The 2017 American College of Neuropychopharmacology (ACNP) conference hosted a Study Group on 4 December 2017, Establishing best practice guidelines to improve the rigor, reproducibility, and transparency of the maternal immune activation (MIA) animal model of neurodevelopmental abnormalities. The goals of this session were to (a) evaluate the current literature and establish a consensus on best practices to be implemented in MIA studies, (b) identify remaining research gaps warranting additional data collection and lend to the development of evidence-based best practice design, and (c) inform the MIA research community of these findings. During this session, there was a detailed discussion on the importance of validating immunogen doses and standardizing the general design (e.g., species, immunogenic compound used, housing) of our MIA models both within and across laboratories. The consensus of the study group was that data does not currently exist to support specific evidence-based model selection or methodological recommendations due to lack of consistency in reporting, and that this issue extends to other inflammatory models of neurodevelopmental abnormalities. This launched a call to establish a reporting checklist focusing on validation, implementation, and transparency modeled on the ARRIVE Guidelines and CONSORT (scientific reporting guidelines for animal and clinical research, respectively). Here we provide a summary of the discussions in addition to a suggested checklist of reporting guidelines needed to improve the rigor and reproducibility of this valuable translational model, which can be adapted and applied to other animal models as well.

Introduction

The role of perinatal diet in postpartum maternal mood disorders, including depression and anxiety, remains unclear. We investigated whether perinatal consumption of a Western-type diet (high in fat and branched-chain amino acids [BCAA]) and associated gestational weight gain (GWG) cause serotonin dysregulation in the central nervous system (CNS), resulting in postpartum depression and anxiety (PPD/A).

Methods

Mouse dams were fed one of four diets (high-fat/high BCAA, low-fat/high BCAA, high-fat, and low-fat) prior to mating and throughout gestation and lactation. Postpartum behavioral assessments were conducted, and plasma and brain tissues assayed. To evaluate potential clinical utility, we conducted preliminary human studies using data from an extant sample of 17 primiparous women with high GWG, comparing across self-reported postpartum mood symptoms using the Edinburgh Postnatal Depression Scale (EPDS) for percent GWG and plasma amino acid levels.

Results

Mouse dams fed the high-fat/high BCAA diet gained more weight per kcal consumed, and BCAA-supplemented dams lost weight more slowly postpartum. Dams on BCAA-supplemented diets exhibited increased PPD/A-like behavior, decreased dopaminergic function, and decreased plasma tyrosine and histidine levels when assessed on postnatal day (P)8. Preliminary human data showed that GWG accounted for 29% of the variance in EPDS scores. Histidine was also lower in women with higher EPDS scores.

Conclusions

These findings highlight the role of perinatal diet and excess GWG in the development of postpartum mood disorders.