Notice Number: NOT-MH-15-013

Key Dates
Release Date: April 16, 2015 (Rescinded June 23, 2021)

Issued by
National Institute of Mental Health (NIMH)

Purpose

NIMH is issuing this Notice to highlight priority areas for research related to women's mental health during pregnancy and the postpartum period. NIMH encourages applications via the parent R21 and R01 funding announcements as well as the NIMH clinical trials funding opportunity announcements.

NIMH has a long-standing commitment to perinatal mental health research, meaning research focused on women’s mental health before, during, and immediately following pregnancy. In addition to perinatal depression and postpartum psychosis, this Notice encourages research on anxiety disorders, obsessive compulsive disorder, post-traumatic stress disorder, eating disorders and such serious mental illnesses as bipolar disorder and schizophrenia that can have profound effects on the health of the mother and child. A subset of women enters the perinatal period with medical conditions that can contribute to neuropsychiatric disorders, such as human immunodeficiency virus (HIV) infection and hepatitis C virus (HCV) infection. These conditions and other comorbid medical conditions need to be further explored at the level of basic, epidemiological, diagnostic, clinical, and intervention research in relation to perinatal mental health. Reduction of the public health burden of mental disorders during the perinatal period will improve the health and well-being of new mothers, their children, and families.

Research Priorities

Basic and Clinical Neuroscience
Advances in our understanding of perinatal mood and other mental disorders are likely to come from several areas of research, including mechanistic studies of hormone-sensitive brain circuits implicated in mood, cognition or social behavior; neurotransmitter systems; and the development of appropriate peripartum model systems. Model systems could be used to examine combined genetic and environmental influences on postpartum hormonal status and/or maternal behavior to investigate the mechanisms during the peripartum period that contribute to the emergence of mental disorders in the mother. Finally, new tools are needed to advance the understanding of neuroendocrine control of mood, cognition and affiliative social behaviors in humans, non-human primates, and other species.

Examples of basic, translational, and clinical research encouraged by NIMH include, but are not limited to, the following:

• Studies of functional changes in brain neurochemistry that occur in conjunction with perinatal hormonal transitions in normal and/or mentally ill populations of women;
• Studies that identify risk factors that predict perinatal mental disorders or susceptibility to hormonally-modulated risk for psychopathology;
• Studies of genetic architecture to identify markers of risk and resilience in high risk women, including women with perinatal mental disorders;
• Studies that examine the combined environmental and genetic influences on maternal resilience and vulnerability to disordered mood, cognition and social behavior during the perinatal period.
• Studies that examine the neurobiological bases of cognitive resilience during the postpartum period;
• Studies that support the development of novel visualization tools to facilitate research on peripartum changes in brain circuits and signaling cascades regulating mood, cognition, and social behavior; or
• Studies to develop and apply novel approaches to assess the neurophysiological impact of perinatal hormonal transitions in normal and/or affected populations with emphasis on approaches that assess activity changes across brain networks with high spatial and temporal resolution.

Clinical Course, Epidemiological and Risk Factors Research
Meeting the goal of personalized medical treatment requires understanding how pregnancy interacts with risk for various mental disorders. Clinical and epidemiological studies can be of optimal value when they seek to identify biomarkers that can help identify risk and when they seek to identify mechanisms that help explain factors that confer risk or protection. Mechanisms are defined as the cascades of social, behavioral, and/or neurobiological processes through which risk and protective factors operate to produce depression, anxiety, and other disorders. NIMH investigators are encouraged to study these mechanisms when appropriate, within the Research Domain Criteria (RDoC) framework.

