| 1. |
- Bernabe, Beatriz Penalver, et al.
(författare)
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Interactions between perceived stress and microbial-host immune components : two demographically and geographically distinct pregnancy cohorts
- 2023
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Higher stress during pregnancy associates with negative outcomes and elevated inflammation. The gut microbiota, reflecting environment and social interactions, alongside host immune responses have the potential to better understand perceived stress and identify when stress is excessive in pregnancy. Two U.S. cohorts of 84 pregnant individuals, composed of urban women of color and suburban white women, completed the Perceived Stress Scale-10 (PSS-10) and provided fecal and blood samples at two time points. Confirmatory Factor Analysis assessed the robustness of a two-factor PSS-10 model (Emotional Distress/ED and Self-Efficacy/SE). Gut microbiota composition was measured by 16 S rRNA amplicon sequencing and the immune system activity was assessed with a panel of 21 T-cell related cytokines and chemokines. ED levels were higher in the suburban compared to the urban cohort, but levels of SE were similar. ED and SE levels were associated with distinct taxonomical signatures and the gut microbiota data improved the prediction of SE levels compared with models based on socio-demographic characteristics alone. Integration of self-reported symptoms, microbial and immune information revealed a possible mediation effect of Bacteroides uniformis between the immune system (through CXCL11) and SE. The study identified links between distinct taxonomical and immunological signatures with perceived stress. The data are congruent with a model where gut microbiome and immune factors, both impacting and reflecting factors such as close social relationships and dietary fiber, may modulate neural plasticity resulting in increased SE during pregnancy. The predictive value of these peripheral markers merit further study.
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| 2. |
- 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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| 3. |
- Kimmel, Mary C., et al.
(författare)
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Heart rate variability in late pregnancy : exploration of distinctive patterns in relation to maternal mental health
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Exploration of photoplethysmography (PPG), a technique that can be translated to the clinic, has the potential to assess the autonomic nervous system (ANS) through heart rate variable (HRV) in pregnant individuals. This novel study explores the complexity of mental health of individuals in a clinical sample responding to a task in late pregnancy; finding those with several types of past or current anxiety disorders, greater trait anxiety, or greater exposure to childhood traumatic events had significantly different HRV findings from the others in the cohort. Lower high frequency (HF), a measure of parasympathetic activity, was found for women who met the criteria for the history of obsessive-compulsive disorder (OCD) (p = 0.004) compared with women who did not meet the criteria for OCD, and for women exposed to greater than five childhood traumatic events (p = 0.006) compared with those exposed to four or less childhood traumatic events. Conversely higher low frequency (LF), a measure thought to be impacted by sympathetic system effects, and the LF/HF ratio was found for those meeting criteria for a panic disorder (p = 0.006), meeting criteria for social phobia (p = 0.002), had elevated trait anxiety (p = 0.006), or exposure to greater than five childhood traumatic events (p = 0.004). This study indicates further research is needed to understand the role of PPG and in assessing ANS functioning in late pregnancy. Study of the impact of lower parasympathetic functioning and higher sympathetic functioning separately and in conjunction at baseline and in relation to tasks during late pregnancy has the potential to identify individuals that require more support and direct intervention.
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| 4. |
- Kimmel, Mary C., et al.
(författare)
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Metabolite trajectories across the perinatal period and mental health : A preliminary study of tryptophan-related metabolites, bile acids and microbial composition
- 2022
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Ingår i: Behavioural Brain Research. - : Elsevier. - 0166-4328 .- 1872-7549. ; 418
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Tidskriftsartikel (refereegranskat)abstract
- Depression and anxiety during pregnancy and postpartum are common, but affected women differ in timing, trajectories, and extent of symptoms. The objective of this pilot, feasibility study is to analyze trajectories of serotonin and tryptophan-related metabolites, bile acid metabolites, and microbial composition, in relation to psychiatric history and current symptoms across the perinatal period. Serum and fecal samples were collected from 30 women at three times points in the perinatal period and assayed with LC-MS/MS and 16S sequencing respectively. We defined mean trajectories for each metabolite, clustered individuals by metabolite trajectories, tested associations between metabolites, and examined metabolite levels in relation to microbial composition. Findings of note include: (1) changes in kynurenine and the ratio of kynurenic acid to kynurenine from second trimester to third trimester were strongly associated with baseline primary and secondary bile acids. (2) Secondary bile acid UDCA and its conjugated forms were associated with lower bacterial diversity and levels of Lachnospiraceae, a taxa known to produce Short Chain Fatty Acids. (3) History of anxiety was associated with UDCA levels, but history of major depression was not associated with any of the bile acids. (4) There was a trend towards lower dietary fiber for those with history of anxiety or depression. Overall, our results reveal substantial temporal variation in tryptophan-related metabolites and in bile acid metabolites over the perinatal period, with marked inter-individual variability. Trajectories of TRP -related metabolites, primary and secondary bile acids, and the absence or presence of microbes that produce Short Chain Fatty Acids (SCFAs) considered in concert have the potential to differentiate individuals based on perinatal adaptations that may impact mental and overall health.
