| 1. |
- Guintivano, Jerry, et al.
(author)
-
Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
-
In: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
-
Journal article (peer-reviewed)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).
|
|
| 2. |
- Pertold, Cino, et al.
(author)
-
Prevalence of skull pathologies in European harbor seals (Phoca vitulina) during 1981–2014
- 2018
-
In: Mammal Research. - : Springer Science and Business Media LLC. - 2199-2401 .- 2199-241X. ; 63:1, s. 55-63
-
Journal article (peer-reviewed)abstract
- Harbor seals (Phoca vitulina) inhabit the seas surrounding Denmark and are an important top predator in the marine food chain. This trophic position exposes them to environmental contaminants with disease epi- demics and hunting being additional threats to this popu- lation. It is therefore important to study how environmen- tal pollution at the current order of magnitude affects the health of the population. Earlier studies have shown that occurrence of periodontitis could be linked to the amount of pollution the seals were subjected to. In order to inves- tigate this further, 380 skulls and 141 mandibles of harbor seals (Phoca vitulina) from the Wadden Sea, the Limfjord, and Kattegat collected during the period 1970–2014 were examined. The skulls were examined for pathological le- sions. The Hounsfield Units (HU) which are correlated to the bone mineral density (BMD) were measured in a sub- sample (n= 34) using CT scans. The macroscopic examination revealed (with the exception of the Swedish part of Kattegat) a significant increase of pathological lesions over the study period of 1981–2014. The exami- nation of HU showed that median HU measured at mul- tiple sites was highest in the healthy skulls compared to the skulls with one or more of the lesions. A discriminant analysis allowed high discriminatory capacity to separate healthy skulls from the skulls with pathologies, simply by the utilization of the HU data. Former studies of BMD in marine mammals have shown that exposure to environ- mental chemicals alter BMD and cause periodontitis. The present study, based on temporal and spatial trends in BMD, confirms the results of previous studies Prevalence of skull pathologies in European harbor seals (Phoca vitulina) during 1981–2014 (PDF Download Available). Available from: https://www.researchgate.net/publication/320586176_Prevalence_of_skull_pathologies_in_European_harbor_seals_Phoca_vitulina_during_1981-2014 [accessed Dec 15 2017].
|
|
| 3. |
- Bang Madsen, Kathrine, et al.
(author)
-
Attention-Deficit Hyperactivity Disorder (ADHD) Medication Use Trajectories Among Women in the Perinatal Period
- 2024
-
In: CNS Drugs. - : Adis International Ltd.. - 1172-7047 .- 1179-1934. ; 38, s. 301-314
-
Journal article (peer-reviewed)abstract
- BACKGROUND: An increasing number of women of reproductive age are treated with attention-deficit hyperactivity disorder (ADHD) medication; however, patterns of ADHD medication use for women in the perinatal period have not been well described.OBJECTIVE: This study aimed to describe ADHD medication use patterns from 1 year before pregnancy to 1 year after delivery, and to describe sociodemographic characteristics and clinical features by medication trajectories.METHODS: The population-based cohort study included pregnancies in Denmark between 1997 and 2020, from the Medical Birth Register, by women who filled at least one prescription for ADHD medication from 12 months before pregnancy until 12 months after delivery. We applied group-based trajectory modeling to classify women into subgroups based on the identification of heterogeneous ADHD medication treatment patterns, and described the characteristics associated with these groups.RESULTS: Overall, we included 4717 pregnancies leading to liveborn singletons by 4052 mothers with a mean (standard deviation) age of 27.5 (5.6) years. We identified four treatment trajectories across pregnancy and the postpartum period: continuers (23.3%), discontinuers (41.8%), interrupters who ceased filling prescriptions during pregnancy but resumed postpartum (17.2%), and postpartum initiators (17.7%). Continuers were older at the time of conception, gave birth in more recent years, were more likely to smoke during pregnancy, and used other psychotropic medications during pregnancy. A large proportion of continuers used methylphenidate (89.1%) compared with the other groups (75.9-84.1%) and had switched ADHD medication type during the whole period (16.4% vs. 7.4-14.8%).CONCLUSION: We found that approximately 60% of women discontinued or interrupted their ADHD medication around pregnancy, and those who continued differed in sociodemographic and clinical factors that may reflect more severe ADHD.
|
|
| 4. |
- Bang Madsen, Kathrine, et al.
(author)
-
In utero exposure to ADHD medication and long-term offspring outcomes
- 2023
-
In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:4, s. 1739-1746
-
Journal article (peer-reviewed)abstract
- Attention Deficit Hyperactivity Disorder (ADHD) medication is increasingly being used during pregnancy. Concerns have been raised as to whether ADHD medication has long-term adverse effects on the offspring. The authors investigated whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The population-based cohort study in the Danish national registers included 1,068,073 liveborn singletons from 1998 to 2015 followed until any developmental diagnosis, death, emigration, or December 31, 2018. Children of mothers who continued ADHD medication (methylphenidate, amphetamine, dexamphetamine, lisdexamphetamine, modafinil, atomoxetine, clonidine) during pregnancy and children of mothers who discontinued ADHD medication before pregnancy were compared using Cox regression. Main outcomes were neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment during childhood or adolescence. In total, 898 children were exposed to ADHD medication during pregnancy compared to 1270 children whose mothers discontinued ADHD medication before pregnancy. After adjustment for demographic and psychiatric characteristics of the mother, no increased risk of any offspring developmental disorders was found combined (aHR 0.97, 95% CI 0.81 to 1.17) or for separate subcategories. Similarly, no increased risk was found for any sub-categories of outcomes in the negative control or sibling controlled analyses. Neurodevelopment and growth in offspring do not differ based on antenatal exposure to ADHD medication. These findings provide reassurance for women with ADHD who depend on ADHD medication for daily functioning and who consider continuing medication in pregnancy.
|
|
| 5. |
- Bang Madsen, Kathrine, et al.
