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Electroconvulsive therapy (ECT) is a widely used treatment for bipolar depression; however, evidence of its effectiveness is not sufficient. This study therefore aimed to evaluate whether early ECT is associated with reduced length of hospital stay.In this retrospective cohort study using the Japanese Diagnosis Procedure Combination database, we identified patients admitted for bipolar depression between April 2010 and March 2018. The primary outcome was length of hospital stay, and the secondary outcome was clinical outcomes and total hospitalization costs. Propensity score-matched analyses were performed to compare the outcomes between patients who received ECT within 8 days of admission (early ECT group) and those who did not (control group).We identified 5941 eligible patients, comprising 219 in the early ECT group and 5722 in the control group. After 1:4 propensity score matching, patients in the early ECT group had significantly shorter lengths of hospital stay than those in the control group (53 days in the early ECT group and 73 days in the control group; difference: -20.2 days; 95 % confidence interval: -29.2 to -11.2 days). There was no significant difference in total hospitalization costs between the two groups. In-hospital mortality and fatal complications were rare in both groups. The result was similar in the sensitivity analysis using inverse probability of treatment weighting.Our study was limited by retrospective design and the possibility of unmeasured confounders.Early ECT was associated with reduced length of hospital stay without increasing total hospitalization costs in patients with bipolar depression.

Background: It is important to make accurate clinical diagnosis of frontotemporal lobar degeneration (FTLD), which in turn, leads to future therapic approaches. The FTLD cases are frequently inaccurately identified, but the frequency of this misidentification according to the underlying pathological subtypes is still unclear. Objective: We aimed to quantify the accuracy of behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) diagnoses by both the patients’ referring physicians and hospital expert psychiatrists, and we investigated whether the physicians’ and psychiatrists’ diagnostic patterns are associated with a specific neuropathology. Methods: We retrospectively analyzed the cases of a series of Japanese patients with pathologically diagnosed FTLD (n = 55): the bvFTD group (n = 47) consisted of patients with FTLD-tau (n = 20), FTLD-TDP (TAR DNA-binding protein of 43-kDA) (n = 19), and FTLD-FUS (fused in sarcoma) (n = 8). The svPPA patients (n = 8) all had FTLD-TDP. Results: Only 31% of the patients’ referring physicians mentioned FTD syndrome. The referring psychiatrists and neurologists showed similar diagnostic accuracy. High diagnostic accuracy was observed for the TDP pathology group (mainly svPPA patients). The FTLD-FUS patients were more likely to be diagnosed as having a psychiatric disorder by referring physicians. The hospital expert psychiatrists’ accuracy for identifying FTLD-tau pathology was low. Conclusion: The results of our analyses revealed a specific diagnostic pattern associated with particular FTLD pathological subtypes, which will help to improve non-specialists’ diagnostic ability.

We examined differences in the severity of neuropsychiatric symptom (NPS) subsyndromes according to education level among patients with amnestic-mild cognitive impairment (a-MCI) with the aim of identifying patient demographics related to NPS subsyndromes.Overall, 140 patients with a-MCI were included. We divided the patients into three groups according to their educational level (primary education, middle education, and high education) and compared their demographics. To explore the severity of NPS subsyndromes according to educational level, we used the Neuropsychiatric Inventory (NPI) after adjustments for the Mini-Mental State Examination (MMSE) score. Finally, NPS subsyndromes that were identified as being related to educational level were further explored using a general linear model (GLM).Significant differences in several demographics were observed among the three groups. Among the NPS subsyndromes, the scores for aggressiveness were significantly higher in the primary and high education groups than in the middle education group, while the apathy/eating problem scores were significantly higher in the primary education group than in the other groups. The GLM analyses showed that aggressiveness was related to marital status and the Zarit Caregiver Burden Interview (ZBI-J) score, while apathy/eating problems were related to the instrumental activities of daily living (IADL) percentage, the ZBI-J score, and the education level in years.Among NPS subsyndromes, aggressiveness and apathy/eating problems differed according to education level in patients with a-MCI. A GLM analysis suggested that not only education level, but also various other factors should be considered when determining the need for NPS interventions.

