Mapping the natural course of comorbid bipolar disorder via integration of multimodal data (MapCoBD): a study protocol.
13 affiliations
- 1Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
- 2Department of Psychiatry, McGill University, Montreal, QC, Canada.
- 3Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
- 4Neuropharmacology Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
- 5Department of Mental Health, Azienda Sanitaria Locale Salerno, Salerno, Italy.
- 6Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
- 7Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
- 8Unit of Clinical Psychiatry, Department of Medical Specialties, University Hospital Agency of Cagliari, Cagliari, Italy.
- 9Unit of Radiology, Department of Health Services, University Hospital Agency of Cagliari, Cagliari, Italy.
- 10Section of Radiology, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
- 11Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
- 12University Hospital "Renato Dulbecco" of Catanzaro, Catanzaro, Italy.
- 13Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
Abstract
Bipolar disorder (BD) is a chronic, disabling psychiatric condition with a high global disease burden. Its course is marked by alternating episodes of mania and depression, with varying degrees of severity. While cyclicity is a defining feature, clinical patterns show significant inter-individual and intra-individual variability. Although naturalistic studies have described the course of BD, the impact of psychiatric comorbidities, particularly attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD), remains underexplored. MapCoBD is a 12-month, naturalistic observational study whose primary objective is to compare the longitudinal clinical course of BD among individuals with classic episodic BD, BD with comorbid ADHD, and BD with comorbid BPD. Secondary objectives are to characterize the clinical, neuropsychological, neuroimaging, and molecular features associated with these distinct clinical courses. This project will recruit 150 BD individuals divided into three groups: (1) classic episodic BD (epiBD, n = 50), (2) BD with comorbid ADHD (BD-ADHD, n = 50), and (3) BD with comorbid BPD (BD-BPD, n = 50). Assessments will be conducted at baseline (T0), 6 months (T1), and 12 months (T2), including: mood symptom ratings, neuropsychological testing, fasting blood sampling (for serum, plasma, and microRNA), and 3T structural brain MRI scans. Daily mood ratings will also be collected prospectively throughout the study. The primary longitudinal clinical endpoint will be illness burden, defined as the proportion of evaluable follow-up days spent with moderate-to-severe psychopathological symptoms, based on prospective NIMH Life Chart Method assessments. Daily affective ratings will additionally be used to characterize mood instability. At each time point, peripheral biomarkers implicated in BD pathophysiology, including endocannabinoid (eCB) signaling, inflammatory cascade (IC), and epigenetic regulation (microRNA), will be quantified. Clinical, neuroimaging, and molecular data will also be integrated using supervised machine-learning approaches to explore the classification of clinical group status and the prediction of longitudinal mood instability and illness burden. This study will determine whether ADHD and BPD comorbidity is associated with distinct longitudinal patterns of illness burden and mood instability in BD. The integration of clinical, neuroimaging, and molecular data may identify group-specific multimodal signatures and candidate predictors of clinical course, which will require independent validation before clinical application.
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BibTeX
@article{comai2026mapping,
title = {{Mapping the natural course of comorbid bipolar disorder via integration of multimodal data (MapCoBD): a study protocol.}},
author = {Stefano Comai and Maria Morena and Luca Steardo and Alessio Squassina and Claudia Pisanu and Anna Meloni and Donatella Congiu and Silvia Lazzardi and Marco Pinna and Martina Contu and Sofia Nasini and Benedetta Barzon and Angelica Maria Zuliani and Stefano Dall'Acqua and Antonella Balestrieri and Patrizia Campolongo and Ilaria Pullano and Anna Maria Iazzolino and Renato de Filippis and Federica Pinna and Luca Saba and Mirko Manchia},
journal = {Frontiers in human neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnhum.2026.1924416},
url = {https://europepmc.org/article/MED/42952819},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mapping the natural course of comorbid bipolar disorder via integration of multimodal data (MapCoBD): a study protocol.
AU - Stefano Comai
AU - Maria Morena
AU - Luca Steardo
AU - Alessio Squassina
AU - Claudia Pisanu
AU - Anna Meloni
AU - Donatella Congiu
AU - Silvia Lazzardi
AU - Marco Pinna
AU - Martina Contu
AU - Sofia Nasini
AU - Benedetta Barzon
AU - Angelica Maria Zuliani
AU - Stefano Dall'Acqua
AU - Antonella Balestrieri
AU - Patrizia Campolongo
AU - Ilaria Pullano
AU - Anna Maria Iazzolino
AU - Renato de Filippis
AU - Federica Pinna
AU - Luca Saba
AU - Mirko Manchia
PY - 2026
DA - 2026/10/14
JO - Frontiers in human neuroscience
DO - 10.3389/fnhum.2026.1924416
UR - https://europepmc.org/article/MED/42952819
AB - Bipolar disorder (BD) is a chronic, disabling psychiatric condition with a high global disease burden. Its course is marked by alternating episodes of mania and depression, with varying degrees of severity. While cyclicity is a defining feature, clinical patterns show significant inter-individual and intra-individual variability. Although naturalistic studies have described the course of BD, the impact of psychiatric comorbidities, particularly attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD), remains underexplored. MapCoBD is a 12-month, naturalistic observational study whose primary objective is to compare the longitudinal clinical course of BD among individuals with classic episodic BD, BD with comorbid ADHD, and BD with comorbid BPD. Secondary objectives are to characterize the clinical, neuropsychological, neuroimaging, and molecular features associated with these distinct clinical courses. This project will recruit 150 BD individuals divided into three groups: (1) classic episodic BD (epiBD, n = 50), (2) BD with comorbid ADHD (BD-ADHD, n = 50), and (3) BD with comorbid BPD (BD-BPD, n = 50). Assessments will be conducted at baseline (T0), 6 months (T1), and 12 months (T2), including: mood symptom ratings, neuropsychological testing, fasting blood sampling (for serum, plasma, and microRNA), and 3T structural brain MRI scans. Daily mood ratings will also be collected prospectively throughout the study. The primary longitudinal clinical endpoint will be illness burden, defined as the proportion of evaluable follow-up days spent with moderate-to-severe psychopathological symptoms, based on prospective NIMH Life Chart Method assessments. Daily affective ratings will additionally be used to characterize mood instability. At each time point, peripheral biomarkers implicated in BD pathophysiology, including endocannabinoid (eCB) signaling, inflammatory cascade (IC), and epigenetic regulation (microRNA), will be quantified. Clinical, neuroimaging, and molecular data will also be integrated using supervised machine-learning approaches to explore the classification of clinical group status and the prediction of longitudinal mood instability and illness burden. This study will determine whether ADHD and BPD comorbidity is associated with distinct longitudinal patterns of illness burden and mood instability in BD. The integration of clinical, neuroimaging, and molecular data may identify group-specific multimodal signatures and candidate predictors of clinical course, which will require independent validation before clinical application.
SN - 1662-5161
ER -