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Introduction: Sickness absence (SA) has been shown to be associated with several negative consequences, both for the affected individual as well as for society on the whole, in terms of economic loss. The most common reason for SA is SA due to common mental disorders (CMDs). Previous studies have indicated that there is an association between exposure to work-related offensive behaviours, such as harassment, bullying, violence and threats of different kinds and CMDs. However, the mechanistic pathway in this association is still largely unknown. For example, the associations between exposure to offensive or abusive behaviours and health outcomes may partially be explained by individual characteristics, including genetic predispositions and early experiences. The aim of the present study was to investigate the role of familial factors (genetics and shared early-life environment) and neuroticism in the associations between exposure to work-related violence/threats and harassment/bullying, and SA due to CMDs. Method: The study sample included 8795 twin individuals from the Swedish Twin project of Disability pension and Sickness absence (STODS), including survey data from the Study of Twin Adults: Genes and Environment (STAGE) linked to national register data. Self-reported work-related violence and/or threats and work-related harassment including bullying and register data on SA due to CMDs were analysed using logistic regression on the whole sample, and conditional logistic regression among complete same-sex twin pairs discordant on exposures. Individuals were followed for a maximum of 13 years or until their first incident SA spell due to CMD. Interactions between neuroticism and exposures were assessed using both multiplicative and additive interaction analyses. Results: Exposure to work-related violence/threats were associated with higher odds of SA due to CMDs when adjusting for age, sex, marital status, children living at home, education, type of residential area

Background Residential regions may impact the possibilities to achieve a sustainable working life (SWL, i.e. not having interruptions due to sickness absence, disability pension or unemployment) due to disparities in social security and labour market. We aimed to investigate concurrent trajectories of regions and SWL among Swedish twins. Methods National register data were used for the degree of SWL in each year, old-age pension, emigration, death and residential regions classified in three categories (cities; towns and suburbs; or rural areas) of Swedish twins in 1998-2016 (n = 80 398). Group-based multi-trajectory modelling and multinomial regression for relative risks with 95% confidence intervals were calculated. Results The six-group solution had the best fit to data with trajectories: stable living in towns and suburbs with SWL (33.8%); stable living in cities with SWL (22.1%); stable living in towns and suburbs with increasing SWL (13.9%); stable living in towns and suburbs with lack of SWL (13.2%); stable living towns and suburbs with decreasing SWL (8.8%); and stable living towns and suburbs with decreasing and ultimately lack of SWL (8.3%). Age and being woman increased and being married and higher education decreased the likelihood of belonging to groups 2-6 (vs. 1). Conclusions The simultaneous assessment of trajectories of three residential regions and SWL indicated that most people in Sweden seem to live continuously over time in towns and suburbs, but the degree of SWL may vary. More fine-grained assessment of residential regions would be needed to clarify the associations with SWL.

The aim of the present study was to investigate the association between exposure to unacceptable behaviors and practices or threats thereof in working life that result in or aim to result in physical, psychological, sexual or economic harm, such as violence and harassment including unwelcome conduct based on e.g. sex or gender (gender-based harassment/discrimination), and future sickness absence due to common mental disorders among Swedish twins. The study included 8795 twins, from the Swedish Study of Twin Adults: Genes and Environment, asked to report exposure to work-related violence or threats of violence and harassment or bullying and whom were followed-up for certified sickness absence (min 12 years of follow-up). Standard logistic regression indicated that exposure increased the odds of sickness absence due to common mental disorders (adjusted OR 2.11; 95% CI 1.52-2.95 for violence/threats, adjusted OR 1.52; 95% CI 1.10-2.11 for harassment/bullying). A co-twin control analyses based on conditional logistic regression restricted to twin pairs discordant for exposure, in which a co-twin control was used as reference, however, resulted in attenuated ORs (2.0; 0.79-5.07 and 1.56; 0.66-3.66, respectively). This indicates that the relationships could be at least partially confounded by familial factors, such as genetics and shared environment. These results suggests that more work is needed to clarify whether there is a causal association between these types of unacceptable behaviors/practices and mental health outcomes considering familial/genetic factors, and whether prevention of such behaviors/practices can keep individuals increasingly healthy, active on the labor market and promote healthy aging.

