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1.
Sci Rep ; 12(1): 11327, 2022 07 05.
Article En | MEDLINE | ID: mdl-35790750

Impaired gamma oscillations found in a 40-Hz auditory steady-state response (ASSR) in patients with schizophrenia are the robust findings that can be used for future biomarker-based therapeutics. To apply these significant observations into the clinical practice, a clinical system for evoked response audiometry (ERA) may be available. In this study, the delayed 40-Hz ASSR, which was reported as a potent biomarker for schizophrenia, was examined using the ERA system in patients with schizophrenia and its clinical relevance was investigated. The phase of ASSR was significantly delayed in patients with schizophrenia compared with the healthy subjects. The delayed phase was associated with severity of the disease symptoms in the patients. A phase delay with aging was found in healthy subjects, but not in patients with schizophrenia. These findings show availability of the ERA system to identify the delayed 40-Hz ASSR and its clinical implication in patients with schizophrenia. Further applications of the ERA system in clinical psychiatry are warranted in developing biological assessments of schizophrenia with 40-Hz ASSR.


Schizophrenia , Audiometry, Evoked Response , Biomarkers , Evoked Potentials, Auditory/physiology , Humans , Physical Therapy Modalities , Schizophrenia/complications , Schizophrenia/diagnosis
2.
Sci Rep ; 12(1): 287, 2022 01 07.
Article En | MEDLINE | ID: mdl-34997139

Gamma oscillations probed using auditory steady-state response (ASSR) are promising clinical biomarkers that may give rise to novel therapeutic interventions for schizophrenia. Optimizing clinical settings for these biomarker-driven interventions will require a quick and easy assessment system for gamma oscillations in psychiatry. ASSR has been used in clinical otolaryngology for evoked response audiometry (ERA) in order to judge hearing loss by focusing on the phase-locked response detectability via an automated analysis system. Herein, a standard ERA system with 40- and 46-Hz ASSRs was applied to evaluate the brain pathophysiology of patients with schizophrenia. Both ASSRs in the ERA system showed excellent detectability regarding the phase-locked response in healthy subjects and sharply captured the deficits of the phase-locked response caused by aberrant gamma oscillations in individuals with schizophrenia. These findings demonstrate the capability of the ERA system to specify patients who have aberrant gamma oscillations. The ERA system may have a potential to serve as a real-world clinical medium for upcoming biomarker-driven therapeutics in psychiatry.


Audiometry, Evoked Response , Brain/physiopathology , Evoked Potentials, Auditory , Gamma Rhythm , Schizophrenia/diagnosis , Acoustic Stimulation , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Schizophrenia/physiopathology , Time Factors , Young Adult
3.
Front Psychiatry ; 12: 704506, 2021.
Article En | MEDLINE | ID: mdl-34475831

Spontaneous brain activity occurs at rest, as represented by the default mode network. A resting paradigm is suitable for investigating brain function of patients with psychiatric diseases who may have difficulties adhering to goal-oriented tasks. Evidence accumulated in neuroimaging studies using functional magnetic resonance imaging has shown that the resting cerebral blood flow is impaired in psychiatric diseases. Near-infrared spectroscopy (NIRS), a simple neuroimaging modality, is an optimal tool for the resting paradigm, because it can offer a comfortable environment for measurement. Recent NIRS studies have demonstrated some promising data of altered resting activity in the prefrontal cortex of patients with schizophrenia, which may be exploited to develop further applications of NIRS in clinical psychiatry. Based on these findings, we emphasize the benefits of NIRS for assessing the prefrontal pathophysiology during the resting state and some methodological issues to be noted while analyzing cerebral blood flow using NIRS; moreover, we focus on interpreting these changes based on the complex nature of the spontaneous brain activity during resting state.

4.
Clin Case Rep ; 9(7): e04482, 2021 Jul.
Article En | MEDLINE | ID: mdl-34257988

A patient with Alzheimer's disease (AD) pathology when cognitive impairment is detected tends to be diagnosed with AD. However, before diagnosing, we make an effort to exclude other diseases, for example, carcinoma.