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.

Given the heterogeneity and possible disease progression in schizophrenia, identifying the neurobiological subtypes and progression patterns in each patient may lead to the development of clinically useful biomarkers. In this cross-sectional study, we adopted data-driven machine-learning techniques to classify and stage the progression patterns of brain morphological changes in schizophrenia and investigate the association with treatment resistance. We included 177 patients with schizophrenia, characterized by treatment response or resistance, with 3D T1-weighted magnetic resonance imaging from 3 institutions. 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 classification and staging. As a result, SuStaIn identified three different subtypes: 1) subcortical volume reduction (SC) type (73 patients, 47.4%), 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, 27.3%), in which globus pallidus hypertrophy initially occurs followed by progressive cortical thinning, 3) cortical thinning (pure CX) type (39 patients, 25.3%), 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 of progression than treatment-responsive cases (p=0.001). The GP-CX type presented in earlier stages than the pure CX type (p=0.009). In conclusion, the brain morphological progressions in schizophrenia can be classified into three subtypes by SuStaIn algorithm. Treatment resistance was associated with more progressed stages of the disease, which may suggest a novel biomarker for schizophrenia.

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.

An 84-year-old woman who had been diagnosed as having dementia with Lewy body (DLB) upon initial examination exhibited cognitive impairments and person delusional misidentification (DMS): she transiently claimed that her spouse was a stranger. She was re-examined at the age of 89 years; her frequency of speech and activities of daily living had both decreased, leading to verbal communication difficulties complicated by sensory aphasia, and brain diffusion-weighted (DW) magnetic resonance imaging (MRI) showed cortical hyperintensities in some areas of both hemispheres. About 4 months later, the DW high-intensity areas were observed to have expanded into diffuse cortical areas. While the clinical features of Creutzfeldt Jakob disease (CJD) (myoclonus; ataxia; parkinsonism; rapidly progressive cognitive impairments; periodic sharp discharges on electroencephalograms) were not observed, a genetic analysis of the prion protein (PRNP) gene, which was performed because of a family history of dementia, revealed a V180I mutation (heterozygosis: valine/isoleucine) suggesting genetic CJD (g-CJD). Her activity progressively decreased, reaching akinetic mutism about 11 months after the re-examination. Finally, she suffered from severe bedsores and died from aspiration pneumonia at the age of 90 years. The present report describes the first case of person DMS as an initial neuropsychiatric symptom for V180I g-CJD; the typical long-term clinical symptoms of CJD were not observed in this patient. The inclusion of person DMS as an initial clinical symptom and the presence of expansive cortical hyperintensity areas may be useful for clinicians attempting to diagnosis V180I g-CJD in patients with elusive symptoms.

Introduction: Repetitive transcranial magnetic stimulation (rTMS) has been employed worldwide for therapy-resistant depression. The Food and Drug Administration has approved a number of therapeutic devices for treating major depressive disorder; however, no studies have examined the differences in efficacy and acceptability among commercially available stimulation devices. The aim of our study was to compare the efficacy and acceptability of 3 stimulation devices (NeuroStar, MagPro, and Magstim) for depressive disorders. Methods: Our study included 31 randomized sham-controlled trials of high-frequency rTMS included in the network meta-analysis by Brunoni. We calculated the risk ratio and 95% confidence intervals, comparing each device with sham for the endpoints of response rate, remission rate, and all-cause discontinuation. We then analyzed the differences among the devices in effect size for those endpoints. Results: After determining the effect sizes for the endpoints, we found no statistically significant subgroup differences in the response rates, all-cause discontinuation, or remission rates among the devices (p = 0.12, p = 0.84, and p = 0.07, respectively). Conclusion: Our results suggest similar efficacy and acceptability for the 3 stimulation devices. Future studies need to perform head-to-head comparisons of the efficacy and acceptability of the stimulation devices for treating depression using the same stimulation protocols.

