Safety of quetiapine fumarate extended release in the treatment of Korean patients with acute schizophrenia.

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of quetiapine fumarate extended release (XR) in the treatment of Korean subjects with acute schizophrenia. METHODS: This was an 8-week, multi-center, open-label, non-comparative study to evaluate the efficacy and safety of quetiapine fumarate XR at a daily dose of 400-800 mg. Changes in total scores on the Positive and Negative Syndrome Scale (PANSS) from baseline to week 8 were analyzed to evaluate the efficacy of quetiapine XR. Additionally, the Clinical Global Impression scale and the Montgomery-Åsberg Depression Rating Scale were administered. RESULTS: The mean change in PANSS total scores was -26.8, and the mean PANSS total score at the endpoint was significantly lower than that at baseline. The mean PANSS positive score, negative score, and general score showed statistically significant reductions at the end of the study. Statistically significant changes were also observed in Clinical Global Impression-Severity and Montgomery-Åsberg Depression Rating Scale scores. The most common treatment-related adverse events in the group receiving quetiapine XR were sedation (10.6%) and constipation (9.6%). CONCLUSIONS: In this study of Korean patients with acute schizophrenia, quetiapine XR showed clinical efficacy and relatively good tolerability.

Sex-different association of DAO with schizophrenia in Koreans.

The gene encoding D-amino acid oxidase (DAO), which acts as a receptor for the schizophrenia-associated neurotransmitter, N-methyl-D-aspartate (NMDA), is regarded as a potential candidate gene for schizophrenia. However, the potential association of the DAO gene with schizophrenia has been the subject of some debate. Here, we tested three single nucleotide polymorphisms (SNPs) of DAO in a group of Korean schizophrenia patients, and found no significant association in the overall study subjects. Interestingly, however, we found gender-specific differences in allele distributions, with SNP rs2070586 appearing to act as a risk allele in female schizophrenia patients, but as a protective allele in males. Our data support the hypothesis that DAO plays a role in schizophrenia, possibly in a gender-dependent manner.

Preliminary evidence on the association between XBP1-116C/G polymorphism and response to prophylactic treatment with valproate in bipolar disorders.

The 116C/G polymorphism in the promoter region of XBP1 is known to be associated with bipolar disorders. The G allele of the XBP1-116C/G polymorphism has reduced XBP1-dependent transcription activity compared with the C allele. Valproate treatment has been known to rescue the impaired response of cells with the G allele. We investigated the hypothesis that the G allele of XBP1-116C/G has better prophylactic treatment response to valproate compared to the C allele. This study involved 51 patients with bipolar disorder who were treated with valproate for prophylactic treatment. Prophylactic treatment response to valproate was retrospectively assessed using a scale described by Grof et al. [Grof, P., Duffy, A., Cavazzoni, P., Grof, E., Garnham, J., MacDougall, M., O'Donovan, C., Alda, M., 2002. Is response to prophylactic lithium a familial trait? Journal of Clinical Psychiatry 63, 942-947.]. We found that the patients with the G allele of XBP1-116C/G showed a better prophylactic treatment response to valproate compared to the C allele. This result is in agreement with in-vitro data showing that valproate ameliorates the endoplasmic reticulum (ER)-stress response compromised by the G allele.

Intramuscular olanzapine versus short-acting typical intramuscular antipsychotics: comparison of real-life effectiveness in the treatment of agitation.

OBJECTIVE: To compare the effectiveness of intramuscular (IM) olanzapine and typical IM antipsychotics in naturalistically treated acutely agitated patients with schizophrenia or acute mania. METHODS: During the acute phase, 2011 inpatients (including emergency settings) were assessed at 2, 24 and 72 h, and 7 days following initial injection and on oral antipsychotic transition. Mean change in agitation was assessed via Positive and Negative Symptom Scale-Excited Component (PANSS-EC) and Clinical Global Impressions-Severity (CGI-S) scores. Response (> or = 40% reduction in baseline PANSS-EC score) was analysed using logistic regression. RESULTS: Significantly greater decreases in PANSS-EC and CGI-S scores were observed in patients receiving IM olanzapine (n = 1294) as their first injection compared with patients receiving other IM antipsychotics (n = 717) (P<0.05; 2 h: effect size 0.1); IM haloperidol treatment (all assessments, P<0.05); and IM zuclopenthixol treatment (2 h, P<0.001). Higher response rates were observed with IM olanzapine compared with other IM antipsychotics at 24 and 72 h, and 7 days (P<0.05). IM olanzapine was associated with fewer extrapyramidal side effects compared with other assessed IM antipsychotics. CONCLUSIONS: IM olanzapine provided somewhat more effective control of acute agitation than other assessed IM antipsychotics.

