Shinsuke Hidese

Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study.

Objective l-theanine, an amino acid uniquely contained in green tea (Camellia sinensis), has been suggested to have various psychotropic effects. This study aimed to examine whether l-theanine is effective for patients with major depressive disorder (MDD) in an open-label clinical trial. Methods Subjects were 20 patients with MDD (four males; mean age: 41.0±14.1 years, 16 females; 42.9±12.0 years). l-theanine (250 mg/day) was added to the current medication of each participant for 8 weeks. Symptoms and cognitive functions were assessed at baseline, 4, and 8 weeks after l-theanine administration by the 21-item version of the Hamilton Depression Rating Scale (HAMD-21), State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), Stroop test, and Brief Assessment of Cognition in Schizophrenia (BACS). Results HAMD-21 score was reduced after l-theanine administration (p=0.007). This reduction was observed in unremitted patients (HAMD-21>7; p=0.004) at baseline. Anxiety-trait scores decreased after l-theanine administration (p=0.012) in the STAI test. PSQI scores also decreased after l-theanine administration (p=0.030) in the unremitted patients at baseline. Regarding cognitive functions, response latency (p=0.001) and error rate (p=0.036) decreased in the Stroop test, and verbal memory (p=0.005) and executive function (p=0.016) were enhanced in the BACS test after l-theanine administration. Conclusion Our study suggests that chronic (8-week) l-theanine administration is safe and has multiple beneficial effects on depressive symptoms, anxiety, sleep disturbance and cognitive impairments in patients with MDD. However, since this is an open-label study, placebo-controlled studies are required to consolidate the effects.

Structural differences in hippocampal subfields among schizophrenia patients, major depressive disorder patients, and healthy subjects.

Many MRI studies have reported a volume reduction of the hippocampus in psychiatric diseases. However, disease-related volume differences in hippocampus subfields remain unclear. Here we compared the volumes of hippocampus subfields in patients with schizophrenia, patients with major depressive disorder (MDD), and healthy subjects as controls. T2-weighted images were acquired in 20 patients with schizophrenia, 36 with MDD, and 35 healthy volunteers by 3-Tesla MRI. Hippocampal subfields were segmented using an automatic algorithm, Automatic Segmentation of Hippocampal Subfields (ASHS). Schizophrenia patients exhibited significant volume reductions in the cornu ammonis (CA)1 compared to the controls, and in the dentate gyrus compared to the controls and MDD patients without medication, whereas there was no significant difference between the MDD patients and controls. There was a nominal negative correlation between the perirhinal cortex volume and depression severity in the MDD patients without medication, whereas there were negative correlations between CA2 volume and both negative symptoms and the duration of illness in the schizophrenia patients. We identified differing volume reductions in hippocampal subfields and varying correlations between disease severity and subfield volumes depending on diagnosis, suggesting that volume differences in hippocampus subfields may provide important information regarding the pathophysiology of schizophrenia and MDD.

Association between the scores of the Japanese version of the Brief Assessment of Cognition in Schizophrenia and whole‐brain structure in patients with chronic schizophrenia: A voxel‐based morphometry and diffusion tensor imaging study

The Brief Assessment of Cognition in Schizophrenia (BACS) is a concise tool designed to evaluate cognitive deficits in schizophrenia. We examined the possible association between BACS scores and whole‐brain structure, as observed using magnetic resonance imaging with a relatively large sample.

Cerebrospinal fluid neural cell adhesion molecule levels and their correlation with clinical variables in patients with schizophrenia, bipolar disorder, and major depressive disorder

Purpose: Neural cell adhesion molecule (NCAM) plays an important role in neural plasticity, and its altered function has been implicated in psychiatric disorders. However, previous studies have yielded inconsistent results on cerebrospinal fluid (CSF) NCAM levels in psychiatric disorders. The aim of our study was to examine CSF NCAM levels in patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD), and their possible relationship with clinical variables. Methods: The participants comprised 85 patients with schizophrenia, 57 patients with BD, 83 patients with MDD and 111 healthy controls, all matched for age, sex, and Japanese ethnicity. The CSF samples were drawn using a lumbar puncture and NCAM levels were quantified by an enzyme‐linked immunosorbent assay. Results: Analysis of covariance controlling for age and sex revealed that CSF NCAM levels were lower in all patients (p = 0.033), and in those with BD (p = 0.039), than in the controls. NCAM levels positively correlated with age in patients with BD (p < 0.01), MDD (p < 0.01), and the controls (p < 0.01). NCAM levels negatively correlated with depressive symptom scores in patients with BD (p = 0.040). In patients with schizophrenia, NCAM levels correlated negatively with negative symptom scores (p = 0.029), and correlated positively with scores for cognitive functions such as category fluency (p = 0.011) and letter fluency (p = 0.023) scores. Conclusion: We showed that CSF NCAM levels were lower in psychiatric patients, particularly bipolar patients than in the controls. Furthermore, we found correlations of NCAM levels with clinical symptoms in patients with BD and in those with schizophrenia, suggesting the involvement of central NCAM in the symptom formation of severe psychiatric disorders. HighlightsCerebrospinal fluid (CSF) NCAM levels were lower in psychiatric, especially bipolar patients than in healthy controls.CSF NCAM levels showed a negative correlation with depressive symptom scores in bipolar patients.CSF NCAM levels correlated negatively with negative symptom scores in patients with schizophrenia.CSF NCAM levels correlated positively with verbal fluency scores in patients with schizophrenia.

