# Accelerating the Diagnosis of Bipolar Disorder Using Genetic and Phenotypic Signatures

> **NIH NIH R00** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $248,800

## Abstract

PROJECT SUMMARY
The diagnosis of Bipolar Disorder (BPD), a heritable disorder characterized by periods of depression and
mania, is extremely challenging in clinical practice and takes on average 5-10 years. One of the main reasons
for this delay is that the majority of patients first manifest depressive symptoms (depression-first BPD), often
resulting in misdiagnosis with major depressive disorder (MDD). Misdiagnosis can lead to poor clinical
outcomes, increased burden for patients and high healthcare costs. The goal of this proposal is to identify
genetic and phenotypic signatures that distinguish depression-first BPD from MDD, in order to accelerate BPD
diagnosis. During the mentored phase (K99) of the award, the PI will perform a genome wide association study
to characterize the genetic architecture of differences between depression-first BPD and MDD, using available
data from the collaborative Psychiatrics Genetics Consortium (Aim 1a). In a Dutch BPD cohort (n=1,750 cases)
she will use machine learning methods to identify molecular, neuro-cognitive and behavioral profiles to classify
depression-first BPD versus mania-first BPD (BPD with first onset of mania) and identify causal relations
among predictive features (Aim 1b). During the independent phase (R00) of the award, the PI will study BPD
diagnosis in a genotyped and extensively phenotyped Colombian cohort of ~5,000 cases with severe mood
disorders, for which high quality electronic health records (EHR) have been collected since 2005. She will i)
predict if and when patients will switch from MDD to BPD diagnosis, ii) distinguish BPD from matched MDD
patients, and iii) classify BPD patients into depression-first and mania-first categories (Aims 2 and 3). She will
estimate heritability of identified signatures and integrate results from both Dutch and Colombian cohorts.
Building upon her expertise in complex trait genetics and method development, this award will allow the PI to
extend her knowledge-base of clinical phenotyping in psychiatry; grow her expertise in statistical modeling; and
strengthen her communication, mentoring, and leadership skills to prepare for a successful career as an
independent researcher. The PI will complete the K99 phase of the award at UCLA, which fosters an ideal
training environment. The strong advisory committee with Drs. Freimer, Ophoff, and Eskin (UCLA) and Dr.
Sabatti (Stanford) will facilitate her scientific and personal development and promote her long-term career goal
of tackling clinically relevant problems in psychiatric illness through the study of genetic, neuro-cognitive and
behavioral mechanisms. The PI will first focus on the diagnosis of BPD, and then expand, in the future, into
other psychiatric trait-mechanisms, such as disease severity and drug response. This award will be
fundamental in support of her career goals. Successful completion of the specific aims of this proposal is likely
to significantly improve the time to BPD diagnosis, and th...

## Key facts

- **NIH application ID:** 10107959
- **Project number:** 4R00MH116115-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Loes Marlein Olde Loohuis
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,800
- **Award type:** 4N
- **Project period:** 2020-04-10 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107959

## Citation

> US National Institutes of Health, RePORTER application 10107959, Accelerating the Diagnosis of Bipolar Disorder Using Genetic and Phenotypic Signatures (4R00MH116115-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10107959. Licensed CC0.

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