Screening for Major Depressive Disorder Using a Wearable Ultra-Short-Term HRV Monitor and Signal Quality Indices.

To encourage potential major depressive disorder (MDD) patients to attend diagnostic sessions, we developed a novel MDD screening system based on sleep-induced autonomic nervous responses. The proposed method only requires a wristwatch device to be worn for 24 h. We evaluated heart rate variability (HRV) via wrist photoplethysmography (PPG). However, previous studies have indicated that HRV measurements obtained using wearable devices are susceptible to motion artifacts. We propose a novel method to improve screening accuracy by removing unreliable HRV data (identified on the basis of signal quality indices (SQIs) obtained by PPG sensors). The proposed algorithm enables real-time calculation of signal quality indices in the frequency domain (SQI-FD). A clinical study conducted at Maynds Tower Mental Clinic enrolled 40 MDD patients (mean age, 37.5 ± 8.8 years) diagnosed on the basis of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and 29 healthy volunteers (mean age, 31.9 ± 13.0 years). Acceleration data were used to identify sleep states, and a linear classification model was trained and tested using HRV and pulse rate data. Ten-fold cross-validation showed a sensitivity of 87.3% (80.3% without SQI-FD data) and specificity of 84.0% (73.3% without SQI-FD data). Thus, SQI-FD drastically improved sensitivity and specificity.

Year-round flowering gene e1, a mutation at the E1 locus on rice chromosome 7 and its combination with green revolution gene sd1 in an isogenic cell line.

Genetic analysis on the year-round flowering gene e1, which was derived from Kanto No. 79, an induced mutant by Koshihikari gamma-ray irradiated, was conducted through the backcross process to combine e1 and sd1 in the genetic background of Koshihikari. e1 strongly forwarded flowering 14 days earlier than the original variety Koshihikairi. Isogenic Koshihiakri combining e1 and sd1 was developed by four times of backcross with either Koshihikari or Koshihikari sd1 as recurrent parents by using the e1sd1 homozygous F3 plant in Koshihikari sd1 × Kanto No. 79 as a non-recurrent parent. As a result, "Koshihikari e1sd1" maturing 14 days earlier was approximately 30 cm shorter than Koshihikari. e1 was linked with DNA markers, which were near to Ghd7 on the short arm of chromosome 7. The whole genome sequencing revealed a single candidate SNP, which is specific to Koshihikari e1sd1, in the Xa21-like sequence, at 35213 bp downstream from Ghd7 on chromosome 7. Koshihikari e1sd1-specific SNP beside Ghd7 is expected to downregulate with Ghd7.

Usefulness of heart rate variability indices in assessing the risk of an unsuccessful return to work after sick leave in depressed patients.

AIM: The present study aimed to examine whether heart rate variability (HRV) indices in depressed patients measured at return to work after sick leave are related to the outcome of reinstatement. METHODS: This study included 30 workers who took a leave of absence due to major depressive disorder. HRV was measured twice, once when participants left work and another when they returned to work. One month after returning to work, 19 participants continued their original work (successful return group), while 11 failed to perform their original work (unsuccessful return group). HRV indices including high- and low-frequency components (HF and LF) were calculated in three conditions within a session lasting for about 5 minutes, initial rest (Rest), mental task (Task), and rest after task (After), and were compared between the two participant groups. Psychological states were evaluated using Self-rating Depression Scale and State-Trait Anxiety Inventory. RESULTS: No significant differences were observed in the HRV indices on leaving work between groups. On returning to work, the "unsuccessful return group" exhibited lower HF Rest score, higher HF Task/Rest ratio, and higher LF/HF Rest score than the "successful return group." Psychological scores improved in both groups. CONCLUSION: These results indicate that autonomic dysregulations revealed by HRV measurement at return to work after a leave of absence in MDD patients were related to the outcome of reinstatement and can serve as useful information for the assessment of the risk of unsuccessful return.

Nitric oxide plays a critical role in methotrexate-induced hyperplasia of enterochromaffin cells containing 5-hydroxytryptamine in rat small intestine.

The role of nitric oxide (NO) in the changes in enterochromaffin cells and ileal 5-hydroxytryptamine (5-HT) content induced by a single i.p. administration of methotrexate was investigated in rats. Methotrexate significantly increased inducible NO synthase (iNOS) mRNA and protein expressions in the intestinal tissue at 96 h. Methotrexate also significantly caused hyperplasia of the enterochromaffin cells at 96 h; this was associated with a significant increase in 5-HT content. The methotrexate-induced hyperplasia of enterochromaffin cells and increase in 5-HT content were, however, completely suppressed by daily treatment with dexamethasone, and with NG-nitro-l-arginine methyl ester (l-NAME); this was not observed when meloxicam was administered. Histological examination showed slight but not pronounced mucosal injury, at 96 h after methotrexate administration. The methotrexate-induced decrease in body weight did not fully recover to the control level up to 96 h; however, the methotrexate-induced decrease in food/water intake slightly returned to the control level up to 96 h. l-NAME had no significant effect on methotrexate-induced body weight loss and anorexia. To conclude, the present study suggests that NO derived from methotrexate-induced iNOS plays a critical role in the mechanism of hyperplasia of enterochromaffin cells containing 5-HT in the intestinal tissue of rats.

