A prospective study to explore the relationship between MTHFR C677T genotype, physiological folate levels, and postpartum psychopathology in at-risk women.

BACKGROUND: The etiology of postpartum psychopathologies are not well understood, but folate metabolism pathways are of potential interest. Demands for folate increase dramatically during pregnancy, low folate level has been associated with psychiatric disorders, and supplementation may improve symptomatology. The MTHFR C677T variant influences folate metabolism and has been implicated in depression during pregnancy. OBJECTIVE: To conduct a prospective longitudinal study to explore the relationship between MTHFR C677T genotype, folate levels, and postpartum psychopathology in at-risk women. HYPOTHESIS: In the first three months postpartum, folate will moderate a relationship between MTHFR genotype and depression, with TT homozygous women having more symptoms than CC homozygous women. METHODS: We recruited 365 pregnant women with a history of mood or psychotic disorder, and at 3 postpartum timepoints, administered the Edinburgh Postnatal Depression Scale (EPDS); Clinician-Administered Rating Scale for Mania (CARS-M) and the Positive and Negative Symptom Scale (PANSS) and drew blood for genotype/folate level analysis. We used robust linear regression to investigate interactions between genotype and folate level on the highest EPDS and CARS-M scores, and logistic regression to explore interactions with PANSS psychosis scores above/below cut-off. RESULTS: There was no significant interaction effect between MTHFR genotype and folate level on highest EPDS (p = 0.36), but there was a significant interaction between genotype, folate level and log(CARS-M) (p = 0.02); post-hoc analyses revealed differences in the effect of folate level between CC/CT, and TT genotypes, with folate level in CC and CT having an inverse relationship with symptoms of mania, while there was no relationship in participants with TT genotype. There was no significant interaction between MTHFR genotype and folate level on the likelihood of meeting positive symptom criteria for psychosis on the PANSS (p = 0.86). DISCUSSION: These data suggest that perhaps there is a relationship between MTHFR C677T, folate level and some symptoms of postpartum psychopathology.

A Matched Cohort Study of Postpartum Placentophagy in Women With a History of Mood Disorders: No Evidence for Impact on Mood, Energy, Vitamin B12 Levels, or Lactation.

OBJECTIVE: Although empirical studies investigating its effects are scarce, postpartum placentophagy is increasing in popularity because of purported benefits on mood, energy, lactation, and overall nutrition. Therefore, this study sought to test the hypotheses that women who consumed their placenta (placentophagy exposed [PE]) would have (1) fewer depressive symptoms, (2) more energy, (3) higher vitamin B12 levels, and (4) less pharmaceutical lactation support during the postpartum than women who did not consume their placenta (non-placentophagy exposed [NE]). METHODS: Using data from a large, longitudinal study of gene × environment effects involving perinatal women with a history of mood disorders, the study investigators identified a PE cohort and matched them 4:1 (by psychiatric diagnosis, psychotropic medication use, supplementation, income, and age) with an NE cohort from the same dataset. The study investigated differences between the PE and NE cohorts with respect to scores on the Edinburgh Postnatal Depression Scale and Sleep-Wake Activity Inventory, vitamin B12 levels, and the use of pharmaceutical lactation support (Canadian Taskforce Classification II-2). RESULTS: The sample of 138 women (28 in the PE cohort, matched to 110 in the NE cohort) provided 80% power at α = 0.0125 to detect an effect of moderate magnitude (which can be used to approximate an effect of clinically significant magnitude).There were no differences in Edinburgh Postnatal Depression Scaleor Sleep-Wake Activity Inventory scales (P = 0.28 and P = 0.39, respectively), vitamin B12 levels (P = 0.68), or domperidone use (P = 1) between the PE and NE cohorts. CONCLUSION: These data provide no support for the idea that postpartum placentophagy improves mood, energy, lactation, or plasma vitamin B12 levels in women with a history of mood disorders.

Short interpregnancy intervals, maternal folate levels, and infants born small for gestational age: a preliminary study in a Canadian supplement-using population.

Short interpregnancy intervals (SIPI) have been associated with increased risks for adverse neonatal outcomes including preterm delivery and infants small for gestational age (SGA). It has been suggested that mechanistically, adverse neonatal outcomes after SIPI arise due to insufficient recovery of depleted maternal folate levels prior to the second pregnancy. However, empirical data are lacking regarding physiological folate levels in pregnant women with SIPI and relationships between quantified physiological folate levels and outcomes like SGA. Therefore, we sought to test 2 hypotheses, specifically that compared with controls women with SIPI would: (i) have lower red blood cell folate (RBCF) levels and (ii) be more likely to have SGA infants (defined as <10th percentile). Using data collected in British Columbia, Canada, for a larger study on perinatal psychopathology, we documented supplementation use and compared prenatal RBCF levels and proportion of SGA infants between women with SIPI (second child conceived ≤24 months after previous birth, n = 26) and matched controls (no previous pregnancies, or >24 months between pregnancies, n = 52). There were no significant differences in either mean RBCF levels (Welch's t test, p = 0.7) or proportion of SGA infants (Fisher's exact test, p = 0.7) between women with SIPI and matched controls. We report the first data about RBCF levels in the context of SIPI. If confirmed, our finding of no relationship between these variables in this population suggests that continued folic acid supplementation following an initial pregnancy mitigates folate depletion. We found no relationship between SIPI and SGA.