5.
J Med Case Rep ; 15(1): 272, 2021 May 26.
Article En | MEDLINE | ID: mdl-34034805

BACKGROUND: Alzheimer's disease is a neurodegenerative disease involving the deposition of pathologic amyloid-ß and tau protein in the cerebral cortex. Alzheimer's disease is commonly characterized by progressive impairment of recent memory. Primary progressive aphasia is also often observed in patients with Alzheimer's disease. Moreover, language-associated symptoms, such as primary progressive aphasia, are diverse and varied in Alzheimer's disease. However, nonfluent/agrammatic variant primary progressive aphasia is not generally considered a symptom of Alzheimer's disease. To date, there has been no longitudinal study of primary progressive aphasia in Japanese-speaking patients or in patients speaking other languages with pathologically diagnosed Alzheimer's disease. Here we present a longitudinal study of primary progressive aphasia in a Japanese patient pathologically diagnosed with Alzheimer's disease. CASE PRESENTATION: A 75-year-old Japanese man, whose wife reported that his memory was impaired, also suffered from suspected aphasia. He was pathologically diagnosed with Alzheimer's disease using 11C-Pittsburgh compound-B positron emission tomography and 18F-THK5351 positron emission tomography. Based on clinical observation and the results of the Japanese standard language test of aphasia, he was also diagnosed with nonfluent/agrammatic variant primary progressive aphasia. During the subsequent 2 years, his cognitive impairment, aphasia, and behavioral and psychological symptoms of dementia progressed. Furthermore, progression of pathologic amyloid-ß and tau protein deposition was revealed through 11C-Pittsburgh compound-B positron emission tomography and 18F-THK5351 positron emission tomography. Although the results of [123I] iodoamphetamine single-photon emission computed tomography suggested corticobasal degeneration, this was not observed on the [123I] FP-CIT single-photon emission computed tomography (SPECT) (DaTscan). A previous study had reported that Alzheimer's disease with a nonfluent/agrammatic variant primary progressive aphasia was accompanied by corticobasal degeneration; however, this was not true in our case. CONCLUSIONS: This is possibly the first longitudinal study of nonfluent/agrammatic variant primary progressive aphasia in a Japanese-speaking patient with pathologically diagnosed Alzheimer's disease, but without corticobasal degeneration.


Alzheimer Disease , Aphasia, Primary Progressive , Neurodegenerative Diseases , Aged , Alzheimer Disease/complications , Alzheimer Disease/diagnostic imaging , Aphasia, Primary Progressive/complications , Aphasia, Primary Progressive/diagnostic imaging , Humans , Longitudinal Studies , Male , Neuropsychological Tests , Positron-Emission Tomography , Tomography, X-Ray Computed
6.
Neuropsychiatr Dis Treat ; 17: 821-833, 2021.
Article En | MEDLINE | ID: mdl-33776438

PURPOSE: This study aimed to describe real-world treatment patterns and medication adherence among patients with bipolar disorder (BD) in Japan. PATIENTS AND METHODS: Adult patients with a BD diagnosis were identified between July 2013 and February 2018, using an employment-based health insurance claims database from the JMDC Inc. Treatment patterns of target drugs (mood stabilizers, antipsychotics) and adherence (measured by the proportion of days covered [PDC]) were assessed during the first- through third-year follow-up. Adherence was also assessed for patient subgroups. RESULTS: The analyzed population included 13,788 patients with BD. They were mostly prescribed sodium valproate, lithium, or aripiprazole (range: 21.1-27.4%) across 3 years of follow-up, whereas lamotrigine was prescribed to 11.2-12.8% of patients. Benzodiazepines (70-87%) and antidepressants (52-71%) were commonly prescribed during all three follow-up periods. The mean PDC among all patients with BD was 0.51 during the first and increased to 0.61 during the third year. The mean PDC was 0.42 (first year) in patients aged <30 years and 0.49 in those aged 30-40 years. The PDC was 0.44-0.61 (depending on the drug class) in those who were prescribed a single-class target drug and 0.68-0.83 in those prescribed two drug classes concomitantly. CONCLUSION: This study documented generally low medication adherence among patients with BD, and those at young age. These patients may require more attention.

