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Adolfsson, Rolf
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Publications (10 of 179) Show all publications
Musliner, K. L., Mortensen, P. B., McGrath, J. J., Suppli, N. P., Hougaard, D. M., Bybjerg-Grauholm, J., . . . Agerbo, E. (2019). Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population. JAMA psychiatry, 76(5), 516-525
Open this publication in new window or tab >>Association of Polygenic Liabilities for Major Depression, Bipolar Disorder, and Schizophrenia With Risk for Depression in the Danish Population
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2019 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 76, no 5, p. 516-525Article in journal (Refereed) Published
Abstract [en]

Importance: Although the usefulness of polygenic risk scores as a measure of genetic liability for major depression (MD) has been established, their association with depression in the general population remains relatively unexplored.

Objective: To evaluate whether polygenic risk scores for MD, bipolar disorder (BD), and schizophrenia (SZ) are associated with depression in the general population and explore whether these polygenic liabilities are associated with heterogeneity in terms of age at onset and severity at the initial depression diagnosis.

Design, Setting, and Participants: Participants were drawn from the Danish iPSYCH2012 case-cohort study, a representative sample drawn from the population of Denmark born between May 1, 1981, and December 31, 2005. The hazard of depression was estimated using Cox regressions modified to accommodate the case-cohort design. Case-only analyses were conducted using linear and multinomial regressions. The data analysis was conducted from February 2017 to June 2018.

Exposures: Polygenic risk scores for MD, BD, and SZ trained using the most recent genome-wide association study results from the Psychiatric Genomics Consortium.

Main Outcomes and Measures: The main outcome was first depressive episode (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code F32) treated in hospital-based psychiatric care. Severity at the initial diagnosis was measured using the ICD-10 code severity specifications (mild, moderate, severe without psychosis, and severe with psychosis) and treatment setting (inpatient, outpatient, and emergency).

Results: Of 34 573 participants aged 10 to 31 years at censoring, 68% of those with depression were female compared with 48.9% of participants without depression. Each SD increase in polygenic liability for MD, BD, and SZ was associated with 30% (hazard ratio [HR], 1.30; 95% CI, 1.27-1.33), 5% (HR, 1.05; 95% CI, 1.02-1.07), and 12% (HR, 1.12; 95% CI, 1.09-1.15) increases in the hazard of depression, respectively. Among cases, a higher polygenic liability for BD was associated with earlier depression onset (β = -.07; SE = .02; P = .002).

Conclusions and Relevance: Polygenic liability for MD is associated with first depression in the general population, which supports the idea that these scores tap into an underlying liability for developing the disorder. The fact that polygenic risk for BD and polygenic risk for SZ also were associated with depression is consistent with prior evidence that these disorders share some common genetic overlap. Variations in polygenic liability may contribute slightly to heterogeneity in clinical presentation, but these associations appear minimal.

Place, publisher, year, edition, pages
Chicago: American Medical Association, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-160324 (URN)10.1001/jamapsychiatry.2018.4166 (DOI)000467491200013 ()30698613 (PubMedID)
Available from: 2019-06-17 Created: 2019-06-17 Last updated: 2019-09-05Bibliographically approved
Åström, E., Rönnlund, M., Adolfsson, R. & Carelli, M. G. (2019). Depressive symptoms and time perspective in older adults: associations beyond personality and negative life events. Aging & Mental Health, 23(12), 1674-1683
Open this publication in new window or tab >>Depressive symptoms and time perspective in older adults: associations beyond personality and negative life events
2019 (English)In: Aging & Mental Health, ISSN 1360-7863, E-ISSN 1364-6915, Vol. 23, no 12, p. 1674-1683Article in journal (Refereed) Published
Abstract [en]

Objectives: To examine the extent to which time perspective, an individual’s habitual way of relating to the past, the present, and the future time frames, accounts for variations in self-reported depressive symptoms among older adults.

Method: Four hundred two participants (60–90 years) completed the Center for Epidemiological Studies Depression scale (CES-D) and the Swedish Zimbardo Time perspective Inventory (S-ZTPI). The influence of personality as reflected by the Temperament and Character Inventory (TCI) and self-reported negative life events (NLEs) were controlled for in hierarchic regression analyses.

Results: The six S-ZTPI dimensions accounted for 24.5% of the variance in CES-D scores beyond age and gender. Half of the variance remained when the TCI factors and NLEs were controlled for. Past Negative, Future Negative, and Past Positive (inverse association) were the significant unique predictors. Significant age interactions were observed for two S-ZTPI dimensions, with a diminished association to depressive symptoms for Future Negative and a magnified association for Present Fatalistic with higher age.

