| 1. |
- Andersson, Anneli, 1992-, et al.
(författare)
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Depression and anxiety disorders during the postpartum period in women diagnosed with attention deficit hyperactivity disorder
- 2023
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 325, s. 817-823
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Tidskriftsartikel (refereegranskat)abstract
- Background: Attention deficit hyperactivity disorder (ADHD) is associated with an increased risk of poor mental health. However, the understanding of ADHD-related burden and impairments in women during the postpartum period is limited. The aim with the present study was to examine the risk of depression and anxiety disorders during the postpartum period among women with and without an ADHD diagnosis.Methods: We used register-based data to identify women who gave birth to their first and/or second child between 2005 and 2013 in Sweden (n = 773,047), of which 0.5 % (n = 3515) had a diagnosis of ADHD prior to pregnancy. Diagnoses of depression and anxiety disorders up to one year after delivery were collected from the national patient register.Results: A total of 16.76 % of the women with an ADHD diagnosis were also diagnosed with depression disorders in the postpartum period, prevalence ratio (PR) 5.09 (95 % confidence interval (CI), 4.68-5.54). A total of 24.92 % of the women with an ADHD diagnosis were also diagnosed with anxiety disorders in the postpartum period, PR 5.41 (5.06-5.78). Stratified results revealed that having a diagnosis of ADHD increased the risk for both depression and anxiety disorders postpartum, beyond other well-known risk factors.Limitations: There is a potential risk of surveillance bias as women diagnosed with ADHD are more likely to have repeated visits to psychiatric care and might have an enhanced likelihood of also being diagnosed with depression and anxiety disorders postpartum, compared to women without ADHD.Conclusions: ADHD is an important risk factor for both depression and anxiety disorders postpartum. Therefore, ADHD needs to be considered in the maternal care, regardless of sociodemographic factors and the presence of other psychiatric disorders.
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| 2. |
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| 3. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 4. |
- Brew, Bronwyn K., et al.
(författare)
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Longitudinal depression or anxiety in mothers and offspring asthma : a Swedish population-based study
- 2018
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 47:1, s. 166-174
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous research has found that maternal stress during pregnancy increases the risk of offspring asthma. However, whether this association is consistent with a causal interpretation has never been tested. The objective is to determine whether there is a critical exposure period for maternal depression or anxiety on offspring asthma or whether cumulative exposure is most important, and to investigate evidence of confounding.Methods: The study population included all children born in Sweden from July 2006 to December 2009 (n = 360 526). Information about childhood asthma, maternal depression or anxiety (diagnosis or medication) and covariates was obtained from the Swedish national health registers. The associations between exposure periods (pre-conception, pregnancy, postnatal or current) and childhood asthma were estimated using structured life course approach hypothesis testing. Paternal and cousin analyses were used to test for evidence of confounding from shared genes and environment.Results: For childhood asthma, cumulative exposure best described the effect of exposure to maternal depression or anxiety up to a maximum of any two exposure periods [adjusted odds ratio 1.44, 95% confidence interval (CI) 1.38, 1.52]. The hypotheses of a critical period were not supported. The paternal and cousin analyses indicated minimal influence from familial confounding.Conclusions: These findings support an association between cumulative exposure to maternal depression or anxiety and asthma development in offspring. This association is unique for maternal depression or anxiety and not due to familial confounding. The clinical implication is that effective psychological management of women with chronic distress may reduce offspring asthma risk.
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| 5. |
- Guintivano, Jerry, et al.
(författare)
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Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
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| 6. |
- Hollis, Chris, et al.
(författare)
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Methylphenidate and the risk of psychosis in adolescents and young adults : a population-based cohort study
- 2019
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Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 6:8, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder.Methods: In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12-30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis.Findings: We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38.7%) individuals were assessed and 37 916 (61.3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2.0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1.04 (95% CI 0.80-1.34) in adolescents and young adults without a history of psychosis and 0.95 (0.69-1.30) among those with a history of psychosis.Interpretation: Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis.
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| 7. |
- Joas, Erik, et al.
(författare)
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Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder.