Aims Patients with severe behavioral and psychological symptoms of dementia (BPSD) are often admitted to mental hospitals, while, inpatient care could also lead to prolonged hospital stay. The present study aims to survey clinical profiles of patients who required inpatient treatment for BPSD, and then establish the criteria for introducing inpatient treatment through assessment by certified psychiatrists. Methods We performed a prospective survey about clinical characteristics of people with dementia who required treatment of BPSD at 12 mental medical institutions. All patients were assessed by certified psychiatrists to determine the optimal treatment settings: outpatient or inpatient. The multivariate logistic regression analysis was performed to specify factors contributed to the judgement of clinicians. Subsequently, the receiver operating characteristic curve analysis was conducted to explore a score derived from the Neuropsychiatric Inventory to divide patients into outpatient or inpatient groups. Results The present study included 386 patients, of which 242 were admitted to mental hospitals. BPSD were classified into four domains, and aggressive BPSD was significantly associated with assessment for inpatient treatment; the adjusted odds ratio was approximately 2 regardless of dementia severity. Furthermore, the composite score of agitation, irritability and aberrant behavior showed the highest area under the curve value (=0.706), which differentiated inpatients from outpatients with a sensitivity of 76% and a specificity of 54%. Conclusions Aggressive BPSD was the risk factor for inpatient treatment. The composite score of the Neuropsychiatric Inventory subdomain-related aggressive BPSD could be a screening tool to introduce inpatient treatment for BPSD. Geriatr Gerontol Int 2021; 21: 825-829.

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.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.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 [P0.001], and history of suicide attempts [P = 0.009]). In the multivariable analysis, behavioral addictions (β = 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.Patients with gambling disorder should be carefully assessed for psychiatric comorbidities and interventions should reflect the individual diagnosis.

Patients with major depressive disorder (MDD) exhibit several clinical symptoms including difficulties in flexible thinking. Flexible thinking mainly relies on a cognitive ability called shifting; however, the mechanisms underlying shifting in patients with MDD have not yet been clarified. Therefore, we conducted a preliminary intervention study to clarify the association between depression and shifting ability. We examined the hemodynamic responses in the frontal regions during the shifting task using functional near-infrared spectroscopy (fNIRS) in 21 patients with MDD who were treated using high-frequency repetitive transcranial magnetic stimulation (rTMS). Behavioral performance on the shifting task did not change between pre- and posttreatments, whereas patients who responded well to rTMS treatment showed a significant decrease in hemodynamic responses posttreatment. On the other hand, the poor responders did not show significant changes in the hemodynamic responses between pre- and posttreatments. These results suggest that the good responders were successfully remedied with rTMS treatment and did not need effortful activity in frontal regions for shifting, which made their brain activity more efficient.

Background: Behavioral and psychological symptoms of dementia (BPSD) cause a heavy burden for both patient and caregivers. These symptoms are diverse, and their mechanism is still unclear. Agitation is the most common and difficult to treat among BPSD. In recent years, while changes in DNA methylation levels have been receiving attention as a biomarker of aging and dementia, associations with BPSD have not been examined. Objective: Focusing on agitation, the objective of the present study was to identify a region where changes in DNA methylation levels are associated with agitation. Methods: Using genome-wide DNA methylation analysis data for 7 dementia subjects with agitation, 5 dementia subjects without agitation, and 4 normal elderly controls, we determined a signaling pathway in the WNT5A gene promoter region to be associated with agitation. Based on this result, we measured DNA methylation levels in this region for 26 dementia subjects with agitation and 82 dementia subjects without agitation by means of methylation-sensitive high-resolution melting (MS-HRM) analysis. Results: The WNT5A DNA methylation level in dementia subjects with agitation was significantly lower than in those without agitation (p = 0.001). Changes in WNT5A DNA methylation levels were not influenced by age, sex, body mass index, APOE ɛ4, medication, or inflammatory cytokines. Conclusion: Our results suggested an association of agitation with Wnt signaling, in particular with changes in WNT5A DNA methylation levels, which could be a potentially useful biomarker for predicting the appearance of agitation. It may contribute to the elucidation of the mechanism of BPSD.

