# Influence of Childhood Maltreatment on Morphometry and Brain Network Architecture in Bipolar Disorder

> **NIH NIH R21** · MCLEAN HOSPITAL · 2020 · $451,000

## Abstract

SUMMARY
Bipolar disorder is a severe psychiatric disorder that affects about 2.5 million Americans and is the 6th leading
cause of disability worldwide. Individuals with bipolar disorder (BD) who were maltreated (MAL) in
childhood typically have an earlier onset, more severe course, more comorbidities and poorer response to
treatments. What is unknown is whether BD patients with MAL represent an etiologically or
pathophysiologically distinct subgroup who may differ in important ways in terms of neurobiology and
treatment from non-MAL patients with BD. Thus, it is critically important to attempt to identify the effects of
experience and timing of MAL in patients with BD in order to determine if and how MAL experiences lead to a
distinct subtype (`ecophenotype') of patients. The ecophenotype hypothesis is most strongly supported by
neuroimaging studies that identify brain abnormalities in the MAL ecophenotype that are not apparent in the
non-MAL patients. This distinction is critically important as, if true, it implies that efforts to identify the
pathophysiological basis and to develop more effective treatments for BD may be different between MAL and
non-MAL patients and may markedly be enhanced by focusing on specific subtypes. Thus, understanding how
MAL modifies the neurobiology of BD may provide new insights that will benefit MAL individuals with BD who
often have a particularly severe form of the disorder. Only a few morphometric studies have addressed this
issue in BD and do not lead to firm conclusions. Hence, there is a critical gap in our knowledge and a pressing
need to definitively establish whether there are or are not fundamental differences in brain structure between
MAL and non-MAL individuals with BD. We have recently reported that MAL is associated with substantial
alterations in global network architecture and have developed a network-based model that distinguished
between MAL individuals with clinically significant psychiatric symptoms, comparably MAL asymptomatic
individuals and unexposed healthy controls with high cross-validated predictive accuracy (N=342). These
abnormalities appeared to be specifically associated with MAL and not attributable to major depression,
anxiety or attention deficit hyperactivity disorder. What is much less certain is whether MAL can produce a
pathophysiologically distinct subtype in far more heritable disorders such as BD. The first aim is to test the
hypothesis that there are distinct neurobiological differences between MAL and non-MAL individuals with BD.
The second aim is to test the hypothesis that MAL individuals with BD differ from MAL individuals without BD
in type and timing of exposure to MAL and to identify sensitive periods when exposure to specific forms of
abuse are the most important risk factors for BD. These aims will be accomplished in a cost-effective manner
by collecting data on type and timing of exposure to MAL in previously imaged BD subjects (estimated N=250)
and comparing t...

## Key facts

- **NIH application ID:** 9957994
- **Project number:** 1R21MH122919-01
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** KYOKO OHASHI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,000
- **Award type:** 1
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957994

## Citation

> US National Institutes of Health, RePORTER application 9957994, Influence of Childhood Maltreatment on Morphometry and Brain Network Architecture in Bipolar Disorder (1R21MH122919-01). Retrieved via AI Analytics 2026-06-07 from https://api.ai-analytics.org/grant/nih/9957994. Licensed CC0.

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