Hirofumi Hirakawa

Introduction: Affective temperaments are stable, biologically based traits that may represent subclinical manifestations or premorbid phenotypes of mood disorders. The thalamus is increasingly recognized as an active component of distributed neural networks involved in cognition, emotion, and behavioral regulation. We focused on the thalamus and conducted an exploratory analysis of the associations between affective temperaments and the volumes of thalamic nuclei in healthy participants. Method: This study included 43 healthy right-handed participants. Affective temperament was assessed using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire. T1-weighted structural magnetic resonance imaging data were acquired using a 3T scanner and processed with FreeSurfer version 7.1.1 to obtain the estimated total intracranial volume (eTIV) and the volumes of 52 thalamic regions, comprising 25 bilateral thalamic nuclei and the bilateral whole thalamus. The primary analyses were partial Spearman correlations adjusted for age, sex, and eTIV. Given that 52 thalamic regions and five affective temperaments were examined, Bonferroni correction was applied to control the family-wise error rate for multiple comparisons. Statistical significance was defined as a Bonferroni-corrected threshold of P < 0.00019 (0.05/[52 × 5]). Additional analyses adjusted for age, sex, and ipsilateral whole thalamus volume were performed as sensitivity analyses. Results: In the primary analysis, higher cyclothymic temperament scores were significantly associated with smaller left paratenial nucleus (Pt) volume (partial ρ = -0.57, P = 0.00015, 95% CI [-0.72, -0.36]). In the sensitivity analysis adjusting for age, sex, and left whole thalamus volume, the association was attenuated (partial ρ = -0.42, P = 0.007, 95% CI [-0.62, -0.17]) and did not meet the Bonferroni-corrected significance threshold. None of the other affective temperaments were significantly associated with left Pt volume. Several other associations of comparable magnitude were observed, but none met the corrected threshold. Discussion: Higher cyclothymic temperament scores were associated with smaller left Pt volume in the primary analysis. However, the association only narrowly met the corrected significance threshold and was attenuated in the sensitivity analysis. Thus, its regional specificity and statistical robustness remain uncertain, and replication in larger independent samples is warranted.

Introduction: Bright light therapy (BLT) is an effective treatment for mood disorders. We previously reported that four weeks of bright light (BL) exposure in patients with mood disorders led to increased volume of the left dentate gyrus (DG). We propose a novel hypothesis that the extent of light-induced volumetric increase in the left DG may be influenced by individual genetic variation in the OPN4 gene, especially rs1079610. This exploratory study aimed to test this hypothesis. Methods: We recontacted 21 patients with mood disorders who had previously participated in a 4-week, randomized controlled trial comparing BL (10,000 lux) and dim light (DL; 50 lux). All participants underwent magnetic resonance imaging and ¹⁸ F-fluorodeoxyglucose (FDG) positron emission tomography at baseline and after 4 weeks of light exposure. Blood samples were collected for genotyping of two Single-Nucleotide Polymorphisms (SNPs) in OPN4 (rs1079610 and rs2675703), which are expressed in intrinsically photosensitive retinal ganglion cells. The primary outcome was the main effect of the rs1079610 genotype for percentage change volume (%ΔV) of the left DG. Analysis of covariance was conducted using a general linear model. Results: The final sample size was 21 (BL group, n = 11; DL group, n = 10). A significant main effect of rs1079610 genotype (C allele carriers versus TT) was observed (F (1,17) = 7.16, P = 0.016, partial η ² = 0.3). Sensitivity analyses were performed with sequential adjustment for potential confounders. The association between rs1079610 genotype and %ΔV of the left DG remained statistically significant after adjustment for age, sex, baseline left DG volume, and diagnosis (F (1,13) = 4.8, P = 0.047, partial η ² = 0.27). Discussion: The findings of this study suggest that rs1079610 in OPN4 might be a potential SNP that affects volumetric change in the left DG following light therapy in mood disorders.