- 2023
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Ingår i: The pharmacogenomics journal. - : Springer Science and Business Media LLC. - 1473-1150 .- 1470-269X. ; 23:1, s. 28-35
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Tidskriftsartikel (refereegranskat)abstract
- Antidepressant medication is used extensively to treat bipolar depression despite uncertain efficacy. The cytochrome P450 (CYP) 2C19 enzyme metabolize several antidepressants, and polymorphisms in the corresponding gene CYP2C19 influence plasma concentration and hence treatment outcomes in major depressive disorder. Here, we investigate if CYP2C19 polymorphisms are associated with antidepressant treatment patterns and the risk of mania when antidepressants are used in bipolar disorder. Two single nucleotide polymorphisms (rs4244285 and rs12248560) were used to classify 5019 bipolar disorder patients into CYP2C19 metabolic phenotypes ranging from poor to ultra-rapid metabolizers. We used Swedish national registry data 2005-2017 on dispensed medications and inpatient care to estimate risks for early-treatment persistence, treatment discontinuation, switching to a new antidepressant medication, and mania within 3 months of treatment initiation in patients treated with citalopram, escitalopram, sertraline, amitriptyline, and clomipramine. Metabolic phenotypes of CYP2C19 were not robustly associated with the investigated treatment outcomes based on dispense patterns. Slower metabolism was associated with an increased risk of treatment emergent mania for sertraline (hazard ratio [HR]=1.3, 95% CI=1.04-1.62, p=0.02) and the tricyclic antidepressants amitriptyline and clomipramine (HR=1.46, 95% CI=1.05-2.02, p=0.024). In a large study of the impact of CYP2C19 metabolic phenotypes on antidepressant treatment of bipolar depression, we found an association between slower CYP2C19 metabolism and higher risk of treatment emergent mania, which is a step towards personalized risk assessments. There were, however, no clear associations with early treatment persistence, treatment discontinuation, and switching to a new antidepressant.
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| 8. |
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| 9. |
- Landén, Mikael, 1966, et al.
(författare)
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Response to Ostacher et al.
- 2015
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 172:6, s. 586-7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Li, Lin, 1989-, et al.
(författare)
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Associations of Prescribed ADHD Medication in Pregnancy with Pregnancy-Related and Offspring Outcomes : A Systematic Review
- 2020
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Ingår i: CNS Drugs. - : Adis International. - 1172-7047 .- 1179-1934. ; 34:7, s. 731-747
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring.OBJECTIVES: The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding.METHODS: We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case-control studies, case-crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prescribed ADHD medications and evaluated any outcome, including both short- and long-term maternal and offspring outcomes. Two independent authors then used the Newcastle-Ottawa Scale to rate the quality of the included studies.RESULTS: Eight cohort studies that estimated adverse pregnancy-related and offspring outcomes associated with exposure to ADHD medication during pregnancy were included in the qualitative review. The included studies had substantial methodological differences in data sources, type of medications examined, definitions of studied pregnancy-related and offspring outcomes, types of control groups, and confounding adjustment. There was no convincing evidence for teratogenic effects according to the relative risk of pregnancy-related and offspring outcomes, and the observed differences in absolute risks were overall small in magnitude. Adjustment for confounding was inadequate in most studies, and none of the included studies adjusted for ADHD severity in the mothers.CONCLUSION: The current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman's specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.
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| 11. |
- Magnusson, Patrik K. E., et al.
(författare)
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The Swedish Twin Registry : establishment of a biobank and other recent developments
- 2013
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Ingår i: Twin Research and Human Genetics. - Cambridge, United Kingdom : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 16:1, s. 317-329
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.
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| 12. |
- Munk-Olsen, Trine, et al.