Association analysis of tissue factor pathway inhibitor polymorphisms and haplotypes with osteonecrosis of the femoral head in the Korean population.

Thrombophilia and hypofibrinolysis have been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Tissue factor pathway inhibitor (TFPI), a multivalent protease inhibitor, is an important regulator of the tissue factor-mediated blood coagulation pathway. Mutations of the TFPI gene can increase the risk of thrombin generation and venous thrombosis. The aim of this study was to evaluate the association of TFPI gene polymorphisms with ONFH. All exons and their boundaries of the TFPI gene, including the -1500 bp promoter region, were directly sequenced in 24 Korean individuals and four sequence variants were identified. These four polymorphisms [-51096 G > A (C-399T), -50984A > G (T-287C), + 24999A > G (Int7 -33T > C), + 37339T > A] were genotyped in 474 ONFH patients and 349 control subjects. The association of genotyped SNPs with ONFH was not found in the present study. The haplotype AAAT of TFPI was significantly associated with total, alcohol-induced, and idiopathic ONFH (p = 0.003, 0.021, and 0.007, respectively), and the haplotype GAAT was significantly associated with total and alcohol ONFH (p = 0.022 and 0.009, respectively). In addition, a new SNP + 37339 T > A in the 3'-UTR of the TFPI gene, was found in the Korean population. To date, this study is the first to show that haplotypes of the TFPI gene are associated with an increased susceptibility for ONFH. The results suggest that genetic variations in TFPI may play an important role in the pathogenesis and risk factors of ONFH.

Brain-derived neurotrophic factor Val/Met polymorphism and bipolar disorder. Association of the Met allele with suicidal behavior of bipolar patients.

BACKGROUND/AIMS: The substitution of valine by methionine in the brain-derived neurotrophic factor (BDNF Val/Met) gene alters the intracellular trafficking and regulated secretion of BDNF. This study tested whether the BDNF Val/Met polymorphism is associated with bipolar disorder in Korean subjects, and whether clinical features vary according to genotype. METHODS: The allelic and genotypic distributions of BDNF Val/Met were determined in a population of 169 bipolar patients and 251 normal controls. Between-genotype comparisons of clinical features were performed without a priori knowledge of the genotype of individual patients. RESULTS: Allelic distributions did not differ significantly between bipolar patients and controls (chi(2) = 0.400, p = 0.821). However, the rate of suicide attempts among the Val/Val (11.3%), Val/Met (28.8%) and Met/Met (38.9%) genotype groups were significantly different (chi(2) = 9.879, p = 0.007). Relative to patients with the Val/Val genotype, those with the Met/Met genotype had a 4.9-fold higher risk of suicide attempts (95% CI, 1.7-14.7). CONCLUSIONS: These findings suggest that BDNF Val/Met is related to the suicidal behavior of bipolar patients, and may have clinical relevance as a biological indicator of bipolar patients at risk of suicide.

Could HTR2A T102C and DRD3 Ser9Gly predict clinical improvement in patients with acutely exacerbated schizophrenia? Results from treatment responses to risperidone in a naturalistic setting.

OBJECTIVE: This study seeks to replicate previous results indicating that T102C in the serotonin 2A receptor (HTR2A) and Ser9Gly in the dopamine D3 receptor (DRD3) were associated with a risperidone response to acutely exacerbated schizophrenia, and to determine whether possession of these alleles predicts clinical improvement in a naturalistic setting. METHODS: We consecutively recruited 100 schizophrenia patients and assessed clinical improvement after 4 weeks of risperidone treatment. RESULTS: The patients with T/T in the HTR2A gene showed less clinical improvement than did those with T/C or C/C (p = 0.044). In the case of the DRD3 gene, we did not find statically significant association with clinical improvement (p = 0.061). When patients were categorized into responders and nonresponders, the C allele was more frequent in responders (OR = 2.28, 95%CI = 1.06-4.91, p = 0.039). When combinations of the two polymorphisms were considered, patients who had T/T in the HTR2A gene and encoded Ser/Ser or Ser/Gly from DRD3 gene had a higher propensity to non-responsiveness compared to other subjects (OR = 3.57, 95%CI = 1.10-11.62, p = 0.039). CONCLUSIONS: Our findings suggest that the HTR2A T102C could be a potential indicator of clinical improvement after risperidone treatment.

