Association between Stimulation-Site Pain and Clinical Improvement during Repetitive Transcranial Magnetic Stimulation for Patients with Major Depressive Disorders: A Prospective Observational Study at Two Sites.

INTRODUCTION: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms. METHODS: We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined. RESULTS: Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003). CONCLUSION: This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain.

Clinico-demographic factors associated with the treatment response to cognitive behavioral therapy for insomnia.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) is among the recommended non-pharmacological treatments for patients with insomnia. While there are multiple reports on the effects of CBT-I treatment, few studies evaluating the factors associated with the treatment response to CBT-I have been reported. The present study aimed to confirm the effects of CBT-I in patients with insomnia and to examine the clinico-demographic factors that can predict the outcomes of CBT-I in these patients. METHODS: Overall, 62 patients were included in the present study. To confirm the effectiveness of CBT-I, we compared the pre- and post-CBT-I therapy values of several sleep parameters. Furthermore, to identify the clinico-demographic factors that could be predictive of the treatment response to CBT-I, we performed generalized linear model (GLM) analysis. RESULTS: The values of several sleep parameters were significantly lower after treatment than at baseline. The results of the GLM analysis revealed that sex and occupation were significantly associated with the treatment response to CBT-I. CONCLUSIONS: The present results suggest that several clinico-demographic factors should be considered in the treatment of patients with insomnia.

Actual Clinical Practice Assessment: A Rapid and Easy-to-Use Tool for Evaluating Cognitive Decline Equivalent to Dementia.

Background Screening tests reveal the early signs of cognitive decline, enabling better self-care and preparation for the future. We developed and evaluated the accuracy of a rapid (20 s) and easy-to-use tool called ONSEI, assessing the cognitive decline equivalent to dementia in actual clinical practice by correlating clinical diagnoses with the ONSEI classification. Methods In this retrospective observational study, data were collected from individuals who visited three neurosurgical clinics in neighboring prefectures of Tokyo, Japan. ONSEI analysis was performed using a smartphone or tablet. The tool adopts a machine-learning algorithm using the speaker's age, time-orientation task score, and acoustic features of spoken responses to that task. Significant differences in accuracy, sensitivity, and specificity were evaluated by Fisher's exact test. Results The overall classification accuracy of ONSEI was 98.1% (p<0.001). The sensitivity and specificity were 97.3% (p<0.001) and 98.5% (p<0.001), respectively. The proportion of correct classifications was consistent across different age groups. Conclusion ONSEI showed high classification accuracy for dementia in cognitively normal individuals in actual clinical practice, regardless of the facility at which the tests were conducted or the age of the participants. Thus, ONSEI can be useful for dementia screening and self-care.

Association between the early repolarization pattern and nocturnal suicide attempts.

AIM: Numerous recent reports have highlighted the association between mental disorders and electrocardiographic findings. The early repolarization pattern (ERP) on electrocardiogram has been linked with a history of suicide attempts and attention deficit hyperactivity disorder, and associations with impulsivity have also been reported. It is known that suicidal intent is more common at night. Patients who have a mental disorder and ERP may have a higher likelihood of impulsivity, potentially increasing the risk of suicide at night. METHODS: The subjects were 43 patients with a history of suicide attempts who had undergone electrocardiographic examination at Jikei University School of Medicine Kashiwa Hospital and received intervention from our department. Due to the diurnal variation in electrocardiographic findings, only patients who underwent the examination during the daytime were included. Patients' clinical backgrounds were compared according to the presence or absence of ERP, and the association between nocturnal suicide attempts and ERP was examined using multivariate analysis. RESULTS: The frequency of nocturnal suicidal behavior was 76.2% in patients with ERP and 31.8% in those without ERP, but the difference was not significant after Bonferroni correction. In the multivariate analysis, there was a significant association of ERP with nocturnal suicide attempts (p = 0.018). CONCLUSION: The finding of an association between ERP and nocturnal suicide attempts indicates that ERP is a biological indicator that can predict nocturnal suicide attempts.

Identification of a strong genetic risk factor for major depressive disorder in the human virome.

The heritability of major depressive disorder (MDD) is reportedly 30-50%. However, the genetic basis of its heritability remains unknown. Within SITH-1, a risk factor for MDD in human herpesvirus 6B (HHV-6B), we discovered a gene polymorphism with a large odds ratio for an association with MDD. It was a sequence whose number of repeats was inversely correlated with SITH-1 expression. This number was significantly lower in MDD patients. Rates for 17 or fewer repeats of the sequence were 67.9% for MDD and 28.6% for normal controls, with an odds ratio of 5.28. For patients with 17 or less repeats, the rate for presence of another MDD patient in their families was 47.4%, whereas there were no MDD patients in the families of patients with more than 17 repeats. Since HHV-6B is transmitted primarily mother to child and within families and persists for life, this gene polymorphism could potentially influence heritability of MDD.

