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Evidence suggests that neurocognitive dysfunction is a transdiagnostic feature of individuals across the continuum between schizophrenia and bipolar disorder. However, there is significant heterogeneity of neuropsychological and social-cognitive abilities in schizophrenia, schizoaffective disorder, and bipolar disorder. The current study aimed to investigate the clinical and developmental characteristics of cognitive subgroups within the schizo-bipolar spectrum. 147 clinically stable patients with schizophrenia, schizoaffective or bipolar disorder were assessed using clinical rating scales for current psychotic and affective symptoms, and a comprehensive neuropsychological battery including measures of social cognition (Hinting and Reading the mind from the Eyes (RMET) task)). Developmental history and premorbid academic functioning were also evaluated. The study also included 36 healthy controls. Neurocognitive subgroups were investigated using latent class analysis (LCA). The optimal number of clusters was determined based on the Bayesian information criterion. A logistic regression analysis was conducted to investigate the predictors of membership to the globally impaired subgroup. LCA revealed two neurocognitive clusters including globally impaired (n = 89, 60.5%) and near-normal cognitive functioning (n = 58, 39.5%) subgroups. The near-normal cognitive functioning subgroup was not significantly different from healthy controls. The globally impaired subgroup had a higher score of developmental abnormalities (p<0.001), poorer premorbid academic functioning, mothers who were less educated and more severe disorganized speech (p = 0.001) and negative symptoms (p = 0.004) compared to the near-normal cognitive functioning group. History of developmental abnormalities and persistent disorganization rather than diagnosis are significant predictors of the subgroup of individuals with global cognitive impairment in the schizophrenia-bipolar disorder continuum.

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Bipolar disorder (BD) has been associated with impaired executive functioning and integrity of fronto-limbic white matter tracts. The evaluation of these factors in young offspring of patients with BD (BDoff) as a high-risk group offers an opportunity to investigate factors that could predict vulnerability to the disorder. This study aims to examine the correlation between neurocognition and neuroimaging findings to evaluate the potential for these findings as biomarkers for the early recognition of BD. We enrolled BDoff (n = 16) who were aged between 12 and 18. Participants were assessed using clinical and neurocognitive tests. In addition, structural brain magnetic resonance and diffusion tensor imaging data were obtained. Mean fractional anisotropy (FA) and mean diffusivity (MD) values of the superior longitudinal fasciculus (SLF) and cingulum were extracted and correlations with neuropsychological data were analyzed. FA values in the SLF were negatively correlated with Stroop interference, the Wisconsin Card Sorting Test, and the Trail Making Test (B-A) scores. MD values in the cingulum were inversely correlated with the Child and Youth Resilience Measure and positively correlated with higher scores on the Barratt Impulsiveness Scale-Attentional. These findings provide a link between features of the brain and cognitive dysfunction in BDoff.

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INTRODUCTION: Previous studies showed significant increases in DNA base damage markers and significant alterations in base excision repair enzymes in patients with unipolar and bipolar depression. We aimed to investigate changes in urine 8-Oxo-2'-deoxyguanosine (8-oxo-dG) and gene expression levels of 8-Oxoguanine DNA glycosylase 1 (OGG1) during a current depressive episode and after remission in bipolar and unipolar disorders. METHODS: Twenty-four acutely depressed bipolar (BD), 33 unipolar depression (UD) patients and 61 healthy controls were included in the study. Clinical evaluations, blood and urine sampling were completed at baseline and at remission after eight weeks. The urine 8-oxo-dG levels were assessed by liquid chromatography tandem mass spectrometry and adjusted for urine creatinine levels. The gene expression levels of OGG1 were determined from cDNA extracted from blood samples, using real time-polymerase chain reaction. RESULTS: At baseline, patients presented significantly higher levels of 8-oxo-dG (p = 0.008), and lower gene expression of OGG1 (p = 0.024) compared to controls. Levels of either 8-oxo-dG or OGG1 expression did not differ between BD and UD. In patients who remitted by the 8th week (n = 30), 8-oxo-dG decreased significantly (p = 0.001), and gene expression levels of OGG1 increased by 2.95 times compared to baseline levels (p = 0.001). All comparisons were adjusted for age, sex, smoking status and body mass index. CONCLUSION: Our results suggest that patients with bipolar and unipolar mood disorders present increased 8-oxo-dG and decreased gene expression levels of OGG1 in current depressive episodes, and that these changes might be reversed by the resolution of depressive symptoms. The causal relationship between DNA damage and repair requires further exploration.

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Bipolar disorder (BD) is associated with cognitive dysfunction which has also been reported in offspring of individuals with BD (BDoff). However, it remains unclear whether cognitive underperformance in BDoff is associated with the presence of history of subclinical syndromes associated with risk for BD. To address this knowledge gap we assessed executive function, visual and verbal memory, working memory, processing speed and verbal fluency in 21 offspring with clinical high risk (CHR; BDoff+CHR), 54 offspring without CHR (BDoff-non-CHR), and 50 healthy individuals without familial risk of BD. BDoff underperformed compared to controls in most cognitive tasks. There was no significant neurocognitive difference between BDoff+CHR and BDoff-non-CHR except in the fluency/central executive domain (Cohen's d = 0.60, p = 0.03). Our results suggest that cognitive dysfunction in multiple domains is associated with familial predisposition to BD regardless of CHR status. On the other hand, abnormalities in central executive processes might be more pronounced in BDoff+CHR than BDoff-non-CHR. Further longitudinal studies investigating cognitive trajectory of BDoff and its interaction with the emergence of subclinical syndromes are needed to fully characterize the relationship between cognition and mood dysregulation in BD.

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BACKGROUND: Bipolar disorder (BD) is associated with significant cognitive heterogeneity. In recent years, a number of studies have investigated cognitive subgroups in BD using data-driven methods and found that BD includes several subgroups including a severely impaired and a neurocognitively intact cluster. Studies in offspring of BD (BDoff) are particularly important to establish the timing of emergence of cognitive subgroups but studies investigating cognitive heterogeneity in BDoff are lacking. Our aim was to investigate cognitive heterogeneity in BDoff and the relationship between cognitive heterogeneity and putative clinical stages of BD. METHODS: Seventy-one euthymic BDoff and 50 healthy controls were assessed using clinical measures and a battery of neuropsychological tests. Neurocognitive subgroups were investigated using latent class analysis. RESULTS: Three neurocognitive subgroups, including a severe impairment group, a good performance cluster, and a subgroup characterized by intermediate/selective impairment was found. Both severe and intermediate level impairment subgroups underperformed healthy controls in processing speed, verbal fluency, visual memory and working memory. Deficits in verbal memory and executive functions were only evident in severe impairment subgroup. The putative stage of the illness had no significant effect on cognitive clustering of BDoff. Trait impulsivity scores were significantly increased in severe and intermediate impairment clusters but not in the cognitively good functioning subgroup of BDoff. LIMITATIONS: The cross-sectional nature of the study was the main consideration. CONCLUSION: These results suggest that cognitive heterogeneity is premorbid characteristic of BD and cognitive subgroups of BDoff emerge prior to the onset of illness and prodromal symptoms.

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