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Background: Major depression is the most common psychiatric disorder, associated with the highest disease burden worldwide when it comes to years lost to disability. Efforts to identify indicators of depression risk have strongly implicated depressive rumination, a negative thinking style characterized by repetitive and passive thoughts about the causes, meanings, and consequences of one's feelings and distress. An increasingly popular theoretical perspective posits that over time depressive rumination becomes a mental habit that is initiated automatically without conscious awareness or intent in response to downward shifts in mood, making it persistent and difficult to control. However, the rumination as-a-habit account has rarely been directly tested and it is still unknown whether depression vulnerability is characterized by elevated levels of mood-reactive habitual rumination at the level of short-term dynamics. Aims: The aim of the current research project was to address gaps in the current knowledge on depression vulnerability by utilizing a combination of experimental and novel mobile in-the-moment assessment strategies to better understand the dynamic interplay between mood and ruminative thinking and its habitual characteristics. Three studies were designed to test specific hypotheses involving: a) effects that fluctuations in mood have on subsequent ruminative thinking, b) the degree to which habitual characteristics of negative thinking predict such mood-reactive rumination, and c) whether mood-reactive rumination varies according to the depression-risk spectrum in line with theoretical accounts of depression vulnerability. Methods: In study 1, a total of 115 university students completed self-report measures and participated in an experimental rumination-induction task and outcome-devaluation task measuring habit vs. goal-directed behaviour control. In study 2, a total of 97 participants recorded affect and rumination ten times daily over six days using Ecological Momentary Assessment, after completing measures of trait ruminative brooding and habitual characteristics of negative thinking (e.g., automaticity, lack of conscious awareness, intent, and control). In study 3, formerly depressed individuals with a recurrent history of depression (n = 94) and non-clinical controls (n = 55) recorded in-the-moment affect and rumination ten times daily over six days, after completing baseline measures of trait ruminative brooding, habitual characteristics of negative thinking, and early-life stress. Results: In study 1, greater habitual characteristics of negative thinking were associated with ruminative brooding but not ruminative reflection, and predicted more persistent dysphoric mood following rumination-induction. Rumination was not, however, consistently associated with an imbalance in habit vs. goal-directed behaviour control. In study 2, momentary fluctuations in negative (increased) and positive (decreased) affect was prospectively associated with greater rumination at the next sampling occasion. The degree to which affect triggered a subsequent ruminative response was moderated by habitual characteristics of negative thinking in a theoretically consistent way. Stronger temporal pairing of negative affect and rumination was also associated with greater emotional inertia but less carry-over of rumination from one moment to the next. In study 3, momentary fluctuations in negative affect were prospectively associated with greater rumination at the next sampling occasion in formerly depressed participants whereas this pattern of mood-reactive rumination was not observed in healthy never-depressed participants. In formerly depressed participants, habitual characteristics of negative thinking were associated with greater mood-reactivity of rumination, particularly among those with a history of early-life stress. Mood-reactive rumination was not, however, associated with depression course nor trait ruminative brooding. Conclusions: The findings of the studies demonstrate that fluctuations in affect can trigger ruminative thinking as a function of habit consistent with recent theoretical frameworks of depression vulnerability. Mood-reactive rumination may be a potential vulnerability marker for depression, with rumination being habitually triggered in response to momentary fluctuations in negative affect with a high degree of automaticity, and with a deleterious effect on mood. The current thesis suggests ways depression vulnerability may emerge as a dynamic relationship between negative affect and rumination across time, not captured by traditional trait measures of rumination frequency. Ecological momentary assessment may be a valuable measurement paradigm to test predictions derived from habit-accounts of depressive rumination, that have rarely been investigated until now, and might provide new insights into research on depression risk., This research was sponsored by the Icelandic Center for Research and the Eimskip Fund of The University of Iceland (Rannís Grant 173803-052, 173803-053).

