Yuki Kako

Tone duration mismatch negativity deficits predict impairment of executive function in schizophrenia

Impairment in mismatch negativity (MMN) potentials is a robust finding in schizophrenia. There are few studies which examined the correlation between MMN deficits and neuropsychological performances. The purpose of this study was to investigate the relationship between deficits of tone duration MMN and various neuropsychological measures in schizophrenic patients (n=23). The results demonstrated a significant correlation between low MMN amplitude and poor performances of executive function in Wisconsin Card Sorting Test, Stroop Test and Trail Making Test. Our finding suggests MMN deficits in schizophrenia predict deficits of executive function and might reflect ongoing functional abnormality of fronto-temporal interaction.

Impaired integrity of the brain parenchyma in non-geriatric patients with major depressive disorder revealed by diffusion tensor imaging

Diffusion tensor imaging (DTI) is considered to be able to non-invasively quantify white matter integrity. This study aimed to use DTI to evaluate white matter integrity in non-geriatric patients with major depressive disorder (MDD) who were free of antidepressant medication. DTI was performed on 19 non-geriatric patients with MDD, free of antidepressant medication, and 19 age-matched healthy subjects. Voxel-based and histogram analyses were used to compare fractional anisotropy (FA) and mean diffusivity (MD) values between the two groups, using two-sample t tests. The abnormal DTI indices, if any, were tested for correlation with disease duration and severity, using Pearson product-moment correlation analysis. Voxel-based analysis showed clusters with FA decrease at the bilateral frontal white matter, anterior limbs of internal capsule, cerebellum, left putamen and right thalamus of the patients. Histogram analysis revealed lower peak position of FA histograms in the patients. FA values of the abnormal clusters and peak positions of FA histograms of the patients exhibited moderate correlation with disease duration and severity. These results suggest the implication of frontal-subcortical circuits and cerebellum in MDD, and the potential utility of FA in evaluation of brain parenchymal integrity.

Assessment of Depressive Symptoms in Japanese School Children and Adolescents Using the Birleson Depression Self-Rating Scale:

Objective: The aim of this study was to investigate the prevalence of depressive symptoms in children and adolescents in the general Japanese population using a depression self-rating scale and determine whether this prevalence varies according to age, gender, or region. Method: The Birleson Depression Self-Rating Scale for children (DSRS) was used to examine the extent to which depressive tendencies were present among 2,453 elementary and middle-school children (6 to 15 years old) in two cities in Japan. Results: The mean DSRS score was high at 8.75 + 5.66. A significant increase in score was observed with increasing age. There were no significant differences between regions. Using a DSRS cutoff score of 15 points as a risk of depression, the scores of 14.9% of the subjects exceeded the cutoff. Conclusions: As determined using the DSRS, a high proportion of Japanese children and adolescents have depressive tendencies.

Temperament and character profiles of Japanese university student suicide completers

OBJECTIVE The aims of this study were to investigate the personality traits of suicide completers using the Temperament and Character Inventory (TCI) scale. METHODS Newly enrolled students who enrolled at Hokkaido University in 1999-2002 and 2004-2007 completed the TCI. Among these students, twenty subjects (2 females and 18 males) later completed suicide. We compared the TCI scales of these subjects with those of 60 (6 females and 54 males) well-matched controls. The controls were matched for age, gender, university department and year of enrollment in the university. Because the number of females was too small, the statistical analyses for the TCI subscales and logistic regression analysis were performed only with the 18 males. RESULTS A univariate analysis of seven personality dimensions on the TCI revealed higher scores of harm avoidance (HA) in subjects with suicide completion (P=0.034). Analysis of the male subjects showed that suicide completers had higher scores for anticipatory worry (HA1, P=0.007) and fear of uncertainty (HA2, P=0.036) and lower scores for spiritual acceptance (ST3, P=0.038) than did the controls. A multivariate analysis, which was performed to adjust confounding factors, demonstrated significantly higher scores for HA1 among suicide completers (P=0.01, OR=1.32). CONCLUSIONS These results suggest that higher HA scores may predict suicide completion.

Neurocognitive impairments and quality of life in unemployed patients with remitted major depressive disorder.

