Predictors of life skills in people with schizophrenia

Objective : The purpose of the present study is to examine clinical factors related to life skills in people with schizophrenia. Method : The participants were 51 stabilized outpatients with schizophrenia. Their mean age was 38.91 (SD = 10.73) years. Life skills were assessed using the Life skills profile (LSP). Cognitive function was evaluated with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Clinical symptoms were assessed using the Positive and Negative Syndrome scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Results : Cognitive function was not correlated with the LSP scores at all. Among clinical symptoms, scores of the PANSS positive and negative syndrome scales, the CDSS, and the DIEPSS had negative correlations with the LSP total score and the subscales. Stepwise regression analyses showed that the CDSS and PANSS negative syndrome scale scores were independent predictors of the LSP total score and two of the subscales. Conclusions : These results indicate that cognitive function is not associated with life skills but clinical symptoms such as depressive and negative symptoms have considerable impacts on life skills in people with schizophrenia. J. Med. Invest. 67 : 75-82, February, 2020.

The Journal of Medical Investigation : JMI


Behavioral and psychological symptoms of dementia (BPSD) and care burden : Examination in the facility staff for elderly residents.

Purpose : We investigated the cognitive function, behavioral and psychological symptoms of dementia (BPSD), and activities of daily living (ADLs) of elderly individuals admitted in care facilities. Moreover, the factors affecting the care burden experienced by facility staffs were examined. Method : 24 care facilities for elderly individuals participated in the study. The Revised Hasegawa Dementia Scale (HDS-R), Japanese version of the Neuropsychiatric Inventory (NPI), and Crichton Geriatric Behavioral Rating Scale (CGBRS) were used to evaluate cognitive function, BPSD, and ADL, respectively. The short Japanese version of the Zarit Burden Interview was used to assess the care burden. A multiple regression analysis was conducted with data obtained from 464 elderly individuals who fulfilled all the scales. Results : The care burden was correlated to the scores of HDS-R, but not with those of dysphoria/depression and disinhibition of NPI, restlessness of CGBRS, and subjective mood of CGBRS (R2 = 0.309, p < 0.005). Conclusion : Dysphoria/depression, disinhibition, restlessness, and subjective mood, but not cognitive decline, have an effect on the care burden experienced by facility staffs who manage elderly individuals. These results indicated that the appropriate diagnosis and treatment of BPSD are important in reducing the burden of facility staffs. J. Med. Invest. 67 : 236-239, August, 2020.


A Case of Bipolar Disorder in which Mood Fluctuation and Symptoms of Eating Disorder Interlocked for a Long Period of Time : Considerations on the Differential Diagnosis and the Interaction between the Pathogeneses of the Disorders

長期にわたり気分の変動と摂食障害の症状が連動した双極性障害の1例 鑑別診断と病因の相互作用に関する考察


Negative and positive self-thoughts predict subjective quality of life in people with schizophrenia.

Recently, cognitive variables such as negative and positive self-belief and thoughts have attracted much attention because they are associated with functional outcomes and quality of life (QOL). However, it is unclear how cognitive variables affect subjective and objective QOL. This study aimed to investigate the relationship of negative and positive self-belief and thoughts with subjective and objective QOL. Thirty-six people with schizophrenia participated in this study. Subjective and objective QOL were assessed with the Schizophrenia Quality of Life Scale (SQLS) and Quality of Life Scale (QLS), respectively. Neurocognitive function was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Clinical symptoms were assessed with the Positive and Negative Syndrome Scale and Calgary Depression Scale for Schizophrenia. Side effects were assessed with the Drug-induced Extrapyramidal Symptoms Scale (DIEPSS). Negative and positive self-belief and thoughts were assessed with the Defeatist Performance Belief Scale and Automatic Thoughts Questionnaire-Revised. A generalized linear model was tested, with subjective and objective QOL as the response variable and symptoms, neurocognitive function, and cognitive variables that were significantly correlated with subjective and objective QOL as explanatory variables. In the schizophrenia group, the common objects score on the QLS was predicted by the composite BACS score, and the total QLS score was predicted by the DIEPSS score. Motivation and Energy, Psychosocial, and Symptoms and Side effects scores on the SQLS were predicted by depression and by negative automatic thought (NAT) and positive automatic thought (PAT). Our results indicated that key targets for improving objective and subjective QOL in people with schizophrenia are side effects, neurocognitive function, depression, and NAT and PAT.


Turning on the Left Side Electrode Changed Depressive State to Manic State in a Parkinson's Disease Patient Who Received Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Case Report.