Women's experiences of participating in a prospective, longitudinal postpartum depression study: insights for perinatal mental health researchers.

Barriers to recruitment for research on mental illness include participant distrust of researchers and social stigma. Though these issues may be acutely important in perinatal mental health research, they remain unexplored in this context. In order to inform strategies to more fully engage women in perinatal mental health research, we explored the motivations and experiences of women with a history of major depressive disorder who participated in a prospective longitudinal research study on postpartum depression (PPD). Sixteen women with a history of depression who had either completed or recently made a decision about participation in a longitudinal research study about PPD were interviewed by telephone. Qualitative, semi-structured interviews explored participants' decision-making about, and experiences of, participation. Interviews were audio-recorded, transcribed, and qualitatively analyzed using elements of grounded theory methodology. Follow-up interviews were conducted with four participants to refine and clarify preliminary results. Foundational elements necessary for women to consider participating in PPD research included personal acceptance of illness and trust in the research team/institution. Other main motivators included perceived personal relevance, anticipated benefits (including access to support/resources, learning opportunities, and improved self-worth), altruism, and accessible study procedures. Our data suggest that participating in perinatal mental health research may help women make meaning of their mental illness experience and is perceived as providing support. The findings-particularly around the importance of participant-researcher rapport and accessibility of study design-may inform strategies that improve participation rates, decrease attrition, and maximize participant benefits in perinatal mental health research.

Obsessive-Compulsive Disorder: The Process of Parental Adaptation and Implications for Genetic Counseling.

Obsessive-compulsive disorder (OCD) has primarily pediatric onset and well-documented unique impacts on family functioning. Limited research has assessed the understanding that parents of children with OCD have of the etiology of the condition, and there are no data regarding potential applications of genetic counseling for this population. We recruited 13 parents of 13 children diagnosed with OCD from the OCD Registry at British Columbia Children's Hospital, and conducted qualitative semi-structured telephone interviews to explore participants' experiences with their child's OCD, causal attributions of OCD, and perceptions of two genetic counseling vignettes. Interviews were audio-recorded, transcribed, and analyzed using elements of grounded theory qualitative methodology. Analysis revealed key components and contextual elements of the process through which parents adapt to their child's OCD. This adaptation process involved conceptualizing the meaning of OCD, navigating its impact on family dynamics, and developing effective illness management strategies. Adaptation took place against a backdrop of stigmatization and was shaped by participants' family history of mental illness and their child's specific manifestations of OCD. Parents perceived genetic counseling, as described in the vignettes, as being empowering, alleviating guilt and blame, and positively impacting treatment orientation. These data provide insight into the process of parental adaptation to pediatric OCD, and suggest that genetic counseling services for families affected by OCD may help facilitate adaptation to this illness.

Perinatal psychosis in mothers with a history of major depressive disorder.

While women with a history of major depressive disorder (MDD) have higher chances for postpartum depressive and manic episodes, little is known about their chance for postpartum psychosis (PPP). We prospectively assessed the frequency of perinatal psychotic symptoms among primiparous women with a history of MDD only (structured clinical interview was used to exclude women with pre-existing histories of mania or psychosis) and explored whether sex of the baby influenced these symptoms.The presence of symptoms of psychosis was defined using previously established cutoff scores on five key items from the Positive and Negative Syndrome Scale (PANSS), which was administered during pregnancy, at 1 week, 1 month, and 3 months postpartum.Fourteen of 60 women (23%) scored above threshold for psychosis at one or more time points, with 6 experiencing postpartum onset. There was a non-significant trend (p = 0.073) towards higher frequency of these symptoms among mothers of girls.If controlled studies using diagnostic interviews confirm that psychotic symptoms are relatively common among women with MDD, monitoring for psychosis during the perinatal period may be indicated in this population. The potential effect of sex of the baby on mothers' chance for PPP requires further study.

A synthetic human kinase can control cell cycle progression in budding yeast.

The DDK kinase complex, composed of Cdc7 and Dbf4, is required for S-phase progression. The two component proteins show different degrees of sequence conservation between human and yeast. Here, we determine that Saccharomyces cerevisiae bearing human CDC7 and DBF4 grows comparably to cells with yeast DDK under standard growth conditions. HsDrf1 (a second human Dbf4-like protein) does not support growth, suggesting that HsDbf4 is the true ortholog of ScDbf4. Both human subunits are required to complement yeast cdc7Δ or dbf4Δ due to the inability of human Cdc7 or Dbf4 to interact with the corresponding yeast protein. Flow cytometry indicates normal cell cycle progression for yeast containing human DDK. However, yeast containing human DDK is sensitive to long-term exposure to hydroxyurea and fails to sporulate, suggesting that human DDK substitutes for some, but not all, of yeast DDK's functions. We mapped the region of Cdc7 required for species-specific function of DDK to the C-terminus of Cdc7 by substituting the yeast C-terminal 55 amino acid residues in place of the equivalent human residues. The resulting hybrid protein supported growth of a cdc7Δ strain only in the presence of ScDBF4. The strain supported by the hybrid CDC7 was not sensitive to HU and formed tetrads. Together, our data indicate that DDK's targeting of its essential substrate is conserved between species, whereas the interactions within DDK are species specific.