(författare)
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Maternal and infant outcomes associated with lithium use in pregnancy : an international collaborative meta-analysis of six cohort studies
- 2018
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Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 5:8, s. 644-652
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Concerns about teratogenicity and maternal and offspring complications restrict the use of lithium during pregnancy for the treatment of mood disorders. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity, and congenital malformations.METHODS: In this meta-analysis, primary data from pregnant women and their children from six international cohorts based in the community (Denmark, Sweden, and Ontario, Canada) and in clinics (the Netherlands, UK, and USA) were analysed. Pregnancies were eligible for analysis if the pregnancy resulted in a liveborn singleton between 1997 and 2015, if health-related information was available for both mother and infant, and if the mother had a mood disorder (bipolar disorder or major depressive disorder) or if she had been given lithium during pregnancy (at least two dispensations of lithium during pregnancy that were dispensed any time from 1 month before conception until the delivery, or a single lithium dispensation during pregnancy when there was at least one other lithium dispensation within 6 months before or after this date). Pregnancies during which the mother had been prescribed known teratogenic drugs were excluded. Pregnancies were grouped into a lithium-exposed group and a mood disorder reference group. The main outcome measures were pregnancy complications, delivery outcomes, neonatal readmission to hospital within 28 days of birth, and congenital malformations (major malformations and major cardiac malformations). Analyses were done at each site by use of a shared protocol. Adjusted odds ratios (aORs) and 95% CIs were calculated by use of logistic regression models, and site-specific prevalence rates and ORs were pooled by use of random-effects meta-analytical models.FINDINGS: 22 124 eligible pregnancies were identified across the six cohorts, of which 727 pregnancies were eligible for inclusion in the lithium-exposed group (557 [77%] from register-based cohorts and 170 [23%] from clinical cohorts). Lithium exposure was not associated with any of the predefined pregnancy complications or delivery outcomes. An increased risk for neonatal readmission within 28 days of birth was seen in the lithium-exposed group compared with the reference group (pooled prevalence 27·5% [95% CI 15·8-39·1] vs 14·3% [10·4-18·2]; pooled aOR 1·62, 95% CI 1·12-2·33). Lithium exposure during the first trimester was associated with an increased risk of major malformations (pooled prevalence 7·4% [95% CI 4·0-10·7] vs 4·3% [3·7-4·8]; pooled aOR 1·71, 95% CI 1·07-2·72) but for major cardiac malformations the difference was not significant (2·1% [0·5-3·7] vs 1·6% [1·0-2·1]; pooled aOR 1·54, 95% CI 0·64-3·70).INTERPRETATION: Considering both the effect sizes and the precision of the estimates in this meta-analysis, treatment decisions for pregnant women with mood disorders must weigh the potential for increased risks of lithium during pregnancy-in particular those associated with use of lithium during the first trimester-against its effectiveness at reducing relapse.FUNDING: None.
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| 13. |
- Tabrizi, Fara, et al.
(författare)
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P117. Predicting Genetic Risk for Depression and Anxiety Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPolygenic scores (PGSs) harness the potential to provide an overall measure of individuals’ genetic liability to develop a disease (Torkamani et al., 2018), though much research is still needed. The aim of the present study was to predict prescription of pharmacological treatment of anxiety or depression from PGSs.MethodsThe target sample comprised two cohorts of genotyped Swedish twins (n = 11037). Cases were defined as individuals prescribed pharmacological treatment of depression (n = 1129) or anxiety (n = 1446). We constructed 6 PGSs based on GWAS on MDD diagnosis, Anxiety, Schizophrenia, Neuroticism scores, the GAD-7 scale, and the PHQ-9. Data were analyzed by logistic regression models with change in pseudo-R2 (above the baseline model with sex, age, cohort, and 20 ancestral PCs) following the inclusion of PGSs to predict the risk of anxiety or depression medication. All results corrected for multiple comparisons.ResultsPredictive performance was estimated to ΔR2depression = 0.028; ΔR2anxiety = 0.025 when all PGSs were included in the same model, with PGS for MDD being the single best predictor for both anxiety and depression. Individuals in the top 10% of the PGS distribution had greater odds of drug prescription (ORdepression = 1.82; CI95% = 1.53—2.17; ORanxiety = 1.65; CI95% = 1.40—1.95), while the bottom 10% had decreased risk (ORanxiety = 0.56; CI95% = 0.45—0.70; ORdepression = 0.58; CI95% = 0.45—0.74) compared to the remaining 90% of the distribution.ConclusionsPGSs can predict drug prescription for anxiety and depression in an independent sample.
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| 14. |
- Tabrizi, Fara, et al.
