Perinatal depression: Heterogeneity of disease and in animal models

Qiu, Wansu; Hodges, Travis E.; Clark, Emily L.; Blankers, Samantha A.; Galea, Liisa A.M.

doi:10.1016/j.yfrne.2020.100854

Cited by 24 publications

(21 citation statements)

References 343 publications

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“…Further, women with PPD, show early remission with SSRI treatment, which fades with longer treatment (Sharp et al, 2010), suggesting short-term but not long-term efficacy of SSRIs. Our own findings mirror the human data as we have found that SSRIs reverse the maternal care deficits seen with postpartum CORT in the short term (PD 2-8) but do not reverse the effects on passive coping or on hippocampal integrity in the long term (PD 23) (Workman et al, 2016; Gobinath et al, 2018, and Qiu et al, 2020a; reviewed by Qiu et al, 2020b). As perinatal depression is most common in women with a previous history of depression it would be important to determine if other PND models of antenatal depression similar effects on the TKP.…”

Section: Discussionsupporting

confidence: 84%

“…However, Haroon and colleagues (2020) found that peripheral plasma TKP activation and metabolites were positively correlated with cerebrospinal fluid TKP activation and metabolites, indicating some consistency between peripheral and central levels. Using postpartum CORT, we see several depressive-like endophenotypes that overlap with the human presentation of de novo postpartum depression (reviewed in Qiu et al, 2020b). As stated earlier, the efficacy for antidepressants is lower for those with postpartum depression compared to antepartum (Cox et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Perinatal depression (PND) is a heterogeneous disease, in which symptoms and remission vary depending on depression onset timing and depression history (reviewed in Qiu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Selective serotonin reuptake inhibitors (SSRIs) are the first line treatment for PND although efficacy of SSRIs with PND is equivocal (reviewed in Qiu et al, 2020). Both inflammation and TKP are implicated in antidepressant efficacy both in humans (Syed et al, 2018; Sun et al, 2020) and in rodents (Qiu et al, 2020a).…”

Section: Introductionmentioning

confidence: 99%

“…Perinatal depression (PND) is a heterogeneous disease, in which symptoms and remission vary depending on depression onset timing and depression history (reviewed in Qiu et al, 2020b). The first three months postpartum is a period of high susceptibility for first time psychiatric disease in females but not in males (Munk-Olsen et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Postpartum corticosterone and fluoxetine shift the tryptophan-kynurenine pathway in dams

Qiu

Lamers

et al. 2021

Preprint

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Perinatal depression (PND) affects 15% of mothers. Selective serotonin reuptake inhibitors (SSRIs) are currently the first-line of treatment for PND, but are not always efficacious. Previously, we found significant reductions in plasma tryptophan concentrations and higher hippocampal proinflammatory cytokine, IL-1B levels, due to maternal SSRI treatment. Both inflammation and tryptophan-kynurenine metabolic pathway (TKP) are associated with SSRI efficacy in individuals with major depressive disorder (MDD). TKP is divided into neuroprotective and neurotoxic pathways. Higher metabolite concentrations of the neurotoxic pathway are associated with depression onset and implicated in SSRI efficacy. Metabolites in TKP were investigated in a rodent model of de novo postpartum depression (PPD) given treatment with the SSRI, fluoxetine (FLX). Dams were administered corticosterone (CORT) (40mg/kg, s.c.), and treated with the SSRI, fluoxetine (FLX) (10mg/kg, s.c.), during the postpartum for 22 days after parturition. Plasma TKP metabolite concentrations were quantified on the last day of treatment. Maternal postpartum CORT increased neurotoxic metabolites and co-enzyme/cofactors in dams (3-hydroxykynurenine, 3-hydroxyanthranilic acid, vitamin B2, flavin adenine dinucleotide). The combination of both CORT and FLX shifted the neuroprotective-to-neurotoxic ratio towards neurotoxicity. Postpartum FLX decreased plasma xanthurenic acid concentrations. Together, our data indicate higher neurotoxic TKP expression due to maternal postpartum CORT treatment, similar to clinical presentation of MDD. Moreover, maternal FLX treatment showed limited efficacy to influence TKP metabolites, which may correspond to its limited efficacy to treat depressive-like endophenotypes. Overall suggesting changes in TKP may be used as a biomarker of de novo PPD and antidepressant efficacy and targeting this pathway may serve as a potential therapeutic target.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

“…Perinatal depression (PND) is a heterogeneous disease, in which symptoms and remission vary depending on depression onset timing and depression history (reviewed in Qiu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%