No previous reports have described a case in which deep brain stimulation elicited an acute mood swing from a depressive to manic state simply by switching one side of the bilateral deep brain stimulation electrode on and off. The patient was a 68-year-old woman with a 10-year history of Parkinson's disease. She underwent bilateral subthalamic deep brain stimulation surgery. After undergoing surgery, the patient exhibited hyperthymia. She was scheduled for admission. On the first day of admission, it was clear that resting tremors in the right limbs had relapsed and her hyperthymia had reverted to depression. It was discovered that the left-side electrode of the deep brain stimulation device was found to be accidentally turned off. As soon as the electrode was turned on, motor impairment improved and her mood switched from depression to mania. The authors speculate that the lateral balance of stimulation plays an important role in mood regulation. The current report provides an intriguing insight into possible mechanisms of mood swing in mood disorders.

Clinical Psychopharmacology and Neuroscience


Relationship between social and cognitive functions in people with schizophrenia

The purpose of the present study was to examine clinical factors related to social function in people with schizophrenia. The participants were 55 stabilized outpatients with schizophrenia. Their mean age was 39.36 (SD =10.65) years. Social function was assessed using the Quality of Life Scale (QLS). Cognitive function was evaluated with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale. Neither the MCCB cognitive domain score nor composite score was correlated with the QLS scores. However, of the 10 MCCB subtests, the Trail Making Test Part A and the Brief Assessment of Cognition in Schizophrenia-Symbol Coding (BACS-SC) scores were positively correlated with the QLS scores. Among clinical variables, especially the PANSS negative syndrome scale score had a strong negative correlation with the QLS scores. Stepwise regression analyses showed that the PANSS negative syndrome scale score was an independent predictor of the QLS scores, and although the BACS-SC score predicted the QLS common objects and activities subscale score, the association was not so strong compared to the PANSS negative syndrome scale score. These results indicate that speed of processing evaluated by BACS-SC could predict some aspect of social function but negative symptoms have a much stronger impact on global social function in people with schizophrenia.


Prefrontal cortex activation during neuropsychological tasks might predict response to pharmacotherapy in patients with obsessive-compulsive disorder.

We investigated oxyhemoglobin change in the prefrontal cortex (PFC) of patients with obsessive-compulsive disorder (OCD) who showed different responses to pharmacotherapy during neuropsychological tasks with near-infrared spectroscopy. A total of 42 patients with OCD (mean age: 35.6±9.6 years, 14 men, 28 women) and healthy control subjects (mean age: 35.4±9.7 years, 13 men, 29 women) were selected. Patients with OCD were divided into three groups (responders to selective serotonin-reuptake inhibitors (SSRIs), responders to SSRIs with antipsychotics, and nonresponders to SSRIs and SSRIs with antipsychotics) based on pharmacological response. We investigated oxyhemoglobin change in the PFC of subjects during Stroop tasks and a verbal fluency test with near-infrared spectroscopy. Responders to SSRIs showed smaller activation compared to control subjects during the Stroop incongruent task and verbal fluency test, but not during the Stroop congruent task. In contrast, responders to SSRIs with antipsychotics showed smaller activation compared to control subjects during all three tasks. Our results suggest that activation of the PFC during Stroop tasks might predict responses to pharmacotherapy of patients with OCD.


1H-magnetic resonance spectroscopy study of glutamate-related abnormality in bipolar disorder.

Previous studies of patients with bipolar disorder (BD) using magnetic resonance spectroscopy (MRS) have shown neurophysiological abnormalities related to the glutamate (Glu)-glutamine (Gln) cycle, membrane turnover, and neuronal integrity, although the results were neither consistent nor conclusive. Recently it has been reported the Gln/Glu ratio is the most useful index, quantifying neuronal-glial interactions and the balance of glutamatergic metabolites In this MRS study, we elucidated the abnormalities of metabolites in a larger sample of patients with BD with a high-field MRI system. Sixty-two subjects (31 patients with BD and 31 healthy controls [HC]) underwent 3T proton MRS (1H-MRS) of the anterior cingulate cortex (ACC) and left basal ganglia (ltBG) using a stimulated echo acquisition mode (STEAM) sequence. After verifying the data quality, 20 patients with BD and 23 age- and gender-matched HCs were compared using repeated-measures analysis of covariance (ANCOVA). Compared to the HC group, the BD group showed increased levels of Gln, creatine (Cr), N-acetyl aspartate (NAA), choline (Cho), and an increased ratio of Gln to Glu in the ACC, and increased Gln and Cho in the ltBG. These findings remained after the participants with BD were limited to only euthymic patients. After removing the influence of lithium (Li) and sodium valproate (VPA), we observed activated glutamatergic neurotransmission in the ACC but not in the ltBG. The present findings are cross-sectional and metabolites were measured in only two regions. Our results support a wide range of metabolite changes in patients with BD involved in glutamatergic neurotransmission, membrane turnover, and neuronal integrity. Moreover, the elevation of Gln/Glu ratio suggested that hyperactivity of glutamatergic neurotransmission in the ACC is a disease marker for BD.


Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder.

Selective serotonin reuptake inhibitors (SSRI) are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics. We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD. While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses. Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients.


