Creatine for the Treatment of Depression

Kious, Brent M.; Kondo, Douglas G.; Renshaw, Perry F.

doi:10.3390/biom9090406

Cited by 44 publications

(33 citation statements)

References 191 publications

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“…Recently, CKB was also differentially expressed in a single-nucleus study of the prefrontal cortex in MDD 59 . Creatine kinase isoenzymes, including CKB, which is specific to the brain, converts creatine to phosphocreatine to efficiently meet energy demands 60 . In rodents, creatine kinase isoenzymes are sexually dimorphic with higher activity in males than females 61 .…”

Section: Discussionmentioning

confidence: 99%

Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression

Howard

Sibille

et al. 2021

Transl Psychiatry

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Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and affects individuals of all ages. It causes significant psychosocial impairments and is a major cause of disability. A recent consortium study identified 102 genetic variants and 269 genes associated with depression. To provide targets for future depression research, we prioritized these recently identified genes using expression data. We examined the differential expression of these genes in three studies that profiled gene expression of MDD cases and controls across multiple brain regions. In addition, we integrated anatomical expression information to determine which brain regions and transcriptomic cell types highly express the candidate genes. We highlight 12 of the 269 genes with the most consistent differential expression: MANEA, UBE2M, CKB, ITPR3, SPRY2, SAMD5, TMEM106B, ZC3H7B, LST1, ASXL3, ZNF184 and HSPA1A. The majority of these top genes were found to have sex-specific differential expression. We place greater emphasis on ZNF184 as it is the top gene in a more conservative analysis of the 269. Specifically, the differential expression of ZNF184 was strongest in subcortical regions in males and females. Anatomically, our results suggest the importance of the dorsal lateral geniculate nucleus, cholinergic, monoaminergic and enteric neurons. These findings provide a guide for targeted experiments to advance our understanding of the genetic underpinnings of depression.

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Section: Discussionmentioning

confidence: 99%

Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression

Howard

Sibille

et al. 2021

Transl Psychiatry

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“…There is mounting evidence for significant involvement of creatine in the pathophysiology of major depressive disorder (MDD) [70]. Several studies have shown that Akt and its downstream molecular targets effect MDD and may be targets for depression treatment [71][72][73].…”

Section: Antidepressant-like Effect Mediated By Fndc5/bdnf/akt In Micmentioning

confidence: 99%

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

et al. 2020

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Fndc5, a well-defined myokine and also identified as an adipokine, has a critical role in modulation of metabolism and protection against obesity. These important functions are mediated by irisin, a secretory peptide produced from proteolytic processing of Fndc5. The other beneficial physiological effects of irisin are alleviation of oxidative stress, neuroprotective effects, and anti-inflammatory properties and associated anti-metastatic effects. Fndc5/irisin exerts its biological effects through several intracellular signaling pathways. The major signaling pathway is thought to be MAPK signaling pathways which are involved in neural differentiation, browning of white adipocytes, as well as osteoblast proliferation and differentiation. Other essential functions of Fndc5/irisin are mediated through additional pathways including AMPK pathway, PI3K/AKT, and STAT3/Snail. Thorough understanding of the mechanisms of irisin actions are essential in order to develop Fndc5/irisin for therapeutic purposes. In the present review, we focus on the current knowledge of the signaling pathways that elicit irisin actions.

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“…results, creatine studies have also found sex-specific signals in the context of depression. Creatine kinase isoenzymes, including CKB, which is specific to the brain, converts creatine to phosphocreatine to efficiently meet energy demands 57 . In rodents, creatine kinase isoenzymes are sexually dimorphic with higher activity in males than females 58 .…”

Section: Mirroring Our Ckbmentioning

confidence: 99%

Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression

Howard

Sibille

et al. 2020

Preprint

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Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and affects individuals of all ages. It causes significant psychosocial impairments and is a major cause of disability. A recent consortium study identified 102 genetic variants and 269 genes associated with depression. To provide targets for future depression research, we prioritized these recently identified genes using expression data. We examined differential expression of these genes in three studies that profiled gene expression of MDD cases and controls across multiple brain regions. In addition, we integrated anatomical expression information to determine which brain regions and transcriptomic cell-types highly express the candidate genes. We highlight 11 of the 269 genes with the most consistent differential expression: MANEA , UBE2M , CKB , ITPR3 , SPRY2 , SAMD5 , TMEM106B , ZC3H7B , LST1 , ASXL3 and HSPA1A . The majority of these top genes were found to have sex-specific differential expression. We place greater emphasis on MANEA as it is the top gene in a more conservative analysis of the 269. Specifically, differential expression of MANEA was strongest in cerebral cortex regions and had opposing sex-specific effects. Anatomically, our results suggest the importance of the dorsal lateral geniculate nucleus, cholinergic, monoaminergic, and enteric neurons. These findings provide a guide for targeted experiments to advance our understanding of the genetic underpinnings of depression.

show abstract

Creatine for the Treatment of Depression

Cited by 44 publications

References 191 publications

Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression

Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways

Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression

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