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Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study.

ABSTRACT: The aim of this propensity-matched cohort study was to evaluate the impact of prenatal SSRI exposure and a history of maternal depression on neonatal brain volumes and white matter microstructure. SSRI-exposed neonates (n=27) were matched to children of mothers with no history of depression or SSRI use (n=54). Additionally, neonates of mothers with a history of depression, but no prenatal SSRI exposure (n=41), were matched to children of mothers with no history of depression or SSRI use (n=82). Structural magnetic resonance imaging and diffusion weighted imaging scans were acquired with a 3T Siemens Allegra scanner. Global tissue volumes were characterized using an automatic, atlas-moderated expectation maximization segmentation tool. Local differences in gray matter volumes were examined using deformation-based morphometry. Quantitative tractography was performed using an adaptation of the UNC-Utah NA-MIC DTI framework. SSRI-exposed neonates exhibited widespread changes in white matter microstructure compared to matched controls. Children exposed to a history of maternal depression but no SSRIs showed no significant differences in brain development compared to matched controls. No significant differences were found in global or regional tissue volumes. Additional research is needed to clarify whether SSRIs directly alter white matter development or whether this relationship is mediated by depressive symptoms during pregnancy.

SUBMITTER: Jha SC

PROVIDER: S-EPMC4930375 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study.

Jha Shaili C SC Meltzer-Brody Samantha S Steiner Rachel J RJ Cornea Emil E Woolson Sandra S Ahn Mihye M Verde Audrey R AR Hamer Robert M RM Zhu Hongtu H Styner Martin M Gilmore John H JH Knickmeyer Rebecca C RC

Psychiatry research. Neuroimaging 20160524

The aim of this propensity-matched cohort study was to evaluate the impact of prenatal SSRI exposure and a history of maternal depression on neonatal brain volumes and white matter microstructure. SSRI-exposed neonates (n=27) were matched to children of mothers with no history of depression or SSRI use (n=54). Additionally, neonates of mothers with a history of depression, but no prenatal SSRI exposure (n=41), were matched to children of mothers with no history of depression or SSRI use (n=82). ...[more]

PMID: 27254086

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Project description:BackgroundAlthough selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, associations with violence are uncertain.Methods and findingsFrom Swedish national registers we extracted information on 856,493 individuals who were prescribed SSRIs, and subsequent violent crimes during 2006 through 2009. We used stratified Cox regression analyses to compare the rate of violent crime while individuals were prescribed these medications with the rate in the same individuals while not receiving medication. Adjustments were made for other psychotropic medications. Information on all medications was extracted from the Swedish Prescribed Drug Register, with complete national data on all dispensed medications. Information on violent crime convictions was extracted from the Swedish national crime register. Using within-individual models, there was an overall association between SSRIs and violent crime convictions (hazard ratio [HR] = 1.19, 95% CI 1.08-1.32, p < 0.001, absolute risk = 1.0%). With age stratification, there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y (HR = 1.43, 95% CI 1.19-1.73, p < 0.001, absolute risk = 3.0%). However, there were no significant associations in those aged 25-34 y (HR = 1.20, 95% CI 0.95-1.52, p = 0.125, absolute risk = 1.6%), in those aged 35-44 y (HR = 1.06, 95% CI 0.83-1.35, p = 0.666, absolute risk = 1.2%), or in those aged 45 y or older (HR = 1.07, 95% CI 0.84-1.35, p = 0.594, absolute risk = 0.3%). Associations in those aged 15 to 24 y were also found for violent crime arrests with preliminary investigations (HR = 1.28, 95% CI 1.16-1.41, p < 0.001), non-violent crime convictions (HR = 1.22, 95% CI 1.10-1.34, p < 0.001), non-violent crime arrests (HR = 1.13, 95% CI 1.07-1.20, p < 0.001), non-fatal injuries from accidents (HR = 1.29, 95% CI 1.22-1.36, p < 0.001), and emergency inpatient or outpatient treatment for alcohol intoxication or misuse (HR = 1.98, 95% CI 1.76-2.21, p < 0.001). With age and sex stratification, there was a significant association between SSRIs and violent crime convictions for males aged 15 to 24 y (HR = 1.40, 95% CI 1.13-1.73, p = 0.002) and females aged 15 to 24 y (HR = 1.75, 95% CI 1.08-2.84, p = 0.023). However, there were no significant associations in those aged 25 y or older. One important limitation is that we were unable to fully account for time-varying factors.ConclusionsThe association between SSRIs and violent crime convictions and violent crime arrests varied by age group. The increased risk we found in young people needs validation in other studies.

