| 1. |
- Nehme, Ralda, et al.
(författare)
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The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia
- 2022
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear how the 22q11.2 deletion predisposes to psychiatric disease. To study this, we generated induced pluripotent stem cells from deletion carriers and controls and utilized CRISPR/Cas9 to introduce the heterozygous deletion into a control cell line. Here, we show that upon differentiation into neural progenitor cells, the deletion acted in trans to alter the abundance of transcripts associated with risk for neurodevelopmental disorders including autism. In excitatory neurons, altered transcripts encoded presynaptic factors and were associated with genetic risk for schizophrenia, including common and rare variants. To understand how the deletion contributed to these changes, we defined the minimal protein-protein interaction network that best explains gene expression alterations. We found that many genes in 22q11.2 interact in presynaptic, proteasome, and JUN/FOS transcriptional pathways. Our findings suggest that the 22q11.2 deletion impacts genes that may converge with psychiatric risk loci to influence disease manifestation in each deletion carrier.
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| 2. |
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| 3. |
- Kowalec, Kaarina, et al.
(författare)
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Increased schizophrenia family history burden and reduced premorbid IQ in treatment-resistant schizophrenia : a Swedish National Register and Genomic Study
- 2021
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 26, s. 4487-4495
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Tidskriftsartikel (refereegranskat)abstract
- A high proportion of those with schizophrenia experience treatment non-response, placing them at higher risk for mortality and suicide attempts, compared to treatment responders. The clinical, social, and economic burden of treatment-resistant schizophrenia (TRS) are substantial. Previous genomic and epidemiological studies of TRS were often limited by sample size or lack of comprehensive genomic data. We aimed to systematically understand the clinical, demographic, and genomic correlates of TRS using epidemiological and genetic epidemiological modelling in a Swedish national population sample (n = 24,706) and then in a subgroup with common variant genetic risk scores, rare copy-number variant burden, and rare exonic burden (n = 4936). Population-based analyses identified increasing schizophrenia family history to be significantly associated with TRS (highest quartile of familial burden vs. lowest: adjusted odds ratio (aOR): 1.31, P = 4.8 × 10-8). In males, a decrease of premorbid IQ of one standard deviation was significantly associated with greater risk of TRS (minimal aOR: 0.94, P = 0.002). In a subset of cases with extensive genomic data, we found no significant association between the genetic risk scores of four psychiatric disorders and two cognitive traits with TRS (schizophrenia genetic risk score: aOR = 1.07, P = 0.067). The association between copy number variant and rare variant burden measures and TRS did not reach the pre-defined statistical significance threshold (all P ≥ 0.005). In conclusion, direct measures of genomic risk were not associated with TRS; however, premorbid IQ in males and schizophrenia family history were significantly correlated with TRS and points to new insights into the architecture of TRS.
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| 4. |
- Kowalec, Kaarina, et al.
(författare)
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The association between family history and genomic burden with schizophrenia mortality : a Swedish population-based register and genetic sample study
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with schizophrenia (SCZ) have a 2-3-fold higher risk of mortality than the general population. Heritability of mortality in psychiatric disorders has been proposed; however, few have investigated SCZ family history and genetic variation, with all-cause and specific causes of death. We aimed to identify correlates of SCZ mortality using genetic epidemiological and genetic modelling in two samples: a Swedish national population sample and a genotyped subsample. In the Swedish national population sample followed from the first SCZ treatment contact until emigration, death or end of the follow-up, we investigated a standardised measure of SCZ family history. In a subgroup with comprehensive genetic data, we investigated the impact of common and rare genetic variation. Cox proportional hazards regression was used to estimate the association between various factors and mortality (all and specific causes). A total of 13727 SCZ cases fulfilled criteria for the population-based analyses (1268 deaths, 9.2%). The genomic subset contained 4991 cases (1353 deaths, 27.1%). Somatic mutations associated with clonal hematopoiesis with unknown drivers were associated with all-cause mortality (HR 1.77, 95% CI: 1.26-2.49). No other heritable measures were associated with all-cause mortality nor with any specific causes of death. Future studies in larger, comparable cohorts are warranted to further understand the association between hereditary measures and mortality in SCZ.
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| 5. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 6. |
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| 7. |
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| 8. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Fifteen years after a ferry disaster : Clinical interviews and survivors’ self-assessment of their experience
- 2013
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Ingår i: European Journal of Psychotraumatology. - : Informa UK Limited. - 2000-8198 .- 2000-8066. ; 4, s. 20650-
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Tidskriftsartikel (refereegranskat)abstract
- Background:Disasters yield increased rates of psychological disorders decades later. Other consequences, however, have received little attention in the past.Objective:We aimed to examine diagnostic status and survivors’ views on disaster-related consequences and social support.Methods:A mixed-methods approach was used with 22 survivors (of 49 eligible) 15 years after a ferry disaster. Data collection included audiotaped interviews with open-ended questions and diagnostic assessment of Axis-I disorders.Results:The post-disaster incidence was 54% (12/22) for Axis-I disorders, and 45% (10/22) for full or subsyndromal posttraumatic stress disorder. Thematic analysis revealed that survivor perception of the longterm consequences included positive (character change) and negative aspects (being ascribed a survivor identity). Participants’ sought social support for several years, yet many felt hindered by experiential dissimilarity and distress of significant others.Conclusions:Axis-I disorders were prevalent, but not salient to survivors’ perceptions in the long-term. Postdisaster interventions need to attend to common barriers to support.
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| 9. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Prospective longitudinal long-term studies 14-20 years after three disasters
- 2011
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Ingår i: European Journal of Psychotraumatology. ; , s. 72-72
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Konferensbidrag (refereegranskat)abstract
- Although clinical experience and past research have shown that posttraumatic stress (PTS) can last for decades after a disaster, long-term follow-ups are scarce and little is known about predictors of chronic PTS. In this presentation, long-term consequences of disasters will be described by a summary of the findings from three surveys of man-made/technological disasters with 2-4 assessments during the first 34-4 years and with a long-term assessment of PTSD and general mental health after 14-20 years (Ns = 33-57). Similarities and dissimilarities in the course of PTS between the disasters will be presented. The influence of traumatic bereavement, psychological or pharmacological treatment, and additional negative life events on long-term PTS will be discussed, and experiences form conducting long-term studies will be communicated.
