Limbic-Sensorimotor Tug of War for the Hippocampus: Dynamic Functional Connectivity as a Transdiagnostic Vulnerability Marker in Offspring of Emotion Dysregulation Patients.
Luigi F Saccaro, Farnaz Delavari, Ben Meuleman, Nader Perroud, Dimitri Van De Ville, Camille Piguet
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Abstract
Background: Emotion dysregulation (ED) is a key transdiagnostic symptom in several psychiatric disorders such as borderline personality disorder (BPD), bipolar disorder (BD), and attention-deficit/hyperactivity disorder (ADHD). These disorders, here defined as ED disorders (EDD), share similarities in symptoms, comorbidity, and heritability, emphasizing the importance of a transdiagnostic approach to identify markers of vulnerability to EDD in high-risk populations, such as EDD patients' offspring (EDDoff). The hippocampus, central to ED, exhibits alterations across EDD.
Methods: We employed a state-of-the-art approach (micro-co-activation patterns, μCAPs) to study the transdiagnostic dynamic functional connectivity (dFC) of hippocampal subregions from resting-state functional MRI of 201 participants (74 EDD patients, 57 EDDoff, 70 controls). μCAPs provide a data-driven differentiation within the seed region.
Results: DFC between the sensorimotor network (SMN) and the hippocampal body was lower in EDD patients (pFDR=0.0002) and EDDoff (pFDR=0.01) compared to controls, with EDDoff displaying an intermediate pattern between EDD patients and controls. dFC between the limbic network (LN) and the hippocampal head was higher in EDD patients than in controls (pFDR=0.01) and in EDDoff (pFDR=0.01). A negative correlation was found between ED and SMN (pFDR=0.01), suggesting increasing ED with decreasing SMN dFC with the hippocampus.
Conclusions: Increased dFC between the hippocampal head and the LN, at the expense of the SMN, may represent a marker of disease in EDD patients. Lower dFC between the SMN and the hippocampal body may represent a marker of vulnerability to EDD in EDDoff, correlating with ED. Such a transdiagnostic construct represents a clinically relevant target for early interventions aimed at reducing vulnerability to EDD in high-risk populations.
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