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

OBJECTIVE: 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. METHODS: We retrospectively examined clinical data for 99 female inpatients (mean age 30.9 ± 10.7 years; range, 9 - 56 years). RESULTS: 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. CONCLUSIONS: 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.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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

AIM: 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). METHODS: 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. RESULTS: PDD patients had significantly reduced oxyHb changes in the prefrontal cortex (PFC) compared to healthy controls. CONCLUSION: PFC dysfunction may exist in PDD.

Clinical correlates associated with cognitive dysfunction in people with schizophrenia.

AIMS: The purpose of the present study was to investigate the correlation between cognitive function and clinical variables in people with schizophrenia. METHODS: The subjects were 61 stabilized outpatients with schizophrenia (DSM-IV). Their mean age was 40.1 (SD = 12.2) years. All subjects gave written informed consent to participate in the research. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale. RESULTS: The Positive and Negative Syndrome Scale Negative syndrome score was significantly correlated with verbal memory score (r = -0.37, P < 0.01), working memory score (r = 0.38, P < 0.01), attention and speed of information processing score (r = -0.51, P < 0.01), verbal fluency score (r = -0.39, P < 0.01), and composite score (r = -0.54, P < 0.01). In addition, the Drug-Induced Extrapyramidal Symptoms Scale score was significantly correlated with attention and speed of information processing (r = -0.45, P < 0.01), and composite score (r = -0.41, P < 0. 01). Dose of antipsychotics and anti-Parkinson drugs was not significantly correlated with the Brief Assessment of Cognition in Schizophrenia scores. CONCLUSIONS: These results indicate that cognitive dysfunction of people with schizophrenia might be associated with negative and drug-induced extrapyramidal symptoms, suggesting that their minimization would be important for improving cognitive dysfunction.

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.

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.

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.

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.

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

PURPOSE: 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. PARTICIPANTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

Lithium effects on brain glutamatergic and GABAergic systems of healthy volunteers as measured by proton magnetic resonance spectroscopy.

Lithium is a first-line medicinal treatment for acute bipolar disorder and is also used prophylactically in manic depressive illnesses; however, its mechanism of action is still largely unknown. Animal and human studies have suggested that lithium modulates glutamatergic and GABAergic neurotransmissions. The aim of this study is to investigate the effects of lithium on brain glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) levels in healthy individuals using proton magnetic resonance spectroscopy (1H-MRS). In vivo 3 Tesla 1H-MRS was performed on the anterior cingulate cortex and bilateral basal ganglia initially and after two weeks of lithium administration on 8 healthy male subjects who had a mean age of 34.9 years. After two weeks of lithium administration, Gln significantly decreased in the left basal ganglia and showed a decreasing trend in the right basal ganglia. Additionally, Glu+Gln (Glx) significantly decreased in the right basal ganglia and showed a decreasing trend in the left basal ganglia. Glu did not significantly change in any of the three tested areas, and GABA exhibited no significant change after the lithium administration when measured in the anterior cingulate cortex and left basal ganglia. This study is the first to demonstrate that subchronic lithium treatment decreases Gln and Glx levels in the bilateral basal ganglia of healthy individuals. Our finding might suggest that the decrease of Glx levels is associated with the pharmacological actions of subchronic lithium treatment.

Subjective and objective quality of life, levels of life skills, and their clinical determinants in outpatients with schizophrenia.

The purpose of the present study is to investigate the relationships among subjective and objective quality of life (QOL), and levels of life skills, and their clinical determinants in outpatients with schizophrenia by using schizophrenia disease-specific QOL measures. Data collected from 64 outpatients were analyzed. Subjective QOL was measured with the Schizophrenia Quality of Life Scale (SQLS) and objective QOL with the Quality of Life Scale (QLS). Patients' family members completed the Life Skills Profile (LSP). Clinical symptoms were also assessed with several scales including the Brief Psychiatric Rating Scale (BPRS) and the Calgary Depression Scale for Schizophrenia (CDSS). Only the motivation/energy scale, but not the other scales of the SQLS, correlated with the QLS. The LSP rated by the family showed significant correlations with both the SQLS and the QLS. The CDSS score predicted each scale of the SQLS, and the BPRS negative symptoms score predicted the QLS. The LSP was predicted by the BPRS negative symptoms score and the CDSS score independently. These results indicate that the patient's QOL could be predicted by the life skills measured by a family member and suggest that active treatment for depressive and negative symptoms might be recommended to improve the patient's QOL and life skills.

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.

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.

Relationship between social and cognitive functions in people with schizophrenia.

PURPOSE: The purpose of the present study was to examine clinical factors related to social function in people with schizophrenia. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

Proton magnetic resonance spectroscopy reveals an abnormality in the anterior cingulate of a subgroup of obsessive-compulsive disorder patients.

Numerous neuroimaging studies have suggested that obsessive-compulsive disorder (OCD) patients had a neurobiological abnormality in the frontal-subcortical circuits. On the other hand, there are distinct differences in the responses to pharmacological treatment among OCD patients. In the present study, we measured the concentration of N-acetyl aspartate (NAA), a putative marker of neuronal viability, with proton magnetic resonance spectroscopy (MRS) in OCD patients with different pharmacological responses. Participants comprised 20 patients and 26 healthy control subjects. OCD patients were divided into three groups according to the pharmacological response; responders to a selective serotonin reuptake inhibitor (SSRI) (group A: n=7), responders to SSRI with an atypical antipsychotic (group B: n=8) and non-responders to either SSRI or SSRI with an atypical antipsychotic (group C: n=5). Short echo proton MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia and the left prefrontal lobe of subjects. A significantly lower NAA concentration was observed only in group B compared with control subjects in the anterior cingulate. Our results suggest that a subgroup of OCD patients who respond to an SSRI with an atypical antipsychotic have distinct biological abnormalities in the anterior cingulate.