No association between BDNF Val66Met polymorphism and treatment response in obsessive-compulsive disorder in the Japanese population.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, and it promotes the development and function of dopaminergic and serotonergic neurons. The Met allele of the BDNF Val66Met polymorphism is associated with a decrease in activity-dependent secretion of BDNF compared with the Val allele, and a number of studies have provided evidence for the association between this polymorphism and obsessive-compulsive disorder (OCD). The purpose of this study was to investigate whether this functional variant of the BDNF gene is associated with OCD and treatment response in patients with OCD in the Japanese population. We first performed a case-control association study between the BDNF Val66Met polymorphism and OCD (175 cases and 2,027 controls). Then, we examined an association between this polymorphism and treatment response in 96 patients with OCD. We found no significant association between the Met allele and OCD risk or between the Met allele and treatment responses to selective serotonin reuptake inhibitors or serotonin reuptake inhibitor with an atypical antipsychotic (P>0.05). Our results suggest that the BDNF Val66Met polymorphism may not be associated as a risk factor for developing OCD or with therapeutic response in patients with OCD in the Japanese population.


Risk factors for refeeding hypophosphatemia in Japanese inpatients with anorexia nervosa.

Refeeding in patients with anorexia nervosa (AN) is associated with a risk of refeeding syndrome, which is a disruption in metabolism with a variety of features including hypophosphatemia. We evaluated the risk factors for refeeding hypophosphatemia (RH) during nutritional replenishment in Japanese patients with AN. We retrospectively examined clinical data for 99 female inpatients (mean age 30.9 ± 10.7 years; range, 9 - 56 years). RH (phosphate < 2.3 mg/dL) occurred within 4.8 ± 3.7 days of hospital admission and was still observed at 28 days after admission in 21 of the 99 cases (21.2%). Oral or intravenous phosphate was given to some patients to treat or prevent RH. Patients with RH had a significantly lower body mass index, were older, and had higher blood urea nitrogen than those without RH. Severe complications associated with RH were recorded in only one patient who showed convulsions and disturbed consciousness at Day 3 when her serum phosphate level was 1.6 mg/dL. The significant risk factors for RH that we identified were lower body mass index, older age, and higher blood urea nitrogen at admission. No significant difference in total energy intake was seen between the RH and no RH groups, suggesting that RH may not be entirely correlated with energy intake. Precisely predicting and preventing RH is difficult, even in patients with AN who are given phosphate for prophylaxis. Thus, serum phosphate levels should be monitored for more than 5 days after admission.

The International Journal of Eating Disorders


成人高機能自閉症スペクトラム障害におけるWechsler式知能検査と自閉症スペクトラム指数との関連


No association between the COMT Val158Met polymorphism and the long-term clinical response in obsessive-compulsive disorder in the Japanese population.

Catechol-O-methyltransferase (COMT) is an enzyme that participates in the metabolic inactivation of dopamine and norepinephrine, and the Met allele of the COMT Val158Met polymorphism is associated with lower enzymatic activity. The purpose of the present study was to investigate whether this functional variant is associated with obsessive-compulsive disorder (OCD) and the clinical responses in OCD. We first performed a case-control association study between the COMT Val158Met polymorphism and OCD (171 cases and 944 controls). Then, we examined the association between this polymorphism and the clinical responses in 91 of the OCD patients. Our study did not find a significant association between the Met allele and OCD risk or between the Met allele and clinical responses (p > 0.05). The present case-control/pharmacogenetic study did not provide clear evidence that the COMT Val158Met polymorphism is a predictor of OCD or of OCD patients' clinical responses.


Association of autism tendency and hemodynamic changes in the prefrontal cortex during facial expression stimuli measured by multi-channel near-infrared spectroscopy.

The aim of this study is to examine the hemodynamic changes induced by the cognitive process of facial expression by using multi-channel near-infrared spectroscopy in healthy subjects with varying degrees of autism tendency. Subjects were 38 volunteers, 20 men and 18 women. Autism tendency was measured by the Autism Spectrum Quotient. The hemodynamic changes in the prefrontal cortex were measured by 24-channel near-infrared spectroscopy system, while subjects were asked to judge their own emotional response to standardized pictures of eight kinds of facial expressions on a computer screen. There were significant negative correlations between Autism Spectrum Quotient scores and accuracy of fearful expression recognition as well as increases in the concentration of oxygenated hemoglobin in response to four kinds of emotional faces (fear, contempt, sadness and disgust). Our findings suggest that the greater tendency to autism that subjects have, the more difficulty they have in recognizing a fearful expression and the less hemodynamic change in the prefrontal cortex they show in response to negative facial expressions.


Japanese Journal of Child and Adolescent Psychiatry

児童青年精神医学とその近接領域


Prefrontal activation during two Japanese Stroop tasks revealed with multi-channel near-infrared spectroscopy.

