Biomarkers of Postpartum Psychiatric Disorders

Jennifer L. Payne, Lauren M. Osborne

• Publisher: Academic Press
• Year: 2019
• Print ISBN: 9780128155080
• eBook ISBN: 9780128158364
• Topic: Psychology
• Subtopic: Neuroscience
• Index: Psychology

Biomarkers of Postpartum Psychiatric Disorders provides an up-to-date reference on the current research relating to biomarkers in psychiatric disorders, including major depressive disorder, OCD and bipolar disorder in the immediate postpartum time-period. It is the only reference on the market that synthesizes and interprets available data and reviews clinical phenotypes. Topics cover hormonal contributions, immunology, epigenetics and neuroimaging. While the risk of psychiatric illness during pregnancy appears to be equivalent to the risk at any other time in a woman's life, the risk in the immediate postpartum time period is dramatically increased, hence the importance of the discussions in this title.- Identifies epigenetic, hormonal, immunological and neuroimaging biomarkers- Provides biomarkers for depression, OCD and psychosis- Includes clinical phenotypes for psychiatric disorders- Discusses future research and directions in the field

Chapter 1

Clinical phenotypes of peripartum depression and time of onset

The PACT Consortium

Jerry Guintivano¹, Karen T. Putnam¹, Patrick F. Sullivan^1,2,3, and Samantha Meltzer-Brody^{1 1}Department of Psychiatry, University of North Carolina at Chapel Hill, NC, United States of America ²Department of Genetics, University of North Carolina at Chapel Hill, NC, United States of America ³Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Abstract

The Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium was created to increase our understanding of the heterogeneity of the perinatal period and to address the gaps in knowledge. This international research consortium subscribes to successful models of team science, whereby collaboration and sharing of clinical phenotypic and genetic data allows for the attainment of the large sample sizes needed to answer some of the challenging questions facing the field and move it forward. This chapter describes the development and work of the PACT Consortium to date and maps out the plans for next steps with a focus on improving outcomes for women and their families that suffer from PPD.

Keywords

Consortium; Genetics; GWAS; Heterogeneity; Peripartum; Personalized medicine; Phenotypes; Postpartum depression

Introduction

The perinatal period is well documented as a high-risk time for onset of psychiatric disorders, including postpartum depression (PPD) and is associated with significant morbidity for mother, infant, and family (Meltzer-Brody et al., 2018). This manifests as an observed increased risk for low birth weight and prematurity, impaired mother–infant attachment, and infant malnutrition during the first year of life (Gavin et al., 2005; Parsons, Young, Rochat, Kringelbach, & Stein, 2012). Perhaps most concerning, maternal suicide in the postpartum period has been identified as a leading cause of maternal mortality (Johannsen et al., 2016). Perinatal depression (PND), broadly defined by the World Health Organization as onset of a major depressive episode during pregnancy or across the first 12 months postpartum, has a lifetime prevalence of 10%–15% (Gavin et al., 2005) in industrialized countries and higher risk in lower-income countries (Sawyer, Ayers, & Smith, 2010). The greatest point prevalence for onset of symptoms is the acute postpartum period (Munk-Olsen, Laursen, Pedersen, Mors, & Mortensen, 2006), but there is growing evidence that many women have onset of symptoms during pregnancy (Biaggi, Conroy, Pawlby, & Pariante, 2016). The public health importance of identifying women who suffer with PND was highlighted by new recommendations of the United States Preventive Services Task Force for depression screening during both pregnancy and postpartum (McKinney, Keyser, Clinton, & Pagliano, 2018; O'Connor, Rossom, Henninger, Groom, & Burda, 2016; O'Connor, Senger, Henninger, Coppola, & Gaynes, 2019). This is also consistent with international guidelines from the United Kingdom (National Institute for Health and Clinical Excellence, 2014), Australia (Australian Government Department of Health, 2013), and the World Health Organization recommendations (World Health Organization, 2015).

The Postpartum Depression: Action Towards Causes and Treatment (PACT; www.pactforthecure.com) Consortium was created to increase our understanding of the heterogeneity of the perinatal period and to address the gaps in knowledge about this important illness. This international research consortium subscribes to successful models of team science, whereby collaboration and sharing of data allows for the attainment of the large sample sizes needed to answer some of the challenging questions facing the field. The PACT Consortium has been focused on elucidating the causes of peripartum psychiatric illness so that tailored prevention is possible and personalized effective treatments are developed. This work is vital given the morbidity associated with PND. Women who experience perinatal psychiatric episodes are at higher mortality risk compared with mothers without psychiatric diagnoses, and the first year after diagnosis represents a time of particularly high relative risk for suicide in this vulnerable group (Johannsen et al., 2016).