Introduction There is evidence for a mismatch between subjective and objective sleep durations not only in individuals with insomnia but also in healthy individuals . However, it is unclear how such discrepancy impacts long-term health outcomes. This study investigated whether and how the discrepancy between subjective and objective sleep duration affected all-cause mortality in a sample of community-dwelling older adult men, aged ≥ 65 years. Methods We conducted a secondary analysis of data obtained via the Osteoporotic Fractures in Men Sleep Study, a community-based, longitudinal, observational, and multicenter study. We included data from 2,674 individuals who underwent an in-home polysomnography, completed morning surveys to assess subjective sleep duration during the polysomnography, and for whom survival or death data were available. 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. MI was treated as both a continuous and categorical predictor: the lowest (≤ -0.19; the overestimation of sleep duration) and highest MI quartiles (> 0.08; the underestimation of sleep duration) were compared to the interquartile range of MI (-0.19 Results During the follow-up with a mean (standard deviation) of 10.8 (4.2) years, 1,596 deaths (59.7%) were observed. As a continuous variable, MI showed a negative association 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). Conclusion The subjective overestimation (“reverse” misperception) of sleep duration, may be a risk factor for all-cause mortality in older men. Further investigations are needed to examine physiological mechanisms through which subjective overestimation of sleep duration leads to negative long-term health outcomes. Support (if any) This work was supported by the Ministry of Health, Labor and Welfare, Government of Japan (Grant numbers #19FA1009 and #21FA1002).

Aim Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the aggregation of amyloid-β and phosphorylated tau proteins. Magnetic resonance imaging (MRI) is a useful means of detecting hippocampal atrophy. However, instead of visual inspection, objective and time-saving tools for automated region of interest (ROI) analysis are needed. Advances in MRI segmentation techniques have enabled a multi-atlas approach with fewer errors than a conventional single-atlas approach. To support the clinical application of multi-atlas segmentation, an automated ROI analytic application consisting of multi-atlas segmentation with joint label fusion and corrective learning was developed: T-Proto. In the present study, we evaluated the inter-method reliability between T-Proto and a reference ROI analytic software, FreeSurfer. Methods This was a database study. MRI data from 30 patients with AD were selected, and the inter-method reliability was assessed in terms of the intra-class correlation coefficient (ICC). A post-hoc comparison according to the severity of AD was also performed. Results Almost all the regional volumes estimated with T-Proto were smaller than those estimated with FreeSurfer. The regional ICC values between the two methods showed moderate to excellent reliability. A post-hoc comparison revealed a similar t-value and effect size between both methods for the hippocampus. Conclusion In the present study, we showed that automated regional analysis using T-Proto was reliable in the hippocampus in terms of ICC, compared with FreeSurfer.