Characteristics of patients with anxiety disorder without selective serotonin reuptake inhibitor prescription over a two-year period of pharmacotherapy.

INTRODUCTION: Pharmacotherapy such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors is recommended for the treatment of anxiety disorders. Although there are patients with persisted symptoms of anxiety disorders who are treated with monotherapy of benzodiazepine anxiolytics without SSRIs, the characteristics of these patients are unclear. In the present study, we investigated the characteristics of patients with persisted symptoms of anxiety disorder without SSRI prescription. METHODS: From a prescription dataset covering 2018 and 2020, the prescriptions of 243 patients with anxiety disorder were analyzed. Patients were classified into two groups: SSRI non-prescription and prescription groups. RESULTS: The SSRI non-prescription group had a higher ratio of females than did the SSRI prescription group (60.1% vs. 44.6%, respectively, p = 3.12 × 10-2 ), but statistically not significant after the Bonferroni correction. No significant differences in age, body mass index, or duration of outpatient visits were found between groups. Among the independent variables, sex (female) was the only variable identified that predicted SSRI non-prescription. CONCLUSION: The present study showed that among patients with anxiety disorders, sex (female) was the only variable that predicted SSRI non-prescription.

Disease Progression Patterns of Brain Morphology in Schizophrenia: More Progressed Stages in Treatment Resistance.

BACKGROUND AND HYPOTHESIS: Given the heterogeneity and possible disease progression in schizophrenia, identifying the neurobiological subtypes and progression patterns in each patient may lead to novel biomarkers. Here, we adopted data-driven machine-learning techniques to identify the progression patterns of brain morphological changes in schizophrenia and investigate the association with treatment resistance. STUDY DESIGN: In this cross-sectional multicenter study, we included 177 patients with schizophrenia, characterized by treatment response or resistance, with 3D T1-weighted magnetic resonance imaging. Cortical thickness and subcortical volumes calculated by FreeSurfer were converted into z scores using 73 healthy controls data. The Subtype and Stage Inference (SuStaIn) algorithm was used for unsupervised machine-learning analysis. STUDY RESULTS: SuStaIn identified 3 different subtypes: (1) subcortical volume reduction (SC) type (73 patients), in which volume reduction of subcortical structures occurs first and moderate cortical thinning follows, (2) globus pallidus hypertrophy and cortical thinning (GP-CX) type (42 patients), in which globus pallidus hypertrophy initially occurs followed by progressive cortical thinning, and (3) cortical thinning (pure CX) type (39 patients), in which thinning of the insular and lateral temporal lobe cortices primarily happens. The remaining 23 patients were assigned to baseline stage of progression (no change). SuStaIn also found 84 stages of progression, and treatment-resistant schizophrenia showed significantly more progressed stages than treatment-responsive cases (P = .001). The GP-CX type presented earlier stages than the pure CX type (P = .009). CONCLUSIONS: The brain morphological progressions in schizophrenia can be classified into 3 subtypes, and treatment resistance was associated with more progressed stages, which may suggest a novel biomarker.

Personality Traits Associated with Treatment Choice with an Explicit Statistical Prediction After an Explanation in a Negative Context: A Study in Patients with Glaucoma.

Purpose: Over 50% of patients with early-stage glaucoma discontinue topical therapy within the first 6 months of treatment initiation. This risk of discontinuation could be reduced by how the ophthalmologist explains the treatment plan. Ophthalmologists can explain the treatment plan to patients in either positive or negative contexts. Although explanations in a negative context can be selected depending on the medical situation, identification of patients who will choose the treatment with explicit statistical prediction after an explanation in a negative context is important; personality traits are related to these emotional decisions. Therefore, in the present study, we examined the personality traits associated with choice of treatment with explicit statistical prediction after an explanation in a negative context. Patients and Methods: A total of 147 patients with glaucoma were recruited for this study. The questionnaire booklets used contained positively framed or negatively framed versions of an "Asian disease problem" to enable examination of the influence of the way in which a problem is framed (framing effect) on the participants' decision-making. The Japanese version of the Ten-Item Personality Inventory was used to estimate the personality traits of the participants. Results: Low conscientiousness was identified as the only variable that was strongly predictive of the choice of treatment with explicit statistical prediction (ß = -0.44, z = 2.19, p = 0.03). In addition, while the association was not statistically significant, low neuroticism was found to be weakly predictive of the choice of uncertain treatment (ß = -0.37, z = 1.73, p = 0.08). Conclusion: In conclusion, we showed that low levels of conscientiousness predict the choice of treatment with explicit statistical prediction (ie, topical treatment) for glaucoma after an explanation in a negative context.