(author)
-
Pregnancy and postpartum psychiatric episodes in fathers : A population-based study on treatment incidence and prevalence
- 2022
-
In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 296, s. 130-135
-
Journal article (peer-reviewed)abstract
- BackgroundFor women, the perinatal period confers an increased risk of severe psychiatric disorders, but similar evidence for fathers is lacking. We examined rates of first-time and recurrent psychiatric disorders in men before and after becoming fathers.MethodsA descriptive prospective study design was applied using information from the Danish National registers. Perinatal psychiatric episodes were assessed as incidence of first-time and prevalence (including recurrence) of recorded in- or outpatient admissions for any mental disorder and redeemed prescriptions for psychotropic medication in fathers to children born from January 1, 1998 until December 31, 2015.ResultsWe identified 929,415 births and 543,555 unique fathers. Incidence and prevalence proportions for paternal psychiatric in- and outpatient episodes showed an increasing trend over the perinatal period and were marginally higher postpartum compared to pregnancy; e.g., median incidence proportion for inpatient treatment during pregnancy was 0.07 (95% CI: 0.04; 0.07) and 0.10 (95% CI: 0.08; 0.11) postpartum per 1000 births. No difference between the periods was found for incidence of prescriptions for psychotropic medication. Psychiatric disorders in expecting and new fathers were mainly treated in primary care with cumulative incidence of prescriptions for psychotropic medication of 14.56 per 1000 births during the first year of fatherhood.LimitationsWe only capture fathers who actively sought and received treatment, and we consequently underestimate milder psychiatric episodes in expecting and new fathers.ConclusionBecoming a father did not appear to trigger a substantially increased risk of severe psychiatric disorders, as it has been observed for new mothers.
|
|
| 6. |
- Karalexi, Maria, et al.
(author)
-
Perinatal mental health : how nordic data sources have contributed to existing evidence and future avenues to explore
- 2022
-
In: Nordic Journal of Psychiatry. - : Taylor & Francis Group. - 0803-9488 .- 1502-4725. ; 76:6, s. 423-432
-
Research review (peer-reviewed)abstract
- Purpose Perinatal mental health disorders affect a significant number of women with debilitating and potentially life-threatening consequences. Researchers in Nordic countries have access to high quality, population-based data sources and the possibility to link data, and are thus uniquely positioned to fill current evidence gaps. We aimed to review how Nordic studies have contributed to existing evidence on perinatal mental health.Methods We summarized examples of published evidence on perinatal mental health derived from large population-based longitudinal and register-based data from Denmark, Finland, Iceland, Norway and Sweden.Results Nordic datasets, such as the Danish National Birth Cohort, the FinnBrain Birth Cohort Study, the Icelandic SAGA cohort, the Norwegian MoBa and ABC studies, as well as the Swedish BASIC and Mom2B studies facilitate the study of prevalence of perinatal mental disorders, and further provide opportunity to prospectively test etiological hypotheses, yielding comprehensive suggestions about the underlying causal mechanisms. The large sample size, extensive follow-up, multiple measurement points, large geographic coverage, biological sampling and the possibility to link data to national registries renders them unique. The use of novel approaches, such as the digital phenotyping data in the novel application-based Mom2B cohort recording even voice qualities and digital phenotyping, or the Danish study design paralleling a natural experiment are considered strengths of such research.Conclusions Nordic data sources have contributed substantially to the existing evidence, and can guide future work focused on the study of background, genetic and environmental factors to ultimately define vulnerable groups at risk for psychiatric disorders following childbirth.
|
|
| 7. |
- Munk-Olsen, Trine, et al.
(author)
-
Maternal and infant outcomes associated with lithium use in pregnancy : an international collaborative meta-analysis of six cohort studies
- 2018
-
In: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 5:8, s. 644-652
-
Journal article (peer-reviewed)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.
|
|
| 8. |
- Munk-Olsen, Trine, et al.
(author)
-
Postpartum depression : a developed and validated model predicting individual risk in new mothers
- 2022
-
In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
-
Journal article (peer-reviewed)abstract
- Postpartum depression (PPD) is a serious condition associated with potentially tragic outcomes, and in an ideal world PPDs should be prevented. Risk prediction models have been developed in psychiatry estimating an individual's probability of developing a specific condition, and recently a few models have also emerged within the field of PPD research, although none are implemented in clinical care. For the present study we aimed to develop and validate a prediction model to assess individualized risk of PPD and provide a tentative template for individualized risk calculation offering opportunities for additional external validation of this tool. Danish population registers served as our data sources and PPD was defined as recorded contact to a psychiatric treatment facility (ICD-10 code DF32-33) or redeemed antidepressant prescriptions (ATC code N06A), resulting in a sample of 6,402 PPD cases (development sample) and 2,379 (validation sample). Candidate predictors covered background information including cohabitating status, age, education, and previous psychiatric episodes in index mother (Core model), additional variables related to pregnancy and childbirth (Extended model), and further health information about the mother and her family (Extended+ model). Results indicated our recalibrated Extended model with 14 variables achieved highest performance with satisfying calibration and discrimination. Previous psychiatric history, maternal age, low education, and hyperemesis gravidarum were the most important predictors. Moving forward, external validation of the model represents the next step, while considering who will benefit from preventive PPD interventions, as well as considering potential consequences from false positive and negative test results, defined through different threshold values.
|
|
