Factors associated with self-perceived treatment-resistance in bipolar disorder.

Patients with bipolar disorder often report self-perceived treatment resistance. However, it is not known to what extent it is due to actual treatment resistance. The Juntendo University provides "Bipolar Disorder Treatment Rebuilding Program," in which patients with self-reported treatment resistant bipolar disorder are hospitalized for 2 weeks and undergo detailed examinations. In this study, we report our experience with the initial 43 patients hospitalized during the one and half years after the launch of the program. Among the patients who underwent full assessment, only one was regarded as having genuine treatment-resistant bipolar disorder without comorbidity. In other cases, ten were not diagnosed with bipolar disorder, 3 had organic brain diseases, 12 had comorbid mental disorders and its symptoms were regarded as treatment-resistant bipolar symptoms by the patients, and 18 did not receive adequate treatment because attendant physicians did not adhere to the treatment guidelines or patients did not adhere to the treatment because of lack of insight. The number of participants was not large, and selection bias hampered the generalization of the findings. Insight and adherence were assessed without the use of validated tools. We could not verify recovery after adequate treatment because of the limited hospitalization period. The findings suggest that most patients with self-perceived treatment-resistant bipolar disorder may not have genuine treatment-resistant bipolar disorder. These results shed light on the difficulties of public education of bipolar disorder and importance of providing appropriate services for diagnosis and treatment of bipolar disorder in the community.

Safety and real-world efficacy of lemborexant in the treatment of comorbid insomnia.

Aim: To investigate the real-world effectiveness and safety of lemborexan for treating comorbid insomnia associated with other psychiatric disorders, and whether lemborexant helps reduce the dose of benzodiazepines (BZs). Methods: This retrospective observational study was conducted on outpatients and inpatients treated by physicians of Juntendo University Hospital Mental Clinic between April 2020 and December 2021. Results: Data of 649 patients who were treated with lemborexant were eventually enrolled. About 64.5% of patients were classified as the responder group. Response rates of ≥60% were recorded for most psychiatric disorders. Upon administration of lemborexant, diazepam-equivalent dose of BZs had been significantly reduced in participants (3.7 ± 8.2 vs. 2.9 ± 7.9, p < 0.001). The results of logistic regression analysis showed that outpatient (odds ratios: 2.310; 95% confidence interval [CI]: 1.32-4.05), shorter duration of BZ use (<1 year) (odds ratios: 1.512; 95% CI: 1.02-2.25), no adverse events (odds ratios: 10.369; 95% CI: 6.13-17.54), larger reduction of diazepam-equivalent dose of BZs upon introducing lemborexant prescription (odds ratios: 1.150; 95% CI: 1.04-1.27), and suvorexant was the replacement drug (odds ratios: 2.983; 95% CI: 1.44-6.19), which were significant predictors of good response. Conclusion: Although this is a retrospective and observational study with many limitations, our study results suggest that lemborexant is effective and safe.

Apolipoprotein E4 increases the risk of depression recurrence.

BACKGROUND: Possession of the ε4 allele of apolipoprotein E (APOE4) is related to the incidence of depression in old age. We investigated whether the presence of APOE4 is also associated with subsequent depression recurrence in a wide range of age groups. METHODS: Altogether, 163 patients with major depressive disorder (MDD) after remission were recruited between August 2004 and March 2016 and followed up prospectively. The patients were divided into two groups: APOE4 carriers and non-carriers. We compared the time to recurrence of depression between the two groups. Kaplan-Meier survival curves, log-rank test for trend for survivor functions, and Cox proportional hazard ratio estimates for a multivariate model were conducted to examine the effect of the APOE4 allele on risk of a depression recurrence. RESULTS: Cumulative probability of developing a depression recurrence was higher in APOE4 carriers than non-carriers. Presence of an APOE4 allele remained significantly associated with the incidence of depression recurrence. LIMITATIONS: All patients were treated with one or two different antidepressants, which may have had different effects on patients with MDD. Second, participants in the present study comprised patients with both first and multiple episodes of MDD. Third, we did not have the statistical power to perform a stratified analysis in consideration of heterozygous or homozygous genotypes of APOE4. CONCLUSION: Possession of an APOE4 allele may increase the risk of depression recurrence.

