Corticolimbic connectivity as a possible biomarker for bipolar disorder

Abstract

Bipolar disorder is a severe, disabling and life-threatening illness, which affects nearly 2% of the general population. The identification of reliable and objective biomarkers may aid early diagnosis and optimize treatment efficacy. Through a careful overview of the neuroimaging studies which investigated the structural, functional, and effective connectivity in bipolar disorder, we explored the role of a disconnected cortico-limbic circuitry in the development and maintenance of the disorder. This review offers perspectives and suggestions for future research, in order to propose the corticolimbic disconnection as a neurobiological underpinning and biomarker for bipolar psychopathology.

Keywords::

• biomarker
• bipolar disorder
• connectivity
• corticolimbic circuitry
• development

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The frontolimbic network has been proposed as a key circuitry in the etiophatology and maintenance of bipolar disorder (BD). A disrupted structural, functional and effective brain connectivity within this network may identify a possible biomarker for the disorder.

• A reduced functional and effective connectivity within the frontolimbic network has been widely displayed in BD and detected across mood states in not affected relatives and in pediatric patients. Furthermore, the amygdala–prefrontal disconnectivity is potentially able to distinguish bipolar and unipolar depression.

• An increased functional connectivity within this network was also related to a better clinical response to mood stabilizer.

• Alterations in structural connectivity have also been confirmed in this network and are detectable in childhood and at-risk subjects, and probably underlie to subsyndromal symptomatology that precedes the onset of the disorder.

• The multimodal data clearly prompt that the frontolimbic disconnection, probably the result of epigenetic abnormal neurodevelopmental processes, identifies a plausible reliable biomarker of the disorder, mediator of the relationship between the underlying susceptibility genes and the clinical expression of BD.