Japanese Project for Telepsychiatry Evaluation during COVID-19: Treatment Comparison Trial (J-PROTECT): Rationale, design, and methodology

IntroductionThe COVID-19 pandemic has had a profound impact on the mental health of people around the world. Anxiety related to infection, stress and stigma caused by the forced changes in daily life have reportedly increased the incidence and symptoms of depression, anxiety disorder and obsessive-compulsive disorder. Under such circumstances, telepsychiatry is gaining importance and attracting a great deal of attention. However, few large pragmatic clinical trials on the use of telepsychiatry targeting multiple psychiatric disorders have been conducted to date. MethodsThe targeted study cohort will consist of adults (>18 years) who meet the DSM-5 diagnostic criteria for either (1) depressive disorders, (2) anxiety disorders, or (3) obsessive-compulsive and related disorders. Patients will be assigned in a 1:1 ratio to either a "telepsychiatry group" (at least 50% of visits to be conducted using telemedicine, with at least one face-to-face treatment [FTF] every six months) or an "FTF group" (all visits to be conducted FTF, with no telemedicine). Both groups will receive the usual treatment covered by public medical insurance. The study will utilize a master protocol design in that there will be primary and secondary outcomes for the entire group regardless of diagnosis, as well as the outcomes for each individual disorder group. DiscussionThis study will be a non-inferiority trial to test that the treatment effect of telepsychiatry is not inferior to that of FTF alone. This study will provide useful insights into the effect of the COVID-19 pandemic on the practice of psychiatry. Trial RegistrationjRCT1030210037, Japan Registry of Clinical Trials (jRCT)

fNIRS Assessment during an Emotional Stroop Task among Patients with Depression: Replication and Extension

OBJECTIVE: Accumulated evidence collected via functional near-infrared spectroscopy (fNIRS) has been reported with regard to mental disorders. A previous finding revealed that emotional words evoke left frontal cortex activity in patients with depression. The primary aim of the current study was to replicate this finding using an independent dataset and evaluate the brain region associated with the severity of depression using an emotional Stroop task. METHODS: Oxygenized and deoxygenized hemoglobin recording in the brain by fNIRS on 14 MDD patients and 20 normal controls. RESULTS: Hyperactivated oxygenized hemoglobin was observed in the left frontal cortex on exposure to unfavorable stimuli, but no significant difference was found among patients with depression compared with healthy controls on exposure to favorable stimuli. This result is consistent with previous findings. Moreover, an evoked wave associated with the left upper frontal cortex on favorable stimuli was inversely correlated with the severity of depression. CONCLUSION: Our current work using fNIRS provides a potential clue regarding the location of depression symptom severity in the left upper frontal cortex. Future studies should verify our findings and expand them into a precise etiology of depression.

Comparative Analysis of the WISC between Two ADHD Subgroups

OBJECTIVE: The prevalence of attention deficit/hyperactivity disorder (ADHD) in school-age children is 7.2%, and ADHD is divided into clinical subtypes. METHODS: The current study explored whether specific cognitive profiles as assessed using the Wechsler Intelligence Scale for Children (WISC)-IV could be obtained for each clinical ADHD subtype (ADHD-Inattentive type and ADHD-Combined type) and investigated the correlation between WISC scores and parental age at their children’s birth or birthweight. The enrolled sample comprised 12 ADHD-I and 15 ADHD-C subjects. RESULTS: An impaired Processing Speed Index was found in ADHD-I. The age of the father at the child’s birth and birthweight positively correlated with the full scale intelligence quotient (FSIQ) score in the WISC assessment. CONCLUSION: Inattentiveness within the behaviors of the children with ADHD-I is partly due to the impaired processing speed, therefore effective support for ADHD will be conducted if educator decreases their speaking speed. Since biological basis of ADHD is still largely unknown, future studies using both psychological and biological methods will reveal the etiology of ADHD. These scientific assessments will provide information for more effective approaches in the care of children with ADHD.

Increases in iPS Transcription Factor (Oct4, Sox2, c-Myc, and Klf4) Gene Expression after Modified Electroconvulsive Therapy

OBJECTIVE: Electroconvulsive therapy (ECT) is a reasonable option for intractable depression or schizophrenia, but a mechanism of action has not been established. One credible hypothesis is related to neural plasticity. Three genes (Oct4, Sox2, c-Myc) involved in the induction of induced pluripotent stem (iPS) cells are Wnt-target genes, which constitute a key gene group involved in neural plasticity through the TCF family. Klf4 is the other gene among Yamanaka's four transcription factors, and increases in its expression are induced by stimulation of the canonical Wnt pathway. METHODS: We compared the peripheral blood gene expression of the four iPS genes (Oct4, Sox2, c-Myc, and Klf4) before and after modified ECT (specifically ECT with general anesthesia) of patients with intractable depression (n=6) or schizophrenia (n=6). Using Thymatron ten times the total bilateral electrical stimulation was evoked. RESULTS: Both assessments of the symptoms demonstrated significant improvement after mECT stimulation. Expression of all four genes was confirmed to increase after initial stimulation. The gene expression levels after treatment were significantly different from the initial gene expression in all twelve cases at the following treatment stages: at the 3rd mECT for Oct4; at the 6th and 10th mECT for Sox2; and at the 3rd, 6th and 10th mECT for c-Myc. CONCLUSION: These significant differences were not present after correction for multiple testing; however, our data have the potential to explain the molecular mechanisms of mECT from a unique perspective. Further studie should be conducted to clarify the pathophysiological involvement of iPS-inducing genes in ECT.