Publisher's version, Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development., The study was supported by the German Federal Ministry of Education and Research (BMBF), through the Integrated Network IntegraMent, under the auspices of the e:Med programme (grants 01ZX1314A to MMN and SC; 01ZX1314G to MR; 01ZX1614J to BMM) through grants 01EE1406C to MR and 01EE1409C to MR and SHW, and through ERA-NET NEURON, “SynSchiz—Linking synaptic dysfunction to disease mechanisms in schizophrenia—a multilevel investigation” (01EW1810 to MR) and BMBF grants 01EE1409C and 01EE1406C to MR and SHW; by the German Research Foundation (DFG grants FOR2107; RI908/11-2 to MR; NO246/10-2 to MMN; MU1315/8-2 to BMM; WI 3439/3-2 to SHW), by the Andalusian regional Health and Innovation Government (grants PI-0060-2017, RC-0006-2015 the Nicolas Monarde Programme for YDO and CTS-546) and by the Swiss National Science Foundation (SNSF grant 156791 to SC). MMN is a member of the DFG-funded cluster of excellence ImmunoSensation. The PGC has received major funding from the US National Institute of Mental Health and the US National Institute of Drug Abuse (U01 MH109528 and U01 MH1095320). We thank the research participants and employees of 23andMe, Inc. for their contribution to the MDD meta-analysis published in [14]. We thank the International Genomics of Alzheimer's Project (IGAP) for providing summary results data for the present analyses. See the Supplementary Data for extended Acknowledgements.

Publisher's version (útgefin grein), Aims: To describe prevalence of symptoms of anxiety and depression in surgical patients at three time points: at hospital postsurgery (T1), 6 weeks (T2) and 6 months (T3) postdischarge from hospital; and detect situations and experiences that predict symptoms of anxiety and depression at T2 and T3. Design: Prospective, explorative two-site follow-up study. Methods: Patients having selected surgeries from January–July 2016 were invited to participate. Final participation was 390 patients. Participation involved answering questionnaires, including the Hospital Anxiety and Depression Scale (HADS). A stepwise multiple linear regression model was employed to calculate predictors of anxiety and depression. Results: The proportion of patients presenting with moderate-to-severe anxiety or depression ranged from 5.4%–20.2% at different times. Major predictors of anxiety at both times were not feeling rested upon awakening and higher scores on HADS-Anxiety at T1 and T2 and at T2 also experiencing more distressing postoperative symptoms. For depression, the major predictors were at both times higher scores on HADS-Depression at T2 and T3 and also at T2 not feeling rested upon awakening and at T3 reporting delayed or very delayed recovery. The four models explained from 43.9%–55.6% of the variance in symptoms of anxiety and depression. Our findings show that patients presenting with psychological distress at the hospital are in a vulnerable position. Also, that benefits of good sleep during the recovery should be emphasized during hospital stay., The authors thank Guðný Bergþóra Tryggvadóttir, specialist at the Social Science Research Institute at the University of Iceland for providing statistical support, nurses at the Landspítali University and at Akureyri Hospital who participated in data collection and the participants who gave valuable information about themselves.

