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

Terao, Takeshi; Ishii, Nobuyoshi

doi:10.1111/bdi.12875

Cited by 9 publications

(5 citation statements)

References 26 publications

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“…Furthermore, operationally diagnosed bipolar II depression may be latent bipolar I depression, true bipolar II depression, or depression with false hypomanic episodes (which is misdiagnosis for mood elevation within euthymic mood) (Figure 2). To clarify this, longitudinal observation is essential, because not a few patients with depression will present with manic and/or hypomanic episodes, resulting in a change of diagnosis to bipolar disorder (Terao et al., 2020). In addition, it is very difficult to determine whether antidepressants can be used in individual patients with bipolar depression.…”

Section: Deliberate Administration Of Ssris To Treat Bipolar Depressionmentioning

confidence: 99%

Neglected but not negligible aspects of antidepressants and their availability in bipolar depression

Terao

2021

Brain and Behavior

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Objectives: Although many antidepressants are available, they are not always used appropriately. For appropriate use of antidepressants, the old concept of a linear doseresponse relationship, in which the dose is linearly increased to achieve a sufficient antidepressant effect, should be reconsidered. Furthermore, there is ongoing debate on the safe and appropriate use of antidepressants in patients with bipolar depression.Antidepressants may be used under certain conditions in patients with bipolar depression. These neglected-but not negligible-aspects of antidepressants have been discussed herein. Methods: A narrative qualitative reviewResults: Dose-response relationships of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are not linear. They may be bell-shaped, with efficacy initially increasing with an increase in dose but decreasing when the dose is increased beyond a certain point. Despite using international diagnostic criteria, uncertainty remains on whether operationally diagnosed depression is latent bipolar I depression, latent bipolar II depression, or true depression. Furthermore, operationally diagnosed bipolar II depression may be latent bipolar I depression, true bipolar II depression, or depression with false hypomanic episodes. Manic/hypomanic switches are most likely to occur in patients receiving tricyclic antidepressants, followed by those receiving serotonin and noradrenaline reuptake inhibitors and SSRIs, in that order. Also, these switches are most likely to occur in patients with bipolar I depression, followed by those with bipolar II depression and true depression, in that order. Conclusions:Considering the diagnostic subtype of bipolar depression and antidepressant properties may help to determine the optimal treatment strategy. K E Y W O R D S5-HT 1A autoreceptor, antidepressants, bipolar depression, dose-response relationship, selective serotonin reuptake inhibitorsThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Deliberate Administration Of Ssris To Treat Bipolar Depressionmentioning

confidence: 99%

Neglected but not negligible aspects of antidepressants and their availability in bipolar depression

Terao

2021

Brain and Behavior

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“…Furthermore, patients with bipolar disorder may suffer from two influencing states, a manic (or hypomanic) state or a depressive episode, both of which may increase the risk of dementia [ 37 ]. One study even indicated a specific genetic influence on the relationship between bipolar disorder and dementia [ 38 ]. Further studies need to be conducted to analyze these associations.…”

Section: Discussionmentioning

confidence: 99%

Which Severe Mental Illnesses Most Increase the Risk of Developing Dementia? Comparing the Risk of Dementia in Patients with Schizophrenia, Major Depressive Disorder and Bipolar Disorder

Chang

Chen

et al. 2023

Clin Psychopharmacol Neurosci

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Objective Previous studies have shown that certain severe mental illnesses (SMIs) increase the risk of dementia, but those that increase the risk to a greater degree in comparison with other SMIs are unknown. Furthermore, physical illnesses may alter the risk of developing dementia, but these cannot be well-controlled. Methods Using the Taiwan National Health Insurance Research Database, patients with schizophrenia, bipolar disorder and major depressive disorder (MDD) were recruited. We also recruited normal healthy subjects as the control group. All subjects were aged over 60 years, and the duration of follow-up was from 2008 to 2015. Multiple confounders were adjusted, including physical illnesses and other variables. Use of medications, especially benzodiazepines, was analyzed in a sensitivity analysis. Results 36,029 subjects (MDD 23,371, bipolar disorder 4,883, schizophrenia 7,775) and 108,084 control subjects were recruited after matching according to age and sex. The results showed that bipolar disorder had the highest hazard ratio (HR) (HR 2.14, 95% confidence interval [CI] 1.99−2.30), followed by schizophrenia (HR 2.06, 95% CI 1.93−2.19) and MDD (HR 1.60, 95% CI 1.51−1.69). The results remained robust after adjusting for covariates, and sensitivity analysis showed similar results. Anxiolytics use did not increase the risk of dementia in any of the three groups of SMI patients. Conclusion SMIs increase the risk of dementia, and among them, bipolar disorder confers the greatest risk of developing dementia. Anxiolytics may not increase the risk of developing dementia in patients with an SMI, but still need to be used with caution in clinical practices.

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“…Studies in human patients suggested that GSK-3 may be a risk gene in BD, since increased protein levels of GSK-3α/β and increased GSK-3β activity could be detected in peripheral blood cells of BD patients (Li et al, 2010;Munkholm et al, 2018). Similarly, elevated GSK-3β mRNA levels were measured in the hippocampus of patients with major depression (Oh et al, 2010), and polymorphisms in the GSK-3β gene were reported in individuals with BD and major depression (Saus et al, 2011;Terao et al, 2020;, and could be correlated with a therapeutic response to lithium (Benedetti et al, 2005). In this context, a GSK-3 polymorphism associated with insomnia in depressed patients (Costemale-Lacoste et al, 2018), also correlates with sleep disturbance in BD patients (Lamont et al, 2010).…”

Section: Psychiatric Disorders Bipolar and Mood Disordersmentioning

confidence: 99%

Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward

Ruiz

Eldar-Finkelman²

2022

Front. Mol. Neurosci.

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The protein kinase, GSK-3, participates in diverse biological processes and is now recognized a promising drug discovery target in treating multiple pathological conditions. Over the last decade, a range of newly developed GSK-3 inhibitors of diverse chemotypes and inhibition modes has been developed. Even more conspicuous is the dramatic increase in the indications that were tested from mood and behavior disorders, autism and cognitive disabilities, to neurodegeneration, brain injury and pain. Indeed, clinical and pre-clinical studies were largely expanded uncovering new mechanisms and novel insights into the contribution of GSK-3 to neurodegeneration and central nerve system (CNS)-related disorders. In this review we summarize new developments in the field and describe the use of GSK-3 inhibitors in the variety of CNS disorders. This remarkable volume of information being generated undoubtedly reflects the great interest, as well as the intense hope, in developing potent and safe GSK-3 inhibitors in clinical practice.

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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

Cited by 9 publications

References 26 publications

Neglected but not negligible aspects of antidepressants and their availability in bipolar depression

Neglected but not negligible aspects of antidepressants and their availability in bipolar depression

Which Severe Mental Illnesses Most Increase the Risk of Developing Dementia? Comparing the Risk of Dementia in Patients with Schizophrenia, Major Depressive Disorder and Bipolar Disorder

Glycogen Synthase Kinase-3 Inhibitors: Preclinical and Clinical Focus on CNS-A Decade Onward

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