7.
Article En | MEDLINE | ID: mdl-32889030

BACKGROUND: Patients with remitted major depressive disorder (rMDD) generally rely on maladaptive coping strategies for stressful situations. These maladaptive copings are associated with an elevated relapse risk of rMDD; however, their neural basis remains poorly understood. METHODS: We enrolled (1) 45 patients with rMDD (17-item Hamilton Depression Rating Scale [HRSD17] total score ≤ 3) and (2) 56 healthy controls (HCs). Coping styles were measured using the Coping Inventory for Stressful Situations (CISS) according to three coping dimensions: avoidance-, emotion-, and task-oriented copings. The cognitive strategic processes of the prefrontal cortex were measured using a verbal fluency task (VFT). Furthermore, regional frontotemporal hemodynamic responses were monitored by near-infrared spectroscopy (NIRS). RESULTS: Patients with rMDD had significantly lower task-oriented coping scores and significantly higher avoidance- and emotion-oriented coping scores than HCs. Predominantly in the left frontotemporal region, patients with rMDD had lower frontotemporal hemodynamic responses during a VFT than HCs. Hemodynamic responses in the right inferior frontal gyrus of patients with rMDD were significantly and negatively associated with avoidance-oriented coping scores, but not of HCs. Conversely, those responses of HCs were significantly and positively associated with task-oriented coping scores, but not of patients with rMDD. DISCUSSION: Alteration in the right inferior frontal cortex plays an important role in dysfunction to stress response in patients with rMDD. Differential functioning patterns of the right inferior frontal cortex associated with coping strategies may link to MDD recurrence vulnerability.


Adaptation, Psychological/physiology , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/psychology , Prefrontal Cortex/physiology , Remission, Spontaneous , Adult , Cross-Sectional Studies , Depressive Disorder, Major/diagnosis , Female , Humans , Male , Middle Aged , Spectroscopy, Near-Infrared/methods
8.
J Med Case Rep ; 14(1): 139, 2020 Sep 03.
Article En | MEDLINE | ID: mdl-32878644

BACKGROUND: Developmental disorder and dementia in older adults have been considered unrelated clinical entities because their timing of diagnosis differs greatly; however, recent studies have suggested an association between them. This case describes a middle-aged patient with language disorder exhibiting progressive amnestic cognitive impairment. CASE PRESENTATION: A 44-year-old Japanese man with long-term language dysfunction presented for his first-ever medical evaluation at age 36 years. Although his conversational ability had been impaired since childhood, he was able to graduate from secondary school and gain unskilled employment. At age 36 years, however, his workplace environment became more stressful, which led to behavioral problems that necessitated medical consultation. He consulted two psychiatrists in vain. At age 44 years, the third attending psychiatrist examined him in detail. The major component of his language disorder was amnestic cognitive impairment in the language domain as shown by logical memory subtests of the Wechsler Memory Scale-Revised. Magnetic resonance imaging showed normal findings for his age and no small vessel disease. Global cerebral hypoperfusion versus cerebellar blood flow was shown on (123I) iodoamphetamine single-photon emission computed tomography, and amyloid-ß deposition was negative on positron emission tomography with 11C-Pittsburgh compound B. Pathologic tau accumulation was negative on 18F-THK5351 positron emission tomography imaging. Laboratory tests show no infections, no vitamin deficiencies, and no other diseases that may cause dementia. Clinical features, results of neurocognitive tests and neuroimaging studies showed no well-known neurodegenerative diseases. Collectively, he was diagnosed with language disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Over a 2-year follow-up period, amnestic cognitive impairment in visual and language domains progressed in parallel with global cerebral hypoperfusion. CONCLUSION: This case suggests a possible link between language disorder as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and progressive amnestic cognitive impairment in middle age, which may ultimately lead to dementia, derived from a neurodegenerative disease.