Objectives: We examined the clinicodemographic and psychosocial factors that relate to the presentation and severity of delusions of theft among female patients with amnestic mild cognitive impairment (a-MCI) and Alzheimer's disease (AD).Methods: We enrolled a total of 177 female patients with a-MCI or AD, of whom 40 presented with delusions of theft. We compared the differences in clinicodemographic and psychosocial factors of the 40 patients (delusions of theft group) with 50 age- and Mini-Mental State Examination (MMSE)-matched controls without delusions (control group). Furthermore, we identified the factors associated with the presentation of delusions of theft using a general linear model (GLM). The severity of delusions of theft was calculated using the Neuropsychiatric Inventory Questionnaire, and correlations between the clinicodemographic and psychosocial factors were examined.Results: Between the two groups, the delusions of theft group had lower scores on the Physical Self-Maintenance Scale and instrumental activities of daily living (IADL) and higher scores on the Japanese version of the Zarit Caregiver Burden Interview (ZBI-J) than the control group. GLM analysis revealed that the IADL score was related to the presentation of delusions of theft. The severity of delusions of theft correlated with the MMSE and the ZBI-J scores in the delusions of theft group.Conclusions: The two groups had several differences regarding clinicodemographic and psychosocial factors. Furthermore, lower IADL scores were related to symptom presentation. Symptom severity correlated with cognitive functioning and caregiver burden.Clinical Implications: In the determination of treatment or care, differences in these factors should be considered.

Alzheimer's disease (AD) is a neurodegenerative disease characterised by neurocognitive impairments, especially memory impairment, as core symptoms linked to reductions in activities of daily life. As marginal symptoms, neuropsychiatric symptoms (NPSs) appear during the progressive course of the disease. A lack of self-awareness (anosognosia) of cognitive and functional impairments is often seen in patients with AD, and associations between anosognosia and other NPSs have been previously reported. To account for anosognosia pathogenesis neurocognitively, the cognitive awareness model (CAM) has been helpful for explaining the stream of events from sensory input to behavioural/affective and metacognitive outputs. According to CAM, there are three types of anosognosia: (i) primary anosognosia, (ii) executive anosognosia, and (iii) mnemonic anosognosia. These types of anosognosia are generated from different neurocognitive modulations leading to metacognitive outputs or behavioural/affective regulations. Primary anosognosia is considered to be caused by deficits in the metacognitive awareness system (MAS). While preserved MAS function is associated with milder depression and anxiety in AD, a severer depressive mood in patients with mild AD can inversely cause self-underestimation. The modulation of executive anosognosia is thought to be associated with dangerous/disinhibition behaviours and apathy among NPS sub-symptoms, via impairments of comparator mechanism (Cm) within the central executive system. Other neurobehavioral reactions linked to self-awareness include 'denying' and 'confabulation', and each of these reactions is thought to be affected by the MAS and a Cm. Denial of one's own memory impairments appears as a defensive reaction to protect against dysphoric feelings, and the confabulatory comment is instantly reaction constructed by fabrications according to misinterpretations of memory information about oneself. Similarly, the innovative development of a theoretical model (CAM) has contributed to explaining the mechanism of anosognosia and some neurobehavioral outputs from a neurocognitive perspective.

Objectives: Major depression is a highly prevalent disorder that causes economic burden in office workers. We conducted a randomized, double-blind, sham-controlled trial to evaluate the efficacy and safety of deep transcranial magnetic stimulation (dTMS) in office workers with treatment-resistant depression. Methods: In this study, we randomized office workers taking administrative leave for treatment-resistant major depressive disorder or bipolar disorder with current major depressive episode. dTMS treatment was applied at 120% resting motor threshold with 18 Hz over the left dorsolateral prefrontal cortex. The treatment sessions delivered a total of 1,980 pulses a day, 5 days a week, for 4–6 weeks. The primary outcome was change in the total score on the 21-item Hamilton Depression Rating Scale (HDRS-21) from baseline to the end of study in an intent-to-treat analysis. The secondary outcomes were the response and remission rates. We also assessed changes in cognitive function and adverse events. Results: Forty patients were randomized to active or sham dTMS groups (1:1). The change in the total score on the HDRS-21 was more significantly improved in the active group than in the sham group at 6 weeks (p = 0.045). There were no significant differences in the response and remission rates or cognitive measures between the active and sham groups. No serious adverse events were observed in either group. Conclusions: These results suggest that dTMS might be effective and safe in office workers with treatment-resistant depression. Further well-designed studies are needed.

