Verification of the brain network marker of major depressive disorder: Test-retest reliability and anterograde generalization performance for newly acquired data.

BACKGROUND: Recently, we developed a generalizable brain network marker for the diagnosis of major depressive disorder (MDD) across multiple imaging sites using resting-state functional magnetic resonance imaging. Here, we applied this brain network marker to newly acquired data to verify its test-retest reliability and anterograde generalization performance for new patients. METHODS: We tested the sensitivity and specificity of our brain network marker of MDD using data acquired from 43 new patients with MDD as well as new data from 33 healthy controls (HCs) who participated in our previous study. To examine the test-retest reliability of our brain network marker, we evaluated the intraclass correlation coefficients (ICCs) between the brain network marker-based classifier's output (probability of MDD) in two sets of HC data obtained at an interval of approximately 1 year. RESULTS: Test-retest correlation between the two sets of the classifier's output (probability of MDD) from HCs exhibited moderate reliability with an ICC of 0.45 (95 % confidence interval,0.13-0.68). The classifier distinguished patients with MDD and HCs with an accuracy of 69.7 % (sensitivity, 72.1 %; specificity, 66.7 %). LIMITATIONS: The data of patients with MDD in this study were cross-sectional, and the clinical significance of the marker, such as whether it is a state or trait marker of MDD and its association with treatment responsiveness, remains unclear. CONCLUSIONS: The results of this study reaffirmed the test-retest reliability and generalization performance of our brain network marker for the diagnosis of MDD.

Left DLPFC activity is associated with plasma kynurenine levels and can predict treatment response to escitalopram in major depressive disorder.

AIM: To establish treatment response biomarkers that reflect the pathophysiology of depression, it is important to use an integrated set of features. This study aimed to determine the relationship between regional brain activity at rest and blood metabolites related to treatment response to escitalopram to identify the characteristics of depression that respond to treatment. METHODS: Blood metabolite levels and resting-state brain activity were measured in patients with moderate to severe depression (n = 65) before and after 6-8 weeks of treatment with escitalopram, and these were compared between Responders and Nonresponders to treatment. We then examined the relationship between blood metabolites and brain activity related to treatment responsiveness in patients and healthy controls (n = 36). RESULTS: Thirty-two patients (49.2%) showed a clinical response (>50% reduction in the Hamilton Rating Scale for Depression score) and were classified as Responders, and the remaining 33 patients were classified as Nonresponders. The pretreatment fractional amplitude of low-frequency fluctuation (fALFF) value of the left dorsolateral prefrontal cortex (DLPFC) and plasma kynurenine levels were lower in Responders, and the rate of increase of both after treatment was correlated with an improvement in symptoms. Moreover, the fALFF value of the left DLPFC was significantly correlated with plasma kynurenine levels in pretreatment patients with depression and healthy controls. CONCLUSION: Decreased resting-state regional activity of the left DLPFC and decreased plasma kynurenine levels may predict treatment response to escitalopram, suggesting that it may be involved in the pathophysiology of major depressive disorder in response to escitalopram treatment.

Age-related white matter changes revealed by a whole-brain fiber-tracking method in bipolar disorder compared to major depressive disorder and healthy controls.

AIM: Several studies have reported altered age-associated changes in white matter integrity in bipolar disorder (BD). However, little is known as to whether these age-related changes are illness-specific. We assessed disease-specific effects by controlling for age and investigated age-associated changes and Group × Age interactions in white matter integrity among major depressive disorder (MDD) patients, BD patients, and healthy controls. METHODS: Healthy controls (n = 96; age range, 20-77 years), MDD patients (n = 101; age range, 25-78 years), and BD patients (n = 58; age range, 22-76 years) participated in this study. Fractional anisotropy (FA) derived from diffusion tensor imaging in 54 white matter tracts were compared after controlling for the linear and quadratic effect of age using a generalized linear model. Age-related effects and Age × Group interactions were also assessed in the model. RESULTS: The main effect of group was significant in the left column and body of the fornix after controlling for both linear and quadratic effects of age, and in the left body of the corpus callosum after controlling for the quadratic effect of age. BD patients exhibited significantly lower FA relative to other groups. There was no Age × Group interaction in the tracts. CONCLUSION: Significant FA reductions were found in BD patients after controlling for age, indicating that abnormal white matter integrity in BD may occur at a younger age rather than developing progressively with age.

White matter abnormalities and cognitive function in euthymic patients with bipolar disorder and major depressive disorder.

