Evaluating endophenotypes for bipolar disorder

Guglielmo, Riccardo; Hasler, Gregor

doi:10.1186/s40345-021-00220-w

Cited by 27 publications

(11 citation statements)

References 230 publications

(268 reference statements)

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“…In addition, the age-modified interaction effect could contribute to evidence supporting the neuroimmune development of bipolar disorder, in which, at the onset of the illness, individuals experience an increased proinflammatory state in adolescence, an anti-inflammatory state during young adulthood and a nearly normalised immune state in later stages of the disease course. 35 The interaction plot revealed an antagonistic interaction effect of vitamin D and NfLs, indicating that in the early stages of bipolar disorder in younger patients, NfL level may serve as a marker for neuro-damage resulting from neuroinflammation, and cognition differed in patients with higher and lower NfL levels, particularly those with extremely low vitamin D levels. In older patients with bipolar disorder who have a longer disease course, neuroinflammatory processes become stable, and the positive effects of vitamin D become more prominent in patients with lower rather than higher NfL levels.…”

Section: Discussionmentioning

confidence: 94%

The interactions between vitamin D and neurofilament light chain levels on cognitive domains in bipolar disorder

Chen

Huang²,

Chiu³

et al. 2022

BJPsych open

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Background Bipolar disorder is a chronic mental disorder related to cognitive deficits. Low serum vitamin D levels are significantly associated with compromised cognition in neuropsychiatric disorders. Although patients with bipolar disorder frequently exhibit hypovitaminosis D, the association between vitamin D and cognition in bipolar disorder, and their neuroaxonal integrity, is unclear. Aims To investigate the interaction effects between vitamin D and neurofilament light chain (NfL) levels on cognitive domains in bipolar disorder. Method Serum vitamin D and NfL levels were determined in 100 euthymic patients with bipolar disorder in a cross-sectional study. Cognitive function was measured with the Brief Assessment of Cognition in Affective Disorders. We stratified by age groups and used general linear models to identify associations between vitamin D and NfL levels and their interaction effects on cognitive domains. Results The mean vitamin D and NfL levels were 16.46 ng/nL and 11.10 pg/mL, respectively; 72% of patients were vitamin D deficient. In the older group, more frequent hospital admissions and lower physical activity were identified in the group with versus without vitamin D deficiency. The age-modified interaction effect of vitamin D and NfL was associated with composite neurocognitive scores and verbal fluency in both age groups, and with processing speed domain in the younger group. Conclusions We observed a high vitamin D deficiency prevalence in bipolar disorder. We identified the interaction of vitamin D and NfL on cognitive domains, and the effect was modified by age. Longitudinal or randomised controlled studies enrolling patients with various illness durations and mood statuses are required to validate our findings.

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Section: Discussionmentioning

confidence: 94%

The interactions between vitamin D and neurofilament light chain levels on cognitive domains in bipolar disorder

Chen

Huang²,

Chiu³

et al. 2022

BJPsych open

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“…Individuals who have a genetic predisposition to BD may display impairments in visual memory, verbal memory, processing speed, attention, and social cognition compared to HCs [46]. Structural and functional alterations in the prefrontal cortex [47][48][49] and white matter abnormalities in the body and splenium of the corpus callosum [50] have been observed in individuals with genetic predisposition to BD, as well as alterations in markers of neuroimmune dysregulation [51,52]. Our results suggest that the BER pathway may genes serve as candidate endophenotypes for BD.…”

Section: Discussionmentioning

confidence: 99%

Oxidative DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder

Arat-Çelik,

Yılmaz,

Akşahin

et al. 2023

Preprint

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Previous evidence suggests elevated levels of oxidative DNA damage, particularly 8-hydroxy-2'-deoxyguanosine (8-OH-dG), and abnormalities in the repair of 8-OH-dG by the base excision repair (BER) in BD. However, the genetic disposition of these abnormalities remains unknown. In this study, we aimed to investigate the levels of oxidative DNA damage and BER mechanisms in individuals with BD and their siblings, as compared to healthy controls (HCs). 46 individuals with BD, 41 siblings of individuals with BD, and 51 HCs were included in the study. Liquid chromatography-tandem mass spectrometry was employed to evaluate the levels of 8-OH-dG in urine, which were then normalized based on urine creatinine levels. The real-time-polymerase chain reaction was used to measure the expression levels of 8-oxoguanine DNA glycosylase 1 (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), poly ADP-ribose polymerase 1 (PARP1), and DNA polymerase beta (POLβ). The levels of 8-OH-dG were found to be elevated in both individuals with BD and their siblings when compared to the HCs. The OGG1 and APE1 expressions were downregulated, while POLβ expressions were upregulated in both the patient and sibling groups compared to the HCs. Age, smoking status, and the number of depressive episodes had an impact on APE1 expression levels in the patient group while body mass index, smoking status, and past psychiatric history had an impact on 8-OH-dG levels in siblings. Both individuals with BD and unaffected siblings presented similar abnormalities regarding oxidative DNA damage and BER, suggesting a link between abnormalities in DNA damage / BER mechanisms and familial susceptibility to BD. Our findings suggest that targeting the oxidative DNA damage and BER pathway could offer promising therapeutic strategies for reducing the risk of age-related diseases and comorbidities in individuals with a genetic predisposition to BD.

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“…These have been linked to clinical severity (Swann, Lijffijt, Lane, Steinberg, & Moeller, 2009). Notably, sustained attention has also been implicated as an endophenotype for BD (Guglielmo, Miskowiak, & Hasler, 2021).…”

Section: Introductionmentioning

confidence: 99%

Impaired Visuospatial Working Memory but Preserved Attentional Control in Bipolar Disorder

Barnes-Scheufler,

Rösler,

Schiweck

et al. 2024

Preprint

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BACKGROUNDPersistent deficits in working memory (WM) and attention have considerable clinical and functional impact in people with bipolar disorder (PBD). Understanding the neurocognitive underpinnings of these interacting cognitive constructs might facilitate the discovery of more effective pro-cognitive interventions. Therefore, we employed a paradigm designed for jointly studying attentional control and WM encoding.METHODSWe used a visuospatial change-detection task using four Gabor Patches with differing orientations in 63 euthymic PBD and 76 healthy controls (HCS), which investigated attentional competition during WM encoding. To manipulate bottom-up attention using stimulus salience, two Gabor patches flickered, which were designated as either targets or distractors. To manipulate top-down attention, the Gabor patches were preceded by either a predictive or a non-predictive cue for the target locations.RESULTSAcross all task conditions, PBD stored significantly less information in visual WM than HCS (significant effect of group). However, we observed no significant group by salience or group by cue interactions. This indicates that impaired WM was not caused by deficits in attentional control.CONCLUSIONSOur results imply that while WM is disturbed in PBD, attentional prioritization of salient targets and distractors as well as the utilization of external top-down cues were not compromised. Consequently, the control of attentional selection appears be intact. These findings provide important constraints for models of WM dysfunction in PBD by indicating that later stages of WM encoding are likely primarily impaired. We also demonstrate that selective attention is not among the main sources of cognitive impairment in PBD.

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Evaluating endophenotypes for bipolar disorder

Cited by 27 publications

References 230 publications

The interactions between vitamin D and neurofilament light chain levels on cognitive domains in bipolar disorder

The interactions between vitamin D and neurofilament light chain levels on cognitive domains in bipolar disorder

Oxidative DNA base damage and base excision repair abnormalities in siblings of individuals with bipolar disorder

Impaired Visuospatial Working Memory but Preserved Attentional Control in Bipolar Disorder

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