Biological aspects and candidate biomarkers for psychotic bipolar disorder: A systematic review

Abstract

Aim:We carried out a systematic review of the available literature about potential biomarkers of psychotic bipolar disorder (BD-P), a specific subset presenting worse outcome and greater risk of relapse than non-psychotic bipolar disorder (BD-NP). Methods:We searched the main psychiatric databases (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles with the main topic of BD-P compared to schizophrenia/BD-NP/healthy controls (HC) written in English from 1994 to 2015 were included.Results: BD-P patients presented higher kynurenic acid levels in the cerebrospinal fluid, elevated antiSaccharomyces cerevisiae antibodies levels, and lower serum levels of dehydroepiandrosterone sulfate and progesterone than BD-NP/HC. Event-related potentials abnormalities have been identified in BD-P with respect to BD-NP. BD-P patients also presented bigger ventricles but similar hippocampal volumes compared to BD-NP/HC. Although the results are contrasting, some cognitive deficits seemed to be related to the psychotic dimension of bipolar affective disorder, such as impairment in verbal/logical memory, working memory, verbal and semantic fluency and executive functioning. Finally, polymorphisms of genes, such as NRG1, 5HTTLPR (s), COMT, DAOA and some chromosome regions (16p12 and 13q), were positively associated with BD-P. Conclusion:Data about the identification of specific biomarkers for BD-P are promising, but most of them have not yet been replicated. They could lead the clinicians to an early diagnosis and proper treatment, thus ameliorating outcome of BD-P and reducing the biological changes associated with a long duration of illness. Further studies with bigger samples are needed to detect more specific biological markers of the psychotic dimension of bipolar affective disorder.Key words: biomarkers, bipolar disorder, psychoneurobiology, psychopathology, psychotic symptoms. B IOLOGICAL MARKERS, AS indicators of a biological or a pathological state and as parameters that can be measured objectively, could provide a valuable support to the clinical decision-making process in many branches of medicine, including psychiatry. Several findings in the field of mood disorders could provide the background for the identification of potential specific and objective biomarkers, which could be an important aid to better understand the course of illness, the mechanisms of vulnerability and of disease expression.A recent paper describing the work of the Biomarkers Network from the International Society for Bipolar Disorders (ISBD-BIONET) cited neuroimaging and genetic findings in bipolar affective disorder (BPAD) (e.g. the loss of gray matter, the altered activation of anterior temporal, ventral prefrontal and subcortical regions in response to emotional stimuli, the identification of several potential candidate genes associated with increased risk for developing *Correspondence: Alice Caldiroli, MD, Department of Psychiatry, University of Milan, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, via Francesco Sforza ...

Biological hypotheses and biomarkers of bipolar disorder

“…The identification of biological markers for subsets of BD may be of importance. Recently, a systematic review revealed that specific biomarkers (particularly in the field of neuroendocrine‐immunology, neuroimaging, and neuropsychology) exist for psychotic BD and that psychotic BD can be considered an intermediate phenotype between schizophrenia and mood disorders …”

Search for plasma biomarkers in drug‐free patients with bipolar disorder and schizophrenia using metabolome analysis

“…Therefore, biomarkers are needed. Candidate biomarkers have already been reported, yet studies continue to lack reproducibility and selectivity …”

Gray matter bases of psychotic features in adult bipolar disorder: A systematic review and voxel‐based meta‐analysis of neuroimaging studies

“…Recent studies were consistent in recognizing P-BD as a subset with specific biological abnormalities in terms of genetic, immunological, endocrine, neurophysiological, brain imaging, and neuropsychological alterations, compared with both NP-BD and schizophrenia (Buoli et al, 2016;Moser et al, 2018;Palaniyappan et al, 2018). A growing body of literature has indicated that biological markers are most likely associated with the psychotic dimension in BD.…”