Bipolarity in depressive patients without histories of diagnosis of bipolar disorder and the use of the Mood Disorder Questionnaire for detecting bipolarity.

OBJECTIVES: The present study was performed to evaluate the frequency of bipolar disorders among patients (a) presenting with depressive episodes but (b) who have never been diagnosed with bipolar disorder (c) in routine clinical practice in Korean subjects and to identify which clinical features were helpful in discriminating bipolar patients from unipolar patients. In addition, authors assessed the practical use of the Mood Disorder Questionnaire (MDQ) to distinguish bipolar from unipolar disorder in these subjects and tested whether modifications of the MDQ scoring could improve its performance. METHODS: We evaluated consecutive patients who satisfied the inclusion criteria of a current depressive episode, plus at least one previous depressive episode. Subjects were interviewed for diagnosis using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders IV after completing the MDQ. To improve assessment of hypomania history, the interviewer made strenuous efforts to explore a possible history of hypomania, and patient-derived data were supplemented by information from family members or close relatives. RESULTS: Fifty-nine patients (53.2%) were classified as having bipolar disorder, leaving a group of 52 (46.8%) with unipolar depression. Among bipolar disorders, 1.8% (n = 2) had bipolar I disorder; 29.7% (n = 33), bipolar II disorder; 6.3% (n = 7), bipolar III disorder (history of antidepressant-induced hypomania without spontaneous hypomanic episode); and 15.3% (n = 17), bipolar disorder not otherwise specified (1-3 days brief hypomania). Postpartum depression (relative risk [RR] [95% confidence interval {CI}], 2.00 [1.23-3.24]), early age of onset (RR [95% CI], 1.85 [1.30-2.64]), mood lability (RR [95% CI], 1.85 [1.30-2.64]), brief depressive episode (RR [95% CI], 1.66 (1.16-2.37]), bipolar family history (RR [95% CI], 1.62 [1.08-2.43]), history of suicide attempt (RR [95% CI], 1.47 (1.05-2.04]), and alcohol problem (RR [95% CI], 1.45 (1.04-2.02]) were found to have higher risks for bipolar disorder among depressive subjects. We found that a modified scoring of the MDQ (ignoring question on functional impairment and co-occurrence of symptoms) yielded a sensitivity of 0.68 and a specificity of 0.63 for bipolar diagnosis, whereas the figures were 0.29 and 0.77, respectively, with the standard MDQ scoring. CONCLUSIONS: The results of this study clearly indicate that a high frequency of bipolar disorders in depressive patients who have never been diagnosed with bipolar disorders and clinical features indicating bipolarity could help to differentiate bipolar subjects from unipolar subjects. Adapting the standard scoring, the MDQ showed limited use for detecting bipolar disorder; however, if the scoring modification is adapted, the MDQ can offer tolerable sensitivity.

New functional single nucleotide polymorphism (Ala72Ser) in the COMT gene is associated with aggressive behavior in male schizophrenia.

A new functional single nucleotide polymorphism (SNP) Ala72Ser in the COMT gene was discovered recently. The purpose of our study is to examine the association between Ala72Ser and Val158Met functional polymorphisms in COMT gene and homicidal behavior in schizophrenia. DNA was genotyped for the Ala72Ser and Val158Met SNPs of the COMT gene in a sample of 93 schizophrenic patients who committed homicide (H-SCZ) and 100 schizophrenic patients who had never committed homicide (NH-SCZ). A statistically significant difference was found in genotype distribution and allele frequencies in SNP Ala72Ser of COMT gene between H-SCZ and NH-SCZ group. In haplotype analysis, the frequency of the combination of high-high activity allele (Ala-Val) was lower in H-SCZ group than in NH-SCZ group (P = 0.000069). Our study showed a highly significant association between a COMT haplotype of two functional SNPs and aggressive behavior in schizophrenia.