Quality of life (QOL) has been reported to be impaired in patients with major depressive disorder (MDD), even after remission according to symptom rating scales. Although a relationship between QOL and neurocognitive dysfunction has been reported during depressive episodes, little is known about this relationship in remitted MDD patients. The aim of the present study was to investigate the relationship between QOL and neurocognitive dysfunction in patients with remitted MDD while controlling for confounding factors. Forty-three remitted MDD patients were assessed with neuropsychological tests and QOL, which was measured by a short-form 36-item health survey. The neurocognitive performances of the patients were compared with those of 43 healthy controls. We next evaluated the relationships between neurocognitive impairments, clinical factors, and QOL. Remitted MDD patients had poorer neurocognitive performances than healthy controls for psychomotor speed, attention, and verbal memory. Residual depressive symptoms were strongly associated with QOL. Delayed verbal recall was associated with general health perceptions, which are part of the QOL assessment, even after the effects of the residual depressive symptoms were considered. The results may indicate that clinicians should try to detect neurocognitive dysfunctions that may interfere with QOL using neurocognitive assessments in their daily practice.

Post-steroid neuropsychiatric manifestations are significantly more frequent in SLE compared with other systemic autoimmune diseases and predict better prognosis compared with de novo neuropsychiatric SLE ☆

In patients with systemic lupus erythematosus (SLE), neuropsychiatric (NP) symptoms sometimes occur after administration of corticosteroids, making differential diagnosis between NPSLE and steroid-induced psychosis challenging for clinicians. The aim of this study was to clarify the characteristics of post-steroid NP disease (PSNP) in patients with SLE. Clinical courses of 146 patients with SLE and 162 with other systemic autoimmune diseases, all in the absence of NP manifestations on admission, were retrospectively analyzed. Forty-three NPSLE patients on admission (de novo NPSLE) were also investigated. All patients were consecutively recruited and treated with 40mg/day or more of prednisolone in Hokkaido University Hospital between April 2002 and March 2015. The prevalence of PSNP was strikingly higher in SLE patients than other systemic autoimmune diseases (24.7% vs. 7.4%, OR 4.09, 95% CI 2.04-8.22). As independent risk factors to develop PSNP in SLE patients, past history of mental disorder and the presence of antiphospholipid syndrome were identified using multiple logistic regression analysis. In patients with PSNP-SLE, mood disorder was significantly more frequent than in de novo NPSLE (47.2% vs. 20.9%, OR 3.38, 95% CI 1.26-9.04). Of PSNP-SLE patients, two-thirds were with one or more abnormal findings in cerebrospinal fluid, electroencephalogram, MRI or SPECT. Majority of our PSNP-SLE patients received intensified immunosuppressive treatments and experienced improvement in most cases. PSNP-SLE had better relapse-free survival than de novo NPSLE (p<0.05, log rank test). In conclusion, PSNP frequently occurred in patients with SLE and treated successfully with immunosuppressive therapy, indicating that NPSLE is likely to harbor patients with PSNP-SLE.

Severity of generalized social anxiety disorder correlates with low executive functioning.

To evaluate neurocognitive functions of patients with social anxiety disorder (SAD) without comorbidity using neuropsychological assessments and to investigate the relation between neurocognitive functions and clinical severity of SAD, this study assessed 30 SAD patients (10 female, 20 male) without comorbidity and 30 healthy subjects matched on gender, education level, and age. The neuropsychological assessment consisted of the Wisconsin card sorting test (WCST), the continuous performance test, the trail-making test, the word fluency test, and the auditory verbal learning test. On the WCST, patients showed lower performance than healthy controls did. The Liebowitz Social Anxiety Scale score correlated significantly with the numbers of perseverative errors of the WCST, although the State anxiety score of State-Trait Anxiety Inventory and the Beck Depression Inventory - Second Edition score showed no correlation with neuropsychological test scores. Results show that the executive functioning of patients with SAD was low and that the low functioning correlates with the SAD symptom severity.