Examples of clinical course, epidemiological, and risk factors research encouraged by NIMH include, but are not limited to, the following:

• Studies to identify novel biomarkers for perinatal mood and anxiety disorders, especially those associated with different clinical histories and trajectories (e.g., reproductive-related mood changes, recurrent depression);
• Studies of the mechanisms of health disparities in perinatal mental disorders and in co-occurring behavioral and medical conditions, including, but not limited to, HIV/AIDS;
• Studies to gain a greater understanding of the impact of maternal mental health on the health of women living with HIV and their infants who have been exposed to HIV in utero; in particular, the effects of mental disorder on mothers ability to engage in care and adhere to their antiretroviral regimen during and after pregnancy;
• Studies of women with serious mental illness such as bipolar disorder or schizophrenia to identify biomarkers of risk for perinatal mood disorder onset;
• Studies to aid in the early identification and treatment of serious perinatal psychosis among high-risk women;
• Studies that empirically evaluate whether perinatal depression is a distinct subtype of depression with a different pathophysiology, suggesting the need for unique interventions;
• Studies which use the RDoC framework to examine the mechanisms that give rise to mental disorders during pregnancy, for example, studies that clarify the underlying causes of disorders during pregnancy with efforts towards integrating genetic, neurobiological, imaging, behavioral, and clinical data; studies that explore dimensions of functioning with identifiable subtypes within broad clinical phenotype; and
• Studies to identify potential mental health consequences of various pregnancy outcomes.

Interventions Research
Establishing an evidence base for effective interventions for diverse groups of pregnant or postpartum women requires inclusion of adequate numbers of members of racial/ethnic and other underrepresented groups in clinical trials. Secondary analysis of existing data sources that will deepen the evidence base for intervention effectiveness in diverse groups of perinatal women is encouraged. Scientific areas of interest for NIMH include, but are not limited to subgroup analyses of treatment outcomes in intervention studies and analyses of potential mediators of treatment efficacy and effectiveness within or across racial/ethnic, sex, socioeconomic, or geographically diverse groups.

It is important to provide empirically supported and/or theoretically robust arguments to justify the adaptation of extant interventions for specified subgroups, including adaptations specifically to address the needs of pregnant/postpartum women belonging to various racial and ethnic minority groups, age groups, or income levels; pregnant/postpartum women with various comorbid conditions or risk factors (e.g., post-traumatic stress disorder, interpersonal violence); or pregnant/postpartum women receiving care in specified settings (e.g., obstetric practices, home visitation, and pediatric practices). Adaptation or extension of proven interventions should only be undertaken if there is a compelling rationale, supported by empirical evidence, that can be justified in terms of: (a) theoretical and empirical support for the adaptation target (e.g., changes a factor that has been associated with non-response, partial response, patient non-engagement, or relapse); (b) clear explication of the mechanism by which that moderator variable functions to disadvantage or advantage a subgroup (ideally, with behavioral and/or biological data that support the mechanism hypothesis); and (c) evidence to suggest that the adapted intervention will result in a substantial improvement in response rate, speed of response, an aspect of care, or uptake in community/practice settings when compared to existing intervention approaches.

NIMH encourages research approaches that are efficient in cost and design; are designed to inform or test prescriptive, personalized intervention approaches, comparative effectiveness, and stepped-care models; and that answer questions about the mediators, moderators and mechanisms of interventions, ultimately leading to more cost-effective, personalized interventions. In order to advance knowledge more rapidly and cost effectively, use of consortia, existing practice-based research networks, large available data sets and other types of research infrastructure are encouraged. Similarly, opportunities for sharing data are encouraged by incorporating standard measures that can be shared across studies, such as those described in NOT-MH-15-009.

NIMH requires a higher level of rigor in studies of mental health-related interventions and has recently issued a set of funding opportunity announcements for clinical trials research that involves an experimental medicine based approach to intervention development and testing. Please note, applicants considering clinical trials should review the NIMH policy NOT-MH-14-007 and the NIMH clinical trials website and contact NIMH Program Officials regarding the match between a potential application and current priorities.

The following are examples of intervention studies encouraged by NIMH:

• Studies of the efficacy, safety, pharmacokinetics, and pharmacodynamics of pharmacotherapies for treatment of perinatal mental disorders, especially those occurring during pregnancy and lactation, as well as their interactions with treatments for co-occurring medical conditions such as HIV/AIDS;
• Maintenance studies to develop effective non-pharmacological interventions to prevent postpartum relapse;
• Studies of pharmacological maintenance treatments during pregnancy and postpartum for women with serious mental illness, such as psychosis and bipolar disorder, and studies of pharmacological prophylaxis strategies for these conditions in women at high risk for a recurrence of psychotic perinatal conditions;
• Development of and controlled studies of innovative non-pharmacological interventions as alternatives to traditional one-on-one interventions for identifying, preventing, and treating perinatal mental disorder; and
• Development and testing of interventions, both pharmacological and non-pharmacological, to address mental disorders among mothers living with HIV during and after pregnancy, especially as treatment relates to health outcomes among the mothers and their infants.