The Stroop task is sometimes used in psychiatric research to elicit prefrontal activity, which presumably reflects cognitive functioning. Although there are two Stroop tasks (Kana script and Kanji script) in Japan, it is unclear whether these tasks elicit the same hemoglobin changes. Moreover, it is unclear whether psychological conditions or characteristics influence hemoglobin changes in the Japanese Stroop task. The aim of this study was to clarify whether hemoglobin changes elicited by the two Japanese Stroop tasks accurately reflected cognitive functioning. Hemoglobin changes were measured with multi-channel near-infrared spectroscopy (NIRS) in 100 healthy Japanese participants performing two Japanese Stroop tasks. The Beck-Depression Inventory (BDI), State-Trait-Anxiety Inventory (STAI), and Maudsley Obsessive Compulsive Inventory (MOCI) were administered to participants to identify psychological conditions or personality characteristics. Compared with the Kanji task, the Kana task produced a greater Stroop effect and a larger increase in oxyhemoglobin (oxy-Hb) concentration. Moreover there were no significant correlations between oxy-Hb concentration and BDI, STAI-trait, STAI-state, or MOCI scores. Therefore we found that a participant's psychological conditions or characteristics did not influence the hemodynamic changes during either task. These data suggest the Kana Stroop task is more useful than the Kanji Stroop task for NIRS studies in psychiatric research.

The Journal of Medical Investigation : JMI


Psychiatric symptoms in a patient with isolated adrenocorticotropin deficiency: case report and literature review.

We report a 59-year-old man with isolated adrenocorticotropin (ACTH) deficiency. The patient presented with sudden onset of delusions and hallucinations at the age of 54, which resolved gradually without treatment. Subsequently, the patient manifested stereotypy, wandering, hypobulia, and autistic symptoms, and was treated with antipsychotics for 1 year without any improvement. He suffered from neuroleptic malignant syndrome-like symptoms at the age of 59. A thorough endocrine assessment revealed isolated ACTH deficiency. After hydrocortisone supplementation, the physical and psychiatric symptoms improved dramatically. Clinicians should consider this rare disease when diagnosing patients with refractory psychiatric symptoms and unique physical symptoms of isolated ACTH deficiency.


[Multi-channel near-infrared spectroscopy shows reduced activation in the prefrontal cortex during facial expression processing in pervasive developmental disorder]


多チャンネル近赤外線スペクトロコピーが示す広汎性発達障害の表情処理過程における前頭前野の賦活反応性の低下


DNA Methylation Signatures of Peripheral Leukocytes in Schizophrenia.

Schizophrenia (SCZ) is a complex psychiatric disease with a lifetime morbidity rate of 0.5-1.0 %. To date, aberrant DNA methylation in SCZ has been reported in several studies. However, no comprehensive studies using medication-free subjects with SCZ have been conducted. In addition, most of these studies have been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions, so little is known about the DNA methylation signatures across the whole genome in SCZ. Genome-wide DNA methylation profiling (485,764 CpG sites) of peripheral leukocytes was conducted in the first set of samples (24 medication-free patients with SCZ and 23 non-psychiatric controls) using Infinium HumanMethylation450 Beadchips. Second, a monozygotic twin study was performed using three pairs of monozygotic twins that were discordant for SCZ. Finally, the data from these two independent cohorts were compared. A total of 234 differentially methylated CpG sites that were common between these two cohorts were identified. Of the 234 CpG sites, 153 sites (65.4 %) were located in the CGIs and in the regions flanking CGIs (CGI: 40.6 %; CGI shore: 13.3 %; CGI shelf: 11.5 %). Of the 95 differently methylated CpG sites in the CGIs, most of them were located in the promoter regions (promoter: 75.8 %; gene body: 14.7 %; 3'-UTR: 2.1 %). Aberrant DNA methylation in SCZ was identified at numerous loci across the whole genome in peripheral leukocytes using two independent sets of samples. These findings support the notion that altered DNA methylation could be involved in the pathophysiology of SCZ.


Clinical correlates associated with cognitive dysfunction in people with schizophrenia.


Relationship between nutrition and risk for dementia

メンタルヘルスと栄養 認知症と栄養

Japan has rapidly been becoming an aged society. Most of people are eager to grow olderhealthily. One of the most important things for aged people is how to prevent risks for dementia.It is well known that hypertention, hyperlipemia and diabetes are risk factors for vasucular dementia.Moreover recently it comes to be clear that diabetes increase the risk not only for vasucular dementiabut also for Alzheimer's disease. Mediterranean diet is well-known to prevent Alzheimerdisease. A number of prospective epidemiologic studies have found association between nutritionand dementia. For example, n‐3fatty acid, vitamins and polyphenol may be associated with decreaseof the risk for dementia. It may also be useful to prevent metabolic syndrome before aging. It isnecessary for all to mind the relationship between diet and dementia.