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| 10. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Psychiatric disorders and suicide attempts in Swedish survivors of the 2004 southeast Asia tsunami : a 5 year matched cohort study
- 2015
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Ingår i: The Lancet Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2215-0366 .- 2215-0374. ; 2:9, s. 817-824
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSurvivors of natural disasters are thought to be at an increased risk of psychiatric disorders, however the extent of this risk, and whether it is linked to pre-existing psychopathology, is not known. We aimed to establish whether Swedish survivors of tsunamis from the 2004 Sumatra–Andaman earthquake had increased risks of psychiatric disorders and suicide attempts 5 years after repatriation.MethodsWe identified Swedish survivors repatriated from southeast Asia (8762 adults and 3742 children) and 864 088 unexposed adults and 320 828 unexposed children matched for sex, age, and socioeconomic status. We retrieved psychiatric diagnoses and suicide attempts from the Swedish patient register for the 5 years after the tsunami (from Dec 26, 2004, to Jan 31, 2010) and estimated hazard ratios (HRs), then adjusted for pre-tsunami psychiatric disorders, and, for children, for parental pre-tsunami disorders.Findings Exposed adults were more likely than unexposed adults to receive any psychiatric diagnosis (547 [6.2%] vs 47 734 [5.5%]; adjusted HR 1.21, 95% CI 1.11–1.32), particularly stress-related disorders (187 [2.1%] vs 8831 [1.0%]; 2.27, 1.96–2.62) and suicide attempts (38 [0.43%] vs 2752 [0.32%]; 1.54, 1.11–2.13), but not mood or anxiety disorders. Risk of psychiatric diagnoses did not differ between exposed and unexposed children and adolescents (248 [6.6] vs 22 081 [6.9%]; 0.98, 0.86–1.11), although exposed children and adolescents had a higher risk for suicide attempts with uncertain intent (1.43; 1.01–2.02) and stress-related disorders (1.79; 1.30–2.46), mainly during the first 3 months after the tsunami.InterpretationThe 2004 tsunami was, independently of previous psychiatric morbidity, associated with an increased risk of severe psychopathology, mainly stress-related disorders and suicide attempts, in children and adults. Survivors of natural disasters should be targeted with early interventions and active long-term follow-up to prevent, detect, and alleviate psychiatric disorders that might follow.
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| 11. |
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| 12. |
- Arnberg, Filip K, 1981-, et al.
(författare)
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Social support moderates posttraumatic stress and general distress after disaster
- 2012
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 25:6, s. 721-727
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Tidskriftsartikel (refereegranskat)abstract
- Social support buffers the negative impact of stressful events. Less, however, is known about the characteristics of this association in the context of disaster and findings have been discrepant regarding direct and buffering effects. This study tested whether the protective effects of social support differed across levels of exposure severity (i.e., buffered distress) and assessed whether the buffering effect differed between event-specific and general distress. Participants were 4,600 adult Swedish tourists (44% of invited; 55% women) repatriated within 3 weeks after the 2004 Indian Ocean tsunami. A survey 14 months after the disaster included the Crisis Support Scale, the Impact of Event Scale-Revised (IES-R), and the General Health Questionnaire (GHQ-12). Social support buffered the negative impact of exposure on both outcomes. The support and distress association ranged from very small in participants with low exposure to moderate in those with high exposure (ηp2 = .004 to .053). The buffering effect was not found to differ between the IES-R and GHQ-12, F(2, 4589) = 0.87, p = .42. The findings suggest that social support moderates the stressor-distress relationship after disasters. This study might help explain discrepant findings and point to refinements of postdisaster interventions.
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| 13. |
- Arnberg, Filip K, et al.
(författare)
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Traumatic bereavement, acute dissociation, and posttraumatic stress : 14 years after the MS Estonia disaster
- 2011
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 24:2, s. 183-190
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Tidskriftsartikel (refereegranskat)abstract
- This prospective longitudinal study aimed to examine posttraumatic stress in survivors 14 years after a ferry disaster, and estimate short- and long-term changes in stress associated with traumatic bereavement and acute dissociation. There were 852 people who perished in the disaster, 137 survived. The 51 Swedish survivors were surveyed with the Impact of Event Scale-Revised (IES-R) at 3 months, 1, 3, and 14 years (response rates 82%, 65%, 51%, and 69%). Symptoms decreased from 3 months to 1 year; no change was found thereafter. After 14 years, 27% reported significant symptoms. Traumatic bereavement, but not acute dissociation, was associated with long-term symptom elevation. Chronic posttraumatic stress can persist in a minority of survivors, and traumatic bereavement appears to hinder recovery.
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| 14. |
- Arnberg, Filip, 1981-
(författare)
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Long-Term Posttraumatic Stress in Survivors from Disasters and Major Accidents
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Disasters and major accidents are a significant cause of distress worldwide. High levels of posttraumatic stress can become chronic after severe and prolonged psychological trauma, raising concerns about the extent of adverse long-term consequences after single events. The present thesis aimed to describe the course and burden of posttraumatic stress in survivors from a ferry disaster in the Baltic Sea, an airliner crash-landing in Gottröra, Sweden, and a bus accident involving Swedish 6th grade schoolchildren in Måbødalen, Norway. The participants were surveyed 1 month to 4 years after the events and again after 14 to 20 years. The follow-up surveys included 33 ferry disaster survivors, 70 airline survivors, and 7 surviving schoolchildren with a comparison group from the same school (n = 33). Short- and long-term changes in posttraumatic stress were estimated separately in generalised regression models refined by linear splines. In-depth interviews were conducted with 22 ferry survivors 15 years after the disaster, including structured clinical interviews and thematic analysis of survivors’ descriptions of consequences of the event and social support. Approximately half of all survivors experienced significant posttraumatic stress at the initial assessments. Significant long-term distress was noted in one fourth of the ferry survivors and one sixth of the airline survivors. The bus crash was not associated with significant long-term posttraumatic stress. A poorer long-term outcome was noted in women and in bereaved survivors. The thematic analysis revealed that long-term consequences not only included negative aspects but also positive ones, including personal growth and existential awareness. There was ample availability of social support, although the need for support extended over a period of several years. Barriers to support from significant others were described in detail by the survivors. The results extend previous research by providing a comprehensive account of long-term consequences of disasters and major accidents in light of early reactions. The interviews provide some new insights into features of social support that warrant further study. Important future challenges include evaluating whether timely attention to survivors at risk for chronic distress and significant others can facilitate recovery.
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| 15. |
- Bahmanyar, S., et al.