Screening and Services Research
NIMH places a high priority on services research that improves the identification of otherwise undetected perinatal mental disorders and connects women who are diagnosed with these disorders with accessible and appropriate evidence-based treatment. Treatment delivery models should take into consideration the many potential barriers to accessing treatment for women with perinatal mental disorders, as well as challenges to treatment engagement, especially for women with low incomes and multiple life stressors. Women’s mental health care preferences, including a preference for care in non-specialty settings, such as OB/GYN, primary care, and other non-traditional settings, should be taken into account. The feasibility of proposed treatment delivery models for the targeted setting, in terms of workforce requirements, training, provider and patient acceptability, and available payment mechanisms, should be carefully considered. Service delivery interventions to improve perinatal mental disorder detection and care at multiple levels patient, practitioner, organizational, community, and systems are encouraged.

As noted above in the section on Interventions Research, NIMH employs an experimental medicine model for all clinical trials research. Investigators should review the policy NOT-MH-14-007 and funding announcements at the Clinical Trials Funding Opportunity Announcements website (http://www.nimh.nih.gov/funding/opportunities-announcements/clinical-trials-foas/index.shtml).

The following are examples of services research encouraged by NIMH:

• Studies that address the strengths and limitations of perinatal mental health assessment tools, including those designed to measure postpartum depression, and factors that may serve as mediator or moderator variables in clinical outcomes, e.g., maternal functional support;
• Studies involving service delivery interventions for the prevention or care of perinatal mood disorders that leverage technology to improve access to care and the mental health and functional outcomes;
• Studies involving service delivery interventions that utilize paraprofessionals in the detection and care of women with perinatal mood disorders, as well as those utilizing staff already employed in the service setting;
• Studies examining the factors involved in clinical decision-making by women in choosing treatment and services, and in clinical decision-making by health care providers in caring for patients with perinatal mood disorders;
• Research on the impact of various provider and financing arrangements and insurance coverage on the detection, assessment, referral and treatment of perinatal mood disorders, and research to examine the value of practice patterns of different health providers and systems in addressing such disorders;
• Research on perinatal mood disorders in relation to engagement in medical care, treatment adherence, and clinical outcomes for comorbid conditions such as HIV/AIDS;
• Studies that identify variations in care that affect mental health and functional outcomes; and
• Research that incorporates issues of culture, social systems, and social networks to increase appropriate help-seeking, use and provision of services, and effectiveness, quality, and outcomes of services.

Funding Opportunity Announcements that can be used to pursue these and other research activities include, but are not limited to:

PA-13-303, NIH Exploratory/Developmental Research Grant Program (Parent R21) and
PA-13-302, Research Project Grant (Parent R01).

Please note that investigators interested in pursuing clinical trials research should review the NIMH Clinical Trials Funding Opportunity Announcements website (http://www.nimh.nih.gov/funding/opportunities-announcements/clinical-trials-foas/index.shtml )
and policy for submitting applications containing clinical trials (NOT-MH-14-007). These sites announce that, beginning with applications submitted for the June 5, 2014 submission date, and all subsequent applicable deadlines, NIMH will not accept R01, R21 or R03 applications that include clinical trials of potential therapies for mental disorders under the NIH parent grant Funding Opportunity Announcement (FOA) PA-13-302, NIH parent R21 FOA PA-13-303 and NIH parent R03 FOA PA-13-304. Specific guidance on application submission procedures are described in NOT-MH-14-007 as well as on the NIMH clinical Trials FOA-Applicant FAQs. Applicants considering such an application are strongly encouraged to consult with NIMH program officials prior to submission.

Inquiries

Please direct all inquiries to:

Tamara Lewis Johnson, MPH, MBA
National Institute of Mental Health (NIMH)
Telephone: (301)594-7963
Email: [email protected]