Cognitive Dysfunction , Language Development Disorders , Neurodegenerative Diseases , Adult , Aged , Brain , Child , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnosis , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Positron-Emission Tomography , Tomography, X-Ray Computed
9.
Neuropsychiatr Dis Treat ; 16: 1695-1704, 2020.
Article En | MEDLINE | ID: mdl-32764945

OBJECTIVE: Comorbid anxiety disorders in patients with mood disorders have a negative impact on outcomes, such as persistence of depressive symptoms, deterioration of quality of life (QoL), increased suicide risk, mood instability with antidepressant treatment, but often go underrecognized in clinical practice. To identify features useful for supporting the confirmation of comorbid anxiety disorders, we investigated the prevalence of comorbid anxiety disorders and their associated factors in Japanese patients with mood disorders using data from our previously reported JET-LMBP study. PATIENTS AND METHODS: Patients with bipolar disorder (BD; n=114) and patients with major depressive disorder (MDD; n=334), all with major depressive episodes (DSM-IV-TR) were analyzed. Comorbid anxiety disorders were confirmed using the Mini-International Neuropsychiatric Interview. Demographic and clinical features were assessed using patient background forms, including the Quick Inventory of Depressive Symptomatology-Self Report Japanese version, 36-Item Short-Form Health Survey (SF-36), and Child Abuse and Trauma Scale (CATS). Multivariate logistic regression analysis adjusted for age, sex, and severity of depressive symptoms was used to identify factors associated with comorbid anxiety disorders (post hoc analysis). RESULTS: The prevalence of comorbid anxiety disorders was significantly higher in patients with BD (53.2%) than in patients with MDD (37.2%). Factors associated with comorbid anxiety disorders in BD included no spouse, interpersonal rejection sensitivity, higher CATS sexual abuse scores, and lower SF-36 mental component summary scores. In MDD, factors included hypersomnia, pathological guilt feelings, higher CATS neglect scores, and lower SF-36 physical component summary scores. CONCLUSION: Comorbid anxiety disorders were commonly seen in Japanese patients with mood disorders. Childhood abuse, atypical depression symptoms, and deterioration of health-related QoL were commonly associated with comorbid anxiety disorders in BD and MDD, suggesting that the presence of these features may be useful to support the confirmation of comorbid anxiety disorders in these patients.

10.
Psychiatry Res ; 290: 113054, 2020 08.
Article En | MEDLINE | ID: mdl-32480116

Aggressiveness is a clinical concern in the stable phase of schizophrenia, as well as in the acute phase. The factors that affect aggressiveness during the stable phase remain unclear. This study investigated factors associated with aggressiveness in patients with stable schizophrenia. Sixty-six patients with schizophrenia who were in the stable phase without acute exacerbation were assessed for aggressiveness using the Buss-Perry Aggression Questionnaire; impulsivity using the Barratt Impulsiveness Scale Version 11, psychotic symptoms using the five-factor model of the Positive and Negative Syndrome Scale (PANSS) including positive symptoms, negative symptoms, disorganization, excitement, and emotional distress; and prefrontal hemodynamic responses using near-infrared spectroscopy. Multivariate regression analyses showed that the excitement factor of the PANSS five-factor model, which comprised four PANSS items (poor impulse control, hyperactivity, hostility, and uncooperativeness), and delayed prefrontal hemodynamic responses were associated with elevated aggressiveness. These findings suggest that in patients with stable schizophrenia, excitement symptoms and prefrontal dysfunction are associated with elevated aggressiveness. Furthermore, the impact of impulsive traits on aggressiveness is less relevant. Our results shed light on a specific aspect of aggressiveness in patients with stable schizophrenia and may indicate factors to consider in the clinical setting.


