In the present study, we examined the relationship between brain volume-related SNPs of the GSK-3β gene and antidepressant treatment effects in patients with MDD.
We now investigate an algorithm-derived comprehensive list of genes encoding proteins that directly interact with GSK3β to identify a genotypic network influencing hippocampal volume in MDD.
We then highlight evidence suggesting that GSK3β influences hippocampal volume in MDD patients, and how this could assist with targeting more precise treatments particularly for cognitive deficits in patients with mood disorders.
Analysis of the genotyping data extracted from our hospital database revealed that rs334558 exhibited exclusive association with MDD in female patients (P=0.015).Our findings suggest that GSK3βrs334558 polymorphisms might be a potential risk for MDD, and females with GSK3βrs334558 polymorphisms might have higher penetrance of MDD.
Our results provide evidence that the GSK3B gene could be a promising region which contains genetic risk for both major depressive disorder and schizophrenia in the Han Chinese population.
Analyzing patient subgroups, GSK3B structural variants were found to be risk factors of BP particularly (P = 0.00001) with an odds ratio of 8.1 while no such effect was shown in the MDD group.
Other interacting molecular signals, i.e., GSK-3β, convergent survival factors (brain-derived neurotrophic factor and heat shock proteins), and transition redox metals are also mentioned to emphasize the vast array of intermediates that could interact via comparable mechanisms in both MDD and AD.
Here we provide supporting observations by showing that polymorphisms in additional genes encoding proteins directly related to GSK3beta biological functions are associated with similar regional grey matter (GM) volume changes in MDD patients.
Under a dominant model, we observed a potential association between the GSK3Brs6782799 and MDD (P=0.07), a significant three-way interaction among BDNF rs6265, GSK3Brs6782799, and negative life events (corrected P-value, 0.011-0.012; cross-validation consistency, 7; prediction error, 0.4349).
Our findings show, for the first time, that GSK3B genetic variants play a role in the SSRI antidepressant therapeutic response and support the hypothesis that drugs regulating GSK3B activity may represent a novel treatment strategy for MDD.