Sú skoðun að kynslóðin sem nú vex úr grasi sé útsettari fyrir depurð en þær sem á undan hafa komið er útbreidd bæði á meðal almennings og fagaðila. Markmið þessarar rannsóknar var að skoða hvernig algengi daglegrar depurðar íslenskra unglinga breyttist á árunum 2006–2018 og hvaða þættir tengdust daglegri depurð í fyrirlögn árið 2018. Notuð voru gögn úr rannsókninni Heilsa og lífskjör skólabarna (e. Health Behaviour in School-Aged Children - HBSC). Frá árinu 2006 hefur þessi rannsókn verið lögð fyrir í 6., 8. og 10. bekk á Íslandi og í síðustu fyrirlögn veturinn 2017–2018 fengust svör frá 7.159 nemendum. Niðurstöðurnar sýndu að tíðni daglegrar depurðar hafði aukist um þriðjung á tímabilinu, eða úr 5,8% árið 2006 í 7,6% árið 2018. Mjög slæm fjárhagsstaða fjölskyldu og svefnörðugleikar á hverri nóttu 25-földuðu líkurnar á því að unglingar fyndu fyrir depurð á hverjum degi. Að finnast maður vera alltof feitur 13-faldaði líkurnar, tíð áfengisneysla tífaldaði þær og einelti oft í viku nífaldaði þær. Þeir unglingar sem skilgreindu kyn sitt sem „annað“ en strákur eða stelpa, voru átta sinnum líklegri en jafnaldrar þeirra til að finna fyrir depurð daglega. Sama átti við um þá sem reyktu sígarettur eða kannabis reglulega. Fimmföldun á áhættu sást meðal þeirra sem notuðu rafrettur reglulega, áttu slök tengsl við foreldra eða við skóla. Slök vinatengsl þrefölduðu líkurnar. Aðrir þættir sem um það bil tvöfölduðu líkurnar voru annað fæðingarland unglings en Ísland og fæðingarland foreldra hans. Stelpur voru líka tvöfalt líklegri en strákar til að finna fyrir depurð nær daglega. Enn aðrir þættir höfðu veikari fylgni. Þannig voru 10. bekkingar helmingi líklegri en 6. bekkingar til að finna fyrir depurð daglega og óeðlileg skjánotkun jók líkurnar um 60%. Af niðurstöðunum má ráða að tíðni daglegrar depurðar meðal íslenskra unglinga hefur sannarlega aukist. Ýmsir þættir hafa fylgni við depurð unglinga en líklegast er að aukning í svefnörðugleikum skýri mest af þeirri aukningu sem sést., Although it is perfectly normal to experience a low mood every now and then during adolescence as in other periods of the life-span, chronic sadness during this period can be a precursor to serious and repeated bouts of depression, anxiety, substance abuse and suicidal behavior. The current generation of adolescents is generally thought, both by the public as well as professionals, to be more susceptible to sadness than previous generations. How susceptible adolescents are to serious bouts of sadness is related to a number of concurrent factors that have to do with genetics, development and social status. The aim of the current study was to document changes in the prevalence of daily sadness amongst Icelandic adolescents from 2006–2018, and identify factors related to daily sadness in 2018. The study is based on information gathered as part of the project Health Behaviour in School-aged Children (HBSC) in which adolescents are asked about various issues relating to health, well-being and social situation. This data has been collected in Iceland every fourth year from 2006 and in the final phase of 2017–2018 a total of 7,159 students responded to the questionnaire. Prior to data collection, the questionnaire, together with a research plan, was submitted to the Icelandic Data Protection Authority and the University of Iceland Ethics Committee, neither of which had any reservations regarding the procedure. Subsequently, the same information was sent to all headmasters in Iceland in schools that had students in 6th, 8th or 10th grade, requesting their permission to conduct the study. As a follow-up, all parents and guardians received a letter of introduction with clear instructions as to how to decline a child’s participation. In the 2017–2019 phase, the questionnaire was in digitized form. The tables in the school-room were moved apart to ensure that students could not see one another’s answers. Then each student accessed the document on their computer. In the beginning there was a short introduction to the study accompanied by a clear statement that even though the study had been approved by school authorities and parents, the students were under no obligation to participate. The anonymity of answers was also emphasized. The results show that the prevalence of daily sadness had increased by a third from 2006 to 2018, from 5.8% to 7.6% respectively. Adolescents coming from the poorest homes and those experiencing sleep difficulties almost every night had an almost 25-fold risk of daily sadness. Adolescents that experience themselves as being far too fat have a 13-fold risk, using alcohol frequently increased it tenfold and being bullied often every week increased the risk ninefold. Adolescents identifying their sex as “Other” than male or female were eight times more likely to experience daily sadness, as were those who frequently smoked cigarettes or cannabis. A fivefold increase in risk was seen amongst most frequent users of e-cigarettes, as well as among those who had poor relations with parents or school. Poor relations with friends tripled the risk. Other factors that approximately doubled the risk were immigration status, and female compared with male gender. Other variables had less impact. Tenth graders were around 50% more likely than sixth graders to experience sadness on a daily basis and disordered use of social media caused a 60% increase. From these results one can conclude that the prevalence of daily sadness amongst Icelandic adolescents has indeed increased during the period from 2006 to 2018. Various factors influence the likelihood of daily sadness but the increase noted is probably related to upsurge in sleeping difficulties. It is important to make risk prevention easier, cheaper and more accessible to adolescents. Emphasis needs to be placed on coping skills, life skills, nurturing communication and healthy life-styles. In Iceland parents need to pay particular attention to their children’s sleeping habits, schools need to focus on reducing bullying and school stress, and society as a whole should stop stigmatizing adolescents based on gender, race, sexual orientation, body composition, economic status or skills.

