Table 3.
Summary of included articles (postpartum).
| POSTPARTUM | ||||
|---|---|---|---|---|
| First Author | Purpose/Aims | Design# | Factor Domain | Summary of significant findings (values) |
| Achytes (2022) (N = 130) US | Investigate whether a pro-inflammatory status in plasma, together with changes in the kynurenine pathway activity, is associated with the development of severe depression and suicidal behavior in the post-partum. | Case-control1 | B, Bh | ↑ IL-6, IL-8 ↑ PPD (OR IL-6 = 3.0, 95% CI = 1.37 – 6.6; OR IL-8 = 3.32, 95% CI = 1.32 – 8.34, per pg/ml increase) |
| ↓ IL-2 ↑ PPD (OR = 2.34, 95%CI = 1.35–4.05, p = 0.002, per pg/ml decrease) | ||||
| ↓ serotonin ↑ odds of PPD (OR = 1.43 per nM decrease in serotonin, 95% CI: 1.07 – 1.92, p = 0.016) | ||||
| ↑ Kynurenine/serotonin ratio ↑ PPD (OR = 1.35 per unit increase, 95% CI: 1.03 – 1.79, p = 0.038) | ||||
| Sensitivity analysis using depression scores: models for IL-8, IL2, serotonin, serotonin/kynurenine, and quinolinic acid were significant; (linear regression, Beta 3.9, Standardized Beta 0.22, p = 0.006), (linear regression, Beta −2.3, Standardized Beta −0.23, p = 0.005), (linear regression, Beta −1.3, Standardized Beta −0.24, p = 0.003), linear regression, Beta −1.1, Standardized Beta 0.22, p = 0.009), linear regression, Beta −4.3, Standardized Beta −0.18, p = 0.022) | ||||
| ↓ serotonin was associated with current and history of suicidal behavior and ↑ odds of completed suicide attempt during pregnancy. (OR : 0.51[0.32, 0.8]1, p = 0.005), (OR: 0.50 [0.29, 0.87], p = 0.013), (OR: 0.51, [0.31, 0.84], p = 0.007) | ||||
| Dhiman2 (2021) (N = 660) India | Explore the association between vitamin B12 and probable PPD in South Indian population. | Cross-sectional1 | B | Those with probable depression were ↑ likely to belong to the middle SES group (p = 0.002), had more than one child (p = 0.002), be dissatisfied with their marriage (p < 0.001), be dissatisfied with the gender of their child (p < 0.001), and had ↑ rates of cesarean delivery (p = 0.014). They also reported ↓ milk (p < 0.001), meat (p = 0.012), and egg (p = 0.002) intake. |
| Median total B12 levels and cB12 were ↓ in cases compared to controls (p < 0.001). Methyl malonic acid (MMA) – marker of functional deficiency of vitamin B12 – was ↑ cases compared to controls (p = 0.002). | ||||
| After adjusting for SES, martial dissatisfaction, unplanned pregnancy, and type of delivery, the regression model indicated the likelihood of postpartum depression to ↓ by 0.39 for ever unit ↑ in total vitamin B12 (OR = 0.394; 95% CI: 0.189–0.822, p = 0.009) and by a factor of 0.29 (OR = 0.293; 95% CI: 0.182–0.470, p < 0.001) for cB12. MMA (OR = 2.04; 95% CI: 1.53–2.11, p < 0.001) and 5-methyl tetrahydrofolate (THF) (OR = 3.18; 95% CI: 1.42–6.08, p = 0.001) were found to be predictors of PPD. | ||||
| After adjusting for SES, martial dissatisfaction, unplanned pregnancy, and type of delivery, a significant negative association among serotonin and depression remained (β = −0.16, p = 0.005), as did a positive association among MMA (β = 0.161, p = 0.001), homocysteine (hcy) (β = 0.155, p = 0.005), and THF (β = 0.118, p = 0.010) and depression. | ||||
| The path analysis model with total vitamin B12 as the predictor, depression score as the outcome variable, and MMA as the mediator was significant (p < 0.001). | ||||
| Rihua2 (2018) (N = 84) China | To determine associations between PPD and plasma neurotransmitters. | Case control1 | B | There were significant differences in education and mode of delivery among those with PPD and those without. |
| Plasma levels of serotonin (5-hydroxytryptamine or 5-HT) and neuropeptide Y (NPY) were ↓ in those with PPD compared to controls (p < 0.05 or p < 0.01) whereas norepinephrine (NE) and substance P (SP) were ↑ in PPD cases versus controls (p < 0.05). No differences were found for dopamine (DA). | ||||
| A negative correlation among depression scores and serotonin and NPY (p < 0.05 or p < 0.01) were present as well as a positive correlation among depression scores with NE and SP (p < 0.01 or p < 0.01). | ||||
| Veen (2016) (N = 42) Netherlands | To investigate if alterations in tryptophan degradation in the postpartum period are associated with the occurrence of postpartum depression and postpartum psychosis. | Case control1 | B | Those considered to be “healthy” postpartum participants were ↑ likely to be breastfeeding at the time of blood collection (p < 0.001). |
