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 ...

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Subjects with MS had impaired premorbid cognition in adolescence and lower educational achievement, irrespective of parental SES. This suggests poor premorbid cognitive functioning is a risk factor for metabolic complications later in life. Future studies are needed to examine whether cognitive interventions have beneficial effects on general health in schizophrenia.

This three-year longitudinal study showed that higher verbal IQ is a protective factor and poor memory and higher number of psychotic episodes are risk factors of the outcome of schizophrenia. This suggests that future research on prediction tools for the outcome of schizophrenia should include assessment of verbal IQ and verbal memory.