Multi-channel near-infrared spectroscopy reveals reduced activation in the prefrontal cortex during the facial expression processing in patients with pervasive developmental disorders

The purpose of the present study was to investigate whether individuals with pervasive developmental disorders (PDD) show differential activation during an emotional activation task compared with age- and sex-matched controls, by measuring changes in the concentration of oxygenated (oxyHb) and deoxygenated (deoxyHb) hemoglobin, using near-infrared spectroscopy (NIRS). Fourteen patients with PDD and 14 age- and sex-matched healthy controls participated in the study. The relative changes of concentrations of oxyHb and deoxyHb were measured on NIRS during an implicit processing task of fearful expression using Japanese standard faces. PDD patients had significantly reduced oxyHb changes in the prefrontal cortex (PFC) compared to healthy controls. PFC dysfunction may exist in PDD.


両側視床下核深部脳刺激術を施行され左側電極Onによってうつ状態から躁状態に転じたパーキンソン病の一例


自閉症スペクトラムと青年成人期精神障害の接点 自閉症スペクトラムと強迫性障害

自閉症スペクトラムと青年成人期精神障害の接点 自閉症スペクトラムと強迫性障害

児童青年精神医学とその近接領域

児童青年精神医学とその近接領域


Quality of life and cognitive dysfunction in people with schizophrenia

The main purpose of the present study was to examine the relationship between quality of life (QOL) and cognitive dysfunction in schizophrenia. Subjects were 61 stabilized outpatients. Quality of life and cognitive function were assessed using the Quality of Life Scale (QLS) and the Brief Assessment of Cognition in Schizophrenia (BACS), respectively. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). The BACS composite score and the BACS Verbal memory score were positively correlated with the QLS total score and two subscales. The BACS Attention and speed of information processing score had positive correlation with the QLS total and all the subscales scores. The PANSS Positive and Negative syndrome scores also had significant correlations with the QLS total score and all of the subscales. In addition, the CDSS score was negatively correlated with the QLS total score and some of the subscales. Stepwise regression analysis showed that the BACS Attention and speed of information processing score was an independent predictor of the QLS total score but it was less associated with the QLS than the PANSS Negative syndrome score and the CDSS score. The results suggest that negative and depressive symptoms are important factors on patients' QOL and also support the view that cognitive performance provides a determinant of QOL in patients with schizophrenia.

Progress in Neuro-Psychopharmacology & Biological Psychiatry


GABA concentration in schizophrenia patients and the effects of antipsychotic medication: a proton magnetic resonance spectroscopy study.

Gamma-amino butyric acid (GABA) is thought to play a role in the pathophysiology of schizophrenia. High magnetic field proton magnetic resonance spectroscopy ((1)H-MRS) provides a reliable measurement of GABA in specific regions of the brain. This study measured GABA concentration in the anterior cingulate cortex (ACC) and in the left basal ganglia (ltBG) in 38 patients with chronic schizophrenia and 29 healthy control subjects. There was no significant difference in GABA concentration between the schizophrenia patients and the healthy controls in either the ACC (1.36+/-0.45 mmol/l in schizophrenia patients and 1.52+/-0.54 mmol/l in control subjects) or the ltBG (1.13+/-0.26 mmol/l in schizophrenia patients and 1.18+/-0.20 mmol/l in control subjects). Among the right handed schizophrenia patients, the GABA concentration in the ltBG was significantly higher in patients taking typical antipsychotics (1.25+/-0.24 mmol/l) than in those taking atypical antipsychotics (1.03+/-0.24 mmol/l, p=0.026). In the ACC, the GABA concentration was negatively correlated with the dose of the antipsychotics (rs=-0.347, p=0.035). In the ltBG, the GABA concentration was positively correlated with the dose of the anticholinergics (rs=0.403, p=0.015). To the best of our knowledge, this is the first study to have directly measured GABA concentrations in schizophrenia patients using (1)H-MRS. Our results suggest that there are no differences in GABA concentrations in the ACC or the ltBG of schizophrenia patients compared to healthy controls. Antipsychotic medication may cause changes in GABA concentration, and atypical and typical antipsychotics may have differing effects. It is possible that medication effects conceal inherent differences in GABA concentrations between schizophrenia patients and healthy controls.


Gene expression and association analyses of the phosphodiesterase 4B (PDE4B) gene in major depressive disorder in the Japanese population.

The phosphodiesterase 4B (PDE4B) interacts with disrupted-in-schizophrenia 1 (DISC1), which is a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). PDE4B is also important in the regulation of cAMP signaling, a second messenger implicated in learning, memory, and mood. In this study, we determined mRNA expression levels of the PDE4B gene in the peripheral blood leukocytes of patients with MDD and control subjects (n = 33, each). Next we performed two-stage case-controlled association analyses (first set; case = 174, controls = 348; second set; case = 481, controls = 812) in the Japanese population to determine if the PDE4B gene is implicated in MDD. In the leukocytes, a significantly higher expression of the PDE4B mRNA was observed in the drug-naïve MDD patients compared with control subjects (P < 0.0001) and the expression of the MDD patients significantly decreased after antidepressant treatment (P = 0.030). In the association analysis, we observed significant allelic associations of four SNPs (the most significant, rs472952; P = 0.002) and a significant haplotypic association (permutation P = 0.019) between the PDE4B gene and MDD in the first-set samples. However, we could not confirm these significant associations in the following independent second-set of samples. Our results suggest that the PDE4B gene itself does not link to MDD but the elevated mRNA levels of PDE4B might be implicated in the pathophysiology of MDD.

