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- 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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| 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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| 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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