Risk factors of frontotemporal dementia compared with Alzheimer disease: Single psychiatric hospital-based research in Japan.

AIM: The objective of this study was to reveal risk factors for incident of frontotemporal dementia (FTD) compared with Alzheimer disease (AD) in Japan. METHOD: Fifty consecutive subjects diagnosed with FTD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) under 75 years old were included retrospectively. As a control group, 48 subjects who were diagnosed with AD according to the DSM-5 and matched by age, sex, educational history, and Mini-Mental State Examination were also included. In order to examine the distinctive risk factors of FTD, we compared the relationship between symptomatologic features, Clinical Dementia Rating, clinical factors, and sociopsychological factors in the two groups. RESULT: Patients with FTD were more likely than patients with AD to have meticulous premorbid personality and less likely to have a history of diabetes than patients with AD. Although the regression analysis was not significant, a history of psychiatric disorders tends to affect the incidence of FTD. CONCLUSIONS: These findings regarding the risk of FTD are expected to lead to early diagnosis and care of FTD. Geriatr Gerontol Int 2023; 23: 932-937.

A Qualitative Study on the Recovery Process and Its Associated Factors in Morita Therapy for Inpatients with Mood Disorders.

Morita therapy (MT) has been re-evaluated and has attracted much attention internationally to date. However, it is not known what kinds of experiences inpatients with mood disorders undergo during the process of recovery through MT. The purpose of this study was therefore to empirically clarify what subjective experiences influence the recovery from depression when it is treated with MT. Patients with mood disorders who were admitted to the Jikei University Center for Morita Therapy were included. Successive assessments of depression were performed using rating scales. Semi-structured interviews were conducted at the time of discharge regarding factors contributing to improvement, and were analyzed using qualitative data analysis methods to identify factors contributing to the recovery from depression among inpatients treated with MT. There were 24 subjects, 19 of whom completed treatment. The completers had significantly lower severity of depression severity upon discharge. Remarkably, qualitative analysis revealed that nine categories of experiences contributed to recovery from depression. In particular, experiences of "isolation bed-resting of MT", "getting stuck in doing things one's way", "identifying maladaptive behavior patterns", "modifying maladaptive behavior patterns", "restoring self-evaluation", and "change in negative emotions" were considered as the key experiences for recovery.

Effectiveness of medical fee revisions for psychotropic polypharmacy in patients with mood disorders in Japan: An interrupted time-series analysis using a nationwide inpatient database.

BACKGROUND: This study aimed to evaluate the effects of medical fee revisions aimed to reduce psychotropic polypharmacy in Japan on the proportion of psychotropic polypharmacy in discharge prescriptions for patients with major depressive disorder (MDD) or bipolar disorder (BD) using a nationwide inpatient database. METHODS: In this retrospective cohort study, we used the Diagnosis Procedure Combination database to identify patients with MDD or BD discharged between April 2012 and March 2021. We targeted medical fee revisions in October 2014, April 2016, and April 2018. The major outcome was the monthly proportion of psychotropic polypharmacy in prescription at discharge using the criteria following the April 2018 revision (antidepressants ≥3, antipsychotics ≥3, anxiolytics ≥3, hypnotics ≥3, or sum of anxiolytics and hypnotics ≥4). We performed interrupted time series analyses to evaluate the changes in level and trend between pre- and post-revisions. RESULTS: We identified 63,289 and 33,780 patients with MDD and BD respectively in the entire study period. In both the patient groups, there were significant decreases in the proportion of psychotropic polypharmacy at revision in October 2014, and no significant trend and level change at revision were observed in April 2016 and April 2018, with a few exceptions. CONCLUSIONS: The medical fee revisions aimed to reduce psychotropic polypharmacy in Japan might have had a limited impact on discharge prescriptions for patients with MDD and BD.

Development of a Daily Living Self-Efficacy Scale for Older Adults in Japan.