Project description:Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a child during pregnancy. In addition, serotonin (5-HT) exerts neurotrophic actions with thus far not fully known effects in the offspring. The neurotrophic growth factor (NGF) is involved in neuronal cell survival and differentiation, and altered placenta levels have been found to increase the risk for pregnancy complications, similar to those found in women treated with SSRIs. We therefore investigated whether the NGF signaling pathway was altered in the placenta from women treated with SSRIs (n = 12) and compared them with placenta from depressed (n = 12) and healthy mothers (n = 12). Results from immunohistochemical stainings revealed that placental NGF protein levels of SSRI-treated women were increased in both trophoblasts and endothelial cells compared with depressed and control women. In addition, downstream of the NGF receptor TrkA, increased levels of the signaling proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells in SSRI-treated women when compared to healthy controls. SSRI-treated women also displayed increased levels of phosphorylated ROCK2 in all placental cell types studied in comparison with depressed and control women. Interestingly, in placental endothelial cells from depressed women, NGF levels were significantly lower compared to control women, but ROCK2 levels were increased compared with control and SSRI-treated women. Taken together, these results show that the NGF signaling and downstream pathways in the placenta are affected by SSRI treatment and/or antenatal depression. This might lead to an altered placental function, although the clinical relevance of our findings still needs to be investigated.

Project description:The physiology of mood regulation in the postpartum is poorly understood despite the fact that postpartum depression (PPD) is a common pathology. Serotonergic mechanisms and their dysfunction are widely presumed to be involved, which has led us to investigate whether lactation induces changes in central or peripheral serotonin (5-HT) systems and related affective behaviors. Brain sections from lactating (day 10 postpartum) and age-matched nulliparous (non-pregnant) C57BL/6J mice were processed for 5-HT immunohistochemistry. The total number of 5-HT immunostained cells and optical density were measured. Lactating mice exhibited lower immunoreactive 5-HT and intensity in the dorsal raphe nucleus when compared with nulliparous controls. Serum 5-HT was quantified from lactating and nulliparous mice using radioimmunoassay. Serum 5-HT concentrations were higher in lactating mice than in nulliparous controls. Affective behavior was assessed in lactating and non-lactating females ten days postpartum, as well as in nulliparous controls using the forced swim test (FST) and marble burying task (MBT). Animals were treated for the preceding five days with a selective serotonin reuptake inhibitor (SSRI, citalopram, 5mg/kg/day) or vehicle. Lactating mice exhibited a lower baseline immobility time during the FST and buried fewer marbles during the MBT as compared to nulliparous controls. Citalopram treatment changed these behaviors in lactating mice with further reductions in immobility during the FST and decreased marble burying. In contrast, the same regimen of citalopram treatment had no effect on these behaviors in either non-lactating postpartum or nulliparous females. Our findings demonstrate changes in both central and peripheral 5-HT systems associated with lactation, independent of pregnancy. They also demonstrate a significant interaction of lactation and responsiveness to SSRI treatment, which has important implications in the treatment of PPD. Although recent evidence has cast doubt on the effectiveness of SSRIs, these results support their therapeutic use in the treatment of PPD.

Dataset Information

Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study.

Publications

Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study.

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