(författare)
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Risk of suicide among operated and non-operated patients hospitalised for peptic ulcers
- 2009
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Ingår i: Journal of Epidemiology and Community Health. - : BMJ. - 0143-005X .- 1470-2738. ; 63:12, s. 1016-1021
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Tidskriftsartikel (refereegranskat)abstract
- Background: Some small studies have reported high risk of suicide after surgical treatment for peptic ulcer. The aim of the present study was to explore the risk of suicide in hospitalised gastric ulcer and duodenal ulcer patients separately among operated and non-operated cohorts. Methods: Retrospective cohorts of 163 579 non-operated patients with gastric ulcer or duodenal ulcer and 28 112 patients with surgical treatment for ulcer, recorded in the Swedish Inpatient Register since 1965, were followed from the first hospitalisation, or operation for the surgery cohort, until death, any cancer, emigration, or 31 December 2003. Standardised mortality ratios (SMRs) were calculated, and Poisson regression produced adjusted relative risk estimates among operated and non-operated patients. Results: Non-operated patients hospitalised for peptic ulcer showed a 70% excess risk of suicide (SMR 1.7, 95% CI 1.6 to 1.9) and those who underwent operation had a 60% increased risk (SMR 1.6, 95% CI 1.4 to 1.8). The risk of suicide was very high during the first year after hospitalisation (SMR 4.0, 95% CI 3.4 to 4.7) and more marked among women, patients under 70 and patients hospitalised without complications of ulcer. Both gastric ulcer and duodenal ulcer patients had high risk of suicide completion. Conclusion: Hospitalised patients with gastric ulcer or duodenal ulcer have an increased risk of suicide regardless of surgical treatment. These patients, especially women, are at very high risk during the first year after first hospitalisation/operation. The evaluation and management of suicidal thoughts in patients in medical settings should be further considered.
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| 16. |
- Bergdahl, Björn, et al.
(författare)
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In the Forefront of Development:The New Undergraduate Medical Curriculu
- 2006. - 1
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Ingår i: Celebrating the Past by Expanding the Future: The Faculty of Health Science, Linköping University 1986–2006. - Linköping : Linköping University Electronic Press. - 9185643076 ; , s. 98-102
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 17. |
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| 18. |
- Bergh Johannesson, Kerstin, 1949-, et al.
(författare)
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Impact of Exposure to Trauma on Posttraumatic Stress Disorder Symptomatology in Swedish Tourist Tsunami Survivors
- 2009
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Ingår i: Journal of Nervous and Mental Disease. - 0022-3018 .- 1539-736X. ; 197:5, s. 316-323
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to examine long-term mental health and posttraumatic stress symptomatology in a Swedish tourist population after exposure to the 2004 Southeast Asian tsunami. Data from 4822 returned questionnaires 14 months after the disaster were analyzed. Respondents were categorized into 3 subgroups: (1) danger-to-life exposure group (having been caught or chased by the waves), (2) nondanger-to-life exposure group (exposed to other disaster-related stressors), and (3) low exposure group. Main outcome measures were General Health Questionnaire-12 and Impact of Event Scale-22-Revised. Danger-to-life exposure was an important factor in causing more severe posttraumatic stress symptoms and in affecting mental health. Female gender, single status, and former trauma experiences were associated with greater distress. Other factors related to more severe symptoms were loss of relatives, physical injuries, viewing many dead bodies, experiencing life threat, and showing signs of cognitive confusion. Disaster exposure has a substantial impact on survivors, which stresses the need for long-lasting support.
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| 19. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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Prolonged Grief Among Traumatically Bereaved Relatives Exposed and Not Exposed to a Tsunami
- 2011
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 24:4, s. 456-464
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Tidskriftsartikel (refereegranskat)abstract
- Numerous studies on the mental health consequences of traumatic exposure to a disaster compare those exposed to those not exposed. Relatively few focus on the effect of the death of a close relative caused by the disaster-suffering a traumatic bereavement. This study compared the impact on 345 participants who lost a close relative in the 2004 Indian Ocean tsunami, but who were themselves not present, to 141 who not only lost a relative, but also were themselves exposed to the tsunami. The focus was on psychological distress assessed during the second year after the sudden bereavement. Findings were that exposure to the tsunami was associated with prolonged grief (B = 3.81) and posttraumatic stress reactions (B 665), and doubled the risk for impaired mental health. Loss of children increased the risk for psychological distress (prolonged grief B = 692; The Impact of Event Scale-Revised: B = 610; General Health Questionnaire-12: OR = 2.34). Women had a higher frequency of prolonged grief For men, loss of children presented a higher risk for prolonged grief in relation to other types of bereavement (B = 636 vs. loss of partner). Further long-term follow-up could deepen the understanding of how recovery after traumatic loss is facilitated.
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| 20. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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The effect of Traumatic Bereavement on Tsunami-Exposed Survivors
- 2009
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Ingår i: Journal of Traumatic Stress. - : Wiley. - 0894-9867 .- 1573-6598. ; 22:6, s. 497-504
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Tidskriftsartikel (refereegranskat)abstract
- Fourteen months after the 2004 tsunami, mental health outcome was assessed in 187 bereaved relatives, 308 bereaved friends, and in 3,020 nonbereaved Swedish survivors. Of the bereaved relatives, 41% reported posttraumatic stress reactions and 62% reported impaired general mental health. Having been caught or chased by the tsunami in combination with bereavement was associated with increased posttraumatic stress reactions. Complicated grief reactions among relatives were almost as frequent as posttraumatic stress reactions. The highest levels of psychological distress were found among those who had lost children. Traumatic bereavement, in combination with exposure to life danger, is probably a risk factor for mental health sequelae after a natural disaster.