Conclusions: The results demonstrate a substantial relation between facets of time perspective and depressive symptoms in old age. They also indicate an age-related shift in the relative importance from concerns about of the future (Future Negative) to the present (Present Fatalistic) with increased age. In young old-age, when the future is more ‘open’, future worries (Future Negative) may be a more frequent source of distress. In late senescence, perceived threats to autonomy (e.g. physical health problems and cognitive deficits), as reflected by higher scores on Present Fatalistic, may instead have more bearing on mood state.

Place, publisher, year, edition, pages
Routledge, 2019
Keywords
Depressive symptoms, time perspective, older adults, personality, negative life events
National Category
Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:umu:diva-153376 (URN)10.1080/13607863.2018.1506743 (DOI)000492447600008 ()30450950 (PubMedID)
Available from: 2018-11-19 Created: 2018-11-19 Last updated: 2019-11-20Bibliographically approved
Huckins, L. M., Dobbyn, A., Ruderfer, D. M., Hoffman, G., Wang, W., Pardinas, A. F., . . . Sullivan, P. F. (2019). Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics, 51(4), 659-+
Open this publication in new window or tab >>Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 4, p. 659-+Article in journal (Refereed) Published
Abstract [en]

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Medical Genetics Genetics
Identifiers
urn:nbn:se:umu:diva-158080 (URN)10.1038/s41588-019-0364-4 (DOI)000462767500013 ()30911161 (PubMedID)
Funder
NIH (National Institute of Health), R01MH085542NIH (National Institute of Health), R01MH093725NIH (National Institute of Health), P50MH066392NIH (National Institute of Health), P50MH080405NIH (National Institute of Health), R01MH097276NIH (National Institute of Health), RO1-MH-075916NIH (National Institute of Health), P50M096891NIH (National Institute of Health), P50MH084053S1NIH (National Institute of Health), R37MH057881NIH (National Institute of Health), R37MH057881S1NIH (National Institute of Health), HHSN271201300031CNIH (National Institute of Health), AG02219NIH (National Institute of Health), AG05138NIH (National Institute of Health), MH06692Novo Nordisk
Available from: 2019-04-15 Created: 2019-04-15 Last updated: 2019-04-15Bibliographically approved
diva2:1304451
Open this publication in new window or tab >>Genetic variants as modifiers of the association of body mass index with bipolar disorder
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2019 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, p. S838-S839Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-158122 (URN)10.1016/j.euroneuro.2017.08.103 (DOI)000462156400232 ()
Conference
25th World Congress of Psychiatric Genetics (WCPG), OCT 13-17, 2017, Orlando, FL
Note

Supplement: 3

Meeting Abstract: SA31

Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-04-12Bibliographically approved
Stahl, E. A., Breen, G., Forstner, A. J., McQuillin, A., Ripke, S., Trubetskoy, V., . . . Sklar, P. (2019). Genome-wide association study identifies 30 loci associated with bipolar disorder. Nature Genetics, 51(5), 793-803
Open this publication in new window or tab >>Genome-wide association study identifies 30 loci associated with bipolar disorder
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 5, p. 793-803Article in journal (Refereed) Published
Abstract [en]

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.

National Category
Medical Genetics
Identifiers
urn:nbn:se:umu:diva-159921 (URN)10.1038/s41588-019-0397-8 (DOI)000466842000007 ()31043756 (PubMedID)
Available from: 2019-06-10 Created: 2019-06-10 Last updated: 2019-06-10Bibliographically approved
Mullins, N., Bigdeli, T. B., Borglum, A. D., Coleman, J. R. ., Demontis, D., Mehta, D., . . . Lewis, C. M. (2019). GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores. American Journal of Psychiatry, 176(8), 651-660
Open this publication in new window or tab >>GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
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2019 (English)In: American Journal of Psychiatry, ISSN 0002-953X, E-ISSN 1535-7228, Vol. 176, no 8, p. 651-660Article in journal (Refereed) Published
Abstract [en]

Objective: More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.

Methods: The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.

Results: Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).

Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

Place, publisher, year, edition, pages
American Psychiatric Publishing, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-164653 (URN)10.1176/appi.ajp.2019.18080957 (DOI)000484756700012 ()31164008 (PubMedID)2-s2.0-85070289870 (Scopus ID)
Available from: 2019-10-25 Created: 2019-10-25 Last updated: 2019-10-25Bibliographically approved
diva2:1346038
Open this publication in new window or tab >>Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 1, p. 211-220Article in journal (Refereed) Published
Abstract [en]

Background: Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development.

Objective: The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time.

