# Three Generations at High and Low Risk for Depression Followed Longitudinally

> **NIH NIH R01** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2020 · $603,846

## Abstract

Project Summary
This is a 4-year renewal for a multi-generation, 30-year longitudinal study of families at high- and low-risk for
Major Depressive Disorder (MDD). The project has yielded important findings on the familial transmission of
mood disorders and has contributed to the field's understanding of the long-term temporal sequences of 
disorders from childhood to adulthood, as well as the neurobiological correlates of these processes. However, 
despite these advances, the mechanisms through which familial risk leads to offspring impairment remains 
underdeveloped. NIMH's Research Domain Criteria (RDoC) offers a compelling model for testing potential 
mechanisms, by proposing functional systems (“constructs”) that combine neurobiological and behavioral 
information. This renewal therefore aims to prospectively test whether RDoC constructs are mechanisms 
(i.e., mediators) through which family history leads to adult functional outcomes and symptom trajectories. Leveraging
a rich, 30-year, 3-generation longitudinal dataset, we will integrate data from multiple units of analysis (multiple
MRI modalities, electrophysiology, behavior, and self-report) to define latent variables corresponding to 3 latent
RDoC constructs: Acute Threat, Approach Motivation, and Response Inhibition. First, we will quantify the 
test-retest reliability of our RDoC indicators (MRI, physiology, behavior, etc.) by re-assessing each of these 
indicators in a representative subsample of participants (Aim 1). This is an important first step as it will afford robust
modeling of the latent RDoC constructs and bolster the premise that the RDoC constructs are trait-like (i.e.,
stable) mechanisms of familial transmission. Second, we will use structural equation modeling to create the 3
RDoC constructs from these indicators and their reliability estimates. We will then prospectively examine
whether the 3 latent RDoC constructs instantiate mechanisms by which family history of MDD leads to 
negative outcomes in adulthood (Aim 2). Third, we will leverage our multigenerational dataset to examine the 
inter-generational transmission of the RDoC constructs. We will test the incremental validity of the RDoC constructs
over DSM defined psychopathology by examining whether their familial transmission is independent of the 
familial transmission of MDD (Aim 3). In sum, this renewal application advances this multi-generation study 
toward a focus on mechanisms of risk – a critical step to developing novel interventions to prevent negative
adulthood outcomes associated with familial depression.
In addition to our Specific Aims, this renewal will also afford the opportunity to furnish the data from this unique
study (i.e., many thousands of clinical and neurobiological data points collected from families from 1982–
present) onto the NIH RDoC repository, making this 30-year longitudinal dataset available to the entire 
scientific community.

## Key facts

- **NIH application ID:** 9895475
- **Project number:** 5R01MH036197-32
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Jonathan E Posner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $603,846
- **Award type:** 5
- **Project period:** 1987-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9895475

## Citation

> US National Institutes of Health, RePORTER application 9895475, Three Generations at High and Low Risk for Depression Followed Longitudinally (5R01MH036197-32). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9895475. Licensed CC0.

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