Serum levels and mutual correlations of amyloid ß in patients with depression.

AIM: Epidemiological studies have shown that depression is a risk factor for Alzheimer's disease (AD). Although the biological mechanism underlying the link between depression and AD is unclear, altered amyloid ß (Aß) metabolism in patients with depression has been suggested as a potential mechanism. Results from previous studies of Aß metabolism in patients with depression have been inconsistent, and Aß polymerization, which is a crucial process in AD pathology, has not previously been assessed. METHODS: Serum levels of Aß40, Aß42 and Aß oligomers were evaluated in 104 inpatients with major depressive disorder (MDD) and 132 healthy control individuals. RESULTS: Lower serum Aß42 levels were observed in patients with MDD, but there was no difference in serum Aß oligomer levels between the MDD group and the healthy control group, even in older adults. Interestingly, serum Aß oligomer levels in patients with MDD were dependent on serum Aß42 levels, regardless of age, and this relationship was not observed in the control group. CONCLUSIONS: These results suggest that Aß42 is more prone to aggregation and polymerization in patients with depression than in healthy individuals, suggesting a possible mechanism underlying the transition from depression to AD. Geriatr Gerontol Int 2020; 20: 125-129.

Serum levels of TDP-43 in late-life patients with depressive episode.

BACKGROUND: Recent reports have suggested a relationship between affective disorder including depression and bipolar disorder (BP) and frontotemporal dementia (FTD). TAR DNA binding protein (TDP) -43 is a protein found in the brain and peripheral fluid of patients with FTD. To examine a possible association between affective disorders and FTD, serum levels of TDP-43 were evaluated in late-life patients with major depressive episode (MDE). METHODS: The subjects were 74 late-life (≥50 years old) inpatients with DSM-IV or -5 MDE (58 had major depressive disorders and 16 had BP) and 58 healthy subjects. Patients were recruited from Juntendo Koshigaya Hospital, Saitama, Japan, between January 2005 and May 2017. Serum TDP-43 levels were measured using an ELISA kit. RESULTS: Serum levels of TDP-43 were significantly higher in the MDE group than the control group independent of age and sex. LIMITATIONS: All patients were on antidepressant medication. CONCLUSIONS: Our finding suggests that some depressive patients may be in a prodromal stage of FTD or very-early stage of FTD comorbid with depression.

Increased Serum Levels of α-Synuclein in Patients With Major Depressive Disorder.

OBJECTIVE: Epidemiologic studies have demonstrated that depression is a risk factor for dementia. In particular, dementia with Lewy bodies (DLB) has been noted to be highly relevant to depression. It has been suggested that α-synuclein (α-syn), a major component of Lewy bodies, is related to the onset and progression of DLB. To investigate the relationship between depression and DLB, we compared serum α-syn levels of patients with depression to those of healthy subjects. METHODS: The subjects were 103 inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), or DSM-5 major depressive disorder (MDD) and 132 healthy comparisons. Patients were recruited from Juntendo Koshigaya Hospital, Saitama, Japan, between June 2010 and November 2016. Serum α-syn levels were measured using an enzyme-linked immunosorbent assay kit. Serum α-syn levels were compared using a 2 (age group [<60 years versus ≥60 years]) × 2 (diagnosis [MDD versus comparison]) analysis of variance. RESULTS: There was no significant main effect of age (F = 1.167, df = 1, 231, p = 0.281). There was a significant main effect of diagnosis (F = 44.657, df = 1, 231, p <0.001), with higher α-syn levels in the MDD group versus the healthy comparison group, regardless of age. CONCLUSION: The present results suggest that depression may affect the metabolism of α-syn; there is a possibility that depression is not only a prodromal symptom of DLB but also a causal risk factor for DLB.