•Inflammatory cytokines have been associated with cognitive dysfunction in BDI.•Yet, the relationship between cytokines and cognition in early stage BDI is unclear.•In this sample of early stage ...patients, TNFα was associated with poorer cognition.•IL-6, IL-1α, IL-4 and IL-10 levels were not significantly associated with cognition.•Thus, TNFα may be a unique mediator of cognitive dysfunction in early BDI.
Increased circulating inflammatory cytokines is a replicated finding in bipolar I disorder (BDI). Pro-inflammatory cytokines such as TNFα, IL-6 and IL-1 have also been associated with poorer cognitive functioning in patients with longer illness duration. However, the effect of inflammatory cytokines on cognition in early stage patients is not yet known. Here, we investigate the relationship between cytokines and cognition in BDI patients within three years of diagnosis.
Serum pro-inflammatory (TNFα, IL-6 and IL-1α) and anti-inflammatory (IL-4 and IL-10) cytokine levels were compared between 51 early stage BDI patients and 20 healthy controls. 46 patients completed neuropsychological testing, and multiple regression analysis was used to assess the association between cytokine levels and cognition after accounting for relevant clinical and demographic variables.
TNFα was elevated at trend level significance in BDI patients compared to healthy controls, and was negatively associated with global cognition, processing speed, and working memory in patients. IL-6, IL-1α, IL-4 and IL-10 levels were comparable between groups and were not significantly associated with cognition.
Direct causation cannot be established in this cross-sectional study; in addition, cytokine levels were not taken on the same day as neuropsychological testing for all patients.
TNFα may negatively impact cognition in early BDI. While replication is required in larger samples, these results suggest that inhibition of TNFα activity might be a strategy to preserve cognition in newly diagnosed BDI patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Introduction: This narrative review of systematic reviews and meta-analyses aims at compiling available evidence in various aspects of neurocognitive functioning in Bipolar Disorder (BD).
Methods: We ...conducted a MEDLINE literature search and identified 38 relevant systematic reviews and metaanalyses.
Results: Current evidence suggests that BD is associated with cognitive impairment across multiple domains and during all clinical states. However, there is a considerable cognitive heterogeneity within BD, which cannot be explained by clinical subtypes, and the pattern of neurocognitive impairment in BD overlaps with other psychiatric conditions such as major depression and schizophrenia. Residual depressive symptoms, poor clinical course and higher number of manic episodes may negatively impact cognitive performance, which is a major predictor of general functioning in BD. Evidence from available prospective studies does not support the notion of progressive cognitive decline in BD while some evidence exists to suggest patients may show some improvements in cognitive functioning following the first manic episode. Furthermore, a subset of patients may show premorbid cognitive abnormalities that could signal an early neurodevelopmental aetiology. Preliminary findings from small studies identify potential pro-cognitive effects of Cognitive Remediation, erythropoietin, intranasal insulin, lurasidone, mifepristone, repetitive Transcranial Magnetic Stimulation and transcranial Direct Current Stimulation in BD.
Discussion: Longitudinal studies in high-risk individuals can provide a better understanding of the development and progression of neurocognitive impairment in BD. Largescale randomised control trials are needed to compare the pro-cognitive efficacy of various pharmacological and non-pharmacological interventions in different cognitive subgroups of patients at different stages of BD.
•Subjective cognition had a strong negative correlation with clinical symptoms.•Clinical symptoms, intelligence and executive functions predict self-appraisal.•Patients in remission had the poorest ...appraisal of their objective performance.•Patients in an acute episode show the greatest underestimation of their cognition.
Objective and subjective cognitive measures are altered in major depressive disorder (MDD), but there is a poor correlation between them. This study aims to explore such discrepancy and the characteristics explaining this phenomenon.
229 patients with MDD subdivided into remitted (n = 57), partially remitted (n = 90) and acute (n = 82) underwent a clinical interview, completed self-report questionnaires and a neuropsychological assessment. The association between objective and subjective cognition was evaluated in the areas of attention and memory. Also, dependent measures of concordance and self-appraisal were calculated for each patient. Potential predictors of these outcomes were evaluated through regression analysis. Depressive symptoms correlated negatively with objective but especially with subjective cognition. Patients in an acute episode showed a significant correlation between objective and subjective attention/memory measures, but also the greatest underestimation of their cognitive performance. In those with fewer depressive symptoms, objective and subjective cognition showed poor correspondence between them. In the regression analyses with the full MDD sample, higher scores on depressive symptoms, intelligence quotient and executive functions predicted lower self-appraisal.
Objective and subjective cognition show poor concordance in MDD patients, especially in those with residual mood symptoms. Higher executive functions also explain this discrepancy. Assessments of both subjective cognitive complaints and objective performance seem necessary as they may be measuring different aspects of cognitive functioning.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
Distinct cognitive subgroups are seen in patients with long duration bipolar I disorder (BDI), possibly reflective of underlying pathophysiological differences. It is unknown whether such ...cognitive heterogeneity is present at illness onset. We applied latent class analysis (LCA) to cognitive test scores in first episode BDI patients. Exploratory analysis elucidated whether impaired subgroups were characterized by ‘early neurodevelopmental’ (low premorbid IQ and intracranial volume) versus ‘later neurodevelopmental’ (decline from premorbid to current IQ, changes in relative grey (GM)/white (WM) matter volumes) pathology.
Methods
Recently recovered first manic episode BDI patients (n = 91) and healthy controls (HC, n = 63) comprised the study sample. LCA identified subgroups based on processing speed, verbal memory, non‐verbal memory, executive functioning, attention and working memory scores. Subgroups were compared amongst each other and HC on premorbid/current IQ, intracranial (ICV), total brain and regional volumes.
