A systematic review of the biomarkers associated with cognition and mood state in bipolar disorder

Bipolar disorder (BD) is a severe psychiatric disorder characterized by changes in mood that alternate between (hypo) mania or depression and mixed states, often associated with functional impairment and cognitive dysfunction. But little is known about biomarkers that contribute to the development and sustainment of cognitive deficits. The aim of this study was to review the association between neurocognition and biomarkers across different mood states.

Search databases were Web of Science, Scopus and PubMed. A systematic review was carried out following the PRISMA guidelines. Risk of bias was assessed with the Newcastle-Ottawa Scale. Studies were selected that focused on the correlation between neuroimaging, physiological, genetic or peripheral biomarkers and cognition in at least two phases of BD: depression, (hypo)mania, euthymia or mixed. PROSPERO Registration No.: CRD42023410782.

A total of 1824 references were screened, identifying 1023 published articles, of which 336 were considered eligible. Only 16 provided information on the association between biomarkers and cognition in the different affective states of BD. The included studies found: (i) Differences in levels of total cholesterol and C reactive protein depending on mood state; (ii) There is no association found between cognition and peripheral biomarkers; (iii) Neuroimaging biomarkers highlighted hypoactivation of frontal areas as distinctive of acute state of BD; (iv) A deactivation failure has been reported in the ventromedial prefrontal cortex (vmPFC), potentially serving as a trait marker of BD.

Only a few recent articles have investigated biomarker-cognition associations in BD mood phases. Our findings underline that there appear to be central regions involved in BD that are observed in all mood states. However, there appear to be underlying mechanisms of cognitive dysfunction that may vary across different mood states in BD. This review highlights the importance of standardizing the data and the assessment of cognition, as well as the need for biomarkers to help prevent acute symptomatic phases of the disease, and the associated functional and cognitive impairment.