| Physiological postpartum period: Healthy postpartum (PP) participants had ↓ serum levels of kynurenic acid (KA) compared to healthy non-PP controls (p < 0.001). All PP participants had ↑ levels of 3-OH-kynurenine (3HK) (p = 0.011); the KA/kynurenine (KYN) ratio was ↓ in healthy PP participants (p < 0.001) suggesting a strong inhibition of the kynurenine aminotransferases (KAT) enzymes during the first 2 months PP. The 3HK/KYN ratio was ↑ in healthy PP participants with a median time of 22 days PP (p = 0.021), but not in healthy PP participants with a median time of blood collection 40 days PP. The authors suggest this indicates ↑ activity of the kynurenine-3-monooxygenase (KMO) enzymes in the first month of the physiological PP period and then the gradual returning to “normal” levels. The serotonergic pathway (5HIAA)/KYN ratio was ↓ in healthy PP participants suggesting that the breakdown of tryptophan (TRP) is biased towards the KYN pathway and away from the serotonergic pathway in the physiological PP period (p = 0.009). “Healthy” PP participants had ↓ serum levels of TRP (p < 0.001), and ↑ levels of KYN (p = 0.002) compared to healthy non-PP participants, and consequently the TRP breakdown index was also ↑ (p < 0.001). | ||||
| KYN was ↓ in cases compared to controls (p = 0.001), and accordingly cases had a ↓ tryptophan breakdown index compared to controls (p = 0.035). | ||||
| Comasco (2011) (N = 272) Sweden | Examine whether genetic variations in the monoaminergic neurotransmitter system, together with environmental stressors, contribute to the development of PPD symptoms | Case control2 | B, S | Associations between genetic polymorphisms and PPD symptoms were significant only at the 6-week time point, not at 6 months (data not shown). |
| COMT-Val158Met with ↑ risk for Met carriers was associated with PPD. | ||||
| Previous psychiatric contact, significant life events, and maternity stressors were associated with PPD symptoms. | ||||
| Gene-by-gene interactions were present for COMT-MAOA in relation to PPD symptoms. Low MAOA activity carriers with the Met variant of COMT was related to PPD symptoms; high MAOA activity variant was associated with PPD symptoms only when combined with the Met allele of COMT; short 5HTT allele was associated with PPD symptoms only when combined with the Met allele of COMT. | ||||
| COMTVal158Met was associated with PPD symptoms in the presence of previous psychiatric contact and maternity stressors, while MAOA-uVNTR was associated with PPD symptoms only in the presence of maternity stressors. | ||||
| The logistic regression analysis demonstrated an association among PPD symptoms and COMTVal158Met, previous psychiatric contact, and maternity stressors. The model explained 30% variance. After stratifying for previous psychiatric contact, the gene-environment interaction model indicated those with previous psychiatric contact had a main effect of COMT-Val158Met and 5HTT-LPR with an explained variance of 40%. | ||||
| Bailara (2006) (N =50) France | Assess the correlation of intensity of baby blues, with the intensity of metabolic changes and brain tryptophan availability | Cross-sectional1 | B | Total plasma TRP exhibited a mild (+19%) ↑. |
| An abrupt ↑ in competitor amino acid concentrations (+77% isoleucine, +55% leucine, +52% tyrosine) led to a ↓ in brain tryptophan availability (BTAI). | ||||
| The BTAI ↓ between the prenatal and postpartum period (−15%, p < 0.01) and was associated with PP blues symptoms. | ||||
| The change in BTAI was negatively correlated with the intensity of postpartum blues (r = −0.283, p < 0.05). | ||||
| Moses-Kolko2 (2008) (N =16) US | To measure brain serotonin-1A (5HT1A) receptor binding potential (BP) in healthy and depressed postpartum women. | Cross-sectional1 | B | There was an effect of breastfeeding status on hypothalamic-pituitary-ovarian axis hormone concentrations estradiol, progesterone, LH, FSH, and prolactin [Wilks’ lambda = 0.2056; F(5, 10) = 7.73, p = 0.003]. A post-hoc analysis showed breastfeeding was associated with ↓ estradiol [F(1, 14) = 8.31, p = 0.01], progesterone [F(1, 14) = 4.33, p = 0.06], and FSH concentrations [F(1, 14) = 5.18, = 0.04] and ↑ prolactin concentrations [F(1, 14) = 26.25, p = 0.0002). |
| Serotonin receptor (5HT1A) binding in the three a prior regions of interest (mesiotemporal cortex, left lateral orbitofrontal cortex, and subgenual anterior cingulate cortex) demonstrated a main effect of depression [F(3, 12) = 13.67, Wilks’ lambda = 0.23, p = 0.0004]. | ||||
| Post hoc analysis detected significant depression effects on ↓ in the mesiotemporal cortex [21.6% mean decrease; F(1, 140 = 22.5, p = 0.0003], subgenual cingulate cortex [27.65 mean decrease; F(1, 14) = 23.4, p = 0.0002], and left lateral orbitofrontal cortex [17.9% mean decrease; F(1, 14) = 7.13, p = 0.018] regions. There were also associations with reductions in the secondary ROI [F(5, 10) = 3.24, Wilks’ lambda = 0.38, p = 0.054], and the most significant ↓ were in the right lateral orbitofrontal cortex [23.4% mean decrease; F(1, 14) = 8.72, p = 0.011] and pregenual anterior cingulate cortex [23.4% mean decrease; F(1,14) = 17.2, p = 0.001]. | ||||
Author2 = secondary analysis; Design# = Design + Number of timepoints investigated; Domain of factors investigated in relation to depression: B = Biological, Bh = Behavioral, E = Environmental, S = Social; Values (when provided) = statistical values respective to analysis; Factors investigated in relation to depression bold; Timeframe and/or groups investigated underlined.
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Study reported race/ethnicity