Evaluation of reliability of traditional and computerized neurobehavioral tests.

Most Korean blue-collar workers are taking government-mandated medical screening periodically. The periodic neurobehavioral test provides a great chance to evaluate the functional change of the central nervous system. To utilize periodic neurobehavioral tests effectively, the reliability of currently used neurobehavioral tests needs to be evaluated. Test-retest of neurobehavioral tests were conducted to evaluate the reliability of neurobehavioral tests that are commonly used for Korean workers. The test-retest of five computerized tests, simple reaction time, additions, symbol digit, digit span, and finger tapping speed, and five traditional tests, Benton visual retention, digit symbol, digit span, pursuit aiming, and pegboard, were administered to 85 college students and 35 hospital workers over a 1 month interval. Computerized additions was found to have the highest test-retest reliability coefficient (r=0.90), followed by finger tapping speed (nondominant hand, r=0.89; dominant hand, r=0.85), symbol digit (r=0.82), and digit span (r=0.74). However, only two traditional tests, digit symbol (r=0.86) and pursuit aiming (r=0.72), showed a reliability coefficient greater than 0.70. These results suggest that the computerized additions, symbol digit, finger tapping speed, and traditional digit symbol are more satisfactory for periodical evaluation of the central nervous system of workers exposed to neurotoxic substances in Korea.

Effects of stimulus parameters on motor seizure duration in electroconvulsive therapy.

OBJECTIVE: This study examined the effect of stimulus parameters on the occurrence of adequate seizures and reconsidered the factors related to motor seizure duration. METHODS: The medical records of 187 patients who received ECT in Asan Medical Center from January 2007 to May 2014 were retrospectively reviewed. The starting stimulus dose was determined using a preselected-dose method and the cutoff value to determine the adequate motor seizure duration was 20-25 seconds. The association between seizure parameters and the occurrence of adequate seizure was assessed with logistic regression using a generalized estimating equation. RESULTS: Age (P<0.001), use of mood stabilizers (P=0.002), and benzodiazepine (P<0.001) were significantly lower in sessions with an adequate seizure duration but use of antidepressants (P<0.001) and clozapine (P=0.025) were significantly higher in sessions with an adequate seizure duration. In the generalized estimating equation analyses, after adjustment for age, benzodiazepine dose, and lamotrigine use, charge (odds ratio [OR] =0.999; 95% confidence interval [CI], 0.998-1.000; P=0.005), and train duration (OR =0.632; 95% CI, 0.490-0.817; P<0.001) were significantly associated with the occurrence of adequate seizure. DISCUSSION: Stimulus charge and train duration are significantly associated with motor seizure duration. However, train duration appears to have a greater effect on motor seizure duration. Additionally, age, benzodiazepine dose, and lamotrigine use independently affect motor seizure duration.

Increased diffusivity in gray matter in recent onset schizophrenia is associated with clinical symptoms and social cognition.

INTRODUCTION: Diffusion weighted MRI (dMRI) is a method sensitive to pathological changes affecting tissue microstructure. Most dMRI studies in schizophrenia, however, have focused solely on white matter. There is a possibility, however, that subtle changes in diffusivity exist in gray matter (GM). Accordingly, we investigated diffusivity in GM in patients with recent onset schizophrenia. METHODS: We enrolled 45 patients and 21 age and sex-matched healthy controls. All subjects were evaluated using the short form of the Wechsler Adult Intelligence Scale, the Positive and Negative Syndrome Scale (PANSS), and the video based social cognition scale. DMRI and T1W images were acquired on a 3 Tesla magnet, and mean Fractional Anisotropy (FA), Trace (TR) and volume were calculated for each of the 68 cortical GM Regions of Interest parcellated using FreeSurfer. RESULTS: There was no significant difference of FA and GM volume between groups after Bonferroni correction. For the dMRI measures, however, patients evinced increased TR in the left bank of the superior temporal sulcus, the right inferior parietal, the right inferior temporal, and the right middle temporal gyri. In addition, higher TR in the right middle temporal gyrus and the right inferior temporal gyrus, respectively, was associated with decreased social function and higher PANSS score in patients with schizophrenia. CONCLUSION: This study demonstrates high sensitivity of dMRI to subtle pathology in GM in recent onset schizophrenia, as well as an association between increased diffusivity in temporal GM regions and abnormalities in social cognition and exacerbation of psychiatric symptoms.

