Hideaki Mitani

Correlation between plasma levels of glutamate, alanine and serine with severity of depression

The goal of this study was to evaluate the utility of using plasma levels of amino acids as an indicator of the severity of depression. The samples were collected from 23 depressed patients receiving antidepressant medication, and were compared to 31 healthy subjects. The plasma levels of amino acids were determined using HPLC with fluorometric detection. The severity of depression was evaluated using the Hamilton Depression Rating Scale (HAM-D) scores. Plasma levels of glutamate, glutamine, glycine and taurine were significantly increased in the depressed patients compared to the controls. Statistical analysis indicated a positive correlation between glutamate and alanine levels and HAM-D scores and a negative correlation of L-serine with HAM-D scores. The results indicate that plasma level of glutamate, alanine and L-serine could reflect the severity of depression rather than glutamine, glycine and taurine.

Plasma levels of homovanillic acid, 5-hydroxyindoleacetic acid and cortisol, and serotonin turnover in depressed patients

Plasma levels of ACTH, cortisol and monoamines were examined in 23 depressed patients and 31 healthy subjects. Patients showed increased plasma cortisol levels, but not plasma adrenocorticotropic hormone (ACTH) levels. The plasma levels of a dopamine metabolite, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), were significantly decreased in the patients. In contrast, the plasma levels of a serotonin (5-HT) metabolite, hydroxyindoleacetic acid (5-HIAA), and 5-HT turnover (5-HIAA/5-HT) were increased in the depressed patients. Therefore, plasma levels of HVA and 5-HIAA are proven to be dissociable. Furthermore, plasma levels of 5-HIAA and L-DOPA have positive relationships with severity of depression. On the basis of this and the previous studies, we speculate that an increase in the plasma 5-HIAA levels might be a compensatory mechanism for stress, whereas 5-HT turnover might reflect depressive state. Taken together, plasma levels of HVA and 5-HIAA, and 5-HT turnover (5-HIAA/5-HT) could be good markers for evaluating depression.

Reduced frontopolar activation during verbal fluency task associated with poor social functioning in late‐onset major depression: Multi‐channel near‐infrared spectroscopy study

Aim:  Functional neuroimaging studies to date have indicated prefrontal dysfunction in late‐onset major depression (LOD). The relationships between prefrontal dysfunction and clinical characteristics including social functioning, however, have been unclear. The objective of the present study was to evaluate prefrontal hemodynamic response related to an executive task in LOD and to assess the relationship between activation in the prefrontal regions and clinical characteristics including social functioning.

A multi-channel near-infrared spectroscopy study of prefrontal cortex activation during working memory task in major depressive disorder

Many neuropsychological studies demonstrate impairment of working memory in patients with major depressive disorder (MDD). However, there are not enough functional neuroimaging studies of MDD patients seeking for the underlying brain activity relevant to working memory function. The objective of this study is to evaluate prefrontal hemodynamic response related to working memory function in patients with MDD. Twenty-four subjects with MDD and 26 age- and gender-matched healthy subjects were recruited for the present study. We measured hemoglobin concentration changes in the prefrontal and superior temporal cortical surface areas during the execution of working memory task (WM; 2-back, letter version) using 52-channel near-infrared spectroscopy (NIRS), which enables real-time monitoring of task-related changes in cerebral blood volumes in the cortical surface areas. MDD patients showed a smaller increase in lateral prefrontal and superior temporal cortex activation during the 2-back task and associated poorer task performance than healthy controls. The results coincided with previous findings in terms of working memory deficits and prefrontal cortex dysfunction in MDD patients, but contradicted with some previous fMRI studies that suggested increased cortical activity during the working memory task in patients with depression. The contradiction may, in part, be explained by a relatively low level of cognitive demand imposed on the subjects in the present study.

The relationship between the prefrontal activation during a verbal fluency task and stress-coping style in major depressive disorder: A near-infrared spectroscopy study

This study aimed to identify coping styles used by patients with major depressive disorder (MDD) in comparison with those used by healthy controls, and to explore their association with prefrontal hemodynamic response related to a cognitive task. Regional hemodynamic changes were monitored during a verbal fluency task (VFT) using a 52-channel near-infrared spectroscopy (NIRS) apparatus in 26 MDD patients in depressive state and 30 matched healthy controls, and their correlation with coping styles assessed by Coping Inventory for Stressful Situations (CISS) were examined. We found the Emotion-oriented coping style was significantly higher, whereas the Task-oriented coping and Avoidance-oriented coping style were lower in the MDD group compared with controls. Emotion-oriented coping style positively correlated with subjective assessment of depression severity. Regional hemodynamic changes were significantly smaller in the MDD group than in the control group in prefrontal and temporal regions, and positively correlated with Task-oriented coping (adaptive coping) in the bilateral ventrolateral and dorsolateral prefrontal cortex, and the midline fronto-polar and bilateral orbitofrontal cortex regions. These findings suggest coping styles may be considered an important source of knowledge for patients who struggle with the illness and for mental health professionals who work with MDD patients, and that hemodynamic response in the ventrolateral and dorsolateral prefrontal cortex, midline fronto-polar, and orbitofrontal cortex regions during a VFT may reflect the adaptive coping (Task-oriented coping) style in MDD patients in depressive state.

P300 abnormalities in patients with severe sleep apnea syndrome

We investigated the mechanism of abnormal P300 findings in the patients with severe sleep apnea syndrome (SAS). Compared with controls, SAS patients showed significantly longer latency of P300. Not the mean sleep latency in multiple sleep latency test but the percentage of total periods in which percentage desaturation time fell below 90% to total sleep time correlated with P300 latency in the patients. During nasal CPAP treatment, P300 latency was significantly shortened in the patients under 45 years, while the elderly patients did not show statistical change. We speculated that P300 latencies might be prolonged due to nocturnal hypoxia with SAS and the abnormality might be irreversible, especially in elderly patients.