Aggression/psychology , Prefrontal Cortex/diagnostic imaging , Psychiatric Status Rating Scales , Schizophrenia/diagnostic imaging , Schizophrenic Psychology , Adult , Aggression/physiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prefrontal Cortex/metabolism , Psychiatric Status Rating Scales/standards , Psychomotor Agitation/diagnostic imaging , Psychomotor Agitation/psychology , Schizophrenia/metabolism , Spectroscopy, Near-Infrared/methods , Surveys and Questionnaires , Young Adult
11.
Sci Rep ; 10(1): 9569, 2020 06 12.
Article En | MEDLINE | ID: mdl-32533029

In functional imaging, accumulating evidence suggests that spontaneous activity decreases during the resting state in the core brain regions of the default-mode network [e.g. medial prefrontal cortex (mPFC)] in schizophrenia. However, the significance of this decreased activity has not been clarified in relation to its clinical symptoms. In this study, near-infrared spectroscopy (NIRS), which is a simple imaging modality suitable for resting state paradigm, was used to evaluate the intensity of the spontaneous activity during the resting state in chronic schizophrenia. Consistent with previous findings of fMRI studies, spontaneous activity decreased in the mPFC of patients with schizophrenia. In addition, the decreased spontaneous activity was associated with severe hallucinations in this region where reality monitoring is fundamentally engaged. These results may encourage additional application of NIRS with the resting state paradigm into daily clinical settings for addressing the broad phenotypes and unstable course of schizophrenia.


Brain Mapping/methods , Hallucinations/etiology , Neural Pathways/physiopathology , Prefrontal Cortex/physiopathology , Schizophrenia/complications , Spectroscopy, Near-Infrared/methods , Adult , Aged , Case-Control Studies , Chronic Disease , Female , Hallucinations/pathology , Humans , Male , Middle Aged
12.
J Affect Disord ; 272: 170-175, 2020 07 01.
Article En | MEDLINE | ID: mdl-32379612

BACKGROUND: Hopelessness may be associated with an increased risk of suicide. However, findings regarding the long-term predictive ability of the Beck Hopelessness Scale (BHS) for suicide are inconsistent. This study investigated the long-term predictive ability of BHS scores for subsequent self-harm episodes in individuals admitted to an emergency department after attempting suicide. METHODS: The BHS was administered to 805 adult patients with a DSM-IV-TR axis I disorder admitted to an emergency department following a suicide attempt. The patients were followed for at least 18 months and up to 5 years. The incidence of the first subsequent suicidal behavior (attempt or dying by suicide) was examined and the numbers per person-year of overall repeat self-harm episodes, suicide attempt episodes, and non-suicidal self-harm episodes were evaluated. RESULTS: The total BHS scores showed significant associations with the overall number of self-harm episodes per person-year (incidence rate ratio [IRR], 1.05; 95% confidence interval [CI], 1.03-1.07; p < 0.0001), the number of suicide attempt episodes per person-year (IRR, 1.05; 95%CI, 1.03-1.08; p < 0.0001), and the number of non-suicidal self-harm episodes per person-year (IRR, 1.05; 95%CI, 1.03-1.07; p < 0.0001). LIMITATIONS: The study excluded children and adolescents. The sample size, while large, was insufficient to ensure generalizability, or to allow subanalyses based on specific disorders. CONCLUSIONS: Hopelessness scores assessed in the emergency department after a self-harming episode were associated with a rate of repetition of suicidal behaviors after discharge. Additional strategies to address hopelessness of these patients are warranted.


Self-Injurious Behavior , Suicide, Attempted , Adolescent , Adult , Emergency Service, Hospital , Humans , Patient Discharge , Risk Factors , Self-Injurious Behavior/epidemiology , Suicidal Ideation
13.
Psychiatry Clin Neurosci ; 74(6): 362-370, 2020 Jun.
Article En | MEDLINE | ID: mdl-32166827