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| 21. |
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| 22. |
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| 23. |
- Bergh Johannesson, Kerstin, 1949-
(författare)
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Traumatic Exposure, Bereavement and Recovery among Survivors and Close Relatives after Disasters
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- International studies of disasters indicate the risk for developing posttraumatic stress reactions among survivors is high. Modern life implicates increased traveling. During the last decades a large number of Swedish citizens were confronted with disasters taking place outside of their country. The prevalence of trauma reactions in a population that does not normally experience natural disasters, but are able to return to a community unaffected by the catastrophe, is not well studied. In addition, the effects of bereavement after traumatic circumstances have not been satisfactorily explored. Longitudinal studies on the effects of natural disasters are underrepresented and there are few studies investigating the course of recovery after traumatic exposure. The aim for this thesis was to examine long-term post-traumatic stress reactions, mental health, and complicated grief after disaster exposure and traumatic bereavement. Data from returned questionnaires were analysed from bereaved Italian and Swedish relatives 18 months after the Linate airplane disaster 2001, and at 14 months and three years from Swedish travelers returning from Southeast Asia after the 2004 tsunami disaster, and from home staying bereaved relatives within the second year after the tsunami disaster. The main outcome measures were GHQ-12, IES-R and Inventory of Complicated Grief. The findings indicated many survivors were resilient and had ability to recover, but severe exposure to a disaster had considerable impact on psychological distress. Life threat was associated with higher levels of post-traumatic stress reactions, and increased the risk for affected mental health and suicidal ideation. Loss in combination with severe life threat exposure indicated a further increased risk of posttraumatic stress reactions and for complicated grief; this should be considered a substantial risk factor for general mental health. Loss of close relatives, especially loss of children, was associated with higher levels of posttraumatic stress and created a greater risk for complicated grief. Many survivors recovered over time; however, severe exposure and traumatic loss appeared to slow the recovery process. The findings have implications for government and health agencies, regarding the importance of knowledge and awareness of these risks for health, and for organizational structure, training, and accessibility of support and adequate treatment.
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| 24. |
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| 25. |
- Bergh Johannesson, Kerstin, et al.
(författare)
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Tsunami-exposed tourist survivors : Signs of recovery in an 3-year perspective
- 2011
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Ingår i: Journal of Nervous and Mental Disease. - 0022-3018 .- 1539-736X. ; 199:3, s. 162-169
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Tidskriftsartikel (refereegranskat)abstract
- Long-term follow-up after disaster exposure indicates increased rates of psychological distress. However, trajectories and rates of recovery in large samples of disaster-exposed survivors are largely lacking. A group of 3457 Swedish survivors temporarily on vacation in Southeast Asia during the 2004 tsunami were assessed by postal questionnaire at 14 months and 3 years after the tsunami regarding post-traumatic stress reactions (IES-R) and general mental health (GHQ-12). There was a general pattern of resilience and recovery 3 years postdisaster. Severe exposure and traumatic bereavement were associated with increased post-traumatic stress reactions and heightened risk for impaired mental health. The rate of recovery was lower among respondents exposed to life threat and among bereaved. Severe trauma exposure and bereavement seem to have considerable long-term impact on psychological distress and appear to slow down the recovery process. Readiness among health agencies for identification of symptoms and provision of interventions might facilitate optimal recovery.
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| 26. |
- Bjork Thordardottir, Edda, et al.
(författare)
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Mortality and major disease risk among migrants of the 1991-2001 Balkan wars to Sweden : A register-based cohort study
- 2020
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 17:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: In recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991-2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period.Methods and findings: We conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991-2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34-1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29-1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08-1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15-1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14-1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96-10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48-0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51-0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.Conclusions: Our findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.
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| 27. |
- Buchmayer, Susanne, et al.
(författare)
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Can Association Between Preterm Birth and Autism be Explained by Maternal or Neonatal Morbidity?
- 2009
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 124:5, s. E817-E825
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We examined whether an association between preterm birth and risk of autistic disorders could be explained by pregnancy complications or neonatal morbidity. METHODS: This Swedish, population-based, case-control study included 1216 case subjects with autistic disorders who were born between 1987 and 2002 and 6080 control subjects who were matched with respect to gender, birth year, and birth hospital. We assessed associations between gestational age and autistic disorders and adjusted for maternal, birth, and neonatal characteristics. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Compared with infants born at term, the unadjusted ORs for autistic disorders among very and moderately preterm infants were 2.05 [95% CI: 1.26-3.34] and 1.55 [95% CI: 1.22-1.96], respectively. When we controlled for maternal, pregnancy, and birth characteristics, ORs were reduced to 1.48 [95% CI: 0.77-2.84] and 1.33 [95% CI: 0.98-1.81], respectively. When we also controlled for neonatal complications, ORs were 0.98 [95% CI: 0.45-2.16] and 1.25 [95% CI: 0.90-1.75], respectively. Reductions in risks of autistic disorders related to preterm birth were primarily attributable to preeclampsia, small-for-gestational age birth, congenital malformations, low Apgar scores at 5 minutes, and intracranial bleeding, cerebral edema, or seizures in the neonatal period. Neonatal hypoglycemia, respiratory distress, and neonatal jaundice were associated with increased risk of autistic disorders for term but not preterm infants. CONCLUSION: The increased risk of autistic disorders related to preterm birth is mediated primarily by prenatal and neonatal complications that occur more commonly among preterm infants.
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| 28. |
- Chang, Hong, et al.
(författare)
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Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1.
- 2017
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Ingår i: Molecular neurobiology. - : Springer Science and Business Media LLC. - 1559-1182 .- 0893-7648. ; 54:7, s. 5166-5176
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide analysis (GWA) is an effective strategy to discover extreme effects surpassing genome-wide significant levels in studying complex disorders; however, when sample size is limited, the true effects may fail to achieve genome-wide significance. In such case, there may be authentic results among the pools of nominal candidates, and an alternative approach is to consider nominal candidates but are replicable across different samples. Here, we found that mRNA expression of the choline dehydrogenase gene (CHDH) was uniformly upregulated in the brains of bipolar disorder (BPD) patients compared with healthy controls across different studies. Follow-up genetic analyses of CHDH variants in multiple independent clinical datasets (including 11,564 cases and 17,686 controls) identified a risk SNP rs9836592 showing consistent associations with BPD (P meta=5.72×10(-4)), and the risk allele indicated an increased CHDH expression in multiple neuronal tissues (lowest P=6.70×10(-16)). These converging results may identify a nominal but true BPD susceptibility gene CHDH. Further exploratory analysis revealed suggestive associations of rs9836592 with childhood intelligence (P=0.044) and educational attainment (P=0.0039), a "proxy phenotype" of general cognitive abilities. Intriguingly, the CHDH gene is located at chromosome 3p21.1, a risk region implicated in previous BPD genome-wide association studies (GWAS), but CHDH is lying outside of the core GWAS linkage disequilibrium (LD) region, and our studied SNP rs9836592 is ∼1.2Mb 3' downstream of the previous GWAS loci (e.g., rs2251219) with no LD between them; thus, the association observed here is unlikely a reflection of previous GWAS signals. In summary, our results imply that CHDH may play a previously unknown role in the etiology of BPD and also highlight the informative value of integrating gene expression and genetic code in advancing our understanding of its biological basis.