Background: Social anxiety disorder (SAD) is associated with aberrant emotional information processing while little is known about non-emotional cognitive processing biases. The dorsal anterior cingulate cortex (dACC) has been implicated in SAD neuropathology and is activated both by emotional and non-affective cognitive challenges like the Multisource Interference Task (MSIT). Methods: Here, we used fMRI to compare dACC activity and test performance during MSIT in 69 SAD patients and 38 healthy controls. In addition to patient-control comparisons, we examined whether neural activity in the dACC correlated with social anxiety, trait anxiety or depression levels. Results: The MSIT activated the dACC as expected but with no differences in task performance or neural reactivity between SAD patients and controls. There were no significant correlations between dACC activity and social or trait anxiety symptom severity. In patients, there was a significant negative correlation between dACC activity and depressive symptoms. Conclusions: In absence of affective challenge, we found no disorder-related cognitive profile in SAD patients since neither MSIT task performance nor dACC neural activity deviated in patients relative to controls., De två sista författarna delar sistaförfattarskapet.

IMPORTANCE Mental health problems in early life are associated with labor market marginalization, especially in youths with persistent internalizing and externalizing problems. However, previous research has not adjusted for familial (genetic and shared environmental) factors. OBJECTIVE To examine associations of early-life internalizing and externalizing problems with adulthood unemployment and work disability, adjusting for familial factors. DESIGN, SETTING, AND PARTICIPANTS This population-based prospective cohort study included Swedish twins whowere born in 1985-1986 and surveyed at 4 consecutivewaves across childhood and adolescence until 2005. Through linkage to nationwide registries, participants were followed up from 2006 to 2018. Data analyses were conducted between September 2022 and April 2023. EXPOSURES Internalizing and externalizing problems, assessed with the Child Behavior Checklist. Participants were differentiated regarding duration of internalizing and externalizing problems (persistent, episodic, and noncases). MAIN OUTCOMES AND MEASURES Unemployment (180 days or more of being unemployed) and work disability (60 days or more of being sickness absent or disability pensioned) during follow-up. Cox proportional hazards regression models were calculated to obtain cause-specific hazard ratios (HRs) with 95% CIs in the whole cohort and exposure-discordant twin pairs. RESULTS Of 2845 participants, 1464 (51.5%) were female. Incident unemployment was experienced by 944 (33.2%) and incidentwork disability by 522 (18.3%) participants. Compared with noncases, persistent internalizing problemswere associated with unemployment (HR, 1.56; 95% CI, 1.27-1.92) and work disability (HR, 2.32; 95% CI, 1.80-2.99). Similarly, compared with noncases, persistent externalizing problems were associated with unemployment (HR, 1.87; 95% CI, 1.55-2.26) andwork disability (HR, 2.38; 95% CI, 1.87-3.03). Persistent cases had overall higher risks of adverse outcomes than episodic

Serotonin and dopamine are putatively involved in the etiology and treatment of anxiety disorders, but positron emission tomography (PET) studies probing the two neurotransmitters in the same individuals are lacking. The aim of this multitracer PET study was to evaluate the regional expression and co-expression of the transporter proteins for serotonin (SERT) and dopamine (DAT) in patients with social anxiety disorder (SAD). Voxel-wise binding potentials (BPND) for SERT and DAT were determined in 27 patients with SAD and 43 age- and sex-matched healthy controls, using the radioligands [11C]DASB (3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile) and [11C]PE2I (N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)nortropane). Results showed that, within transmitter systems, SAD patients exhibited higher SERT binding in the nucleus accumbens while DAT availability in the amygdala, hippocampus, and putamen correlated positively with symptom severity. At a more lenient statistical threshold, SERT and DAT BPND were also higher in other striatal and limbic regions in patients, and correlated with symptom severity, whereas no brain region showed higher binding in healthy controls. Moreover, SERT/DAT co-expression was significantly higher in SAD patients in the amygdala, nucleus accumbens, caudate, putamen, and posterior ventral thalamus, while lower co-expression was noted in the dorsomedial thalamus. Follow-up logistic regression analysis confirmed that SAD diagnosis was significantly predicted by the statistical interaction between SERT and DAT availability, in the amygdala, putamen, and dorsomedial thalamus. Thus, SAD was associated with mainly increased expression and co-expression of the transporters for serotonin and dopamine in fear and reward-related brain regions. Resultant monoamine dysregulation may underlie SAD symptomatology and constitute a target for treatment.

