A specific group of patients with diagnostic conversion from depression to bipolar disorder and finally to dementia as a mental GSK-3 disease: A hypothesis

Abstract

Objectives: To focus on a specific group of patients whose diagnoses were changed from unipolar depression to bipolar disorder, and finally to dementia. Methods: Qualitative review of the relevant articles. Results: A substantial portion of patients with unipolar depression manifest manic and/or hypomanic episodes, resulting in a change of diagnoses to bipolar disorder. Further, a substantial portion of bipolar patients develop dementia. Previous research suggests that genetic variants in the glycogen synthase kinase 3β (GSK-3β) gene are associated with early onset of unipolar depression, a subset of which may be bipolar depression, with three SNPs (rs334555, rs119258668, and rs11927974) identified. Notably, another promotor SNP (rs334558) of the GSK-3β gene is reportedly associated with unipolar depression, bipolar disorders, and dementia. Additionally, lithium, which is reported to inhibit GSK-3, is generally accepted to be effective for bipolar disorder and recently reported to be effective for dementia. Conclusions: There is a specific group of patients whose diagnoses longitudinally change from depression to bipolar disorder and finally to dementia, and GSK-3 may be a common etiological factor in these diseases and in diagnostic conversions.