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| 29. |
- Charney, Alexander W, et al.
(författare)
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Contribution of Rare Copy Number Variants toBipolar Disorder Risk Is Limited to Schizoaffective Cases.
- 2019
-
Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 86:2, s. 110-119
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p= .001), BD I (p= .0003), and BD II (p= .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p= .0007, PRS p= .004), and BD I without psychosis (CNV p= .0004, PRS p= 3.9× 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p= .005) but not CNV burden.CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
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| 30. |
- Dahlin, Anna M., 1979-, et al.
(författare)
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Genetic Variants in the 9p21.3 Locus Associated with Glioma Risk in Children, Adolescents, and Young Adults : A Case-Control Study
- 2019
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 28:7, s. 1252-1258
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Genome-wide association studies have identified germline genetic variants in 25 genetic loci that increase the risk of developing glioma in adulthood. It is not known if these variants increase the risk of developing glioma in children and adolescents and young adults (AYA). To date, no studies have performed genome-wide analyses to find novel genetic variants associated with glioma risk in children and AYA.Methods: We investigated the association between 8,831,628 genetic variants and risk of glioma in 854 patients diagnosed up to the age of 29 years and 3,689 controls from Sweden and Denmark. Recruitment of patients and controls was population based. Genotyping was performed using Illumina BeadChips, and untyped variants were imputed with IMPUTE2. We selected 41 established adult glioma risk variants for detailed investigation.Results: Three adult glioma risk variants, rs634537, rs2157719, and rs145929329, all mapping to the 9p21.3 (CDKN2B-AS1) locus, were associated with glioma risk in children and AYA. The strongest association was seen for rs634537 (odds ratioG = 1.21; 95% confidence interval = 1.09–1.35; P = 5.8 × 10−4). In genome-wide analysis, an association with risk was suggested for 129 genetic variants (P <1 × 10−5).Conclusions: Carriers of risk alleles in the 9p21.3 locus have an increased risk of glioma throughout life. The results from genome-wide association analyses require validation in independent cohorts.Impact: Our findings line up with existing evidence that some, although not all, established adult glioma risk variants are associated with risk of glioma in children and AYA. Validation of results from genome-wide analyses may reveal novel susceptibility loci for glioma in children and AYA.
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| 31. |
- Danielsson, L, et al.
(författare)
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Human monoclonal antibodies with different fine-specificity for digoxin derivatives: Cloning of heavy and light chain variable region sequences
- 1991
-
Ingår i: Immunology. - 0019-2805. ; 74:1, s. 50-54
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Tidskriftsartikel (refereegranskat)abstract
- Human-mouse hybridoma cell lines producing human monoclonal antibodies against the cardiac glycoside digoxin were established after in vitro immunization or direct immortalization of human peripheral blood lymphocytes with digoxin. Three antibodies, designated M06, LH92 and LH 1 14, displayed different patterns of fine specificity against digoxin and several digoxin analogues, as elucidated by inhibition ELISA. All three monoclonal antibodies had p heavy chains, two of them (M06 and LH 114) had K light chains and one (LH92) A light chains. DNA encoding the variable regions of both heavy and light chains of the three antibodies were amplified from cDNA using the polymerase chain reaction (PCR). The nucleotide sequences of the amplified DNA were determined after subcloning of PCR fragments in M13 vectors. The deduced amino acid sequences revealed considerable sequence differences in the complementarity determining regions between the three antibodies.
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| 32. |
- de Zwarte, Sonja M. C., et al.
(författare)
-
Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder
- 2022
-
Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 414-430
-
Tidskriftsartikel (refereegranskat)abstract
- First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
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| 33. |
- de Zwarte, Sonja M. C., et al.
(författare)
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The association between familial risk and brain abnormalities is disease specific : an ENIGMA-relatives study of schizophrenia and bipolar disorder
- 2019
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:7, s. 545-556
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects.CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
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| 34. |
- Eckerdal, Patricia, 1972-
(författare)
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Perinatal Complications: Associations with Postpartum depressive symptoms and Neuroticism
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Even though most pregnancies and deliveries are uncomplicated, still fifteen percent of all women in developed countries suffer pregnancy-related complications. The aim of this thesis was to explore the associations between perinatal complications and perinatal maternal health, with emphasis on postpartum depressive symptoms (PPDS) and neuroticism taking into account potential confounding or mediating factors such as history of depression, antenatal depressive symptoms and delivery experience.In the first study (n=446), the association between heavy postpartum haemorrhage and PPDS at six weeks postpartum was delineated by using path-analysis in order to provide insight into the complex mediating roles of several consequences of postpartum haemorrhage. There was no direct association between postpartum haemorrhage and PPDS, only an indirect one via anaemia at discharge and negative delivery experience.The second study (n=3888) examined the association of mode of delivery with PPDS at 6 weeks postpartum. The results indicate that the association between elective caesarean section and PPDS is highly confounded by history of depression and fear of delivery, while emergency caesarean section and vacuum extraction increase odds for PPDS by leading to postpartum complications and negative delivery experience.The third study (n=1503) investigated the association between the use of epidural analgesia during delivery and PPDS. A positive association in the crude analysis was no longer present after adjustment for sociodemographic, psychosocial and obstetrical variables, indicating that pain relief through epidural analgesia is not likely to affect risk for PPDS.In the last study (n=1969), the association between neuroticism and perinatal complications was explored. Neuroticism was not associated with adverse perinatal outcomes, except for gestational diabetes mellitus. The association, however, became statistically non-significant after adjusting for psychiatric morbidity.In summary, the current studies do no find evidence for a direct association between perinatal complications and postpartum depressive symptoms or neuroticism. However, several important mediators have been identified, among which postpartum anaemia and negative delivery experience deserve special attention. Also, earlier psychiatric history needs to be addressed as an important confounder.
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| 35. |
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| 36. |
- Ekerfelt, Christina, 1957-, et al.