(författare)
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Prediction of anxiety and depression from polygenic scores in Swedish twins
- 2021
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Ingår i: Abstracts of the WASAD Congress 2021. - : Springer. ; , s. 1802-1803
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Konferensbidrag (refereegranskat)abstract
- Recent genome-wide association studies (GWAS) have identified several common variants associated with depression (Howard et al. 2019; Levey et al. 2021) and anxiety disorders (Levey et al. 2020; Meier et al. 2019; Purves et al. 2020), and these findings have been harnessed to develop polygenic scores (PGS) in order to provide an overall measure of individuals’ genetic liability to develop a disease (Torkamani et al. 2018). Research on the utility of PGSs as predictors of risk for disease is gaining traction, with studies on somatic illness showing that disease risk increases sharply in the right tail of the PGS distribution (Khera et al. 2018). Thus, PGS stratification could be of clinical relevance if it provides an opportunity to target those in need of preventive interventions with increased precision. The current potential of PGS stratification for depression and anxiety disorders remains an open question. In the current study, we applied 36 predefined PGSs from the polygenic index repository (Becker et al. 2021) on a target sample of 11,210 genotyped twins. Cases were defined as those with prescribed medication, where the prescription explicitly stated that a drug was ordinated for indication of depression or anxiety, respectively. Drugs included antidepressants (SSRI and SNRI), Benzodiazepines, Antihistamines, Buspirone, and Betablockers.
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| 15. |
- Viktorin, Alexander, et al.
(författare)
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Heritability of perinatal depression and genetic overlap with nonperinatal depression
- 2016
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Ingår i: The American Journal of Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0002-953X .- 1535-7228.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The authors investigated the relative importance of genetic and environmental influences on perinatal depression, and the genetic overlap between perinatal depression and nonperinatal depression. METHOD: Analyses were conducted using structural equation modeling for 1) the lifetime version of the Edinburgh Postnatal Depression Scale in 3,427 Swedish female twins and 2) clinical diagnoses of depression separated into perinatal depression and nonperinatal depression in a Swedish population-based cohort of 580,006 sisters. RESULTS: In the twin study, the heritability of perinatal depression was estimated at 54% (95% CI=35%-70%), with the remaining variance attributable to nonshared environment (46%; 95% CI=31%-65%). In the sibling design, the heritability of perinatal depression was estimated at 44% (95% CI=35%-52%) and the heritability of nonperinatal depression at 32% (95% CI=24%-41%). Bivariate analysis showed that 14% of the total variance (or 33% of the genetic variance) in perinatal depression was unique for perinatal depression. CONCLUSIONS: The heritability of perinatal depression was estimated at 54% and 44%, respectively, in separate samples, and the heritability of nonperinatal depression at 32%. One-third of the genetic contribution was unique to perinatal depression and not shared with nonperinatal depression, suggesting only partially overlapping genetic etiologies for perinatal depression and nonperinatal depression. The authors suggest that perinatal depression constitutes a subset of depression that could be prioritized for genomic discovery efforts. The study findings have direct translational impact that can assist clinicians in the counseling of their patients regarding risk and prognosis of perinatal depression.
