Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression

Benedetti, Francesco; Radaelli, Daniele; Poletti, Sara; Locatelli, Clinio; Falini, Andrea; Colombo, Cristina; Smeraldi, Enrico

doi:10.1016/j.jad.2011.07.006

Cited by 151 publications

(108 citation statements)

References 66 publications

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“…In those with suicidal history, compared to without, there was an increased activation during emotional tasks (such as exposure to emotionally-charged faces) in the rostral ACC, and decreased activation during non-emotional cognitive tasks (such as the IGT (decision-making), or the Go/No-go task (cognitive control)) in the dorsal ACC (van Heeringen et al, 2014). Previous studies have demonstrated decreased grey matter in the OFC, ACC, and prefrontal cortex (PFC) associated with suicide attempts (Benedetti et al, 2011;Monkul et al, 2007), and volume changes of the right amygdala (Monkul et al, 2007). These structural abnormalities may impair the functioning of the amygdalo-orbitofrontal-cingulate network, thereby preventing the amygdala from inhibiting the OFC and PFC, and the OFC from inhibiting the ACC appropriately (de Cates and Broome, 2016).…”

Section: Other Important Findings From Imaging Studiesmentioning

confidence: 99%

Are neurocognitive factors associated with repetition of self-harm? A systematic review

Cates

Rees

Jollant

et al. 2017

Neuroscience & Biobehavioral Reviews

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Background:Prediction of self-harm is limited clinically. Early identification of individuals likely to repeat self-harm could improve outcomes and reduce suicide risk. Various neurocognitive deficits have been found in people who self-harm, but the ability of these to predict repetition has yet to be established Aims:Identify neurocognitive factors that may predict repetition of self-harm. Methods:Systematic narrative review of English language publications assessing neurocognitive functioning and self-harm repetition, searching multiple databases from inception to March 2015. Quality of studies was appraised. A narrative synthesis was performed. Results:7026 unique records were identified, and 169 full-texts assessed. 15 unique studies provided data. No imaging studies could be included. Most studies assessed cognitive control or problem solving, but neither factor was consistently associated with repetition. However, specific tasks may show promise. Two studies in adolescents suggest that value-based decision-making impairments could be predictive of repetition. There were too few results for memory to draw specific conclusions. Conclusions:Selected studies suggest promise for particular neurocognitive factors and specific cognitive tasks in terms of repetition of self-harm.

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Section: Other Important Findings From Imaging Studiesmentioning

confidence: 99%

Are neurocognitive factors associated with repetition of self-harm? A systematic review

Cates

Rees

Jollant

et al. 2017

Neuroscience & Biobehavioral Reviews

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“…Similarly alterations in sleep patterns are a clinically long recognised precipitant and symptom of mood disturbances: most therapeutic work in this regard has explored monoaminergic effects on the thalamus, but there is now evidence for lithium modulating circadian patterns and suprachiasmatic nuclear functioning and expression of clock genes. Lithium's evidenced ability to prevent or partly reverse the grey-matter deficits seen in bipolar patients [Sassi et al 2002] has also been linked to specific therapeutic effects, including its effects on suicidality, potentially through impacting on goal directed behaviour and affecting cognitive distortions [Benedetti et al 2011]. …”

Section: Conclusion: Pulling the Evidence Togethermentioning

confidence: 99%

Lithium: the pharmacodynamic actions of the amazing ion

Brown

Tracy

2012

Therapeutic Advances in Psychopharmacology

110

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Lithium has been used for the treatment of mood disorders for over 60 years, yet the exact mechanisms by which it exerts its therapeutic effects remain unclear. Two enzymatic chains or pathways emerge as targets for lithium: inositol monophosphatase within the phosphatidylinositol signalling pathway and the protein kinase glycogen synthase kinase 3. Lithium inhibits these enzymes through displacing the normal cofactor magnesium, a vital regulator of numerous signalling pathways. Here we provide an overview of evidence, supporting a role for the inhibition of glycogen synthase kinase 3 and inositol monophosphatase in the pharmacodynamic actions of lithium. We also explore how inhibition of these enzymes by lithium can lead to downstream effects of clinical relevance, both for mood disorders and neurodegenerative diseases. Establishing a better understanding of lithium's mechanisms of action may allow the development of more effective and more tolerable pharmacological agents for the treatment of a range of mental illnesses, and provide clearer insight into the pathophysiology of such disorders.

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“…rs334558*C itself was associated with protective effects against gray matter (GM) loss in schizophrenia (Benedetti et al, 2010), whereas other SNPs either directly related to GSK3-b, or to its substrate proteins, were associated with GM volumes in major depressive disorder (Inkster et al, 2009(Inkster et al, , 2010. Lithium administration was followed by an increase of GM volumes in healthy humans (Monkul et al, 2007) and in patients affected by BD (Bora et al, 2010), thus possibly counteracting GM volume reductions in critical cortical areas (Benedetti et al, 2011b). Pivotal prospective studies confirmed that the lithium-associated GM volume increase during treatment correlated with treatment response in BD (Lyoo et al, 2010;Moore et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Lithium and GSK3-β Promoter Gene Variants Influence White Matter Microstructure in Bipolar Disorder

Benedetti

Bollettini

Barberi

et al. 2012

Neuropsychopharmacol

Self Cite

147

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Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase 3-b (GSK3-b). The less active GSK3-b promoter gene variants have been associated with less detrimental clinical features of BD. GSK3-b gene variants and lithium can influence brain gray matter structure in psychiatric conditions. Diffusion tensor imaging (DTI) measures of white matter (WM) integrity showed widespred disruption of WM structure in BD. In a sample of 70 patients affected by a major depressive episode in course of BD, we investigated the effect of ongoing long-term lithium treatment and GSK3-b promoter rs334558 polymorphism on WM microstructure, using DTI and tract-based spatial statistics with threshold-free cluster enhancement. We report that the less active GSK3-b rs334558*C gene-promoter variants, and the long-term administration of the GSK3-b inhibitor lithium, were associated with increases of DTI measures of axial diffusivity (AD) in several WM fiber tracts, including corpus callosum, forceps major, anterior and posterior cingulum bundle (bilaterally including its hippocampal part), left superior and inferior longitudinal fasciculus, left inferior fronto-occipital fasciculus, left posterior thalamic radiation, bilateral superior and posterior corona radiata, and bilateral corticospinal tract. AD reflects the integrity of axons and myelin sheaths. We suggest that GSK3-b inhibition and lithium could counteract the detrimental influences of BD on WM structure, with specific benefits resulting from effects on specific WM tracts contributing to the functional integrity of the brain and involving interhemispheric, limbic, and large frontal, parietal, and fronto-occipital connections.

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Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression

Cited by 151 publications

References 66 publications

Are neurocognitive factors associated with repetition of self-harm? A systematic review

Are neurocognitive factors associated with repetition of self-harm? A systematic review

Lithium: the pharmacodynamic actions of the amazing ion

Lithium and GSK3-β Promoter Gene Variants Influence White Matter Microstructure in Bipolar Disorder

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