(författare)
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Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis : HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication of Borrelia burgdorferi in C3H/HeN mice
- 2007
-
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 150:1, s. 189-197
-
Tidskriftsartikel (refereegranskat)abstract
- Lyme borreliosis is a complex infection, where some individuals develop so-called ‘chronic borreliosis’. The pathogenetic mechanisms are unknown, but the type of immune response is probably important for healing. A strong T helper cell type 1 (Th1)-like response has been suggested as crucial for eradication of Borrelia and for avoiding development of chronic disease. Many studies aimed at altering the Th1/Th2 balance in Lyme arthritis employed mice deficient in cytokine genes, but the outcome has not been clear-cut, due possibly to the high redundancy of cytokines. This study aimed at studying the importance of the Th1/Th2 balance in murine Borrelia arthritis by using the Th2-deviating effect of subtoxic doses of inorganic mercury. Ninety-eight C3H/HeN mice were divided into four groups: Borrelia-infected (Bb), Borrelia-infected exposed to HgCl2 (BbHg), controls exposed to HgCl2 alone and normal controls. Mice were killed on days 3, 16, 44 and 65 post-Borrelia inoculation. Arthritis severity was evaluated by histology, spirochaetal load determined by Borrelia culture, IgG2a- and IgE-levels analysed by enzyme-linked immunosorbemt assay (ELISA) and cytokine-secreting cells detected by enzyme-linked immunospot (ELISPOT). BbHg mice showed less severe histological arthritis, but delayed eradication of spirochaetes compared to Bb mice, associated with increased levels of IgE (Th2-induced) and decreased levels of IgG2a (Th1-induced), consistent with a Th2-deviation. Both the numbers of Th1 and Th2 cytokine-secreting cells were reduced in BbHg mice, possibly explained by the fact that numbers of cytokine-secreting cells do not correlate with cytokine concentration. In conclusion, this study supports the hypothesis that a Th1-like response is required for optimal eradication of Borrelia.
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| 37. |
- Fang, Fang, et al.
(författare)
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Suicide among patients with amyotrophic lateral sclerosis
- 2008
-
Ingår i: Brain. - Oxford, United Kingdom : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 131, s. 2729-2733
-
Tidskriftsartikel (refereegranskat)abstract
- Studies on the suicide risk among patients with amyotrophic lateral sclerosis (ALS) in countries without legalized euthanasia or assisted suicide are important additions to data on the wish to die of these patients. We conducted a population-based cohort study in Sweden between 1965 and 2004, which comprised of 6642 patients with incident ALS identified from the Swedish Inpatient Register. We calculated the standardized mortality ratios (SMRs) of suicide among the patients using the suicide rates of the general Swedish population as a reference. In total, 21 patients committed suicide during follow-up, compared to the predicted 3.6 suicides. Thus, we noted an almost 6-fold increased risk for suicide among ALS patients [SMR 5.8, 95% confidence interval (CI) 3.6-8.8]. Patients who committed suicide were, on average, around 7 years younger at the time of their first period of hospitalization than patients who did not commit suicide. The highest relative risk for suicide was observed within the first year after the patients first period of hospitalization (SMR 11.2, 95% CI 5.8-19.6). After that, the relative risks decreased with time after hospitalization (P-value for trend = 0.006), but remained elevated 3 years later. The relative risks of suicide among ALS patients did not show a clear trend over time in contrast to the decreasing trend of relative risks for suicide among patients with cancer during the same period. Patients with ALS are at excess risk of suicide in Sweden and the relative risk is higher during the earlier stage of the disease.
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| 38. |
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| 39. |
- Fryland, Linda, et al.
(författare)
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Mapping of T-cell subsets in relation to disease course in experimental Borrelia burgdorferi infection
- 2012
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Resolution of Lyme borreliosis has previously been shown to be associated with a strong initial Th1 response, followed by a subsequent Th2 response, shutting off inflammation. We mapped markers for Th1, Th2, Th17, cytotoxic and T regulatory subsets in a murine model, where the outcome of Borrelia (B.) burgdorferi sensu stricto (s.s.) infection was altered by immune-deviation towards Th2 by exposure to a subtoxic dose of mercury. Twenty-one B. burgdorferi s.s.-infected (Bb), 21 immune-deviated B. burgdorferi s.s.-infected (BbId), and seven control C3H/HeN mice were sacrificed on days 15, 28 and 43 post-infection (p.i.) with B. burgdorferi s.s. BbId mice had increased joint swelling compared with Bb at the height of the disease (28 p.i.), and also showed a trend for increased spirochaetal load that became significant on day 43 p.i. BbId had an increased histopathology score on day 28 p.i. compared with both earlier and later time points. mRNA expression of IL-4 (p=0.018), IL-10 (p=0.018) and EBI-3 (p=0.009) decreased in Bb mice, but not in BbId, over the course of infection. A trend for higher expression of IL-12p40 mRNA in Bb mice compared with BbId was seen late in the disease course, while BbId showed trends for higher levels of Foxp3 and GM-CSF. At the protein level, BbId showed decreased levels of CXCL9 compared to the Bb group on day 15 p.i (p=0.007). Bb mice showed increases of CXCL9 and CXCL10 at all time points compared with day 0 p.i. (p≤0.014), whereas BbId mice showed an initial decrease in both chemokines at day 15 p.i. compared with day 0 (p≤0.008). In conclusion, both the clinical signs of infection and the trends for increased expression of pro-inflammatory GM-CSF and T-regulatory marker Foxp3 in BbId mice suggested ongoing inflammation. Although our findings support the need for a strong Th1 response followed by anti-inflammatory response for optimal resolution, the anti-inflammatory response seems to be more complex than only dampening the inflammation by a Th1-antagonistic Th2 response.
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| 40. |
- Ganna, Andrea, et al.
(författare)
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Utilizing Twins as Controls for Non-Twin Case-Materials in Genome Wide Association Studies
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e83101-
-
Tidskriftsartikel (refereegranskat)abstract
- Twin registries around the globe have collected DNA samples from large numbers of monozygotic and dizygotic twins. The twin sample collections are frequently used as controls in disease-specific studies together with non-twins. This approach is unbiased under the hypothesis that twins and singletons are comparable in terms of allele frequencies; i.e. there are no genetic variants associated with being a twin per se. To test this hypothesis we performed a genome-wide association study comparing the allele frequency of 572,352 single nucleotide polymorphisms (SNPs) in 1,413 monozygotic (MZ) and 5,451 dizygotic (DZ) twins with 3,720 healthy singletons. Twins and singletons have been genotyped using the same platform. SNPs showing association with being a twin at P-value < 1 × 10-5 were selected for replication analysis in 1,492 twins (463 MZ and 1,029 DZ) and 1,880 singletons from Finland. No SNPs reached genome-wide significance (P-value < 5 × 10-8) in the main analysis combining MZ and DZ twins. In a secondary analysis including only DZ twins two SNPs (rs2033541 close to ADAMTSL1 and rs4149283 close to ABCA1) were genome-wide significant after meta-analysis with the Finnish population. The estimated proportion of variance on the liability scale explained by all SNPs was 0.08 (P-value=0.003) when MZ and DZ were considered together and smaller for MZ (0.06, P-value=0.10) compared to DZ (0.09, P-value=0.003) when analyzed separately. In conclusion, twins and singletons can be used in genetic studies together with general population samples without introducing large bias. Further research is needed to explore genetic variances associated with DZ twinning.