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics


Metabolite changes and gender differences in schizophrenia using 3-Tesla proton magnetic resonance spectroscopy (1H-MRS).

A change in the glutamatergic system is thought to play an important role in the pathophysiology of schizophrenia. The aim of this study was to investigate the changes in metabolites, including glutamate (Glu), in the anterior cingulate cortex (ACC) and the left basal ganglia (ltBG) of patients with chronic schizophrenia using proton magnetic resonance spectroscopy ((1)H-MRS). In addition, since gender differences in this illness were known, we examined the effects of gender on these metabolites. The (1)H-MRS was performed on the ACC and ltBG of 30 patients with schizophrenia and 25 healthy individuals who acted as the control group. The levels of Glu, glutamine (Gln), creatine plus phosphocreatine (Cre), myo-inositol (mI), N-acetylaspartate (NAA), and choline-containing compounds (Cho) were measured. Two-way analysis of variance revealed that the illness significantly affected the levels of Glu and mI in the ACC; both metabolites were lower in the patients with schizophrenia as compared to the control subjects. The results also revealed that gender significantly affected the level of Gln in the ACC and the levels of Cre and NAA in the ltBG; the level of Gln in the ACC were higher in male subjects versus female subjects, whereas Cre and NAA levels in the ltBG were lower in male subjects as compared to female subjects. These results confirmed a change in the glutamatergic system and suggested an involvement of mI in the pathophysiology of schizophrenia.


Predictors of subjective and objective quality of life in outpatients with schizophrenia.

AIM: In recent years, greater attention has been given to quality of life (QOL) in schizophrenia and several studies reported that negative and depressive symptoms and cognitive dysfunction are related to patient QOL. But because a variety of QOL measures have been used in the previous studies, there seems to be no unanimous predictors for subjective and objective QOL. The purpose of the present study was to elucidate the relationship between clinical variables and subjective and objective QOL in outpatients with schizophrenia, using schizophrenia disease-specific QOL measures. Particular attention was paid to cognitive function as a predictor of QOL. METHODS: Schizophrenia symptoms of the Positive and Negative Syndrome Scale (PANSS) were divided into five factors: positive factor, negative factor, cognitive factor, emotional discomfort, and hostility. The study sample consisted of 84 schizophrenia outpatients. Subjective and objective QOL were assessed with Schizophrenia Quality of Life Scale (SQLS) and the Quality of Life Scale (QLS), respectively. RESULTS: Subjective QOL correlated significantly with emotional discomfort, positive factor, negative factor, extrapyramidal symptoms and cognitive factor, while objective QOL correlated with negative factor, cognitive factor, emotional discomfort, extrapyramidal symptoms, and dose of antipsychotics. Total score and three of four subscales in the QLS correlated significantly with cognitive factor, while cognitive factor had a significant correlation with only one of three scales of SQLS. Stepwise regression showed that subjective QOL was significantly predicted by emotional discomfort and extrapyramidal symptoms, while negative factor was the most important predictor of objective QOL. CONCLUSION: Cognitive dysfunction had a greater influence on objective QOL than subjective QOL. Treating depressive and negative symptoms and extrapyramidal symptoms might contribute to enhanced subjective and objective QOL.


Positive association of the PDE4B (phosphodiesterase 4B) gene with schizophrenia in the Japanese population.

The phosphodiesterase 4B (PDE4B) gene is located at 1p31, a susceptibility region for schizophrenia (SZ). Moreover, PDE4B interacts with DISC1, which is a known genetic risk factor for SZ. Recently, it was reported that the PDE4B gene is associated with SZ in Caucasian and African American populations. In this study, case-controlled association analyses were performed in the Japanese population to determine if the PDE4B gene is implicated in SZ. Thirteen single nucleotide polymorphisms (SNPs) were analyzed in 444 schizophrenic patients and 452 control subjects. Three SNPs (rs2180335, rs910694 and rs472952) were significantly associated with SZ after applying multiple test correction (p=0.039, 0.004 and 0.028). In addition, a significant association was found between specific haplotypes (rs2180335 and rs910694) and SZ (permutation p=0.001). Our result suggests that variations at the PDE4B locus may play a significant role in the etiology of SZ in the Japanese population.


FKBP5, SERT and COMT mRNA expressions in the peripheral leukocytes during menstruation cycle in healthy reproductive females.