AIM: Suicide attempters have a high risk of repeated suicide attempts and completed suicide. There is evidence that assertive case management can reduce the incidence of recurrent suicidal behavior among suicide attempters. This study evaluated the effect of an assertive-case-management training program. METHODS: This multicenter, before-and-after study was conducted at 10 centers in Japan. Participants were 274 medical personnel. We used Japanese versions of the Attitudes to Suicide Prevention Scale, the Gatekeeper Self-Efficacy Scale, the Suicide Intervention Response Inventory (SIRI), and the Attitudes Toward Suicide Questionnaire. We evaluated the effects with one-sample t-tests, and examined prognosis factors with multivariable analysis. RESULTS: There were significant improvements between pre-training and post-training in the Attitudes to Suicide Prevention Scale (mean: -3.07, 95% confidence interval [CI]: -3.57 to -2.57, P < 0.001), the Gatekeeper Self-Efficacy Scale (mean: 10.40, 95%CI: 9.48 to 11.32, P < 0.001), SIRI-1 (appropriate responses; mean: 1.15, 95%CI: 0.89 to 1.42, P < 0.001), and SIRI-2 (different to the expert responses; mean: -4.78, 95%CI: -6.18 to -3.38, P < 0.001). Significant improvements were found on all Attitudes Toward Suicide Questionnaire subscale scores, except Unjustified Behavior. The effect of training was influenced by experience of suicide-prevention training and experience of working with suicidal patients. CONCLUSION: The training program (which was developed to implement and disseminate evidence-based suicide-prevention measures) improved attitudes, self-efficacy, and skills for suicide prevention among medical personnel. Specialized suicide-prevention training and experience with suicidal patients are valuable for enhancing positive attitudes and self-efficacy; furthermore, age and clinical experience alone are insufficient for these purposes.


Attitude of Health Personnel , Case Management , Evidence-Based Practice/education , Health Knowledge, Attitudes, Practice , Health Personnel/education , Suicide, Attempted/prevention & control , Adult , Female , Humans , Male , Middle Aged , Professional Competence , Program Development , Program Evaluation , Self Efficacy
14.
J Med Case Rep ; 14(1): 5, 2020 Jan 09.
Article En | MEDLINE | ID: mdl-31915061

BACKGROUND: The Landscape Montage Technique was originally developed by Hisao Nakai, a Japanese psychiatrist, to pursue the possibility and application of a psychotherapeutic approach using drawing for patients with schizophrenia. Drawing was initially adopted to evaluate patients with an impaired ability for verbal expression, particularly for the diagnosis and treatment of patients with schizophrenia. Since its development, the Landscape Montage Technique has been utilized in various clinical settings throughout Japan. This study aimed to evaluate the psychiatric conditions of a patient diagnosed as having primary progressive aphasia using the Landscape Montage Technique at a 3-year follow-up. CASE PRESENTATION: We present the case of a 64-year-old, right-handed Japanese woman initially diagnosed as having logopenic variant primary progressive aphasia or logopenic aphasia. At a 3-year follow-up, logopenic aphasia progressed to behavioral variant frontotemporal dementia or frontotemporal dementia. According to her husband, she began to have speech difficulties approximately 5 years before her first visit. The results of neurocognitive tests suggested mild cognitive impairment or early stages of dementia. Her clinical dementia rating score was 0.5, suggesting a diagnosis of mild cognitive impairment. She had a Raven's Colored Progressive Matrices score of 31 out of 36, which indicated a nonverbal cognitive ability that was greater than the 90th percentile for her age. The Japanese Standard Language Test of Aphasia, which was performed at two points during the follow-up, indicated the possibility for a diagnosis of primary progressive aphasia given the progression of her aphasia. Based on her clinical symptoms and Japanese Standard Language Test of Aphasia results, a diagnosis of logopenic variant primary progressive aphasia was established. Magnetic resonance imaging revealed severe predominant left frontal and anterior temporal atrophy, as well as bilateral parietal atrophy. Amyloid beta deposition was negative. At the 3-year follow-up, logopenic variant primary progressive aphasia had progressed to behavioral variant frontotemporal dementia. However, the Landscape Montage Technique allowed for the diagnosis of behavioral variant frontotemporal dementia only 2 years after baseline. CONCLUSIONS: The present study showed that the Landscape Montage Technique can be useful for diagnosing behavioral variant frontotemporal dementia that starts as logopenic variant primary progressive aphasia at earlier stages.