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| 5. |
- Kimmel, Mary C.
(författare)
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Pregnancy—A Critical Time for Mental Health : Interrogating Psychiatry with Microbiota-Gut-Brain Axis and Autonomic Nervous System Biomarkers
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Perinatal mood and anxiety disorders (PMADs) are common and impact the parent and child beyond the perinatal period of pregnancy and postpartum. The aim of this thesis was to study biomarkers that might reflect perinatal mental health. This work focused on multiple methods of mental health characterization and the autonomic nervous system as reflected by heart rate variability (HRV), the immune system, and the gut microbiome.Three observational longitudinal cohorts of pregnant individuals from three geographic regions were studied: 1) the Biology, Affect, Stress, Imaging and Cognition (BASIC) and the follow-up study U-BIRTH from Uppsala University Hospital; 2) the University of Illinois at Chicago (UIC) MoMent cohort; and 3) the University of North Carolina at Chapel Hill (UNC) cohort.The first paper assessed HRV before and after a mental task and in relation to psychiatric diagnoses, exposure to trauma, and self-report of mental distress. The second paper studied the Perceived Stress Scale (PSS-10) in relation to microbial composition and T-cell related cytokines and chemokines. The third paper studied the Edinburgh Postnatal Depression Scale (EPDS) in relation to whole genome sequencing and Gut Brain Modules for functioning. The fourth paper assessed trajectories of infant temperament in relation to depression and anxiety from the EPDS.The PSS-10 and the EPDS factored differently in the cohorts. HRV patterns differed based on anxiety disorder type, greater trait anxiety, and greater exposure to childhood traumatic eventsut microbiome data improved the prediction of PSS-10 self-efficacy; and self-efficacy was associated with a bacteria type more beneficial in the presence of dietary fiber that also associated with an immune factor important in immune tolerance. Greatest variation in microbial community functioning was due to cortisol degradation and synthesis of inositol, menaquinone, and the short chain fatty acid (SCFA) acetate. nxiety in pregnancy was associated with children who had higher levels of sensitivity and greater negative affectivity that increased over early life.These four papers highlight: 1) the course of mental health in pregnancy is critical to the development of parent and child; 2) the characterization of perinatal mental health requires a mix of methods that recognize there may be differences in the use of the methods based on the population; and 3) biomarkers of perinatal mental health need to reflect dynamic systems, and the components may not be as important as the patterns and interactions.
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| 6. |
- Kimmel, Mary, et al.
(författare)
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Maternal and Infant Autonomic Nervous System Dysfunction
- 2021
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 89:9, s. S335-S335
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background:Studying heart rate variability (HRV) in thebehavioral laboratory provides the opportunity to understandAutonomic Nervous System function during stress. Specificaspects of maternal mental distress may help identify womenand infants with greater ANS dysfunction.Methods:A cohort of women was followed through theperinatal period with the Mood and Anxiety Symptoms Ques-tionnaire (MASQ) . The Trier Social Stress Test (TSST) and aninfant stressor (giving the infant a heel stick) were administeredwith HRV monitoring at the postpartum visit. HRV values wereaveraged for segments before, during, and after the stressor.There were 70 mothers and 32 infants with complete HRV datafrom the larger cohort. Maternal sleep was measured by thePittsburgh Sleep Quality Index. The relationship betweenMASQ symptoms, sleep, and maternal and infant HRV mea-sures was analyzed with linear regressions.Results:Maternal irritability, sleep difficulty, and restlessnessfrom the MASQ was associated with alterations in HRV mea-sures after the stressor (High Frequency (HF), p¼0.019; LowFrequency (LF), p¼0.007). The same maternal symptoms werealso associated with similar alterations for the infant after thestressor (p¼0.013; LF, p¼0.009). Poorer sleep quality in thethird trimester was similarly related to infant HRV measures(HF, p¼0.013; LF, p¼0.047).Conclusions:Mothers with higher amounts of irritability,restlessness, and sleep difficulty had associated ANS differ-ences in navigating a stressor that was also mirrored in theirinfants navigating a stressor. Maternal sleep in the thirdtrimester may be an area of intervention to improve stressreactivity for mother and infant.
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| 7. |
- 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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| 8. |
- 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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