Introduction: Environmental light is associated with the presence of depressive symptoms in healthy individuals, major depression, and postpartum depression. We hypothesized that women for delivery assigned to window-side beds (window-side group: WG) may exhibit lower levels of depressive symptoms at discharge than those assigned to corridor-side beds (corridor-side group: CG). Methods: This retrospective study involved postpartum women who were hospitalized for delivery in the obstetric ward of Oita University Hospital. We analyzed data of the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS) assessed within approximately 1 week after delivery (within 7-days EPDS) and at an outpatient visit approximately 1 month after delivery (1-month EPDS). Analysis of covariance and binomial logistic regression analyses were conducted to evaluate between-group differences in EPDS scores and in the proportion of participants with EPDS scores of 9 or higher adjusting for relevant covariates. Pearson’s correlation analysis was used to assess the relationship between within 7-days and 1-month EPDS scores. Results: A significant between-group difference was observed for within 7-day EPDS scores, with mean scores of 3.4 and 5.0 in the WG and CG, respectively. In the binomial logistic regression analysis of within 7-days EPDS, bed location and cesarean delivery were significant in the final model. No significant between-group difference was observed in 1-month EPDS. A significant positive correlation was observed between the within 7-days and 1-month EPDS scores. Discussion: These findings suggest that increasing exposure to ambient light during hospitalization for delivery may help reduce depressive symptoms.

Background and Objectives The efficacy and safety of lemborexant, a dual orexin receptor antagonist, for treating insomnia associated with depressive episodes remain unclear. This pilot study aimed to evaluate the changes in clinical symptoms following the initiation of lemborexant treatment and its safety in patients with insomnia comorbid with depressive episodes. Methods The inclusion criteria for this multicenter, prospective, interventional, open-label pilot study conducted in Japan were adults (≥ 18 years) diagnosed with insomnia and either major depressive disorder (MDD) or bipolar disorder (BD) according to DSM-5, receiving treatment for a depressive episode for ≥ 4 weeks, and having a baseline Hamilton Depression Rating Scale (HAM-D-17) score of ≥ 8. Patients were classified into four cohorts on the basis of their MDD or BD diagnosis and concomitant insomnia medication use (lemborexant add-on or monotherapy). After a 2-week lead-in period with unchanged prior medications for insomnia MDD or BD, 12-week lemborexant treatment was administered. The primary endpoint was the change from baseline in the Insomnia Severity Index (ISI) total score at week 4, which was analyzed using paired t-tests with a two-sided significance level of 5%. For other endpoints, summary statistics and 95% confidence intervals (CIs) for observed values and changes from baseline were calculated by cohort. Safety outcomes included the evaluation of the safety and tolerability of lemborexant during the treatment period. Results A total of 83 patients with comorbid insomnia and depressive episodes were enrolled (MDD add-on cohort, n = 29; MDD monotherapy, n = 23; BD add-on, n = 16; and BD monotherapy, n = 15). The average age was 47.2 years and 64.6% were female. Mean baseline ISI total score (SD) was 14.5 (4.8), 13.2 (5.5), 13.5 (6.0), and 11.8 (4.6), respectively. At week 4, mean change from baseline in the ISI total score [95% CI, p-value] was − 2.3 [− 3.9, − 0.7, p = 0.0065], − 3.2 [− 5.0, − 1.3, p = 0.0018], − 5.2 [− 7.9, − 2.5, p = 0.0012], − 4.5 [− 6.3, − 2.6, p = 0.0001], respectively. Improvements were sustained through week 12. Sleep diary measures such as sleep onset latency and total sleep time improved in some cohorts, but the results were inconsistent. Mean baseline HAM-D-17 scores were 13.6 (5.1), 12.6 (5.1), 13.9 (4.3), and 11.4 (3.4), respectively, with mean changes at week 12 of − 6.4 [− 7.8, − 4.9], − 6.2 [− 7.7, − 4.6], − 5.2 [− 8.4, − 2.1], and − 5.4 [− 7.2, − 3.5], respectively. No serious treatment-emergent adverse events (TEAEs) were reported, with TEAE incidence ranging from 30% to 40%, all mild to moderate in severity. Somnolence was the most common adverse reaction, reported in 10.3–25.0% of cohorts except BD monotherapy. Nightmare followed, occurring in 4.3–12.5% across cohorts. Conclusions Lemborexant was associated with improvements in insomnia severity and depressive symptoms related to MDD or BD, with no new safety concerns. It may be a treatment option for residual insomnia following treatment for depression associated with MDD or BD, though somnolence and nightmares warrant attention. Confirmatory studies are needed to establish its therapeutic value. Study Registration Japan registry of clinical trials (jRCTs071220037; registered on 4 August 2022)