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| 16. |
- Viktorin, Alexander
(författare)
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Mood disorders and consequences of pharmacological treatment
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mental health issues are medical problems getting increased attention throughout the world, and depression, only one among several types of mental illnesses, are currently reported as the second leading cause of disability world wide by the World Health Organization. Along this development, increased number of psychiatric diagnoses and increased utilization of medication can be observed. However, whether this increase is because of an actual increase in number of individuals suffering from these disorders, or due to improvements in diagnostics and understanding, or both, is not fully known. What is known, however, is that mental health related suffering is nothing new and can be traced back several thousands of years in human history. Throughout this history, our understanding and view of these disorders that affect our mood and behavior have changed substantially, from being assumed caused by gods or magic, to our modern view of combined environmental and genetic causes. But psychiatry is still a comparatively recent field of medicine and it was not long ago effective drugs targeting these disorders were first introduced. Our understanding of the underlying mechanisms of this suffering is still limited, but recent developments in psychiatric genetics have provided some of the first stable biological underpinnings to mental disorders. In light of these findings, a complicated picture is beginning to take form, in which the etiology appears caused by thousands of genetic factors, but also that a lot of the underlying genetics is shared among the disorders previously thought of as separate. It is within this setting, where many of the current disorder definitions are starting being questioned and the appreciation of genetics behind these disorder is increasing, the studies within thesis have been conducted. In study I, the potential side effect of manic switching due to antidepressant treatment was investigated in a population sample of 3,240 individuals with bipolar disorder. A within-individual design was used to adjust for otherwise unmeasured genetic confounding, and the results indicated that manic switching was confined to bipolar disorder patients treated with an antidepressant monotherapy, whereas patients treated with an antidepressant in combination with a mood stabilizer rather displayed a reduced risk. Study II instead focused on depression around the time of pregnancy, perinatal depression, and to what extent genetics explain the variance in this disorder, and to what extent perinatal depression genetically overlap with depression at other time of life. This was studied with a twin design in a sample of twin mothers (N=3,427) that had answered the Edinburgh Postnatal Depression Scale, and with a sibling design in a sample of sisters (N=580,006) using register data of healthcare contacts. The genetic contribution to, or heritability of, perinatal depression was estimated at 54 and 44% in the twin and sibling designs respectively. Using a bivariate model, a third of the genetic contribution to perinatal depression was found unique for the disorder and not shared with depression at other times of life. Study III was also related to perinatal depression, but focused on potential side effects of antidepressants. In a sample of 392,029 pregnancies, associations between prenatal SSRI exposure and offspring birth size and gestational age was observed. This was followed by within-family analyses (N=1,007) that adjusted for genetic and familial environmental confounding, where the associations between SSRIs and offspring birth size was attenuated, indicating that these associations were likely due to familial confounding. An association between prenatal SSRI exposure and reduced gestational age was observed in both analyses, and could be either due to a causal effect of the medication, or due to confounding factors that the withinfamily design could not adjust for. Perinatal depression was further explored in study IV, where patterns of healthcare utilization were studied among both mothers and fathers based on register data. This included 3.6 million parents and 3.5 million pregnancies, and the occurrence of diagnoses for depressive illness, anxiety disorders, and mental illness in general around the time of pregnancy was contrasted to the occurrence of these diagnoses at other times of life. Overall, a reduction in healthcare utilization for all studied disorder types were observed around this time of life, which may indicate barriers to getting a diagnosis during this time of life. In conclusion, the studies within this thesis demonstrate that genetically informed designs are very useful in epidemiological research. And through the application of these designs with large-scale register data, the studies of this thesis provide enhanced understanding of mental illness in general, and bipolar disorder and perinatal depression in particular.
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| 17. |
- Viktorin, Alexander, et al.
(författare)
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Selective serotonin re-uptake inhibitor use during pregnancy : association with offspring birth size and gestational age
- 2016
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Ingår i: International Journal of Epidemiology. - Oxford, United Kingdom : Oxford University Press. - 0300-5771 .- 1464-3685. ; 45:1, s. 170-177
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Tidskriftsartikel (refereegranskat)abstract
- Background: Depression around the time of pregnancy affects at least 1 in 8 women and treatment with selective serotonin re-uptake inhibitors (SSRIs) in pregnant women has been increasing, but research on adverse effects on the fetus have so far commonly used designs unable to account for confounding. We aimed to examine the effects of prenatal SSRI exposure on offspring size outcomes and gestational age, and disentangle whether associations observed were due to the medication or other factors.Methods: We used a Swedish population-based cohort of 392,029 children and national registers to estimate the associations between prenatal exposure to SSRIs and depression on the outcomes birthweight, birth length, birth head circumference, gestational age at birth and preterm birth. A sub-sample of 1007 children was analysed in a within-family design that accounts for unmeasured parental genetic and environmental confounders.Results: Crude analyses revealed associations between prenatal SSRI exposure, and offspring birth size and gestational age. However, in the within-family analyses, only the association between SSRI exposure and reduced gestational age (-2.3 days; 95% confidence interval -3.8 to -0.8) was observed.Conclusions: This study indicates that prenatal SSRI exposure may not be causally related to offspring birth size. Rather, our analyses suggest that the association could be caused by other underlying differences instead of the medication per se. A small reduction of gestational age was associated with SSRI exposure in the within-family analysis and could be due to either the exposure, or other factors changing between pregnancies.