Risperidone dosing pattern and clinical outcome in psychosis: an analysis of 1713 cases.

BACKGROUND: In treating patients with psychosis, practicing clinicians use various dosing strategies of antipsychotic medications, including risperidone. To evaluate the outcome of different risperidone dosing strategies in clinical practice, we undertook a large, prospective, naturalistic study in which daily dosage was determined freely by local standards of care. METHOD: In a 6-week trial between December 2000 and January 2002, 1713 patients with DSM-IV schizophrenia and related psychoses were treated with risperidone, with the dose, daily changes in dose, and weekly changes in Brief Psychiatric Rating Scale score documented. Cluster analysis was performed to identify homogeneous dosing patterns among the heterogeneous total population. RESULTS: Of the 6 dosing patterns identified by cluster analysis, a 2-week titration cluster, with a starting dose of 1.8 mg/day titrated to a maximum dose of 4.7 mg/day at day 14, and a 1-week titration cluster, with a starting dose of 2.6 mg/day titrated to a maximum dose of 5.4 mg/day at day 7, showed superior clinical outcomes compared with the other clusters, in which titrations were slower and higher. CONCLUSION: Our results indicate that the current consensus regarding risperidone dosing is appropriate for clinical practice, whereas a slower titration schedule does not guarantee a better clinical outcome, thus emphasizing the need for appropriate early titration.

Efficacy, safety, and impact on hospitalizations of paliperidone palmitate in recent-onset schizophrenia.

OBJECTIVE: To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable paliperidone palmitate (PP) treatment, in patients with recent-onset schizophrenia who had not responded satisfactorily to oral antipsychotics. METHODS: In this 18-month, open-label, Phase-IIIb study from Asia-Pacific region, patients (18-50 years) with recent-onset (≤5 years) schizophrenia unsatisfactorily treated with previous oral antipsychotics were initiated on PP 150 mg eq on day 1, 100 mg eq on day 8, followed by flexible once monthly maintenance doses of 50-150 mg eq. The number and duration of hospitalizations were compared using a mirror analysis method between two periods: retrospective (12 months before PP initiation) and prospective (12 and 18 months after PP treatment) periods. RESULTS: A total of 303 out of 521 (58%) patients (mean age, 28.7 years; 65.5% men, 92.5% Asian) completed the study. Positive and Negative Syndrome Scale (PANSS) total score improved significantly from baseline to month 18 (mean [standard deviation, SD] change: -11.3 [21.38], P<0.0001, primary endpoint). Subgroup analysis revealed greater improvements among patients with worse disease severity at baseline: PANSS ≥70 versus <70 (mean [SD] change: -23.1 [24.62] vs -4.7 [15.98], P<0.0001 each). Secondary efficacy endpoints such as Clinical Global Impression of Schizophrenia (CGI-SCH), Medication Satisfaction Questionnaire (MSQ) scores showed significant improvements (P<0.0001) from baseline; 33.3% patients achieved symptom remission. In mirror analyses set (N=474), PP significantly (P<0.0001) reduced mean number of hospitalization days/person/year (12-month: 74.3 vs 19.7; 18-month: 74.3 vs 18.9) as well as percentage of patients requiring hospitalization in past 12 months (12-month: 39.7% vs 24.6%; 18-month: 39.7% vs 25%), and PP treatment increased the proportion of patients not requiring hospitalization (12-month: 60.3% vs 75.4%; 18-month: 60.3% vs 75%) from retrospective to prospective period. Adverse events (≥15%) were extrapyramidal symptoms-related (31.3%), injection-site pain (18.6%), and insomnia (15.2%). CONCLUSION: PP was efficacious and generally tolerable with significant reductions observed in both number of hospitalizations and days spent in hospital.

Calcification mimicking manganese-induced increased signal intensities in T1-weighted MR images in a patient taking herbal medicine: case report.