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| 41. |
- Genovese, Giulio, et al.
(författare)
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Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence.
- 2014
-
Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 371:26, s. 2477-87
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Tidskriftsartikel (refereegranskat)abstract
- Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent.
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| 42. |
- Goes, Fernando S, et al.
(författare)
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Exome Sequencing of Familial Bipolar Disorder.
- 2016
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 73:6, s. 590-7
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Tidskriftsartikel (refereegranskat)abstract
- Complex disorders, such as bipolar disorder (BD), likely result from the influence of both common and rare susceptibility alleles. While common variation has been widely studied, rare variant discovery has only recently become feasible with next-generation sequencing.
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| 43. |
- Halim, Joseph, 1985-
(författare)
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Synthesis and transport properties of 2D transition metal carbides (MXenes)
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since the isolation and characterization of graphene, there has been a growing interest in 2D materials owing to their unique properties compared to their 3D counterparts. Recently, a family of 2D materials of early transition metal carbides and nitrides, labelled MXenes, has been discovered (Ti2CTz, Ti3C2Tz, Mo2TiC2Tz, Ti3CNTz, Ta4C3Tz, Ti4N3Tz among many others), where T stands for surface-terminating groups (O, OH, and F). MXenes are mostly produced by selectively etching A layers (where A stands for group A elements, mostly groups 13 and 14) from the MAX phases. The latter are a family of layered ternary carbides and/or nitrides and have a general formula of Mn+1AXn (n = 1-3), where M is a transition metal and X is carbon and/or nitrogen. The produced MXenes have a conductive carbide core and a non-conductive O-, OH- and/or F-terminated surface, which allows them to work as electrodes for energy storage applications, such as Li-ion batteries and supercapacitors.Prior to this work, MXenes were produced in the form of flakes of lateral dimension of about 1 to 2 microns; such dimensions and form are not suitable for electronic characterization and applications. I have synthesized various MXenes (Ti3C2Tz, Ti2CTz and Nb2CTz) as epitaxial thin films, a more suitable form for electronic and photonic applications. These films were produced by HF, NH4HF2 or LiF + HCl etching of magnetron sputtered epitaxial Ti3AlC2, Ti2AlC, and Nb2AlC thin films. For transport properties of the Ti-based MXenes, Ti2CTz and Ti3C2Tz, changing n from 1 to 2 resulted in an increase in conductivity but had no effect on the transport mechanism (i.e. both Ti3C2Tx and Ti2CTx were metallic). In order to examine whether the electronic properties of MXenes differ when going from a few layers to a single flake, similar to graphene, the electrical characterization of a single Ti3C2Tz flake with a lateral size of about 10 μm was performed. These measurements, the first for MXene, demonstrated its metallic nature, along with determining the nature of the charge carriers and their mobility. This indicates that Ti3C2Tz is inherently of 2D nature independent of the number of stacked layers, unlike graphene, where the electronic properties change based on the number of stacked layers.Changing the transition metal from Ti to Nb, viz. comparing Ti2CTz and Nb2CTz thin films, the electronic properties and electronic conduction mechanism differ. Ti2CTz showed metallic-like behavior (resistivity increases with increasing temperature) unlike Nb2CTz where the conduction occurs via variable range hopping mechanism (VRH) - where resistivity decreases with increasing temperature.Furthermore, these studies show the synthesis of pure Mo2CTz in the form of single flakes and freestanding films made by filtering Mo2CTz colloidal suspensions. Electronic characterization of free-standing films made from delaminated Mo2CTz flakes was investigated, showing that a VRH mechanism prevails at low temperatures (7 to ≈ 60 K). Upon vacuum annealing, the room temperature, RT, conductivity of Mo2CTx increased by two orders of magnitude. The conduction mechanism was concluded to be VRH most likely dominated by hopping within each flake.Other Mo-based MXenes, Mo2TiC2Tz and Mo2Ti2C3Tz, showed VRH mechanism at low temperature. However, at higher temperatures up to RT, the transport mechanism was not clearly understood. Therefore, a part of this thesis was dedicated to further investigating the transport properties of Mo-based MXenes. This includes Mo2CTz, out-of-plane ordered Mo2TiC2Tz and Mo2Ti2C3Tz, and vacancy ordered Mo1.33CTz. Magneto-transport of free-standing thin films of the Mo-based MXenes were studied, showing that all Mo-based MXenes have two transport regimes: a VRH mechanism at lower temperatures and a thermally activated process at higher temperatures. All Mo-based MXenes except Mo1.33CTz show that the electrical transport is dominated by inter-flake transfer. As for Mo1.33CTz, the primary electrical transport mechanism is more likely to be intra-flake.The synthesis of vacancy ordered MXenes (Mo1.33CTz and W1.33CTz) raised the question of possible introduction of vacancies in all MXenes. Vacancy ordered MXenes are produced by selective etching of Al and (Sc or Y) atoms from the parent 3D MAX phases, such as (Mo2/3Sc1/3)2AlC, with in-plane chemical ordering of Mo and Sc. However, not all quaternary parent MAX phases form the in-plane chemical ordering of the two M metals; thus the synthesis of the vacancy-ordered MXenes is restricted to a very limited number of MAX phases. I present a new method to obtain MXene flakes with disordered vacancies that may be generalized to all quaternary MAX phases. As proof of concept, I chose Nb-C MXene, as this 2D material has shown promise in several applications, including energy storage, photothermal cell ablation and photocatalysts for hydrogen evolution. Starting from synthetizing (Nb2/3Sc1/3)2AlC quaternary solid solution and etching both the Sc and Al atoms resulted in Nb1.33C material with a large number of vacancies and vacancy clusters. This method may be applicable to other quaternary or higher MAX phases wherein one of the transition metals is more reactive than the other, and it could be of vital importance in applications such as catalysis and energy storage.
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| 44. |
- Halvorsen, Matthew, et al.