OBJECTIVES: Older adults tend to experience decreased enjoyment and fulfillment in life, social interactions, and independent living, with aging. These situations often result in lower levels of daily living self-efficacy in activities, which is one of the factors resulting in a decline in the quality of life (QOL) among older individuals. For this reason, interventions that help maintain daily living self-efficacy among older adults may also help maintain a good QOL. The objective of this study was to develop a daily living self-efficacy scale for the elderly that can be used to evaluate the effects of interventions aimed at enhancing self-efficacy. METHODS: An expert meeting involving specialists in dementia treatment and care was held, to prepare a draft for a daily living self-efficacy scale. In the meeting, previous studies on self-efficacy among older adults, which were collected in advance, were reviewed, and the experiences of the specialists were discussed. Based on the reviews and discussions, a draft of a daily living self-efficacy scale comprising 35 items was prepared. This study on daily living self-efficacy was conducted from January 2021 to October 2021. The internal consistency and concept validity of the scale were evaluated based on the assessment data. RESULTS: The mean age ± standard deviation of the 109 participants was 84.2 ± 7.3 years. The following five factors were extracted based on factor analysis: Factor 1, "Having peace of mind"; Factor 2, "Maintaining healthy routines and social roles"; Factor 3, "Taking personal care of oneself"; Factor 4, "Rising to the challenge"; and Factor 5, "Valuing enjoyment and relationships with others". The Cronbach's alpha coefficient exceeded 0.7, thereby suggesting sufficiently high internal consistency. Covariance structure analysis confirmed sufficiently high concept validity. CONCLUSIONS: The scale developed in this study was confirmed to be sufficiently reliable and valid, and when used during dementia treatment and care to assess the levels of daily living self-efficacy among older adults, it is expected to contribute to the improvement of QOL among older adults.

Prevalence and Clinical Significance of Psychiatric Comorbidities With Gambling Disorder in 12 Clinical Settings in Japan.

OBJECTIVES: This study investigated the occurrence rate of psychiatric disorders comorbid with gambling disorder, and their clinical significance in the severity of gambling disorder using a retrospective cross-sectional design. METHODS: The medical records of 359 patients (men/women, 326/33; median age, 37.0 years) with gambling disorder as the primary disorder from 12 treatment facilities specializing in addiction (9 clinics and 3 hospitals) in Japan were studied. We investigated patients' comorbid psychiatric disorders, demographic and clinical characteristics, and the severity of gambling disorder based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. RESULTS: Of all patients, 58.3% had comorbidities (tobacco use disorder, 20.9%; alcohol use disorder, 13.9%; major depressive disorder, 13.1%; behavioral addictions, 13.1%; attention-deficit hyperactivity disorder, 6.1%; etc.). Statistical analysis indicated that as the number of comorbid psychiatric disorders increased, psychosocial problems also increased (e.g., proportion of adverse childhood experiences [ P < 0.001], and history of suicide attempts [ P = 0.009]). In the multivariable analysis, behavioral addictions ( ß = 0.666; t = 3.151) were significantly associated with gambling disorder severity. Specifically, individuals with gambling disorder comorbid with behavioral addictions including kleptomania, excessive buying, and excessive sex-related behavior may present more severe gambling problems than those without behavioral addictions. CONCLUSIONS: Patients with gambling disorder should be carefully assessed for psychiatric comorbidities and interventions should reflect the individual diagnosis.

Effect of a short video on patients' motivation for dose reduction or cessation of hypnotics.

Recently, addiction to regular doses of hypnotics has become a problem. While many patients report a desire to reduce their dosage, many do not agree with their physicians' suggestions for reduction. In this study, we created an online short video targeting patient motivation to reduce hypnotics usage and examined its efficacy and factors associated with the intention to reduce medication. We created a 10 min video that included "sleep education," "guidance for reducing the use of hypnotics," and "systematic motivation for reducing the use of hypnotics" and posted it on our website. For 1 year, we conducted a questionnaire survey to determine the effectiveness of the video and factors associated with the intention to reduce hypnotics use. Of 4548 viewers, 609 (13.4%) completed the questionnaire, 369 (67.9%) of whom used hypnotics. Most respondents were older adults. The intention to reduce medication use was significantly strengthened after watching the video in 37.7% of medication users (effect size 0.404). In the group that was not inclined toward medication reduction before viewing, 85.2% of patients had stronger intentions to reduce medication use after watching the video (effect size 0.818). "Memorable content about side effects" was extracted as a factor related to reinforcement of the intention to reduce medication use, suggesting that prescribing physicians' descriptions of current insomnia treatment is inadequate in explaining side effects to patients. A short informational video can have beneficial effects on patients' motivation for dose reduction or cessation of hypnotics. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00446-4.

The association between subjective-objective discrepancies in sleep duration and mortality in older men.