Suicidal ideation is associated with reduced prefrontal activation during a verbal fluency task in patients with major depressive disorder.

BACKGROUND Despite the known relationship between prefrontal function and increased suicidality during major depressive episodes, the links between prefrontal function and suicidality remain unclear in major depressive disorder (MDD). Suicidal ideation usually precedes a suicide attempt. If prefrontal cortex (PFC) activity is a biomarker for suicidal ideation in depression, monitoring it could be useful for suicide prevention. Therefore, in this study, we assessed the association between prefrontal function and suicidal ideation in MDD. METHODS Prefrontal function in 67 patients with MDD (31 with suicidal ideation and 36 without) and 67 age-, gender-, and intelligence quotient-matched healthy controls (HCs) was evaluated using near-infrared spectroscopy (NIRS) during a verbal fluency task (VFT). Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD). RESULTS Regional hemodynamic changes were significantly smaller in patients with MDD than in HCs in prefrontal and temporal regions. Hemodynamic changes in the right dorsolateral PFC (DLPFC), orbitofrontal cortex (OFC), and right frontopolar cortex (FPC) regions in patients with MDD with suicidal ideation were significantly smaller than in those without suicidal ideation. In addition, hemodynamic changes correlated negatively with the severity of suicidal ideation in the DLPFC, OFC, and FPC in patients with MDD. LIMITATIONS Further studies with a larger sample size are required to verify our findings. CONCLUSIONS These results suggest that the DLPFC, OFC, and FPC are brain substrates of suicidal ideation in depressive states in patients with MDD, and that NIRS data can be employed as a clinically useful biomarker for the assessment of suicide risk.

Reduced prefrontal cortex activation during the working memory task associated with poor social functioning in late-onset depression: Multi-channel near-infrared spectroscopy study

A number of studies have demonstrated impairment of working memory (WM) in patients with major depressive disorder (MDD). However, the relationship between the underlying brain activity associated with impairment of WM function in MDD patients and their clinical characteristics is not yet clear. The objective of this study is to evaluate prefrontal hemodynamic response related to a WM task in patients with late-onset depression (LOD) and to assess the relationship between activation in the prefrontal cortex and clinical characteristics. Thirty-six patients with LOD and 35 age- and gender-matched healthy controls were recruited for the present study. We measured hemoglobin concentration changes in the prefrontal and temporal regions during a WM (2-back, letter version) task using 52-channel near-infrared spectroscopy (NIRS). LOD patients were associated with reduced increase in prefrontal and temporal activation compared with healthy controls. Moreover, reduced activation in the prefrontal and temporal regions was significantly related to lower scores on the Social Adaptation Self-Evaluation Scale (SASS) in the patient group. More specifically, the reduced hemodynamic response in the frontopolar region was associated with functional impairment related to interpersonal relationship factor scores on the SASS. These findings suggest that hemodynamic response in prefrontal and temporal regions during a WM task may act as a biological marker of social functioning in LOD patients.

Individual and additive effects of neuromodulators on the slow components of afterhyperpolarization currents in layer V pyramidal cells of the rat medial prefrontal cortex

The effects of 5-hydroxytryptamine (5-HT), noradrenaline (NA), dopamine (DA) and the muscarinic receptor agonist carbachol (CCh) on the voltage step-induced outward currents underlying afterhyperpolarization (AHP), consisting of a medium (I(mAHP)) and slow (I(sAHP)) component, were investigated in layer V pyramidal cells of the rat medial prefrontal cortex (mPFC). Whole-cell voltage clamp recordings were performed in vitro to quantitatively measure I(mAHP) and I(sAHP) and to examine their functional link to spike-frequency adaptation in the presence of agonists. CCh, 5-HT and NA all reduced the I(sAHP) and the spike adaptation, and, in some cells, replaced the I(sAHP) by the slow inward currents (I(sADP)) underlying the slow afterdepolarization (sADP). DA, however, failed to increase the frequency despite its comparable inhibition of the I(sAHP) over a range of concentrations. In order to test the neuromodulator agonists to see if they have additive actions on the I(sAHP), the effects of co-application of two agonists that increased spike-frequency, 5-HT+NA, 5-HT+CCh and CCh+NA, all at the concentration 30 microM were examined. Specific combinations that included CCh showed additive effects on the slow afterpolarization currents, possibly via both inhibition of I(sAHP) and generation of I(sADP). These findings suggest that neuromodulators have differential effects on the link between the I(sAHP) modulation and spike-frequency adaptation, and that they could exert additive effects on the slow aftercurrents following a strong excitation and, therefore, regulate the repetitive firing properties of the output cells of the rat mPFC.

Treatment of periodic leg movement disorder and restless leg syndrome with talipexole.

In order to investigate the bedtime dose of talipexole, a D2 and α2 stimulant, on patients with periodic leg movement disorder (PLMD) and restless leg syndrome (RLS), we made a comparison of polysomnographic findings and subjective symptom ratings before and during 4 weeks of the treatment on five cases with RLS and PLMD. A significant decrease in both the frequencies of periodic leg movements and subjective symptom ratings and significant improvement of sleep composition were recognized during the treatment. We speculate that the combination of the agonistic action of D2 and α2 receptor with the drug might not only suppress PLMD and RLS but also improve sleep quality.