State‐related alterations of gene expression in bipolar disorder: a systematic review

Munkholm, Klaus; Vinberg, Maj; Berk, Michael; Kessing, Lars Vedel

doi:10.1111/bdi.12005

Cited by 41 publications

(32 citation statements)

References 81 publications

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“…In fact, only few studies on potential biomarkers in mood disorders have included longitudinal assessment of healthy control individuals [52,53]. We have previously suggested a number of methodological considerations, including repeated measures and within-subject comparisons, for studies of other potential biomarkers in BD [54,55] and have applied these in clinical studies [56,57]; these methodological issues have recently been emphasized by others [58]. Future clinical case-control studies of GSK-3β should consider including repeated measures of both cases and healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

Glycogen Synthase Kinase-3β: Variation over Time and the Possible Association with Mood and Cognition in Healthy Individuals

Munkholm

Lenskjold²,

Jacoby³

et al. 2016

Neuropsychobiology

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Evidence indicates a role for glycogen synthase kinase-3β (GSK-3β) in the pathophysiology of mood disorders and in cognitive disturbances; however, the natural variation in GSK-3β activity over time is unknown. We aimed to investigate GSK-3β activity over time and its possible correlation with emotional lability, subjective mood fluctuations and cognitive function in healthy individuals. Thirty-seven healthy subjects were evaluated with neuropsychological tests and blood samples at baseline and 12-week follow-up. Total GSK-3β and serine-9-phosphorylated GSK-3β in peripheral blood mononuclear cells were quantitated using enzyme immunometric assays. The activity of GSK-3β (serine-9-phosphorylated GSK-3β/total GSK-3β) was lower at baseline compared with follow-up. No significant mean change over time was observed in levels of total GSK-3β and serine-9-phosphorylated GSK-3β. Exploratory analysis revealed lower activity of GSK-3β in spring and summer compared with the fall season. No correlation was observed between GSK-3β activity and emotional lability, subjective mood fluctuations or cognitive function. The results suggest that intra- and interindividual variation in GSK-3β activity over time could contribute to the heterogeneity of findings in clinical studies. The stability of GSK-3β activity and the role of potential moderators of GSK-3β activity warrant further investigation. Clinical studies of GSK-3β should consider including repeated measures of both cases and healthy individuals.

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Section: Discussionmentioning

confidence: 99%

Glycogen Synthase Kinase-3β: Variation over Time and the Possible Association with Mood and Cognition in Healthy Individuals

Munkholm

Lenskjold²,

Jacoby³

et al. 2016

Neuropsychobiology

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“…Candidate gene and genome-wide microarray expression analyses of postmortem human brains have shown that transcriptional dysregulation plays a role in the etiology of bipolar disorder (for a review, see reference 3). Some notable genes have been identified through these studies (4,5); however, very few passed corrections for multiple testing, and findings from these studies have largely not been replicated (3,5,6). RNA sequencing, a technique that takes advantage of the recent development of high-throughput sequencing technologies, offers a number of advantages in comparison to previous methodologies, such as microarray studies, in that it provides direct estimates of transcript abundance, as well as nucleotide-level sequence.…”

Section: Methodmentioning

confidence: 99%

Transcriptome Sequencing of the Anterior Cingulate in Bipolar Disorder: Dysregulation of G Protein-Coupled Receptors

Cruceanu¹,

Tan²,

Rogić³

et al. 2015

AJP

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By using RNA sequencing in the postmortem bipolar disorder brain, an interesting profile of G protein-coupled receptor dysregulation was identified, several new bipolar disorder genes were indicated, and the noncoding transcriptome in bipolar disorder was characterized. These findings have important implications with regard to fine-tuning our understanding of the bipolar disorder brain, as well as for identifying potential new drug target pathways.

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“…Instead, currently available data reinforce the polygenic basis of BD, with significant state-related abnormalities in gene expression. Nevertheless, some findings regarding genes that display state-related changes in expression in BD were not replicated across studies (Munkholm et al 2012). …”

Section: Methodsmentioning

confidence: 99%

Multiple levels of impaired neural plasticity and cellular resilience in bipolar disorder: Developing treatments using an integrated translational approach

Machado‐Vieira

Soeiro-de-Souza

Richards

et al. 2013

The World Journal of Biological Psychiatry

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Objectives This paper reviews the neurobiology of bipolar disorder (BD), particularly findings associated with impaired cellular resilience and plasticity. Methods PubMed/Medline articles and book chapters published over the last 20 years were identified using the following keyword combinations: BD, calcium, cytokines, endoplasmic reticulum (ER), genetics, glucocorticoids, glutamate, imaging, ketamine, lithium, mania, mitochondria, neuroplasticity, neuroprotection, neurotrophic, oxidative stress, plasticity, resilience, and valproate. Results BD is associated with impaired cellular resilience and synaptic dysfunction at multiple levels, associated with impaired cellular resilience and plasticity. These findings were partially prevented or even reversed with the use of mood stabilizers, but longitudinal studies associated with clinical outcome remain scarce. Conclusions Evidence consistently suggests that BD involves impaired neural plasticity and cellular resilience at multiple levels. This includes the genetic and intra- and intercellular signalling levels, their impact on brain structure and function, as well as the final translation into behaviour/cognitive changes. Future studies are expected to adopt integrated translational approaches using a variety of methods (e.g., microarray approaches, neuroimaging, genetics, electrophysiology, and the new generation of –omics techniques). These studies will likely focus on more precise diagnoses and a personalized medicine paradigm in order to develop better treatments for those who need them most.

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State‐related alterations of gene expression in bipolar disorder: a systematic review

Cited by 41 publications

References 81 publications

Glycogen Synthase Kinase-3β: Variation over Time and the Possible Association with Mood and Cognition in Healthy Individuals

Glycogen Synthase Kinase-3β: Variation over Time and the Possible Association with Mood and Cognition in Healthy Individuals

Transcriptome Sequencing of the Anterior Cingulate in Bipolar Disorder: Dysregulation of G Protein-Coupled Receptors

Multiple levels of impaired neural plasticity and cellular resilience in bipolar disorder: Developing treatments using an integrated translational approach

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