Methods: The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.

Results: Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001).

Conclusion: In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

Place, publisher, year, edition, pages
IOS Press, 2019
Keywords
Alzheimer’s disease, APOE ɛ4, apolipoprotein E4, cognitive impairment, cohort study, dementia, epidemiological study, episodic memory, herpes simplex virus
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-162728 (URN)10.3233/JAD-171162 (DOI)000457778000017 ()30636735 (PubMedID)
Available from: 2019-08-27 Created: 2019-08-27 Last updated: 2019-09-10Bibliographically approved
Figueira, J., Adolfsson, R., Nordin Adolfsson, A., Nyberg, L. & Öhman, A. (2019). Serum Metabolite Markers of Dementia Through Quantitative NMR Analysis: The Importance of Threonine-Linked Metabolic Pathways. Journal of Alzheimer's Disease, 69(3), 763-774
Open this publication in new window or tab >>Serum Metabolite Markers of Dementia Through Quantitative NMR Analysis: The Importance of Threonine-Linked Metabolic Pathways
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2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 69, no 3, p. 763-774Article in journal (Refereed) Published
Abstract [en]

There is a great need for diagnostic biomarkers of impending dementia. Metabolite markers in blood have been investigated in several studies, but inconclusive findings encourage further investigation, particularly in the pre-diagnostic phase. In the present study, the serum metabolomes of 110 dementia or pre-diagnostic dementia individuals and 201 healthy individuals matched for age, gender, and education were analyzed by nuclear magnetic resonance spectroscopy in combination with multivariate data analysis. 58 metabolites were quantified in each of the 311 samples. Individuals with dementia were discriminated from controls using a panel of seven metabolites, while the pre-diagnostic dementia subjects were distinguished from controls using a separate set of seven metabolites, where threonine was a common significant metabolite in both panels. Metabolite and pathway alterations specific for dementia and pre-diagnostic dementia were identified, in particular a disturbed threonine catabolism at the pre-diagnostic stage that extends to several threonine-linked pathways at the dementia stage.

Place, publisher, year, edition, pages
IOS Press, 2019
Keywords
Alzheimer's disease, biomarker, dementia, metabolomics/metabonomics, NMR, serum, vascular dementia
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-161551 (URN)10.3233/JAD-181189 (DOI)000471781600013 ()31127768 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationThe Kempe Foundations
Available from: 2019-07-10 Created: 2019-07-10 Last updated: 2019-07-10Bibliographically approved
Crowley, J., Mudgal, P., Nordin Adolfsson, A., Åberg, K., Alaerts, M., Genovese, G., . . . Sullivan, P. (2019). The genomics of bipolar and schizophrenic disorders in a large pedigree from a northern Swedish isolate. Paper presented at 25th World Congress of Psychiatric Genetics (WCPG), OCT 13-17, 2017, Orlando, FL. European Neuropsychopharmacology, 29, S902-S903
Open this publication in new window or tab >>The genomics of bipolar and schizophrenic disorders in a large pedigree from a northern Swedish isolate
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2019 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, p. S902-S903Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-158123 (URN)10.1016/j.euroneuro.2017.08.217 (DOI)000462156400346 ()
Conference
25th World Congress of Psychiatric Genetics (WCPG), OCT 13-17, 2017, Orlando, FL
Note

Supplement: 3

Meeting Abstract: SU28

Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-04-12Bibliographically approved
Szatkiewicz, J., Crowley, J. J., Nordin Adolfsson, A., Åberg, K. A., Alaerts, M., Genovese, G., . . . Sullivan, P. F. (2019). The genomics of major psychiatric disorders in a large pedigree from Northern Sweden. Translational Psychiatry, 9, Article ID 60.
Open this publication in new window or tab >>The genomics of major psychiatric disorders in a large pedigree from Northern Sweden
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2019 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 9, article id 60Article in journal (Refereed) Published
Abstract [en]

We searched for genetic causes of major psychiatric disorders (bipolar disorder, schizoaffective disorder, and schizophrenia) in a large, densely affected pedigree from Northern Sweden that originated with three pairs of founders born around 1650. We applied a systematic genomic approach to the pedigree via karyotyping (N = 9), genome-wide SNP arrays (N = 418), whole-exome sequencing (N = 26), and whole-genome sequencing (N = 10). Comprehensive analysis did not identify plausible variants of strong effect. Rather, pedigree cases had significantly higher genetic risk scores compared to pedigree and community controls.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-157590 (URN)10.1038/s41398-019-0414-9 (DOI)000459834400001 ()30718465 (PubMedID)
Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2019-03-29Bibliographically approved
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