Characteristic high signal intensities confined to the globus pallidus on T1-weighted magnetic resonance image (MRI) can be observed in manganese (Mn)-exposed workers, however, these high signals should be differentiated from those due to other causes such as fat, hemoglobin breakdown products, melanoma, neurofibromatosis, and calcification. A 39-year-old woman was admitted with mutism and involuntary movements which had developed the day before. She had ingested two packs of liquid herbal medicine containing 0.53 mg of Mn daily for 4 months prior to visiting our hospital. Her MRI showed high signals, confined mainly to the globus pallidus on T1-weighted images. Follow-up brain MRI at an interval of 11 months showed no interval change. Brain computed tomography (CT) at the time of the second MRI showed symmetric calcification on both globus pallidus. Blood levels of liver function tests, calcium, phosphorus, and parathyroid hormone were within normal ranges. The increased signals, which were first presumed to be induced by Mn, were concluded to be due to calcification based on the following reasons. First, follow-up brain MRI at an interval of 11 months did not show any interval change. Second, the ingested amount of 1.06 mg Mn daily for 4 months is even less than that added to mineral supplements for adults. Third, Mn-induced high signals in T1-weighted MRI do not show any abnormal findings in brain CT. The present case report suggests that brain CT should be performed to rule out symmetric calcification on basal ganglia in patients showing increased signals in T1-weighted MRI, but who do not have a significant exposure history to Mn. The present report also showed that the amount of 1.06 mg Mn daily ingested for 4 months did not cause the high signal in brain MRI.

Cross-cultural comparison of neurobehavioral performance in Asian workers.

Widely-used neurobehavioral tests have been developed and standardized on Western populations, but studies on subject factors for Asian populations have been very limited. For the effective application and interpretation of neurobehavioral tests in Asian populations, an evaluation of the effects of subject factors, including cultural background, is necessary. A cross-cultural study was conducted to evaluate the effects of cultural background and the interaction between cultural background and education on neurobehavioral tests in Asian populations. The Korean version of the Swedish Performance Evaluation System (Simple Reaction Time, Symbol Digit, and Finger Tapping Speed) and a pegboard test were administered to 537 workers who were not exposed to chemicals at work from Fareast (Korea and Chinese), Central (Uzbekistan and Tajikistan), and South Asia (Sri Lanka and Indonesia). The Fareast Asian group exhibited better performance in adjusted test scores than other Asian groups, achieving significance for Symbol Digit and Finger Tapping Speed in both genders. The magnitude of the effect of cultural background on Symbol Digit was comparable to the effect of about 10 years of education. Cultural background did not modify the relation between years of education and Symbol Digit in either males or females. This study may provide the first evidence that cultural background has a large impact on neurobehavioral test performance, even within Asian populations, and suggests that cultural background is a critical confounding factor that must be controlled in epidemiologic studies which include Asian populations in the sample.

Cementless Metasul metal-on-metal total hip arthroplasty in patients less than fifty years old.

BACKGROUND: Durable results of total hip arthroplasty have been difficult to achieve in young patients. We reviewed the intermediate-term clinical and radiographic results in a series of active, higher-demand patients who were less than fifty years old when they underwent cementless total hip arthroplasty with the use of the Metasul metal-on-metal articulation. METHODS: Seventy total hip arthroplasties were performed in sixty-two patients who were younger than fifty years of age (average age, thirty-seven years). Two patients (two hips) had had a resection arthroplasty because of deep infection less than five years postoperatively and were excluded. Sixty patients (sixty-eight hips) were available for complete clinical and radiographic analysis after a mean duration of follow-up of seven years. RESULTS: The mean preoperative Harris hip score of 49 points improved to 95 points at the time of final follow-up; fifty-six patients (93%) had an excellent result. No component was seen to be loose radiographically at the time of final follow-up. Only one focal area of pelvic osteolysis in one patient and two small focal areas of femoral osteolysis in another patient were identified. The hip with focal pelvic osteolysis underwent revision surgery with a liner change and bone-grafting of the osteolytic lesion around a stable component. CONCLUSIONS: At a mean of seven years after arthroplasties with a Metasul metal-on-metal articulation, there was a low rate of osteolysis and aseptic loosening in this group of young patients. However, additional follow-up is necessary to determine any possible long-term deleterious effects associated with this metal-on-metal articulation.

18F-Fluorodeoxyglucose Positron-Emission Tomography Findings with Anti-N-Methyl-D-Aspartate Receptor Encephalitis that Showed Variable Degrees of Catatonia: Three Cases Report.