(författare)
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Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1, s. 1842-
-
Tidskriftsartikel (refereegranskat)abstract
- Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.
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| 45. |
- Hannon, Eilis, et al.
(författare)
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DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia
- 2021
-
Ingår i: eLIFE. - : eLife Sciences Publications. - 2050-084X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.
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| 46. |
- Harlow, Bernard L, et al.
(författare)
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Incidence of hospitalization for postpartum psychotic and bipolar episodes in women with and without prior pregnancy or prenatal psychiatric hospitalizations
- 2007
-
Ingår i: Archives of General Psychiatry. - : American Medical Association (AMA). - 0003-990X .- 1538-3636. ; 64:1, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Postpartum psychosis occurs in 1 to 2 cases per 1000 live births. Most studies have not distinguished postpartum psychosis from bipolar disorder or the proportion of the incidence attributable to prepregnancy psychiatric morbidity. OBJECTIVE: To determine the incidence of postpartum psychosis and bipolar disorder attributable to previous psychiatric hospitalization. DESIGN: Population-based study using linked registry data to determine postpartum onset of psychotic and bipolar episodes within 90 days after the first birth, by women with and without prepregnancy or prenatal psychiatric hospitalization. We assessed the type, number, and recency of previous hospitalizations on the incidence of hospitalization for postpartum psychotic and bipolar episodes. SETTING: Nationwide Swedish Hospital Discharge and Medical Birth registers. PATIENTS: Swedish women delivering a first live infant between January 1, 1987, and December 31, 2001. MAIN OUTCOME MEASURES: Postpartum hospitalization for psychosis or bipolar disorder. RESULTS: The cumulative incidences for postpartum psychotic and bipolar episodes (adjusted for age at first birth) were 0.07% and 0.03%, respectively. The incidence of psychiatric hospitalizations for postpartum psychotic or bipolar episodes among women without previous psychiatric hospitalizations was 0.04% and 0.01% of first births, respectively; for women with any psychiatric hospitalization before delivery, the incidence was 9.24% and 4.48%, respectively. For postpartum psychotic and bipolar episodes, the risk increased significantly with the recency of prepregnancy hospitalizations, number of previous hospitalizations, and length of most recent hospitalization. More than 40% of women hospitalized during the prenatal period for a bipolar or a psychotic condition were hospitalized again during the postpartum period. Approximately 90% of all postpartum psychotic and bipolar episodes occurred within the first 4 weeks after delivery. CONCLUSIONS: Almost 10% of women hospitalized for psychiatric morbidity before delivery develop postpartum psychosis after their first birth. This underscores the need for obstetricians to assess history of psychiatric symptoms and, with pediatric and psychiatric colleagues, to optimize the treatment of mothers with psychiatric diagnoses through childbirth.
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| 47. |
- Hedelin, M., et al.
(författare)
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Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33 000 women from the general population
- 2010
-
Ingår i: BMC Psychiatry. - 1471-244X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women. Methods: Dietary intake was estimated using a food frequency questionnaire among 33 623 women aged 30-49 years at enrolment (1991/92). Information on psychotic- like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic- like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression. Results: 18 411 women were classified as having a low level of psychotic- like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic- like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic- like symptoms. Conclusion: Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic- like symptoms.
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| 49. |
- Heir, Trond, et al.
(författare)
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Tsunami-affected Scandinavian tourists : Disaster exposure and post-traumatic stress symptoms
- 2011
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 65:1, s. 9-15
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of short- and long-term mental effects of natural disasters have reported a high prevalence of post-traumatic stress. Less is known about disaster-exposed tourists repatriated to stable societies. Aims: To examine the association between exposure to the 2004 Southeast Asian tsunami and symptoms of post-traumatic stress in three Scandinavian tourist populations. Methods: Postal survey of Norwegian, Danish and Swedish Southeast Asia tourists registered by the police when arriving at national airports. Follow-up time was 6 (Norway), 10 (Denmark) and 14 months (Sweden) post-disaster; 6772 individuals were included and categorized according to disaster exposure: danger exposed (caught or chased by the waves), non-danger exposed (other disaster-related stressors) and non-exposed. Outcome measures were the Impact of Event Scale-Revised (IES-R) and Post Traumatic Stress Disorder Check List (PCL). Results: Danger exposed reported more post-traumatic stress than non-danger exposed, and the latter reported more symptoms than non-exposed (each P<0.001). Comparison of the Norwegian and Swedish data suggested that symptoms were attenuated at 14 months follow-up (P<0.001). Female gender and low education, but not age, predicted higher levels of symptoms. Conclusions: Disaster-exposed tourists repatriated to unaffected home environments show long-term post-traumatic stress disorder symptoms related to the severity of exposure.
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| 50. |
- Hellstadius, Ylva, et al.
(författare)
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A longitudinal assessment of psychological distress after oesophageal cancer surgery
- 2017
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 56:5, s. 746-752
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Tidskriftsartikel (refereegranskat)abstract
- Background: Psychological distress is common among patients with oesophageal cancer. However, little is known about the course and predictors of psychological distress among patients treated with curative intent. Therefore, the aim of this study was to explore the prevalence, course and predictors of anxiety and depression in patients operated for oesophageal cancer, from prior to surgery to 12 months post-operatively. Methods: A prospective cohort of patients with oesophageal cancer (n ¼ 218) were recruited from one high-volume specialist oesophago-gastric treatment centre (St Thomas’ Hospital, London, UK). Anxiety and depression were assessed prior to surgery, 6 and 12 months post-operatively. Mixed-effects modelling was performed to investigate changes over time and to estimate the association between clinical and socio-demographic predictor variables and anxiety and depression symptoms. Results: The proportion of patients with anxiety was 33% prior to surgery, 28% at 6 months, and 37% at 12 months. Prior to surgery, 20% reported depression, 27% at 6 months, and 32% at 12-month follow-up. Anxiety symptoms remained stable over time whereas depression symptoms appeared to increase from pre-surgery to 6 months, levelling off between 6 and 12 months. Younger age, female sex, living alone and more severe self-reported dysphagia (i.e., difficulty swallowing) predicted higher anxiety symptoms. In-hospital complications, greater limitations in activity status and more severe selfreported dysphagia were predictive of higher depression. Conclusions: Many patients report psychological distress during the first year following oesophageal cancer surgery. Whether improving the experience of swallowing difficulties may also reduce distress among these patients warrants further study.
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