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| 18. |
- Viktorin, Alexander, et al.
(författare)
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The risk of switch to mania in patients with bipolar disorder during treatment with antidepressants alone and in combination with a mood stabilizer
- 2014
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Ingår i: The American Journal of Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0002-9556 .- 0002-953X .- 1535-7228.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study examined the risk of antidepressant-induced manic switch in patients with bipolar disorder treated either with antidepressant monotherapy or with an antidepressant in conjunction with a mood stabilizer. Method: Using Swedish national registries, the authors identified 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year. Patients were categorized into those receiving antidepressant monotherapy and those receiving an antidepressant plus a mood stabilizer. A within-individual design was used to control for confounding by disorder severity, genetic makeup, and early environmental factors. Cox regression analyses conditioned on individual were used to compare the rate of mania 0–3 months and 3–9 months after the start of antidepressant treatment with a preceding non-treatment period. Results: Nearly 35% of the patients were treated with antidepressant monotherapy. The increased risk of treatment-emergent mania was confined to patients on antidepressant monotherapy (hazard ratio=2.83, 95% CI=1.12, 7.19). Among patients treated with a concurrent mood stabilizer, no acute change in risk of mania was observed during the 3 months after the start of antidepressant treatment (hazard ratio=0.79, 95% CI=0.54, 1.15), and a decreased risk was observed during the period 3–9 months after treatment initiation (hazard ratio=0.63, 95% CI=0.42, 0.93). Conclusions: In this national registry study, antidepressant monotherapy was associated with an increased risk of mania. However, no risk of mania was seen in patients receiving an antidepressant while treated with a mood stabilizer. The results highlight the importance of avoiding antidepressant monotherapy in the treatment of bipolar disorder.
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| 19. |
- Viktorin, Alexander, et al.
(författare)
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The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder
- 2017
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Ingår i: American Journal of Psychiatry. - Arlington, USA : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 174:4, s. 341-348
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder.Method: Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods.Results: Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted.Conclusions: No evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolar patients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.
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| 20. |
- Zhang, Le, et al.
(författare)
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Prediction of treatment dosage and duration from free-text prescriptions : an application to ADHD medications in the Swedish prescribed drug register
- 2021
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Ingår i: Evidence-Based Mental Health. - : BMJ Publishing Group Ltd. - 1362-0347 .- 1468-960X. ; 24:4, s. 146-152
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Accurate estimation of daily dosage and duration of medication use is essential to pharmacoepidemiological studies using electronic healthcare databases. However, such information is not directly available in many prescription databases, including the Swedish Prescribed Drug Register.OBJECTIVE: To develop and validate an algorithm for predicting prescribed daily dosage and treatment duration from free-text prescriptions, and apply the algorithm to ADHD medication prescriptions.METHODS: We developed an algorithm to predict daily dosage from free-text prescriptions using 8000 ADHD medication prescriptions as the training sample, and estimated treatment periods while taking into account several features including titration, stockpiling and non-perfect adherence. The algorithm was implemented to all ADHD medication prescriptions from the Swedish Prescribed Drug Register in 2013. A validation sample of 1000 ADHD medication prescriptions, independent of the training sample, was used to assess the accuracy for predicted daily dosage.FINDINGS: In the validation sample, the overall accuracy for predicting daily dosage was 96.8%. Specifically, the natural language processing model (NLP1 and NLP2) have an accuracy of 99.2% and 96.3%, respectively. In an application to ADHD medication prescriptions in 2013, young adult ADHD medication users had the highest probability of discontinuing treatments as compared with other age groups. The daily dose of methylphenidate use increased with age substantially.CONCLUSIONS: The algorithm provides a flexible approach to estimate prescribed daily dosage and treatment duration from free-text prescriptions using register data. The algorithm showed a good performance for predicting daily dosage in external validation.CLINICAL IMPLICATIONS: The structured output of the algorithm could serve as basis for future pharmacoepidemiological studies evaluating utilization, effectiveness, and safety of medication use, which would facilitate evidence-based treatment decision-making.
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