Catatonia is one of the main symptoms of anti-N-Methyl-D-aspartate receptor (NMDAR) encephalitis. However, it is unknown whether metabolic changes observed with (18)F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) are correlated with the severity of the catatonic symptoms and clinical course. Three patients with anti-NMDAR encephalitis showing variable degrees of catatonia were performed with FDG-PET scans during the acute and recovery phase. PET findings showed hypermetabolism in the frontotemporoparietal regions and bilateral basal ganglia in the patient with mild catatonia, but more widespread hypermetabolic regions including the thalamus and brainstem were observed in the patients with more severe catatonia. Follow-up PET scans in one patient showed mild hypermetabolism in the right basal ganglia that correlated with mild rigidity and tonic posturing in the left extremities. Extent of cerebral metabolic changes correlates with the severity of catatonia accompanied by behavioural, motor, autonomic, and breathing abnormalities in anti-NMDAR encephalitis.

Age structure at diagnosis affects aggression in a psychiatric inpatient population: age structure affecting inpatient aggression.

Study of inpatient aggression in psychiatric inpatient units (PIUs), where vulnerable patients interact intensely in small groups, is hampered by a lack of systematic monitoring of aggressive events in the context of group dynamics. Our current study examines the relationship between aggression and group structure in the PIU of a general tertiary-care hospital over a 9-month period. The severity of aggression was monitored daily using the Overt Aggression Scale (OAS). Clinical data including the daily number and mean age of subpopulations with different diagnoses were acquired. Cross-correlation function and autoregressive integrated moving average modeling were used to assess the effects of various group structure parameters on the incidence of aggressive events in the PIU. The daily total OAS score correlated positively with the daily mean age of patients with schizophrenia and bipolar disorder. By contrast, the OAS total score demonstrated a negative correlation with the daily mean age of patients with major depression. The age of the patients at diagnosis is an important group structure that affects the incidence of aggression in a PIU.

A prospective, open-label study to evaluate symptomatic remission in schizophrenia with risperidone long-acting injectable in Korea.

This study was designed to investigate long-term clinical outcomes of risperidone long-acting injectable (RLAI) in patients with schizophrenia or schizoaffective disorder. An open-label, 48-week, prospective study of RLAI treatment was carried out at 63 centers in South Korea. Initial and maintenance dosage of RLAI were adjusted according to clinical judgment. Efficacy was measured by the remission rate, continuation rate, and changes in the clinical measurements such as eight items of the Positive and Negative Symptom Scale (PANSS), the Clinical Global Impression - Severity, and the Schizophrenia Quality of Life Scale. In terms of the safety, Simpson-Angus rating Scale, adverse events (AEs), and BMI were investigated. Of the 522 patients who were enrolled, 472 patients who had been assessed on the eight items of PANSS at baseline and at least once during RLAI treatment were included in the intention-to-treat (ITT) population. The per-protocol (PP) population included 184 patients (39.0%), who completed all assessments during 48 weeks of the follow-up period. Total scores of eight items of PANSS, Clinical Global Impression - Severity, and Schizophrenia Quality of Life Scale were reduced significantly from baseline to endpoint in both ITT and PP populations. The mean dose (SD) of RLAI was 33.2 (7.6) mg. In the PP population, the number of patients who scored 1-3 on eight items of PANSS were 47 (25.5%) at baseline and 144 (78.3%) at 48 weeks. According to the remission defining as scores 1-3 on eight items of PANSS sustaining of at least 6 months' duration by Andreasen, the numbers of patients who achieved remission were 45 (24.5%) at 24 weeks and 120 (65.2%) at 48 weeks. A significant decrease in the mean score of Simpson-Angus rating Scale and a significant increase in BMI over time in last observation carried forward were observed, and patients who fulfilled the remission criteria during the study showed more weight gain than those who did not. During the study period, a total of 645 AEs were noted in 233 patients (49.3%) who were included in the ITT population. Sixty-nine serious AEs in 51 patients were reported, but all of them were not directly attributable to administration of RLAI. This prospective, open-label study showed improvements in symptom and AEs and a significant increase in BMI during 48 weeks of biweekly RLAI treatment. The rate of study completion was 39.0% and the remission rate among those who completed the study was 65.2%. None of the serious AEs were directly related to the administration of RLAI.