Results
Three cognitive subgroups emerged: (i) globally impaired (GI, n = 31), scoring 0.5‐1 SD below demographically corrected norms across domains, (ii) selectively impaired (SI, n = 47), with predominant processing speed deficits and (iii) high performing (HP, n = 13), with above‐average cognitive performance. GI patients showed a ‘later neurodevelopmental’ pattern, with normal ICV, significant decline from premorbid to current IQ, higher total GM and lower total WM (with respect to total brain volume) versus SI and HC (p = 0.003). GI patients had higher left frontal pole GM versus HC (p < 0.05, FWE corrected).
Conclusions
A globally impaired patient subgroup is identifiable in first episode BDI, possibly characterized by unique neurodevelopmental pathologic processes proximal to illness onset.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
We previously reported that in early-stage bipolar disorder (BD), frontal and temporal lobe volume reductions were more pronounced in patients with elevated BMI and more rapidly progressive in ...patients with additional weight gain. Elevated BMI is a pro-inflammatory state, and inflammation may contribute to brain volume reductions in BD. However, few studies have investigated the relationship between inflammation and brain volumes.
We conducted a proof-of-concept analysis to investigate whether a composite measure of total peripheral inflammation derived from 9 cytokines predicted lower frontal and temporal lobe volumes, measured with 3 T MRI, in early-stage BD.
In 25 early-stage patients, linear regression models showed that greater total inflammation predicted lower white matter (WM) volumes in the left frontal lobe (β = −0.691, p = 0.001) and bilateral temporal lobes (left: β = −0.617, p = 0.003; right: β = −0.636, p = 0.001). Greater inflammation also predicted lower right frontal WM, although this did not survive correction for multiple comparisons (β = −0.557, p = 0.020). It did not predict frontal or temporal GM. Total inflammation was a stronger predictor of lower WM volumes than were individual cytokines.
Although the magnitude of the association between total inflammation and lower WM volumes was large, our sample was small. Our findings require confirmation in further studies, with samples large enough to determine whether inflammation mediates the relationship between elevated BMI and brain volumes.
This study supports the hypothesis that inflammation contributes to brain volume reductions in BD and suggests that total inflammatory burden best captures the impact of inflammation on the brain.
•Total peripheral inflammation predicts lower frontal and temporal white matter (WM) in early bipolar disorder.•The relationship between total peripheral inflammation and WM volumes is large (βs 0.617–0.691).•Total inflammation is a stronger predictor of lower WM volumes than are individual cytokines.•This study supports the hypothesis that inflammation contributes to brain illness severity in bipolar disorder.•Total inflammatory burden best captures the impact of inflammation on the brain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Precision agriculture is a growing field in the agricultural industry and it holds great potential in fruit and vegetable harvesting. In this work, we present a robust accurate method for the ...detection and localization of the peduncle of table grapes, with direct implementation in automatic grape harvesting with robots. The bunch and peduncle detection methods presented in this work rely on a combination of instance segmentation and monocular depth estimation using Convolutional Neural Networks (CNN). Regarding depth estimation, we propose a combination of different depth techniques that allow precise localization of the peduncle using traditional stereo cameras, even with the particular complexity of grape peduncles. The methods proposed in this work have been tested on the WGISD (Embrapa Wine Grape Instance Segmentation) dataset, improving the results of state-of-the-art techniques. Furthermore, within the context of the EU project CANOPIES, the methods have also been tested on a dataset of 1,326 RGB-D images of table grapes, recorded at the Corsira Agricultural Cooperative Society (Aprilia, Italy), using a Realsense D435i camera located at the arm of a CANOPIES two-manipulator robot developed in the project. The detection results on the WGISD dataset show that the use of RGB-D information (mAP=0.949) leads to superior performance compared to the use of RGB data alone (mAP=0.891). This trend is also evident in the CANOPIES Grape Bunch and Peduncle dataset, where the mAP for RGB-D images (mAP=0.767) outperforms that of RGB data (mAP=0.725). Regarding depth estimation, our method achieves a mean squared error of 2.66 cm within a distance of 1 m in the CANOPIES dataset.
•New bunch and peduncle detection method based on a combination of instance segmentation and monocular depth estimation.•New methods to estimate the peduncle depth.•Combination of depth estimation methods and direct stereo camera measurement.•Improvement of bunch and peduncle detection with respect to the state-of-art.•Tests in WGISD dataset and a new dataset created within the EU CANOPIES project.•Accurate detection of bunches and peduncles in real life experiments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Repetitive transcranial magnetic stimulation (TMS) is increasingly used to treat neurocognitive symptoms in mood disorders. Intermittent theta burst stimulation (iTBS) is a brief version of TMS that ...may preferentially target cognitive functions. This study evaluated whether iTBS leads to cognitive improvements and associated increased hippocampal volumes in bipolar depression.
In a two-site double-blind randomised sham controlled trial (NCT02749006), 16 patients received active iTBS to the Left Dorsolateral Prefrontal Cortex (DLPF) and 15 patients received sham stimulation across four weeks. A composite neuropsychological score and declarative memory scores served as the cognitive outcomes. Hippocampal volumes were derived from T1 weighted MRI scans using the longitudinal ComBat method to harmonise data across sites.
No significant improvements were observed in any cognitive variables in the active relative to the sham group; however, there was a trend for increased left hippocampal volume in the former. Left hippocampal volume increases were associated with improvements in nonverbal memory in the active group.
Although cognitive improvements were not associated with iTBS, the finding that hippocampal volume increases were associated with memory improvement suggests there may be some level of prefrontal-temporal neuroplasticity that could support cognitive change in future studies of iTBS in bipolar disorder.