Aphasia, Primary Progressive/classification , Aphasia, Primary Progressive/diagnosis , Frontotemporal Dementia/diagnosis , Neuropsychological Tests , Cerebral Cortex/diagnostic imaging , Female , Humans , Japan , Middle Aged , Time Factors
15.
Neuropsychopharmacology ; 44(12): 2119-2124, 2019 11.
Article En | MEDLINE | ID: mdl-31476763

Suicide is a significant public health problem worldwide, and several Asian countries including Japan have relatively high suicide rates on a world scale. Twin, family, and adoption studies have suggested high heritability for suicide, but genetics lags behind due to difficulty in obtaining samples from individuals who died by suicide, especially in non-European populations. In this study, we carried out genome-wide association studies combining two independent datasets totaling 746 suicides and 14,049 non-suicide controls in the Japanese population. Although we identified no genome-wide significant single-nucleotide polymorphisms (SNPs), we demonstrated significant SNP-based heritability (35-48%; P < 0.001) for completed suicide by genomic restricted maximum-likelihood analysis and a shared genetic risk between two datasets (Pbest = 2.7 × 10-13) by polygenic risk score analysis. This study is the first genome-wide association study for suicidal behavior in an East Asian population, and our results provided the evidence of polygenic architecture underlying completed suicide.


Multifactorial Inheritance , Suicide, Completed , Age Factors , Asian People/genetics , Female , Genome-Wide Association Study , Humans , Japan , Male , Polymorphism, Single Nucleotide , Self-Injurious Behavior/genetics
16.
Psychiatry Res ; 278: 141-145, 2019 08.
Article En | MEDLINE | ID: mdl-31176830

A recent genome-wide association study (GWAS) for major depressive disorder (MDD) in Chinese women identified a single-nucleotide polymorphism (SNP), rs12415800, near the Sirtuin1 (SIRT1) gene as one of the top candidate loci. However, no study has shown a genetic association between SIRT1 and completed suicide, which is one of the most serious outcomes of MDD. In this study, 778 suicide completers and 760 controls in a Japanese population were genotyped for two SNPs in strong linkage disequilibrium (rs12415800 and rs4746720 in 3'UTR). We found significant associations between both SNPs and completed suicide among women aged ≥50 years. Additional analysis using postmortem brain tissues (10 suicide brains and 13 non-suicide brains) revealed the following: while SIRT1 gene expression in the prefrontal cortex did not differ between suicide and non-suicide brains, DNAJC12 gene expression, potentially implicated by the SNPs genotyped here, was significantly decreased in suicide brains (p = 0.003). In conclusion, regarding the genetic association of SIRT1 with MDD that was previously identified in women by the Chinese GWAS, we successfully validated our results using a female suicidal cohort in the same Asian population with the same direction of allelic effect.


Depressive Disorder, Major/genetics , Prefrontal Cortex/metabolism , Sirtuin 1/genetics , Suicide, Completed/statistics & numerical data , Aged , Cohort Studies , Female , Genome-Wide Association Study , Humans , Japan , Middle Aged , Prefrontal Cortex/pathology
17.
Front Psychiatry ; 10: 312, 2019.
Article En | MEDLINE | ID: mdl-31139101

Background: Given a lack of markers, diagnoses of bipolar disorder (BD) and major depressive disorder (MDD) rely on clinical assessment of symptoms. However, the depressive mood states of BD and depressive symptoms of MDD are often difficult to distinguish, which leads to misdiagnoses, which in turn leads to inadequate treatment. Previous studies have shown that the hemodynamic responses of the left frontopolar cortex measured by near-infrared spectroscopy (NIRS) differ between BD and MDD; these hemodynamic responses are associated with altered mitochondrial metabolism; and mitochondrial DNA copy number (mtDNAcn), an index of mitochondrial dysfunction, tends to decrease in BD and increase in MDD patients. In this study, we confirmed that mtDNAcn trends in opposite directions in BD and MDD. We then determined whether mtDNAcn could enhance the utility of NIRS as a diagnostic marker to distinguish between BD and MDD. Methods: We determined mtDNAcn in peripheral blood samples from 58 healthy controls, 79 patients with BD, and 44 patients with MDD. Regional hemodynamic responses during a verbal fluency task (VFT) in 24 BD patients and 44 MDD patients, matched by age and depression severity, were monitored using NIRS. Results: Measurements of mtDNAcn were lower in BD patients and higher in MDD patients than in controls. The left frontopolar region exhibited the most significant differences in mean VFT-related oxy-Hb changes between the BD and MDD groups. Multivariate logistic regression analysis with variables including age, sex, hemodynamic response of the left frontopolar region, and mtDNAcn showed high accuracy for distinguishing BD from MDD (area under the curve = 0.917; 95% confidence interval = 0.849-0.985). For the BD group, we observed a positive correlation between hemodynamic responses in the left frontopolar region and mtDNAcn, while for the MDD group, we observed a negative correlation. Conclusions: Our findings suggest that the association between hemodynamic response and mitochondrial dysfunction in BD or MDD plays an important role in differentiating the pathophysiological mechanisms of BD from those of MDD.