Temperament and character profiles of Japanese university students with depressive episodes and ideas of suicide or self-harm: A PHQ-9 screening study

OBJECTIVE The aim of our study was to reveal the personality traits of individuals with major and other depressive episodes among the young adult population. Furthermore, character traits of individuals with ideas of suicide or self-harm were also investigated in this study. METHODS The subjects of this study were 1421 university students who completed the Patient Health Questionnaire (PHQ-9) and the Temperament and Character Inventory (TCI). The subjects were divided into three separate groups: the major depressive episode group (N = 41), the other depressive episode group (N = 97), and the non-depressive controls (N = 1283). This separation was achieved using the PHQ-9 algorithm diagnosis. We compared the TCI scores using an analysis of variance. Moreover, the Cochran-Armitage trend test was used to determine the diagnosis, ideas of suicide or self-harm, and analysis of character profiles. RESULTS The major depressive episode group had significantly higher HA (P < 0.001), lower RD (P < 0.001), lower SD (P < 0.001), and lower C (P < 0.001) scores than non-depressive controls. The other depressive episode group had significantly higher HA scores (P < 0.001) and lower SD scores (P < 0.001) than non-depressive controls. The Cochran-Armitage trend test revealed that the prevalence of depressive episodes decreased as the character profiles matured (χ(2)(trend) = 57.2, P < 0.0001). The same tendency was observed in individuals who had ideas of suicide or self-harm (χ(2)(trend) = 49.3, P < 0.0001). CONCLUSION High HA and low SD scores were common personality traits among young adults with major depressive episodes. Furthermore, the immaturity of character profiles was clearly associated with depressive episodes and ideas of suicide or self-harm.

The association between suicide risk and self-esteem in Japanese university students with major depressive episodes of major depressive disorder.

Background The suicide risk among young adults is related to multiple factors; therefore, it is difficult to predict and prevent suicidal behavior. Aim We conducted the present study to reveal the most important factors relating to suicidal ideation in Japanese university students with major depressive episodes (MDEs) of major depressive disorder (MDD). Methods The subjects were 30 Japanese university students who had MDEs of MDD, and were aged between 18 and 26 years old. They were divided into two groups – without suicide risk group (n=15), and with suicide risk group (n=15) – based on the results of the Mini-International Neuropsychiatric Interview. Additionally, healthy controls were recruited from the same population (n=15). All subjects completed the self-assessment scales including the Beck Depression Inventory 2nd edition (BDI-II), the Beck Hopelessness Scale (BHS), Rosenberg’s Self-Esteem Scale (RSES), and SF-36v2™ (The Medical Outcomes Study 36-item short-form health survey version 2), and they were all administered a battery of neuropsychological tests. Results The RSES score of the suicide risk group was significantly lower than the RSES score of the without suicide risk group, whereas the BDI-II score and the BHS score were not significantly different between the two groups. The mean social functioning score on the SF-36v2 of the with suicide risk group was significantly lower than that of the without suicide risk group. Conclusion The individual’s self-esteem and social functioning may play an important role in suicide risk among young adults with MDEs of MDD.

Screening for diabetes using monitoring guidance in schizophrenia patients treated with second-generation antipsychotics: a 1-year follow-up study.

Second-generation antipsychotics (SGAs) tend to induce weight gain, dyslipidemia and diabetes mellitus. For those reasons, patients treated with SGAs should receive appropriate monitoring to avoid morbidity and mortality associated with cardiovascular disease. We conducted a one-year follow-up study using Japanese blood glucose monitoring guidance in schizophrenia patients treated with SGAs to evaluate the detection capability of the guidance in real clinical settings and to assess the importance of longitudinal monitoring. This retrospective cohort study included schizophrenia patients receiving at least one SGA, who were enrolled during June 2008-January 2009 at multiple sites and who had both baseline data and follow-up monitoring data at month 12. After one-year follow-up, the probable diabetes type (fasting blood glucose is higher than 125 mg/dL, casual blood glucose is higher than 179 mg/dL, or glycosylated hemoglobin (Hb(A1c)) is greater than 6.4%) was detected in 30 (8%) of the patients, and the pre-diabetes type (fasting blood glucose is 110-125 mg/dL, or casual blood glucose is 140-179 mg/dL, or Hb(A1c) is 6.0-6.4%) in 65 (17.4%) out of the total of 374 patients. During the follow-up period, 1.5% of patients had advanced from the normal (fasting blood glucose is less than 110 mg/dL, casual blood glucose is less than 140 mg/dL, or Hb(A1c) is less than 6.0%) to probable diabetes type and 42.4% had progressed from the pre-diabetes to probable diabetes type. Predictive factors for worsening of the diabetic state were a family history of diabetes, and high serum total-cholesterol and triglyceride levels at baseline. Not only cross-sectional baseline screening but also longitudinal follow-up screening is important to detect glucose abnormalities in patients treated with SGAs.