Aims: This research was designed to explore the extent to which the use of alcohol or drugs by one member of a family affects the psychosocial state of other family members. The study asks whether family members of substance abusers are more likely to report increased depression, anxiety and stress then the general population in Iceland? Are there significant differences between family members; e.g., spouses, parents, adult children and siblings by gender, age, education and income? Data and methods: The instrument used for this purpose is the Depression Anxiety Stress Scale (DASS), which is designed to measure those three related mental states. It was administered to 143 participants (111 women and 32 men) with ages ranging from 19–70 years on the first day of a four-week group therapy programme for relatives of substance use disorder (SUD) at The Icelandic National Centre for Addiction Treatment (SÁÁ) from August 2015 to April 2016. Thirty participants are adult children of a parent with SUD, 47 are a spouse, 56 are parents of a child with SUD and 10 are siblings. The subscales of the DASS for depression, anxiety, and stress were utilised to examine which family member – parent, child, partner, or sibling – presented the behaviour associated with SUD. Results: 36% or more of the respondents in all three subscales had average, serious, or very serious depression, anxiety, and/or stress. This is higher than in DASS studies of the general population in Iceland. However, the analysis indicates that it made little difference to the family’s wellbeing which family member was affected by SUD., The University of Iceland Research fund

Publisher's version (útgefin grein), Objective: To evaluate the effect of intrusive thoughts at diagnosis on quality of life, depressed mood and waking up with anxiety up to two years after radical prostatectomy. Method: The Laparoscopic Prostatectomy Robot Open (LAPPRO) trial was a prospective, longitudinal multicenter study of 4003 patients undergoing radical prostatectomy. Questionnaire data were collected preoperatively, at 3, 12 and 24 months after surgery. Results: The group of patients with intrusive thoughts at diagnosis had a statistically significant higher postoperative prevalence of impaired quality of life, depressed mood and waking up with anxiety as compared with the group of patients with no or minor intrusive thoughts. The highest risk increase for impaired QoL, depressed mood and waking up with anxiety ≥1/week was at 12, 3 and 3 months, respectively, where the three outcomes increased by 38% (RR: 1.38; 95%CI: 1.27–1.49)), 136% (RR: 2.36; 95%CI: 1.74–3.19)) and 165% (RR: 2.65; 95%CI: 2.22–3.17)), respectively. Conclusions: The demonstrated link between intrusive thoughts and quality of life, depressed mood and waking up with anxiety deliver is further evidence to the idea that intrusive thoughts has potential as an endpoint for assessing and predicting psychological distress among men with prostate cancer diagnosis. Trial registration number: ISRCTN06393679 (www.isrctn.com). Date of registration: 07/02/2008. Retrospectively registered., This study was supported by research grants from the Swedish Cancer Society [2008/922, 2010/593, 2016/362], The Swedish Research Council [2012?1770, 2015?02483], ALF grants [138751, 146201 and 4307771, HTA?VGR 6011], the Mrs. Mary von Sydow Foundation, the Anna and Edvin Berger Foundation and the Assar Gabrielsson?s Foundation [FB 18-19]. The authors gratefully acknowledge the participants in the LAPPRO trial.

Publisher's version (útgefin grein), Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR, The present study is supported by a Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (STRADL) (Reference 104036/Z/14/Z) and MRC Mental Health Data Pathfinder Award (Reference MC_PC_17209). Data acquisition and analyses were conducted using the UK Biobank Resource under approved project #4844. Participation of the UK Biobank subjects is gratefully appreciated. We also thank UK Biobank team for collecting and preparing data for analyses. Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. The PGC has received major funding from the US National Institute of Mental Health (5 U01MH109528-03). We thank the research participants and employees of 23andMe for supporting this study. X.S. receives support from China Scholarship Council (No. 201506040037). H.C.W. is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. D.M.H. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Reference 213674/Z/18/Z) and a 2018 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Reference 27404). W.D.H. is supported by a grant from Age UK (Disconnected Mind Project). A.M.M. is supported by the Sackler Trust. I.J.D. is a participant in UK Biobank.