There have been several evidences that the mRNA expressions in the peripheral leukocytes may indicate not only physical but also psychological states. The purpose of this study is whether the mRNA expressional changes in the leukocytes are related to the mental states across the menstrual cycle in reproductive healthy female subjects. Thirty-eight female subjects (22.4+/-1.4 year-old) were participated in this study at three menstruation cycle periods (menstrual, follicular and luteal phase). The FKBP5 (FK506-binding protein gene), SERT (serotonin transporter gene) and COMT (catechol-o-methyltransferase gene) mRNA expressions in the leukocytes were determined with hormonal data. The psychological changes were assessed with self-rating hospital anxiety and depression scale (HADS). Only one thirds of subjects (n=12) had regular menstrual cycles during the experiment. So we analyzed the data from these 12 subjects. The anxiety score of each subject was changed across the menstrual cycle (Friedman test: P<0.05). The FKBP5 mRNA expression was significantly lower in the follicular phase than in the other phases but no changes were seen in either SERT or COMT mRNA expressions among the phases. In conclusion, there are differences of HADS anxiety score and FKBP5 mRNA expression in the leukocytes across the menstrual cycle but there is no correlation between anxiety scores and FKBP5 mRNA.


Association between PNPO and schizophrenia in the Japanese population

Accumulating evidence suggests that both homocysteine metabolism and monoaminergic neurotransmitter systems are important in schizophrenia pathology. We hypothesized that the gene PNPO (pyridoxine 5'-phosphatase oxidase gene) might be a candidate for susceptibility to schizophrenia because PNPO encodes pyridoxamine 5'-phosphate oxidase (EC 1.4.3.5), a rate-limiting enzyme in pyridoxal 5'-phosphate (PLP, vitamin B(6)) synthesis. PLP is a metabolically-active form of vitamin B(6) and thus, is required as a co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. We examined 8 single nucleotide polymorphisms (SNPs) in PNPO and its 5'-flanking regions in 359 schizophrenia patients and 582 control subjects. Four marker regions of PNPO showed significant levels of allelic associations with schizophrenia (the highest was rs2325751, P=0.004). In addition, the haplotype case-control study revealed a significant association (permutation P<0.00001) between PNPO and schizophrenia. These findings suggest that variations in PNPO may contribute to overall genetic risk for schizophrenia in the Japanese population.


Clinical Features of Patients with Obsessive-compulsive Disorder showing Different Pharmacological Responses

強迫性障害の薬物応答性と臨床特徴について


Subjective and objective measures of quality of life have different predictors for people with schizophrenia.

This study investigated the relationship between subjective and objective quality of life and assessed predictors in people with schizophrenia. The study population consisted of 99 stabilized outpatients with schizophrenia (DSM-IV) who had been regularly receiving outpatient treatment at the Department of Psychiatry, The Tokushima University Hospital. Subjective and objective quality of life were estimated using the Schizophrenia Quality of Life Scale and the Quality of Life Scale, respectively. Psychiatric symptoms were also measured with the Brief Psychiatric Rating Scale and the Calgary Depression Scale for Schizophrenia. Scores on the Schizophrenia Quality of Life Scale Motivation and Energy scales significantly correlated with the Quality of Life Scale total scores -.40 (p <.001), and with the scores on Interpersonal Relations subscale -.42 (p <.001), Instrumental Role subscale -.28 (p = .005), Intrapsychic Foundations subscale -.39 (p<.001), and Common Objects and Activities subscale -.25 (p =.014). The Schizophrenia Quality of Life Scale Psychosocial scale significantly correlated with only the Quality of Life Scale total score -.20 (p =.05), and there was no significant correlation between the scores on the Schizophrenia Quality of Life Scale Symptoms and Side-effects scales and the Quality of Life Scale. Stepwise regression analyses showed that the Calgary Depression Scale for Schizophrenia score was the most important predictor of each scale of the Schizophrenia Quality of Life Scale, and the Brief Psychiatric Rating Scale Negative Symptoms score was the most important predictor of the Quality of Life Scale total score and each subscale. These results suggest that subjective and objective quality of life have different predictors and should be considered as separate and complementary outcome variables.


Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that promotes several functions of neurons and modulates neurotransmissions. It has been reported that there are alterations of BDNF levels in schizophrenic brains and that BDNF gene expressional changes would be responsible for the etiology of schizophrenia. Recent studies have shown that a variation of BDNF gene (Val66Met polymorphism) affects the function of neurons, and is associated with several neurological and psychiatrical disorders. We investigated the relationship between BDNF Val66Met polymorphism and the onset age as well as levels of clinical symptoms in 159 of chronic schizophrenia in-patients diagnosed by DSM-IV. The mean onset ages were 27.5+/-9.5 for BDNF Val/Val, 25.5+/-7.4 for BDNF Val/Met and 22.9+/-6.0 for BDNF Met/Met and this polymorphism was significantly associated with age at onset (P=0.023). The mean Brief Psychiatric Rating Scale scores (BPRS) were significantly different among those three groups (P=0.003). No significant differences were demonstrated comparing the BDNF genotype distributions of positive and negative family history (P=0.21). Our investigation indicates that the BDNF gene Val66Met polymorphism is related to the onset age of schizophrenia and the levels of clinical symptoms that remain after long-term antipsychotic treatment.