Adolescent depression is linked to adult ill-health and functional impairment, but recent research suggests that individual/contextual factors might account for this association. This study aimed to test whether the clinical heterogeneity of adolescent depression is related to marginalization from the labor market across early to middle adulthood. Data were drawn from the Uppsala Longitudinal Adolescent Depression Study, a community-based cohort initially assessed with structured clinical interviews at age 16-17. The cohort (n = 321 depressed; n = 218 nondepressed) was followed up after 2+ decades through linkage to nationwide population-based registries. Outcomes included consecutive annual data on unemployment, work disability, social welfare recipiency, and a composite marginalization measure, spanning from age 21 to 40. Longitudinal associations were examined using logistic regression analysis in a generalized estimating equations modeling framework. Subsequent depressive episodes and educational attainment in early adulthood were explored as potential pathways. The results showed that adolescent depression was associated with adult marginalization outcomes, but the strength of association varied across depressed subgroups. Adolescents with persistent depressive disorder had higher odds of all outcomes, including the composite marginalization measure (adjusted OR = 2.0, 95% CI = 1.4-2.7, p < 0.001), and this was partially (31%) mediated by subsequent depressive episodes in early adulthood. Exploratory moderation analysis revealed that entry into tertiary education mitigated the association with later marginalization, but only for adolescents with episodic major depression. In conclusion, the risk for future labor market marginalization is elevated among depressed adolescents, particularly those presenting with persistent depressive disorder. Targeted interventions seem crucial to mitigate the long-lasting impact of early-onset depression., Funding Agencies:Uppsala University Uppsala-Örebro Regional Research Council RFR-738411 RFR-652841 RFR-840891Uppsala County Council's Funds for Clinical Research LUL-713161 LUL-828241 LUL-914571Sven Jerring Foundation Foundation in Memory of Professor Bror Gadelius

It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [11C]DASB and [11C]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response.

AIMS: The few available studies on early-onset depression and future earnings offer ambiguous findings, and potential sources of heterogeneity are poorly understood. We examined the differences in adult earnings of males and females with and without a history of depressive disorder in adolescence, with specific focuses on (1) future earnings in clinical subtypes of adolescent depression; (2) the growth and distribution of earnings over time within these subgroups and (3) the mediating role of subsequent depressive episodes occurring in early adulthood. METHODS: Data were drawn from the Uppsala Longitudinal Adolescent Depression Study, a community-based cohort study initiated in Uppsala, Sweden, in the early 1990s. Comprehensive diagnostic assessments were conducted at age 16-17 and in follow-up interviews 15 years later, while consecutive data on earnings for the years 1996 to 2016 (ages 20-40) were drawn from population-based registries. The current study included participants with a history of persistent depressive disorder (PDD) (n = 175), episodic major depressive disorder (MDD) (n = 82), subthreshold depression (n = 64) or no depression (n = 218) in adolescence. The association of adolescent depression with earnings in adulthood was analysed using generalised estimating equations. Estimates were adjusted for major child and adolescent psychiatric comorbidities and parental socioeconomic status. The indirect (mediated) effect of depression in early adulthood (ages 19-30) on earnings in mid-adulthood (31-40) was estimated in mediation analysis. The study followed the 'STrengthening the Reporting of OBservational studies in Epidemiology' (STROBE) guidelines. RESULTS: Earnings across early to middle adulthood were lower for participants with a history of a PDD in adolescence than for their non-depressed peers, with an adjusted ratio of mean earnings of 0.85 (0.77-0.95) for females and 0.76 (0.60-0.95) for males. The differences were consistent over time, and more p

