mtDNA and Hemodynamics in Mood Disorders

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

Protocol for a prospective multicentre registry cohort study on suicide attempters given the assertive case management intervention after admission to an emergency department in Japan: post-ACTION-J Study (PACS)

Introduction Suicide attempt is the most important risk factor for later suicide. A randomised-controlled, multicentre trial of postsuicide attempt case management for the prevention of further suicide attempts in Japan, named ACTION-J, has established effective interventions for prevention of suicide reattempts. The ACTION-J assertive case management intervention programme was adopted by the Japanese Ministry of Health, Labour and Welfare in 2016, when medical fees were revised. This nationwide programme is provided to patients who attempt suicide and who are admitted to emergency departments in Japan.The aim of the present study is to examine the current implementation status of the ACTION-J programme. The present study also aims to clarify which patients’ and hospitals’ factors affect the implementation of the programme.Methods and analysis This is a prospective, multicentre, patient registry cohort study. Participants will be suicide attempters admitted to the emergency departments of medical facilities with both psychiatry and emergency departments. The assertive case management programme will be delivered to participants by a case manager for up to 24 weeks, based on psychiatric diagnoses, social risks and patient needs. The core feature of the programme is to encourage patients to participate in psychiatric treatment.The primary outcome will be the proportion of patients still participating in the case management intervention at 24 weeks after registration. The secondary outcomes will include measures of the fidelity of the case management intervention. The fidelity will be evaluated using a fidelity assessment manual developed by the study group.Ethics and dissemination This observational study has been approved by the ethics board of Sapporo Medical University. Enrolment began in October 2016 and will continue until December 2018. Dissemination plans include presentations at scientific conferences and scientific publications

Repetition of verbal fluency task attenuates the hemodynamic activation in the left prefrontal cortex: Enhancing the clinical usefulness of near-infrared spectroscopy.

In applications of near-infrared spectroscopy (NIRS) in clinical psychiatry settings in Japan, a phonemic verbal fluency test (VFT) that includes "switching" (the ability to shift efficiently to a new word subcategory) to assess phonemic fluency is employed to capture disease-specific hemodynamic changes in the prefrontal cortex (PFC). In this study, to extend the specific features of this test, the VFT was repeated to examine an activation change in NIRS measurements in 20 healthy males. Without task performance change, the hemodynamic activation induced by the VFT was significantly attenuated in the left PFC through repetition of the task. These findings suggest that the left PFC is involved in processing of the VFT. Further, it may be possible to extend the current VFT using this repetition to provide a more sensitive examination of the left PFC, whose dysfunction has been reported in several psychiatric diseases such as major depression, bipolar disorder, and schizophrenia

〈Originals〉Is hyperactivity associated with the number of movements in boys with attention deficit-hyperactivity disorder ?

[Abstract] This study investigated the nature of the hyperactivity component of attention deficithyperactivity disorder (ADHD) by comparing the number of movements made by boys with ADHD with a subjective evaluation of their hyperactive behavior. Fifteen boys with combined-type ADHD and 18 age-matched healthy boys wore an actigraph while attending elementary school, and the mean number of movements during formal in-seat classes and intervening free recess periods were compared between the two groups. In addition, the Japanese version of the ADHD Rating Scale-IV was dministered to each boy with ADHD by the teacher in charge in the morning at the end of the study period. No significant difference was seen between the twogroups in the mean number of movements during either formal in-seat classes or free recess periods ; however, the mean hyperactivity impulsivityscores on the teacher\u27s ADHD rating scale exceeded the cutoff score of the 93rd percentile in both situations. Given these findings, an increased number of movements may not constitute a core component of hyperactivity in ADHD but rather an additional component in which increases occur only in specific situations. Additional studies are needed to investigate the intensity and variability of movements as well as the number of movements at school and home and compare them with a subjective evaluation of hyperactivity

〈Case Reports〉Diagnostic problems of childhood-onset bipolar disorder comorbid with attention-deficit hyperactivity disorder: three-year follow-up study of six cases

[Abstract]　The aim of this follow-up study was to investigate whether severe non-episodic irritability without elevated or expansive mood exhibited by children under 9 years old with attention deficit-hyperactivity disorder (ADHD) is the first prodromal symptom of childhood-onset bipolar disorder (BP). From among 32 children aged under 9 years old who were referred to our outpatient department for assessment and treatment of ADHD in 2008, 6 children exhibiting severe temper tantrums and anger outbursts were the participants in this study. All participants were followed every few months for 3 years after the initial assessment. At each follow-up visit to our hospital, we administered the Kiddie Schedule for Affective Disorders- Present (K-SADS) modules for ADHD, mania, and depression in an interview with the child and/or parent and/or teacher to assess their symptoms. Among the 6 participants, 2 experienced an episode of hypomania during the followup period, and 3 were symptom-free during the follow-up period once their irritability had subsided. One participant repeatedly experienced severe non-episodic irritability and was symptom-free for no more than 2 months at any one time during the follow-up period. Our findings suggest that children with ADHD under the age of 9 years may have a developmental presentation of BP when exhibiting severe non-episodic irritability, and environmental factors surrounding a child should be also considered when deciding the treatment

Shared and differential cortical functional abnormalities associated with inhibitory control in patients with schizophrenia and bipolar disorder

Abstract Schizophrenia (SZ) and bipolar I disorder (BD-I) share genetic risk factors and cognitive impairments, but these conditions may exhibit differences in cortical functioning associated with inhibitory control. We measured hemodynamic responses during a stop-signal task using near-infrared spectroscopy (NIRS) in 20 patients with SZ, 21 patients with BD-I and 18 healthy controls (HCs). We used stop-signal reaction time (SSRT) to estimate behavioural inhibition. Compared with HCs, patients with either SZ or BD-I exhibited significantly reduced activation in the bilateral inferior, middle and superior frontal gyri. Furthermore, patients with BD-I showed inactivation of the right superior temporal gyri compared with patients with SZ or HCs. Patients with SZ or BD-I demonstrated significant negative correlations between SSRT and hemodynamic responses of the right inferior frontal gyrus. Moreover, patients with SZ exhibited correlations in the middle and superior frontal gyri. Our findings suggest that right inferior frontal abnormalities mediate behavioural inhibition impairments in individuals with SZ or BD-I. Differential patterns of orbitofrontal or superior temporal functional abnormalities may reflect important differences in psychopathological features between these disorders

The Effect of Interpersonal Counseling for Subthreshold Depression in Undergraduates: An Exploratory Randomized Controlled Trial

Background. Subthreshold depression and poor stress coping strategies are major public health problems among undergraduates. Interpersonal counseling (IPC) is a brief structured psychological intervention originally designed for use in primary care to treat depressive patients whose symptoms arose from current life stress. Objectives. This study examined the efficacy of IPC in treating subthreshold depression and coping strategies among undergraduates in school counseling. Materials and Methods. We carried out an exploratory randomized controlled trial comparing the efficacy of IPC with counseling as usual (CAU). Participants were 31 undergraduates exhibiting depression without a psychiatric diagnosis. Results. The Zung Self-Rating Depression Scale total score decreased significantly in the IPC group (n=15; Z=-2.675, p=.007), but not in the CAU group (n=16). The task-oriented coping score of the Coping Inventory for Stressful Situations showed a tendency towards a greater increase in the IPC group than in the CAU group (t=1.919, df=29, p=.065). Conclusions. The IPC might be more useful for student counseling because it can teach realistic coping methods and reduce depressive symptoms in a short period. Further studies using more participants are required