OBJECTIVES: In recent years, a growing number of diffusion tensor imaging (DTI) studies have compared white matter integrity between patients with major depressive disorder (MDD) and bipolar disorder (BD). However, few studies have examined the pathophysiological significance of different degrees of white matter abnormalities between the two disorders. The present study comprehensively assessed white matter integrity among healthy controls (HC) and euthymic patients with MDD and BD using whole-brain tractography and examined associations between white matter integrity and cognitive functioning. METHODS: We performed neurocognitive examinations and DTI with 30 HCs, 30 patients with MDD, and 30 patients with BD. We statistically evaluated white matter integrity and cognitive function differences across the three groups, assessing associations between white matter integrities and cognitive function. RESULTS: The BD group showed lower fractional anisotropy (FA) for the corpus callosum body, as well as lower, sustained attention and set-shifting scores compared to the other groups. FA for the left body of the corpus callosum was correlated with sustained attention in patients with BD. CONCLUSIONS: The significant reduction of white matter integrity in the corpus callosum in BD, compared to MDD, was associated with an impairment of sustained attention. This result promotes the understanding of the significance of white matter integrity in mood disorders.

Yokukansan treatment of chronic renal failure patients receiving hemodialysis, with behavioral and psychological symptoms of dementia: an open-label study.

OBJECTIVE: The efficacy and safety of yokukansan (YKS) for chronic renal failure (CRF) patients receiving hemodialysis with behavioral and psychological symptoms of dementia (BPSD) was evaluated. METHODS: Twelve CRF patients receiving hemodialysis with BPSD were recruited and 7.5 g of YKS powder was added to ongoing therapy with antipsychotics. Neuropsychiatric Inventory (NPI) criteria and Barthel Index before and after 4-week YKS treatment were compared. RESULTS: Analysis of the mean score for NPI revealed a significant improvement during the period of YKS administration (25.3 ± 17.6 versus 8.36 ± 4.46; p = 0.0069). The mean score for the Barthel Index showed no significant difference during the period of YKS administration. Mean level of serum potassium was still within the normal range. No subjects had severe adverse reactions necessitating discontinuation from the study. CONCLUSION: Yokukansan significantly improved the symptoms of BPSD in CRF patients receiving hemodialysis without critical side effects.

A case of platypnea-orthodeoxia syndrome in a patient with a pulmonary arteriovenous fistula and a patent foramen ovale.

We describe a case of a rare clinical disorder, platypnea-orthodeoxia syndrome. A 57-year-old man was admitted with progressive dyspnea. While breathing room air, arterial oxygen saturation decreased from 92% in a recumbent position to 83% in an upright position. Transthoracic echocardiography revealed normal left and right ventricular function, but intravenous infusion of air-blood-saline resulted in the appearance of microbubbles in the left side of the heart, indicating the presence of right-to-left shunt. Transesophageal echocardiography demonstrated a small amount of right-to-left shunting through a patent foramen ovale. Further, the left lower pulmonary vein was dilated, and contrast echocardiography revealed drainage of microbubbles mainly from the left lower pulmonary vein. A pulmonary angiogram revealed the presence of a pulmonary arteriovenous fistula. The patient underwent embolization of the arteriovenous fistula with subsequent resolution of dyspnea and hypoxemia. Platypnea-orthodeoxia syndrome is rare, and patients with this syndrome require an extensive workup to determine its cause.

[Usefulness of conscious sedation with midazoram during transesophageal echocardiographic examination].

OBJECTIVES: Although transesophageal echocardiography is useful to identify various cardiovascular diseases, the semi-invasive nature of the examination hampers its routine application. We investigated whether conscious sedation using a low dose of intravenous midazoram was safe and useful during the examination. METHODS: We asked 55 consecutive patients undergoing transesophageal echocardiography (44 with midazoram, mean age 59 +/- 16 years, and 11 without midazoram, mean age 62 +/- 8 years) and the examiners about the effects of midazoram using a questionnaire. RESULTS: The mean dose of midazoram was 2.2 mg (range 1-3.5 mg). All examinations were done without any adverse events. Eighty-two percent of the patients with midazoram considered the examination under conscious sedation tolerable, whereas 91% without midazoram felt it untolerable. Most examiners felt manipulation of the echo probe was easier in patients with midazoram than in those without (69% vs 27%). CONCLUSIONS: Conscious sedation with a low dose of intravenous midazoram facilitated and increased patient tolerance during transesophageal echocardiographic examination.