Publisher's version (útgefin grein), Objective Few studies have explored the potential interrelated associations of screen time and physical activity with mental health in youth, particularly using objective methods. We examined cross-sectional associations of these variables among Icelandic adolescents, using objective and subjective measurements of physical activity. Methods Data were collected in the spring of 2015 from 315 tenth grade students (mean age 15.8 years) in six elementary schools in metropolitan Reykjavík, Iceland. Participants reported, via questionnaire, on demographics, weekly frequency of vigorous physical activity, daily hours of screen time and mental health status (symptoms of depression, anxiety and somatic complaints, self-esteem and life satisfaction). Total physical activity was measured over one week with wrist-worn accelerometers. Body composition was determined by DXA-scanning. Poisson regression analysis was used to explore independent and interactive associations of screen time and physical activity with mental health variables, adjusting for gender, body fat percentage and maternal education. Results Less screen time (below the group median of 5.3 h/day) and more frequent vigorous physical activity (≥4x/week) were each associated with reporting fewer symptoms of depression, anxiety, low self-esteem, and life dissatisfaction. No significant associations were observed between objectively measured physical activity and mental health outcomes. Interactive regression analysis showed that the group reporting both less screen time and more frequent vigorous physical activity had the lowest risk of reporting symptoms of depression, anxiety, low self-esteem, and life dissatisfaction. Conclusions Reports of less screen time and more frequent vigorous physical activity were associated with lower risk of reporting mental health problems among Icelandic adolescents. Those who reported a combination of engaging in less screen time and more frequent vigorous physical activity had the lowest risk, suggesting a synergistic relationship between the two behaviors on mental health outcomes. Our results support guiding youth towards more active and less sedentary/screen-based lifestyle., The study was funded by The University of Iceland Research Fund (grant number HI16120043, http://sjodir.hi.is/node/16129; authors receiving grant: smh, saa) and the Icelandic Centre for research (RANNIS) (grant number 152509-051, https://en.rannis.is/funding/research/icelandic-research-fund/, all authors).

Töflur eru aftast í skjalinu, The literature on sexual minority adolescents and young adults has highlighted a poor mental status among those groups compared to their heterosexual peers. Sexual minorities are also more likely to experience stress factors such as bullying and physical violence. However, sexual minority young adults have not been studied much in Iceland, a Nordic country renowned for a high degree of sexual equality. Given what the literature has shown to date, a noteworthy question is whether patterns of mental well-being of sexual minority adolescents and young adults in Iceland are comparable to other countries. The aim of the present study was to provide an assessment of mental well-being in sexual minority young adults in Iceland. We used population data to examine a selection of mental well-being indicators in 16–20 year-olds, both-sex-attracted and same-sex-attracted participants, and compared them to other-sex-attracted peers. Findings indicated that sexual minority young adults exhibited significantly greater levels of depressed mood, anger, and perceived stress than other-sex-attracted young adults. However, when stratified by gender and sexual attraction pattern, the analyses revealed that both-sex-attracted young women scored significantly higher on all indicators than any other group. We conclude that studies in this area should strive to distinguish between same-sex and both-sex attraction as well as to stratify analyses by gender. The well-being of both-sex-attracted young women is a compelling topic for future research.

Publisher's version (útgefin grein), Introduction: Several monoclonal antibodies (mAbs) have been linked to neuropsychiatric adverse efects in patients, including depression and suicidal ideation and behavior. Objective: The aim of this study was to quantify and characterize spontaneously reported adverse drug reactions (ADRs) of depression and suicidal ideation and behavior related to mAb users, and to explore a possible association with their mechanism of action. Methods: We included mAb ADRs that were reported in VigiBase, and identifed those related to depression and suicidal ideation and behavior. Reporting odds ratios (RORs) were estimated for each mAb (bevacizumab as the reference) and according to their infuence on the immune system (not directly targeting [reference], stimulating, or suppressing). Those suppressing the immune system were further divided into their intended indication (auto-immune diseases, cancer). Results: Overall, 2,924,319 ADRs for 44 mAbs were included; 9455 ADRs were related to depression and 1770 were related to suicidal ideation and behavior. The association was strongest for natalizumab and belimumab, both for depression (ROR 5.7, 95% confdence interval [CI] 5.0–6.4; and ROR 5.1, 95% CI 4.2–6.2) and suicidal ideation and behavior (ROR 12.0, 95% CI 7.9–18.3; and ROR 20.2, 95% CI 12.4–33.0). Those suppressing the immune system showed higher ROR, i.e. 1.9 (95% CI 1.8–2.0) for depression and 3.6 (95% CI 3.0–4.4) for suicidal ideation and behavior. This fnding was only seen for mAbs used for treating autoimmune diseases. Conclusion: Depression and suicidal ideation and behavior are seen in patients using mAbs, particularly mAbs used for treating autoimmune diseases that suppress the immune system. For interpretation of these data, the indications for use and other characteristics require further consideration., No external sources of funding were used to assist in the preparation of this article. The authors would like to thank the Uppsala Monitoring Centre for providing the data.