Association of depression with body mass index classification, metabolic disease, and lifestyle: A web-based survey involving 11,876 Japanese people

Body mass index (BMI) and lifestyle-related physical illnesses have been implicated in the pathology of depression. We aimed to investigate the association of depression wih BMI classification (i.e., underweight, normal, overweight, and obese), metabolic disease, and lifestyle using a web-based survey in a large cohort. Participants were 1000 individuals who have had depression (mean age: 41.4 ± 12.3 years, 501 men) and 10,876 population-based controls (45.1 ± 13.6 years, 5691 men). The six-item Kessler scale (K6) test was used as a psychological distress scale. Compared to in the controls, obesity and hyperlipidemia were more common and frequency of a snack or night meal consumption was higher, whereas frequencies of breakfast consumption and vigorous and moderate physical activities were lower in the patients. K6 test scores were higher for underweight or obese people compared to normal or overweight people. A logistic regression analysis showed that the K6 test cut-off score was positively associated with being underweight, hyperlipidemia, and the frequency of a snack or night meal consumption, whereas it was negatively associated with the frequency of breakfast consumption in the patients. Logistic regression analyses showed that self-reported depression was positively associated with metabolic diseases and the frequency of a snack or night meal consumption, whereas it was negatively associated with the frequency of breakfast consumption. The observed associations of depression with BMI classification, metabolic disease, and lifestyle suggest that lifestyle and related physical conditions are involved in at least a portion of depressive disorders.

Sexually dimorphic deficits of prepulse inhibition in patients with major depressive disorder and their relationship to symptoms: A large single ethnicity study

BACKGROUND Sensorimotor gating deficits as measured by prepulse inhibition (PPI) of acoustic startle reflex have been repeatedly observed in patients with schizophrenia. However, studies investigating PPI in patients with major depressive disorder (MDD) are scarce, and this issue remains to be elucidated. METHODS Subjects were 221 patients with MDD and 250 age-matched healthy comparison subjects. Depressive symptoms were assessed by the 21-item version of the Hamilton Depression Rating Scale (HAM-D21), and the scores were divided into six factors. Thirty-five trials of startle reflex to pulse alone and pulse with prepulse were measured by electromyography. Startle magnitude, habituation, and PPI were compared between patients and comparisons stratified by sex. Relationships of startle measures to symptoms and antidepressant medication were assessed. RESULTS Male patients showed significantly reduced PPI compared to male comparisons, while no significant PPI difference was found between female patients and comparisons. HAM-D21 total score and several subscales were significantly correlated with PPI only in male patients. The effect of antidepressant medication was not significant for either male or female patients. LIMITATIONS Possible effects of the menstrual cycle could not be excluded among female subjects. CONCLUSIONS These findings suggest that male patients with MDD show sensorimotor gating deficits in a state-dependent manner. However, we obtained no evidence for such abnormalities in female patients with MDD.

Association between iron‐deficiency anemia and depression: A web‐based Japanese investigation

This web‐based survey aimed to examine the relation between iron‐deficiency anemia and depression in 11 876 Japanese participants.