Activation of the prefrontal cortex during the Wisconsin Card Sorting Test as measured by multichannel near-infrared spectroscopy.

The Wisconsin Card Sorting Test (WCST) is a neuropsychological test to evaluate the function of the prefrontal cortex (PFC). However, inconsistent results have been reported concerning whether this task activates the PFC symmetrically or asymmetrically. To investigate the brain activation in the PFC during the WCST, we examined blood oxygenation changes of healthy subjects by using multichannel near-infrared spectroscopy (NIRS). Subjects were 32 healthy volunteers, 18 males and 14 females. The WCST was administered using a computerized version, and the hemodynamic changes of the PFC during the WCST were measured by a 24-channel NIRS system. A bilateral increase in oxygenated hemoglobin (oxyHb) was observed in the PFC in 20 subjects during the WCST. However, 5 subjects showed predominant activation on the left side and 3 subjects one on the right side. No oxyHb change was observed in 4 subjects, although they had good performances in the WCST. These results directly confirmed that the PFC was activated during the WCST in vivo by using the optical technique and suggested that the distribution of the activation in the PFC is different among healthy individuals.


Hemodynamic changes in the prefrontal cortex during mental works as measured by multi channel near-infrared spectroscopy (NIRS)

To investigate the brain activation in the prefrontal cortex (PFC) during mental works, we examined blood oxygenation changes of healthy subjects by using multi channel near infrared spectropcopy (NIRS). It was directly confirmed that the PFC was activated during mental tasks in vivo and it was suggested that distribution of the activation in the PFC is different among healthy individuals.

The Journal of Medical Investigation : JMI


長期にわたる摂食障害が躁状態発症とともに消失した一症例

長期にわたる摂食障害が躁状態発症とともに消失した一症例


発作後もうろう状態時に多飲水し水中毒の症状を呈したてんかん患者の1症例

発作後もうろう状態時に多飲水し水中毒の症状を呈したてんかん患者の1症例


Paroxetineが著効した幼児期発症の社会恐怖の一症例

Paroxetineが著効した幼児期発症の社会恐怖の一症例


薬原性錐体外路症状を有する症例におけるquetiapineへの切り替え効果

薬原性錐体外路症状を有する症例におけるquetiapineへの切り替え効果


強迫性障害におけるproton MRSによる評価 --- 特にグルタミン酸とグルタミン代謝に対して

Japanese Journal of Magnetic Resonance in Medicine


長期にわたる過食と嘔吐がfluvoxamineにより消失した中年男性の一症例

長期にわたる過食と嘔吐がfluvoxamineにより消失した中年男性の一症例


Fluvoxamineとrisperidoneの併用が効果的であった分裂病性人格障害を伴うOCDの一症例

Japanese Journal of Psychiatric Treatment


行為障害 --- 症例と考察

行為障害 --- 症例と考察


研究に関する男女共同参画・ダイバーシティの推進状況に関するアンケート調査-全国の集計結果との比較から見える徳島大学の現状-

本調査では，全国ダイバーシティネットワークの幹事機関である大阪大学と，日本学術会議科学者委員会男女共同参画分科会・同アンケート検討小分科会が共同で実施した「大学・研究機関における男女共同参画・ダイバーシティの推進状況調査」のうち「大学・研究機関における男女共同参画の推進状況に対する意見・感想」について，徳島大学回答分(男性60 件，女性21 件)のみ抽出されたデータを用いて，本学における男女共同参画・ダイバーシティ推進に関する研究者の意識調査を実施した．男女別に集計し，公開されている全国集計結果(計10，105 件)と比較検討することで，全国における本学の位置付けについて分析した． 調査項目は， 1 ．男女共同参画の推進(全般) 2 ．男女共同参画の取り組み 3 ．ワークライフバランス・育児支援サービス 4 ．ダイバーシティ対応 5 ．ハラスメント防止体制 6 ．医学系 の6 項目にわたる．全国と徳島での回答差，また男女間の回答差から，現在の徳島大学の研究者における男女共同参画に対する意識について考察する．

徳島大学人と地域共創センター紀要

徳島大学人と地域共創センター紀要


ステロイド補充により精神症状が改善したACTH単独欠損症の1例

ステロイド補充により精神症状が改善したACTH単独欠損症の1例


Restless legs syndrome with chest and back restlessness as the initial symptom


不安障害に対する評価尺度の使い方

不安障害に対する評価尺度の使い方

第27回国際神経精神薬理学会(CINP)2010総会ニュースレター

第27回国際神経精神薬理学会(CINP)2010総会ニュースレター