High fish consumption has been associated with a reduced risk of depression. In this study, we examined the association between the frequency of blue fish intake of healthy participants and ¹⁸F-fluorodeoxyglucose (FDG) uptake using positron-emission tomography (PET). Data were extracted from a questionnaire on the frequency of blue fish intake, clinical assessments of depression using the Beck Depression Inventory (BDI), and ¹⁸F-FDG PET images. Sixty-two participants were grouped based on the frequency of blue fish consumption: more than 2 or 3 days per week (frequent intake group; F-Fish group) and once per week or less (infrequent intake group; IF-Fish group). A two-sample t-test and chi-square test were used for continuous and categorical variables, respectively. Furthermore, a two-sample t-test was performed to assess the difference in ¹⁸F-FDG uptake between the F-Fish group and the IF-Fish group using Statistical Parametric Mapping 12. The F-Fish group exhibited significantly lower BDI scores than the IF-Fish group. Whole-brain analysis revealed a cluster with significantly lower ¹⁸F-FDG uptake in the right cerebellum VI in the F-Fish group than in the IF-Fish group. In conclusion, the frequency of blue fish consumption is associated with the function of the right cerebellum VI. Further studies are warranted to clarify the mechanism underlying the preventive effect of blue fish consumption on depression.

Background: It is unknown whether light preference (brightness or darkness) is associated with Cloninger’s temperament and character traits. This study examined the association between Cloninger’s temperament, character, and light preference in healthy individuals. The aim of the present study was to investigate the hypotheses that self-transcendence but not self-directedness may be associated with brightness preference, whereas harm avoidance may be associated with darkness preference.Methods: Data from 130 healthy participants were analyzed in an opt-out study. First, the data distribution of temperament and character scores was investigated by Shapiro-Wilk test. If the distribution was not normal, we used non-parametric test to compare temperament and character scores based on light preference (brightness or darkness), morning light exposure (yes or no), and bedtime mobile phone use (yes or no). Second, binomial logistic regression analyses were performed for each temperament and character scores as dependent variables in which the subjects were divided into two groups using median as a cut-off point (less than median = 0, equal to or more than median = 1), with age, sex, light preference, morning light exposure, and bedtime mobile phone use as independent variables.Results: Self-directedness was significantly associated with brightness preference and no bedtime mobile phone use. Our hypotheses were not supported.Conclusions: The present findings suggest that self-directedness may be associated with brightness preference and no bedtime mobile phone use. Further studies are required to determine the causal relationships.

Background: Professional choice is an important aspect of one’s life and is associated with biopsychosocial and economic factors. Medical and co-medical professional choices may involve a noble intention to contribute to patients. Thus, this study aimed to investigate the association between medical and co-medical professional choices and affective temperament, parental bonding, and intelligence.Methods: The dataset included 130 individuals (19 with medical or co-medical professional choices and 111 without). Data on participants’ demographics, intelligence levels, affective temperament, and parental bonding were collected and subsequently compared among the two groups using an unpaired t-test and χ² test. Thereafter, binomial logistic regression analysis using the likelihood ratio and forward method was performed, with medical or co-medical professional choice as the dependent variable and potentially significant variables (p < 0.2) in the above t-test or χ² test as independent variables.Results: Only higher paternal care was significantly associated with medical and co-medical professional choices.Conclusion: Our study findings suggest that paternal care is associated with medical or co-medical professional choices. Further prospective studies are required to determine causal relationships and investigate other factors related to such choices, given the non-association of all other variables in the study.