate precursor of serotonin, 5-hydroxytryptophan (5-HTP), radiolabelled by 11C in the beta-3 position, was performed in the follicular and luteal phases for 12 women with PMD and 8 control women. Brain radioactivity-a proxy for serotonin precursor uptake and synthesis-was measured in 9 regions of interest (ROIs): the right and left sides of the medial prefrontal cortex, dorsolateral prefrontal cortex, putamen and caudate nucleus, and the single "whole brain". RESULTS: There were no significant quantitative differences in brain 5-HTP-derived activity between the groups in either of the menstrual phases for any of the 9 ROIs. However, multivariate analysis revealed a significant quantitative and qualitative difference between the groups. Asymptomatic control women showed a premenstrual right sided relative increase in dorsolateral prefrontal cortex 5-HTP derived activity, whereas PMD women displayed the opposite (p = 0.0001). Menstrual phase changes in this asymmetry (premenstrual-follicular) correlated with changes in self ratings of 'irritability' for the entire group (rs = -0.595, p = 0.006). The PMD group showed a strong inverse correlation between phase changes (premenstrual-follicular) in plasma levels of estradiol and phase changes in the laterality (dx/sin) of radiotracer activity in the dorsolateral prefrontal ROI (rs = -0.635; 0.027). The control group showed no such correlation. CONCLUSION: Absence of increased premenstrual right-sided relative 5-HTP-derived activity of the dorsolateral prefrontal cortices was found to strongly correlate to premenstrual irritability. A causal relationship here seems plausible, and the findings give further support to an underlying frontal brain disturbance in hormonally influenced serotonergic activity in women with PMD. Because of the small number of subjects in the study, these results should be considered preliminary, requiring verification in larger studies.

Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder.

It is disputed whether anxiety disorders, like social anxiety disorder, are characterized by serotonin over- or underactivity. Here, we evaluated whether our recent finding of elevated neural serotonin synthesis rate in patients with social anxiety disorder could be reproduced in a separate cohort, and whether allelic variation in the tryptophan hydroxylase-2 (TPH2) G-703T polymorphism relates to differences in serotonin synthesis assessed with positron emission tomography. Eighteen social anxiety disorder patients and six healthy controls were scanned during 60 minutes in a resting state using positron emission tomography and 5-hydroxy-L-[ß -(11)C]tryptophan, [(11)C]5-HTP, a substrate of the second enzymatic step in serotonin synthesis. Parametric images were generated, using the reference Patlak method, and analysed using Statistical Parametric Mapping (SPM8). Blood samples for genotyping of the TPH2 G-703T polymorphism were obtained from 16 social anxiety disorder patients (T carriers: n=5, GG carriers: n=11). A significantly elevated [(11)C]5-HTP accumulation rate, indicative of enhanced decarboxylase activity and thereby serotonin synthesis capacity, was detected in social anxiety disorder patients compared with controls in the hippocampus and basal ganglia nuclei and, at a more lenient (uncorrected) statistical threshold, in the amygdala and anterior cingulate cortex. In patients, the serotonin synthesis rate in the amygdala and anterior cingulate cortex was significantly elevated in TPH2 T carriers in comparison with GG homozygotes. Our results support that social anxiety disorder entails an overactive presynaptic serotonergic system that, in turn, seems functionally influenced by the TPH2 G-703T polymorphism in emotionally relevant brain regions.

Psychological Resources Are Independently Associated with Markers of Inflammation in a Middle-Aged Community Sample.

PURPOSE: To elucidate possible independent associations of psychological resources with inflammatory markers, all linked with coronary heart disease (CHD). METHOD: In a middle-aged general population (n = 944), psychological resources (coping, self-esteem, and sense of coherence (SOC)), a global measure of quality of life (Cantril's self-anchoring ladder, also called "ladder of life"), and psychological risk factors (hopelessness, vital exhaustion, and depressive symptoms) were used in linear regression models to evaluate associations with the inflammatory markers interleukin (IL)-6, C-reactive protein (CRP), and matrix metalloproteinase (MMP)-9. Adjustments were done for age, sex, medical conditions, and cardiovascular risk factors. RESULTS: After full adjustments, self-esteem was independently associated with all three biomarkers. Ladder of life was associated with IL-6 and log-CRP; coping, vital exhaustion, and depressive symptoms with IL-6; and SOC with MMP-9 (p < 0.05 for all associations). CONCLUSION: Numerous significant associations of psychological resources and risk factors with IL-6, CRP, and MMP-9 were found in a community-based sample. The associations of psychological resources were mostly independent, while the psychological risk factors seemed preferentially dependent on lifestyle factors as smoking, physical activity, and body mass index (BMI). This suggests that the psychological resources' (in particular self-esteem) protective effects on CHD are linked to inflammatory markers.

A systematic review including meta-analysis of work environment and depressive symptoms.

BACKGROUND: Depressive symptoms are potential outcomes of poorly functioning work environments. Such symptoms are frequent and cause considerable suffering for the employees as well as financial loss for the employers. Accordingly good prospective studies of psychosocial working conditions and depressive symptoms are valuable. Scientific reviews of such studies have pointed at methodological difficulties but still established a few job risk factors. Those reviews were published some years ago. There is need for an updated systematic review using the GRADE system. In addition, gender related questions have been insufficiently reviewed. METHOD: Inclusion criteria for the studies published 1990 to June 2013: 1. European and English speaking countries. 2. Quantified results describing the relationship between exposure (psychosocial or physical/chemical) and outcome (standardized questionnaire assessment of depressive symptoms or interview-based clinical depression). 3. Prospective or comparable case-control design with at least 100 participants. 4. Assessments of exposure (working conditions) and outcome at baseline and outcome (depressive symptoms) once again after follow-up 1-5 years later. 5. Adjustment for age and adjustment or stratification for gender. Studies filling inclusion criteria were subjected to assessment of 1.) relevance and 2.) quality using predefined criteria. Systematic review of the evidence was made using the GRADE system. When applicable, meta-analysis of the magnitude of associations was made. Consistency of findings was examined for a number of possible confounders and publication bias was discussed. RESULTS: Fifty-nine articles of high or medium high scientific quality were included. Moderately strong evidence (grade three out of four) was found for job strain (high psychological demands and low decision latitude), low decision latitude and bullying having significant impact on development of depressive symptoms. Limited evidence (grade two) was shown for psychological demands, effort reward imbalance, low support, unfavorable social climate, lack of work justice, conflicts, limited skill discretion, job insecurity and long working hours. There was no differential gender effect of adverse job conditions on depressive symptoms CONCLUSION: There is substantial empirical evidence that employees, both men and women, who report lack of decision latitude, job strain and bullying, will experience increasing depressive symptoms over time. These conditions are amenable to organizational interventions.