Association of obesity with cognitive function and brain structure in patients with major depressive disorder

BACKGROUND Obesity has been implicated in the pathophysiology of major depressive disorder (MDD), which prompted us to examine the possible association of obesity with cognitive function and brain structure in patients with MDD. METHODS Three hundred and seven patients with MDD and 294 healthy participants, matched for age, sex, ethnicity (Japanese), and handedness (right) were recruited for the study. Cognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). Gray and white matter structures were analyzed using voxel-based morphometry and diffusion tensor imaging in a subsample of patients (n = 114) whose magnetic resonance imaging (MRI) data were obtained using a 1.5 T MRI system. RESULTS Verbal memory, working memory, motor speed, attention, executive function, and BACS composite scores were lower for the MDD patients than for the healthy participants (p < 0.05). Among the patient group, working memory, motor speed, executive function, and BACS composite scores were lower in obese patients (body mass index ≥ 30, n = 17) than in non-obese patients (n = 290, p < 0.05, corrected). MRI determined frontal, temporal, thalamic, and hippocampal volumes, and white matter fractional anisotropy values in the internal capsule and left optic radiation were reduced in obese patients (n = 7) compared with non-obese patients (n = 107, p < 0.05, corrected). LIMITATIONS Sample size for obese population was not very large. CONCLUSIONS Obesity is associated with decreased cognitive function, reduced gray matter volume, and impaired white matter integrity in cognition-related brain areas in patients with MDD.

Sensorimotor Gating in Depressed and Euthymic Patients with Bipolar Disorder: Analysis on Prepulse Inhibition of Acoustic Startle Response Stratified by Gender and State

Background Prepulse inhibition (PPI) of the acoustic startle reflex is an operational measure of sensorimotor gating. The findings on PPI deficits in bipolar disorder (BD) are inconsistent among studies due to various confounding factors such as gender. This study aimed to assess sensorimotor gating deficits in patients with BD stratified by gender and state (depressed/euthymic), and to explore related clinical variables. Methods Subjects were 106 non-manic BD patients (26 BD I and 80 BD II; 63 with depression and 43 euthymic) and 232 age-, gender-, and ethnicity-matched (Japanese) healthy controls. Depression severity was assessed using the Hamilton Depression Rating Scale-21. The electromyographic activity of the orbicularis oculi muscle was measured by a computerized startle reflex test unit. Startle magnitude, habituation, and PPI were compared among the three clinical groups: depressed BD, euthymic BD, and healthy controls. In a second analysis, patients were divided into four groups using the quartile PPI levels of controls of each gender, and a ratio of the low-PPI group (<1st quartile of controls) was compared. Effects of psychosis and medication status were examined by the Mann–Whitney U test. Clinical correlates such as medication dosage and depression severity with startle measurements were examined by Spearman’s correlation. Results Male patients with depression, but not euthymic male patients, showed significantly lower PPI at a prepulse of 86 dB and 120 ms lead interval than did male controls. More than half of the male patients with depression showed low-PPI. In contrast, PPI in female patients did not differ from that in female controls in either the depressed or euthymic state. Female patients with active psychosis showed significantly lower PPI than those without psychosis. Female patients on typical antipsychotics had significantly lower PPI, than those without such medication. PPI showed a significant positive correlation with lamotrigine dosage in male patients and lithium dosage in female patients. Conclusion These findings suggest that sensorimotor gating is impaired in male BD patients with depression. However, we obtained no evidence for such abnormalities in female BD patients except for those with current psychosis. The observed associations between medication and startle measurements warrant further investigation.

Association between lower estimated premorbid intelligence quotient and smoking behavior in patients with schizophrenia

Aim We aimed to investigate the involvement of premorbid intelligence quotient in higher prevalence of smoking in patients with schizophrenia. Methods Participants included 190 patients with schizophrenia (mean ± standard deviation age: 37.7 ± 10.8 years; 88 males and 102 females) and 312 healthy individuals (mean ± standard deviation age: 38.1 ± 13.8; 166 males and 146 females), matched for age, sex, and ethnicity (Japanese). Premorbid intelligence quotient was estimated using the Japanese Adult Reading Test and distress symptoms were assessed using the Hopkins Symptom Check List. Current smoking information was collected according to self-declarations. Results As expected, the smoking rate was higher, while mean education level and Japanese Adult Reading Test scores were significantly lower, in patients with schizophrenia than in healthy individuals (p < 0.01). The mean education level and Japanese Adult Reading Test scores were significantly lower in the smoker group than in the non-smoker group in both patients and healthy individuals (p < 0.05). In the patient group alone, Hopkins Symptom Check List subscale and total scores were significantly higher in the smoker group than in the non-smoker group (p < 0.05). A multivariate regression analysis showed that the Japanese Adult Reading Test score was a significant and negative predictor for smoking (p < 0.001, odds ratio = 0.97; 95% confidence interval: 0.96–0.99). Conclusion Our results suggest that lower estimated premorbid intelligence quotient is an important variable in elucidating smoking behavior in humans and may be associated with higher prevalence of smoking in patients with schizophrenia.