18.
Sci Rep ; 9(1): 5283, 2019 03 27.
Article En | MEDLINE | ID: mdl-30918285

Near-infrared spectroscopy (NIRS) is an optimal imaging modality used to examine spontaneous brain activity because it can quietly measure blood flow changes with less physical restriction during the resting state. Here, NIRS was used at rest to measure spontaneous activity in the medial prefrontal cortex (mPFC), a main locus of default mode network. Consistent with previous fMRI studies, magnitude of the spontaneous activity in this region declined with increasing age in healthy subjects. The magnitude reduced in the mPFC of patients with schizophrenia. Additionally, in the mPFC of patients with schizophrenia, the spontaneous activity did not show any age-related decline; the activity was already low in younger patients. Further analysis using fractional amplitude of low-frequency fluctuations confirmed the reduction of spontaneous activity in the mPFC of patients with schizophrenia, consistent with the findings of fMRI studies. Our findings demonstrate the ability of NIRS to evaluate the spontaneous activity in the mPFC of patients with schizophrenia, particularly younger patients. Considering the safety and ease of the NIRS measurements, the current NIRS study of the resting-state activity indicates its utility for clinical applications to schizophrenia, which may facilitate chronological assessment of larger cohorts of patients with schizophrenia in further studies.


Prefrontal Cortex/physiopathology , Schizophrenia/physiopathology , Adult , Aged , Brain Mapping , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Prefrontal Cortex/diagnostic imaging , Schizophrenia/diagnostic imaging , Spectroscopy, Near-Infrared , Young Adult
20.
Neuropsychiatr Dis Treat ; 14: 2331-2336, 2018.
Article En | MEDLINE | ID: mdl-30254445

PURPOSE: The rating discrepancy for patients with major depressive disorder (MDD) is believed to be associated with hopelessness, risk of suicidal behavior, and personality characteristics, such as high neuroticism. However, it remains to be elucidated whether the discrepancy is also mediated by coping styles, which are conceptualized as personality characteristics. PATIENTS AND METHODS: We enrolled 154 participants and divided them into three groups: patients with MDD with a rating discrepancy (MDD-WD; n=46), patients with MDD without a rating discrepancy (MDD-WoD; n=50), and healthy controls (HCs; n=58). A rating discrepancy was defined as a high Beck Depression Inventory score and low Hamilton Depression Rating Scale score. Coping styles and hopelessness were compared among the groups. RESULTS: The MDD-WD group exhibited a higher level of hopelessness than those in the MDD-WoD and HC groups. They also demonstrated a significantly increased number of suicide attempts compared with the MDD-WoD group. Both the MDD-WD and MDD-WoD groups exhibited lesser task-oriented and greater emotion-oriented coping styles than those in the HC group, with the MDD-WD group demonstrating even greater emotion-oribented coping than that in the MDD-WoD group. Overall, high levels of hopelessness, a history of suicide attempts, and frequent use of emotion-oriented coping mechanisms were associated with rating discrepancy. CONCLUSION: Patients with MDD who showed rating discrepancy tended to use emotion-oriented coping. Planning for minimal use of emotion-oriented coping may be a psychotherapeutic intervention for such patients. Reduced emotion-oriented coping may also reduce the feeling of hopelessness and risk of developing suicidal behavior.

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