Cisplatin increases the number of enterochromaffin cells containing substance P in rat intestine.

We previously reported that cisplatin potentiated ileal 5-hydroxytryptamine (5-HT) metabolism and caused pathological changes with an inflammatory response in the delayed phase (72 h) after administration to rats. In the present study, we further investigated the time-dependent effect of cisplatin on ileal 5-HT metabolism and the effects of combining cisplatin and anti-inflammatory drugs on ileal tryptophan hydroxylase expression and pica (the consumption of non-nutritive materials such as kaolin). Cyclooxygenase-2 (COX-2) expression was significantly increased at 24 h after cisplatin (5 mg/kg, intraperitoneal) administration. Cisplatin significantly increased ileal 5-HT content at 48 h after administration and the number of L-tryptophan hydroxylase-expressing cells (i.e., enterochromaffin cells) in the ileal mucosa within 24 h after administration. It also caused a significant increase in the number of substance P-expressing cells. Immunohistochemical double staining revealed that most of the enterochromaffin cells contained substance P. Neither daily treatment with dexamethasone (1 mg/kg, subcutaneous) nor meloxicam (3 mg/kg, subcutaneous), a selective COX-2 inhibitor, affected the cisplatin-induced increase in the number of enterochromaffin cells. Meloxicam had no effect on cisplatin-induced pica, although dexamethasone almost completely inhibited it. This study demonstrated that cisplatin administration induced COX-2 expression and increased the number of enterochromaffin cells in the acute phase (i.e., within 24 h). However, COX-2 expression in the ileum seems to have little direct effect on the mechanism of the induction of enterochromaffin cells and pica.

Increase of frontal cerebral blood volume during transcranial magnetic stimulation in depression is related to treatment effectiveness: A pilot study with near-infrared spectroscopy.

AIM: Alterations of cerebral blood flow have been reported in studies of depression treated by transcranial magnetic stimulation (TMS). However, the relation between these changes in activity during stimulation and the effectiveness of TMS is not known. The aim of this study was to determine whether changes in frontal cerebral blood volume measured as frontal hemoglobin concentration (fHbC) during TMS are correlated with clinical outcomes of treatment. METHODS: Fifteen drug-resistant patients with depression underwent a standard treatment regimen of TMS to the left dorsolateral prefrontal cortex. We recorded fHbC during stimulation at the start and end of the TMS treatment series using near-infrared spectroscopy. Symptom severity was determined using the Montgomery-Åsberg Depression Rating Scale. RESULTS: At the start of the TMS series, fHbC increased during stimulation in a majority of patients with no relation to symptom severity. However, at the end of the series, fHbC increase during stimulation was negatively correlated with the Montgomery-Åsberg Depression Rating Scale score and positively with the score reduction. Patients showing a decreasing response of fHbC during TMS at the end of the series experienced less clinical improvement. CONCLUSION: These results suggest that the maintenance of frontal activation during stimulation in the course of TMS series is related to the effectiveness in the treatment of depression. Measurement of fHbC during stimulation is informative in the clinical use of TMS.

Methotrexate causes a change in intestinal 5-hydroxytryptamine metabolism in rats.

The effects of methotrexate on 5-hydroxytryptamine (5-HT) metabolism in the intestinal tissue of rats were investigated during the delayed phase after a single administration. Rats were i.p. injected with methotrexate or with saline as a control, and kaolin and food intakes were measured by an automatic monitoring apparatus. At 96 h after administration, dissected-out ileal tissue was frozen rapidly in liquid nitrogen for further analysis or fixed for immunohistochemical staining. Methotrexate at a dose of 50 mg/kg caused a time-dependent increase in kaolin intake lasting up to 72 h after administration, which returned to the control level at 96 h after administration. This dose of methotrexate caused a gradual decrease in body weight, food intake, and water intake lasting up to 72 h, which approached the control level at 96 h. Methotrexate caused pathologic changes, including a moderate inflammatory response in the ileal tissue and an increase in the number of L-tryptophan hydroxylase (TPH)-expressing cells in the ileal mucosa. Methotrexate also caused a significant increase in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content and in TPH1 mRNA expression in the ileal tissues. It had no significant effects on mRNA expression of serotonin transporter, COX-1, or COX-2 or on myeloperoxidase activity. This study demonstrated, for the first time, that methotrexate caused a change in the ileal 5-HT metabolism associated with hyperplasia of mucosal enterochromaffin cells.