Rationale and creation of the PACT Consortium

There is a great need to increase our understanding of the phenotypic differences, course, and prognosis for PND. The past decade has seen significant progress in terms of documentation of the prevalence and has considered “hot button” questions that elicit discussion within the field, namely: (1) is PPD a distinct disorder that is fundamentally different from major depression outside of the perinatal period or is it a subtype of major depression? (2) Is childbirth a trigger for the onset of postpartum psychiatric illness? (3) What is the most scientifically logical approach to define postpartum depression? Specifically, should the definition of PPD refer only to onset of symptoms in the immediate postpartum period, or should the definition be broadened to also include onset of symptoms during pregnancy? (4) Does onset of symptoms during pregnancy constitute a different illness than onset of symptoms in the postpartum period? These are complex questions that require very large sample sizes and also provide a significant impetus for forming a scientific consortium that can collaborate using a team-science approach to conduct novel investigations and increase our understanding about PND. Furthermore, improved understanding of the phenotypic and biological underpinnings of PND may also increase our understanding of the etiology of major depression in general. PPD has the advantage of occurring in reproductive-aged women who give birth and are exposed to a similar biopsychosocial stressor.

Figure 1.1 Time of PACT milestones.

The PACT Consortium was formed in 2010 and data analyses to date include investigators from 19 institutions in seven countries. Each investigator contributed previously collected data and agreed to submit this to the PACT Consortium. An overview of PACT accomplishments to date is depicted in Fig. 1.1.

Membership and committees

Membership is an open and democratic process offered to investigators or groups who express interest in contributing anonymized individual-level clinical and/or biological data for analyses. The clinical data are harmonized within PACT with the intent to examine specific PND phenotypes and contain detailed descriptions of the study designs and methods, recruitment, and clinical variables. The biological data include either biospecimens to be used for genomic analyses and/or existing genotyped data with corresponding phenotypic information. Study participants vary by investigator and included perinatal women recruited from a range of clinical settings such as psychiatric clinics, obstetric clinics, primary care, and community advertisements. Individual investigators/studies obtain consent from participants and approval from respective institutional review boards for data sharing. All investigators read and agreed to the rules of conduct described in the PACT memorandum of understanding (MOU) and responded in writing or via e-mail agreeing to follow the terms of the MOU. The PACT MOU was modeled after the successful version created and widely used by the Psychiatric Genomics Consortium (PGC; https://www.med.unc.edu/pgc). The PGC is the largest consortium in the history of psychiatry, with the main purpose of conducting high-quality genomic analyses, and has been very successful. The PACT consortium is following this model and is made up of three committees: the coordinating, phenotyping, and PPD ACT committees.

Coordinating committee. The role of the coordinating committee has been to adjudicate issues of relevance to the whole consortium and plan for next steps of PACT. The coordinating committee is meant to primarily facilitate the collaborative efforts of the PACT investigators.

Phenotyping committee. The phenotyping committee has worked to address the phenotypic characterization and determine the common data elements available in the clinical data from PACT investigators. Harmonization of clinical data is a vital step. Prior work has demonstrated that this step must be performed with great rigor or the subsequent interpretation of results becomes unreliable. Given the lack of an international standardized diagnosis of PND, the phenotyping committee had to come up with consensus on how best to operationalize definitions. For example, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), defines PPD as onset of symptoms occurring either during pregnancy or the first month postpartum (American Psychiatric Association & American Psychiatric Association. DSM-5 Task Force, 2013). In contrast, the International Statistical Classification of Diseases, 10th revision (ICD-10), has a more narrow definition of PPD, that is, onset of symptoms within 6 weeks following childbirth. Additionally, the Centers for Disease Control and Prevention and the World Health Organization extend the time of onset of symptoms to the first year postpartum. Thus, the phenotyping committee was tasked with creating a codebook of common and harmonized diagnostic constructs to achieve comparable results across multiple cohorts. This codebook has served a vital role for the work of the PACT Consortium and particularl...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• Chapter 1. Clinical phenotypes of peripartum depression and time of onset: The PACT Consortium
• Chapter 2. Genetic basis for postpartum depression
• Chapter 3. Epigenetic biomarkers of postpartum depression
• Chapter 4. Potential hormonal and neurochemical biomarkers for postpartum depression
• Chapter 5. Immunological biomarkers of postpartum depression
• Chapter 6. Phenomenology of perinatal obsessive–compulsive disorder
• Chapter 7. Genetics of perinatal obsessive–compulsive disorder: A focus on past genetic studies to inform future inquiry
• Chapter 8. Hormonal contributions to perinatal obsessive–compulsive disorder
• Chapter 9. Immunological biomarkers of postpartum obsessive–compulsive disorder
• Chapter 10. Clinical phenotypes of postpartum psychosis
• Chapter 11. Genetic basis for postpartum psychosis
• Chapter 12. Hormonal and immunological factors in postpartum psychosis
• Chapter 13. Functional MRI biomarkers of peripartum psychiatric disorders
• Chapter 14. Synthesis and future directions
• Index