Purpose: To present the Uppsala Longitudinal Adolescent Depression Study, initiated in Uppsala, Sweden, in the early 1990s. The initial aim of this epidemiological investigation was to study the prevalence, characteristics and correlates of adolescent depression, and has subsequently expanded to include a broad range of social, economic and health-related long-term outcomes and cost-of-illness analyses. Participants: The source population was first-year students (aged 16-17) in upper-secondary schools in Uppsala during 1991-1992, of which 2300 (93%) were screened for depression. Adolescents with positive screening and sex/age-matched peers were invited to a comprehensive assessment. A total of 631 adolescents (78% females) completed this assessment, and 409 subsequently completed a 15year follow-up assessment. At both occasions, extensive information was collected on mental disorders, personality and psychosocial situation. Detailed social, economic and health-related data from 1993 onwards have recently been obtained from the Swedish national registries for 576 of the original participants and an age-matched reference population (N=200 000). Findings to date: The adolescent lifetime prevalence of a major depressive episode was estimated to be 11.4%. Recurrence in young adulthood was reported by the majority, with a particularly poor prognosis for those with a persistent depressive disorder or multiple somatic symptoms. Adolescent depression was also associated with an increased risk of other adversities in adulthood, including additional mental health conditions, low educational attainment and problems related to intimate relationships. Future plans: Longitudinal studies of adolescent depression are rare and must be responsibly managed and utilised. We therefore intend to follow the cohort continuously by means of registries. Currently, the participants are approaching mid-adulthood. At this stage, we are focusing on the overall long-term burden of adolescent depre

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD). METHODS: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram (20mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605. FINDINGS: Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n=24) as compa, Vanda Faria and Malin Gingnell contributed equally

BACKGROUND: An individual's subjective perception of well-being is increasingly recognized as an essential complement to clinical symptomatology and functional impairment in children's mental health. Measurement of quality of life (QoL) has the potential to give due weight to the child's perspective. SCOPE AND METHODOLOGY: Our aim was to critically review the current evidence on how childhood mental disorders affect QoL. First, the major challenges in this research field are outlined. Then we present a systematic review of QoL in children and adolescents aged 0-18 years formally diagnosed with a mental and behavioural disorder, as compared to healthy or typically developing children or children with other health conditions. Finally, we discuss limitations of the current evidence base and future directions based on the results of the systematic review and other relevant literature. FINDINGS AND CONCLUSIONS: The systematic review identified 41 eligible studies. All were published after the year 2000 and 21 originated in Europe. The majority examined QoL in neurodevelopmental disorders, including attention-deficit hyperactivity disorder (k = 17), autism spectrum disorder (k = 6), motor disorders (k = 5) and intellectual disability (k = 4). Despite substantial heterogeneity, studies demonstrate that self-reported global QoL is significantly reduced compared to typical/healthy controls across several disorders and QoL dimensions. Parents' ratings were on average substantially lower, casting doubt on the validity of proxy-report. Studies for large diagnostic groups such as depressive disorders, anxiety disorders, (early onset) schizophrenia and eating disorders are largely lacking. We conclude that representative, well-characterized normative and clinical samples as well as longitudinal and qualitative designs are needed to further clarify the construct of QoL, to derive measures of high ecological validity, and to examine how QoL fluctuates over time and is attributable

Social anxiety disorder (SAD) is associated with altered brain function and structure, but most structural studies include small samples and findings are mixed. This study compared regional gray matter volume between 48 SAD patients and 29 healthy controls (HC) as well as the relationship between volume and symptom severity. Structural magnetic resonance images from SAD patients and HC were evaluated using standard voxel-based morphometry (VBM) processing in the SPM8 software package. Social anxiety symptom severity was rated in SAD patients by a clinician using the Liebowitz Social Anxiety Scale (LSAS). SAD patients had greater regional gray matter volume in the lingual gyrus and lateral occipital cortex than the controls, and within the SAD group a positive correlation was found between symptom severity and regional gray matter volume in the lingual gyrus and the retrosplenial cortex. These findings replicate and extend earlier reports of enlarged visual processing areas in SAD. Increased gray matter volume in regions involved in visual processing and self-consciousness could underlie, or be the result of, abnormal emotional information processing and self-focused attention previously demonstrated in patients with SAD.