BackgroundAesthetically 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.MethodsOne hundred and forty-seven patients with glaucoma were surveyed anonymously regarding their personality traits and how often adverse periocular reactions were experienced.ResultsThe 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 (pConclusionThe experience of adverse reactions differed according to patient age and personality traits. Therefore, eye-drops should be chosen based on these factors.Trial registration numberUMIN000035155.

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.

The factors associated with the clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) in patients with major depressive disorder (MDD) remain largely unexplored. Therefore, this study aimed to examine whether rTMS can change the functional laterality of the prefrontal hemodynamic response and whether baseline functional laterality can predict the clinical outcomes of rTMS using functional near-infrared spectroscopy (fNIRS). We included 19 patients with MDD who were treated with high-frequency rTMS. The verbal fluency task was used as the activation task. We calculated the laterality index (LI) based on the task-related oxygenation response in the frontal region. First, the LI was compared before and after rTMS treatment. Second, the reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) score was compared between the rightward dominance group (pre-LI0) and the leftward dominance group (pre-LI ≥ 0). The findings showed a significant change in the LI after rTMS treatment. The rightward dominance group had a significantly greater reduction in MADRS score than the leftward dominance group. Subsequently, the laterality of the task-related hemodynamic response of the prefrontal region shifted leftward following left high-frequency rTMS treatment. Thus, the pre-LI calculated using fNIRS data is a possible predictor of rTMS outcomes in patients with MDD.

There is strong evidence for an association between major depressive disorder (MDD) and inflammation. However, some studies have not observed an increase in inflammatory cytokines in MDD, and the mechanism behind this is unknown. In the present study, we evaluated MDD severity using the Montgomery–Åsberg Depression Rating Scale (MADRS) and quantified mRNA levels of the blood inflammatory cytokines interleukin (IL) 1β, IL-6 and tumor necrosis factor alpha (TNF-α), as well as negative regulators of cytokine signaling—comprising IL-10, IL-1RA, SOCS1, SOCS2 and SOCS3—in MDD patients (n = 36), with a focus on mild MDD, and normal controls (NC, n = 30). We also measured the serum levels of IL-1β and IL-6. Neither the blood mRNA nor the protein levels of inflammatory cytokines were significantly elevated in the MDD group compared with the NC group. However, we observed significant decreases in SOCS1, SOCS2 and SOCS3 mRNA in the MDD group compared to the NC group. A significant finding was a decrease in SOCS3 mRNA after remission from MDD, suggesting that SOCS3 is a trait marker in depressive symptoms. We consider that our findings would be useful in elucidating the pathophysiological mechanism of depression.

IntroductionRecent studies have shown a high frequency of abnormal electrocardiograms in patients with schizophrenia. The objective of this study was to associate schizophrenia diagnoses with early repolarization patterns in a sample of hospitalized patients from a single hospital in Japan.MethodsWe conducted a retrospective age, sex and coronary risk factors matched case-control study on 85 patients with schizophrenia and 89 controls from medical checkups. First, we compared the presence of early repolarization patterns in both groups. Secondly, we elucidated an association between the presence of an early repolarization pattern and clinical findings in the patients’ groups. We also evaluated J-point elevation patterns.ResultsAs a result, we found that both early repolarization patterns and J-point elevation patterns observed were significantly higher in the schizophrenic group than in the matched control group (early repolarization pattern 23;6 P < 0.001; J-point elevation pattern 34:12; P = 0.001). After multivariable logistic regression among the patients and controls, schizophrenia was the independent predictor for early repolarization pattern (P = 0.001) and J-point elevation (P < 0.001). Among the patients, the independent predictor for early repolarization pattern was psychiatric family history (P = 0.006), while older age (P = 0.038) and psychiatric family history (P = 0.014) were predictors for J-point elevation patterns.ConclusionThese findings suggest that an association between early repolarization pattern or J-point elevation pattern and schizophrenia in a single Japanese center.