Developmental Model of Depression Applied to Prenatal Depression: Role of Present and Past Life Events, Past Emotional Disorders and Pregnancy Stress

Several risk factors for depression during pregnancy have already been established. However, very few studies have conducted a multivariate analysis incorporating both the major predictors of depression in women, in accordance with comprehensive developmental models of depression, and specific stressors associated with the biological and psychosocial state of the mother-to-be.We used a cross-sectional cohort design to analyze the associations between prenatal depression and potential risk factors. 693 French-speaking women with singleton pregnancies at 20-28 weeks' gestation were consecutively recruited at Caen University Hospital. Fifty women with missing values were subsequently excluded from the analysis. Depressive symptoms were assessed on the Edinburgh Postnatal Depression Scale. Risk factors were either extracted from the computerized obstetric records or assessed by means of self-administered questionnaires. The associations between prenatal depression and the potential risk factors were assessed using log-binomial regression models to obtain a direct estimate of relative risk (RR). The following factors were found to be significant in the multivariate analysis: level of education (p<0.001), past psychiatric history (adjusted RR=1.8, 95% confidence interval (CI): 1.1;2.8, p=0.014), stress related to the health and viability of the fetus (adjusted RR=2.6, 95% CI: 1.6;4.1, p<0.001), and stress related to severe marital conflicts (adjusted RR=2.4, 95% CI: 1.5;3.9, p<0.001) or to serious difficulties at work (adjusted RR=1.6, 95% CI :1.04;2.4, p=0.031). An association was also found with the previous delivery of a child with a major or minor birth defect (adjusted RR=2.0, 95% CI: 1.04;4.0, p=0.038). Univariate analyses revealed a strong association with childhood adversity (parental rejection: RR=1.8, 95% CI: 1.2;2.8, p=0.0055 and family secrets: RR=2.0, 95% CI: 1.2;3.1, p=0.0046) and with lack of partner support (RR=0.50, 95% CI: 0.30;0.84, p=0.0086).Our study identifies several risk factors that could easily be assessed in clinical practice. It draws attention to the impact of previously delivering a child with a birth defect. The association with childhood adversity warrants further study

An observational treatment study of metacognition in anxious-depression

Prior studies have found metacognitive biases are linked to a transdiagnostic dimension of anxious-depression, manifesting as reduced confidence in performance. However, previous work has been cross-sectional and so it is unclear if under-confidence is a trait-like marker of anxious-depression vulnerability, or if it resolves when anxious-depression improves. Data were collected as part of a large-scale transdiagnostic, four-week observational study of individuals initiating internet-based cognitive behavioural therapy (iCBT) or antidepressant medication. Self-reported clinical questionnaires and perceptual task performance were gathered to assess anxious-depression and metacognitive bias at baseline and 4-week follow-up. Primary analyses were conducted for individuals who received iCBT (n=649), with comparisons between smaller samples that received antidepressant medication (n=82) and a control group receiving no intervention (n=88). Prior to receiving treatment, anxious-depression severity was associated with under-confidence in performance in the iCBT arm, replicating previous work. From baseline to follow-up, levels of anxious-depression were significantly reduced, and this was accompanied by a significant increase in metacognitive confidence in the iCBT arm (β=0.17, SE=0.02, p<0.001). These changes were correlated (r(647)=-0.12, p=0.002); those with the greatest reductions in anxious-depression levels had the largest increase in confidence. While the three-way interaction effect of group and time on confidence was not significant (F(2, 1632)=0.60, p=0.550), confidence increased in the antidepressant group (β=0.31, SE = 0.08, p<0.001), but not among controls (β=0.11, SE = 0.07, p=0.103). Metacognitive biases in anxious-depression are state-dependent; when symptoms improve with treatment, so does confidence in performance. Our results suggest this is not specific to the type of intervention

An observational treatment study of metacognition in anxious-depression

Prior studies have found metacognitive biases are linked to a transdiagnostic dimension of anxious-depression, manifesting as reduced confidence in performance. However, previous work has been cross-sectional and so it is unclear if under-confidence is a trait-like marker of anxious-depression vulnerability, or if it resolves when anxious-depression improves. Data were collected as part of a large-scale transdiagnostic, four-week observational study of individuals initiating internet-based cognitive behavioural therapy (iCBT) or antidepressant medication. Self-reported clinical questionnaires and perceptual task performance were gathered to assess anxious-depression and metacognitive bias at baseline and 4-week follow-up. Primary analyses were conducted for individuals who received iCBT (n=649), with comparisons between smaller samples that received antidepressant medication (n=82) and a control group receiving no intervention (n=88). Prior to receiving treatment, anxious-depression severity was associated with under-confidence in performance in the iCBT arm, replicating previous work. From baseline to follow-up, levels of anxious-depression were significantly reduced, and this was accompanied by a significant increase in metacognitive confidence in the iCBT arm (β=0.17, SE=0.02, p<0.001). These changes were correlated (r(647)=-0.12, p=0.002); those with the greatest reductions in anxious-depression levels had the largest increase in confidence. While the three-way interaction effect of group and time on confidence was not significant (F(2, 1632)=0.60, p=0.550), confidence increased in the antidepressant group (β=0.31, SE = 0.08, p<0.001), but not among controls (β=0.11, SE = 0.07, p=0.103). Metacognitive biases in anxious-depression are state-dependent; when symptoms improve with treatment, so does confidence in performance. Our results suggest this is not specific to the type of intervention

DNA methylation differences at the glucocorticoid receptor gene in depression are related to functional alterations in hypothalamic-pituitary-adrenal axis activity and to early life emotional abuse

Depression is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis activity. A proposed mechanism to explain these alterations are changes in DNA methylation levels, secondary to early life adversity (ELA), at stress-related genes. Two gene regions that have been implicated in the literature, the glucocorticoid receptor gene (NR3C1) exon 1F and the FKBP5 gene intron 7 were examined in 67 individuals (33 depressed patients and 34 controls). We investigated whether cortisol concentrations, evaluated in 25 depressed patients and 20 controls, and measures of ELA were associated with the degree of methylation at these candidate gene regions. Mean NR3C1 exon 1F DNA methylation levels were significantly increased in the depressed cohort and the degree of methylation was found to be positively associated with morning cortisol concentrations. DNA methylation levels at specific CG sites within the NR3C1 exon 1F were related to childhood emotional abuse severity. DNA methylation at CG38 was related to both HPA axis and childhood emotional abuse measures in the depressed group. No FKBP5 differences were revealed. Our findings suggest that hypermethylation at the NR3C1 exon 1F may occur in depression. This locus-specific epigenetic change is associated with higher basal HPA axis activity, possibly reflecting acquired glucocorticoid receptor resistance