The cover image is based on the article The Role of the Complement C3-Hippocampus Pathway in Relation With Mood Symptoms in Offspring of Parents With Bipolar Disorder by Robin Shao et al., https://doi.org/10.1111/bdi.70056.
Bipolar disorder (BD), characterized by anomalous neurostructural phenotypes, is also strongly associated with cardiovascular disease. Here we examined polygenic risk for coronary artery disease (CAD) in relation to gray matter structure in youth BD.
Youth participants (mean age 17.1 years; n = 66 BD, n = 45 healthy controls [HC]) underwent T1-weighted magnetic resonance imaging. CAD polygenic risk scores (CAD-PRS) were calculated using independent, adult genome-wide summary statistics. Covariate-adjusted vertex-wise analyses examined the association of CAD-PRS with cortical volume, thickness, and surface area (SA) in the overall sample, and within BD and HC groups. Additional region-of-interest (ROI) analyses were conducted to examine the anterior cingulate cortex (ACC), amygdala, and hippocampus. Exploratory sex-stratified analyses were also undertaken.
In the overall sample, higher CAD-PRS was associated with lower right inferior temporal gyrus volume (β = −0.32, p = 0.03). There were also negative associations between CAD-PRS and brain structure within BD (5 cortical thickness clusters) and HC (1 SA cluster). Within the BD group, sex-stratified analyses revealed significant findings for females, but not for males. ROI analyses revealed a nominal association of higher CAD-PRS with lower ACC thickness in the BD group (β = −0.31, puncorrected = 0.05, pcorrected = 0.20).
Higher CAD-PRS was associated with lower regional gray matter structure in youth, in regions implicated in BD. Findings were more pronounced in the BD group, particularly among females, and related to cortical thickness specifically. Future longitudinal studies are needed to examine the association of CAD-PRS with neurodevelopmental changes over time and to discern mechanisms underlying the observed findings.
Bipolar disease (BD) has been strongly associated with the etiologies of mitochondrial reactive oxygen species (mROS), apoptosis, and Ca2+ influx. With the exception of BD, a number of neurological disorders have been linked to apoptosis and neuronal death mediated by mROS-dependent activated TRPM2 channel stimulation. Lamotrigine (LMT), lithium (Li), and valproic acid (VPA) are mood stabilizers in BD, and they have strong antioxidant roles. However, the molecular mechanisms underlying LMT, Li, and VPA neuroprotection through TRPM2 channel inhibiton remain elusive in BD.
We evaluated the protective actions of LMT, Li, and VPA on BD (ouabain, OUA)-induced oxidative neurotoxicity in SH-SY5Y neuronal cells by modulating TRPM2.
The SH-SY5Y cells were divided into nine groups as follows: control, Li, VPA, LMT, OUA, OUA + Li, OUA + VPA, LMT + VPA, and OUA + TRPM2 antagonists (N-(p-amylcinnamoyl)anthranilic acid or carvacrol).
OUA exposure and TRPM2 agonist (H2O2 and ADP-ribose)-induced TRPM2 stimulation and TRPM2 current densities were downregulated by the treatments of TRPM2 antagonist, Li, VPA, and LMT. The OUA-induced upregulations of mROS, cytosolic ROS, lipid peroxidation, mitochondrial membrane dysfunction, apoptosis, Zn2+, cell death, and caspase-3, -8, and -9 values were also downregulated through the increases of cell viability, glutathione, and glutathione peroxidase by the treatments.
The treatments of Li, VPA, and LMT modulate OUA-mediated mROS, apoptosis, Zn2+, glutathione, and TRPM2-mediated excess Ca2+ influx. This could potentially offer protection against BD linked to elevated levels of mROS, Ca2+, and Zn2+.
Studies have reported changes in the transcriptome in the brain and blood from people with bipolar disorders (BD). We completed this study to test the hypothesis that there would be changes in the blood transcriptome that would mirror cortical changes in RNA levels in BD.
Levels of RNA were measured in blood from 19 people with BD and 19 controls using Affymetrix Human Exon 1.0 ST Arrays. Significant differences in levels of RNA with diagnosis were identified using JMP Genomics 9.0, and the potential biological impact of changes in RNA was investigated using the Panther Classification System.
Levels of RNA for 19,473 coding and non-coding RNAs were detected. Compared to controls, there were changes in levels of 98 (65 with higher levels than controls) coding and non-coding RNAs at the criteria of fold ≥ ±20% and p < 0.05 in BD. The changes in levels of RNA were predicted to impact toll-like receptor function and Wnt signalling, response to virus, cell–cell signalling, and protein metabolic processing as well as post-synaptic organisation, dendritic spine morphogenesis, and pattern recognition receptor signalling pathways. Four of the RNAs found to be altered in blood in this study were also found to be altered in our previous study of the cortical transcriptome using tissue of people with BD.
This, and other studies, suggest changes in the blood transcriptome are affecting peripheral biochemical homeostasis in BD and some of the changes are present in the cortex of those with the disorder. Therefore, it could be possible that changes in the blood transcriptome in people with BD could contain diagnostic or theranostic markers for the disorder.
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