Cortico-limbic connectivity as a possible biomarker for bipolar disorder: where are we now?

ABSTRACT

Introduction: The fronto-limbic network has been suggested as a key circuitry in the pathophysiology and maintenance of bipolar disorder. In the past decade, a disrupted connectivity within prefrontal-limbic structures was identified as a promising candidate biomarker for the disorder.

Areas Covered: In this review, the authors examine current literature in terms of the structural, functional and effective connectivity in bipolar disorder, integrating recent findings of imaging genetics and machine learning. This paper profiles the current knowledge and identifies future perspectives to provide reliable and usable neuroimaging biomarkers for bipolar psychopathology in clinical practice.

Expert Opinion: The replication and the translation of acquired knowledge into useful and usable tools represents one of the current greatest challenges in biomarker research applied to psychiatry.

KEYWORDS:

• Bipolar disorder
• biomarker
• cortico-limbic circuitry
• connectivity
• imaging genetics
• machine learning

Article Highlights

• Despite the availability of effective interventions, the burden of mood disorders is constantly growing and roughly 60% of depressed patients with bipolar disorder are clinically misdiagnosed. An urgent need exists to identify biomarkers.

• A disrupted connectivity within the prefrontal-limbic system has been identified as a promising candidate biomarker for BD.

• This hypothesis is widely supported by more recent evidence. Studies of FC confirmed a reduced functional connectivity between PFC and limbic areas, especially amygdala, detected across mood states, in not affected relatives, and in pediatric patients during both cognitive or emotional processing and resting state. An increased connectivity also related to a better clinical response.

• The structural disruption of white matter connectivity has been confirmed in these years in several meta-analyses, and enriched in new graph theory studies: BD shows a reduced global particularly expressed in the limbic and frontal network in BD.

Imaging genetics are clearly showing that corticolimbic circuitry connectivity is directly moderated by the underlying genetic vulnerability, strengthening its role as an endophenotype of the disorder, and ML studies are confirming the utility of these markers in clinical practice as supports for differential diagnosis.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was funded by the Italian Ministry of Health [RF-2011-02350980] and B Vai was supported by Fondazione Umberto Veronesi.