A discrepancy in subjective and objective estimations of sleep duration, which often diverge, could have long-term adverse effects on health outcomes in older adults. Using data from 2674 older adult men (≥ 65 years of age) of the Osteoporotic Fractures in Men Sleep Study, we assessed the longitudinal association between misperception index (MI), calculated as MI = (objective sleep duration - subjective sleep duration)/objective sleep duration, and all-cause mortality. During the follow-up with a mean (standard deviation) of 10.8 (4.2) years, 1596 deaths were observed. As a continuous variable, MI showed a linear relationship with all-cause mortality after adjusting for multiple covariates, including polysomnography-measured objective sleep duration [fully adjusted hazard ratio (HR), 0.69; 95% confidence interval [CI], 0.56-0.84]. As a categorical variable, the lowest MI quartile (vs. the interquartile MI range) was associated with increased mortality (fully adjusted HR, 1.28; 95% CI, 1.12-1.46), whereas the highest MI quartile was not associated with mortality (fully adjusted HR, 0.97; 95% CI, 0.85-1.11). The subjective overestimation of sleep duration may be a risk factor for all-cause mortality in older men. Future studies should examine why subjective overestimation of sleep duration is associated with all-cause mortality from a physiological perspective.

Association between functional recovery and medication adherence in schizophrenia.

AIM: Medication adherence is important for achieving functional recovery from schizophrenia and is commonly assessed using the Drug Attitude Inventory-30 (DAI-30). Subscales of the DAI-30, including "awareness of the need for medication," "awareness of the effects of psychiatric drugs," and "impression of medication," have been used to assess medication adherence. To determine which of these subscales are associated with the prognosis of schizophrenia, this study followed patients with schizophrenia to identify the prognosis and examine the subscales related to "recovery." METHODS: In total, 89 patients were recruited, 78 of whom were registered in the study. After assessing adherence using the DAI-30, Positive and Negative Syndrome Scale and Global Assessment of Functioning scores were assessed at 0 and 24 week to define the functional prognosis. RESULTS: At the end of the 24-week follow-up period, 36% of patients showed recovery from schizophrenia. A comparison of subscales revealed that the score for "impression of medication" was significantly higher in the recovery than in the non-recovery group. Logistic regression analysis identified only the "impression of medication" score as being predictive of recovery. CONCLUSION: The results indicated that among the three DAI-30 subscales, "impression of medication" was the most closely associated with recovery in patients with schizophrenia.

Pathogenesis and Personalized Interventions for Pharmacological Treatment-Resistant Neuropsychiatric Symptoms in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia, with cognitive impairment as a core symptom. Neuropsychiatric symptoms (NPSs) also occur as non-cognitive symptoms during the disease course, worsening the prognosis. Recent treatment guidelines for NPSs have recommended non-pharmacological treatments as the first line of therapy, followed by pharmacological treatments. However, pharmacological treatment for urgent NPSs can be difficult because of a lack of efficacy or an intolerance, requiring multiple changes in psychotropic prescriptions. One biological factor that might be partly responsible for this difficulty is structural deterioration in elderly people with dementia, which may cause a functional vulnerability affecting the pharmacological response. Other causative factors might include awkward psychosocial interpersonal relations between patients and their caregiver, resulting in distressful vicious circles. Overlapping NPS sub-symptoms can also blur the prioritization of targeted symptoms. Furthermore, consistent neurocognitive reductions cause a primary apathy state and a secondary distorted ideation or perception of present objects, leading to reactions that cannot be treated pharmacologically. The present review defines treatment-resistant NPSs in AD; it may be necessary and helpful for clinicians to discuss the pathogenesis and comprehensive solutions based on three major hypothetical pathophysiological viewpoints: (1) biology, (2) psychosociology, and (3) neurocognition.

Association between personality traits and experience of adverse periocular reactions to topical prostaglandin analogues.

BACKGROUND: Aesthetically unappealing adverse periocular reactions to prostaglandin (PG) eye-drops are a major challenge in glaucoma treatment. This study analysed the personality traits of patients with glaucoma based on a five-factor model and examined the associations between these factors and adverse periocular reactions. METHODS: One hundred and forty-seven patients with glaucoma were surveyed anonymously regarding their personality traits and how often adverse periocular reactions were experienced. RESULTS: The analysis included 117 valid responses (71 men and 46 women, age: 61.9±11.5 years). Patients who experienced hypertrichosis of the eyelashes scored significantly higher on extraversion (p<0.05), with no significant differences in the other four personality traits. Patients who experienced eyelid hyperpigmentation and deepening of the upper eyelid sulcus showed no significant differences in any of the personality traits. Younger patients scored significantly higher on hypertrichosis (p<0.05). CONCLUSION: The experience of adverse reactions differed according to patient age and personality traits. Therefore, eye-drops should be chosen based on these factors. TRIAL REGISTRATION NUMBER: UMIN000035155.