Increased sensitivity to error during decision-making in bipolar disorder patients with acute mania

BACKGROUND: Decision-making is a complex and important function for daily life that can be assessed quantitatively using a simple two-choice prediction task. Bipolar disorder (BD) patients are thought to show altered responsivity to positive and negative feedback. In this study we examined whether BD patients with psychotic mania show altered patterns of decision-making as a function of the frequency of incorrect predictions or error rate. METHODS: Fourteen adult DSM-IV-diagnosed BD patients with psychotic mania and 14 normal comparison subjects (NC) were tested with a two-choice prediction task using three error rate conditions (20%, 50%, or 80%). RESULTS: BD patients showed an increased sensitivity to error rate changes and switched more frequently at high error rates than NC subjects. In comparison, there were no differences between BD and NC subjects on the degree to which the response or stimulus during a previous trial predicts the current response. CONCLUSIONS: Decision-making in BD patients with psychotic mania appears to be highly sensitive to high error rates. Moreover, the patterns of responses appear distinct from what has been previously observed in acutely and chronically ill schizophrenia patients. The results of this study are informative as to the effects of errors on decision-making strategies in psychotic BD manic patients.     

Subjective and Response-Related Determinants of CNV Amplitude

The effect on contingent negative variation (CNV) of varying the difficulty of obtaining reaction time (RT) feedback and the relationship of CNV and RT were studied. Subjects (Ss) were run in a reaction-time-foreperiod experiment with 4 conditions of varying RT feedback duration. Subjective reactions to the experiment were recorded by Ss on a questionnaire and were divided by the experimenters into two highly significant sets of mean CNVs based on the most “positive’ and most “negative’ responses to the conditions. CNVs and their associated RTs were analyzed, and a significant rank order correlation over all Ss showed there was a trend for individuals with faster RTs to have larger CNVs. Individual correlations were low and highly variable. Only the very slowest RTs were associated with small CNVs. The failure of explicit RT feedback to have any effect upon CNV amplitude is in agreement with previous studies, and the significant association of CNV amplitude with written reactions of Ss might prove a useful tool for further CNV analysis. The RT data indicated that CNVs and RTs reflect relatively independent functions and that very slow RTs may reflect qualitative changes in S's psychological state which affect both RT and CNV; and such trials might appropriately be eliminated from CNV data analysis.     

Memory mood congruency phenomenon in bipolar I disorder and major depression disorder patients

The objective of the present study was to evaluate memory performance in tasks with and without affective content (to confirm the mood congruency phenomenon) in acutely admitted patients with bipolar I disorder (BD) and major depression disorder (MDD) and in healthy participants. Seventy-eight participants (24 BD, 29 MDD, and 25 healthy controls) were evaluated. Three word lists were used as the memory task with affective content (positive, negative and indifferent). Psychiatric symptoms were also evaluated with rating scales (Young Mania Rating Scale for mania and Hamilton Depression Rating Scale for depression). Patients were selected during the first week of hospitalization. BD patients showed higher scores in the word span with positive tone than MDD patients and healthy controls (P = 0.002). No other difference was observed for tests with affective tone. MDD patients presented significantly lower scores in the Mini-Mental State Exam, logical memory test, visual recognition span, and digit span, while BD patients presented lower scores in the visual recognition test and digit span. Mood congruency effect was found for word span with positive tone among BD patients but no similar effect was observed among MDD patients for negative items. MDD patients presented more memory impairment than BD patients, but BD patients also showed memory impairment.     

The clinical significance of a pathergy reaction in patients with Behcet's disease

This study was done to evaluate the frequency, intensity, and specificity of a positive pathergy reaction (PR) in Behcet's disease (BD) patients, to clarify an association between the PR and the clinical features or disease severity, and to assess whether patients with pustule formation at the venous puncture site (PFVPS) without positive PR could be regarded as a positive reaction. The PR was tested in 64 BD patients, 74 disease controls, and 20 healthy controls. Venous PR was performed in 8 BD patients with PFVPS. Follow-up PR was done in 14 patients with positive reaction during inactive phase. The PR was positive in 35.9% of BD patients, in 1 patient among disease controls, and in none of healthy controls. The pustule formation was observed in one BD patient. There was no statistical significance between positive PR and the clinical variables. The mean clinical activity score of BD patients with positive PR was similar to patients with negative reaction. Venous PR was positive in 7 patients. The follow-up PR was positive in 2 patients during inactive phase. Conclusively the positive PR appeared to be specific for BD, and was not associated with the clinical variables or disease severity, but was usually found during active phase in cases with positive reaction. The PFVPS in patients with negative PR might be considered to be positive.     

Association of transporter associated with antigen processing genes with Behçet's disease in Japanese

Contribution of transporter associated with antigen processing (TAP) genes to the pathogenesis of Beh?et's disease (BD) was studied. Restriction fragment length polymorphic analysis of TAP genes was carried out in 46 Japanese patients with BD and 95 healthy subjects. There were no significant differences in allele frequencies of TAP1 and TAP2 genes between whole patients with BD and control population. No significant differences in the frequencies of TAP alleles were observed, when patients of BD with complete type or incomplete type were compared with control population, respectively. An allele frequency of TAP2C was, however, slightly but significantly high in patients with BD who had symptom of erythema nodosum (24.1%) as compared to the control group (11.6%). [p < .05, RR = 2.4]. The allele frequency of TAP2C was slightly high in HLA*B5101 positive patients with BD (28.6%) as compared to HLA*B5101 negative patients (10.9%), but the difference did not reach statistical significance. The absence of genotype TAP2B/C was observed in whole patients group, though it was present in control subjects (14.7%). [p = 0.003, RR = 0.06]. A genotype frequency of TAP2C/H was high in patients with BD who had symptom of skin lesions (7.5%) as compared to the control group (0.0%). [p = 0.03, RR = 15.4]. These results suggest the possibility that TAP molecule play some part in formation of skin lesion, such as erythema nodosum in BD in Japanese.     

The comparison between Beh?et's disease and spondyloarthritides: does Beh?et's disease belong to the spondyloarthropathy complex?

This study was to clarify whether Behcet's disease (BD) could be classified into the spondyloarthropathy (SpA) complex. It was undertaken on 58 patients with BD (BD group), 56 patients with SpA (SpA group), and 3 patients who concurrently satisfied the criteria for BD and SpA (BDSpA group). The clinical parameters and known susceptible HLA antigens were compared between BD group and SpA group. In addition, 3 patients in BDSpA group were reviewed. The prevalence of definitive sacroiliitis (SI) in BD group and SpA group was 46.4% and 5.2%, respectively. However, none had a definitive SI in healthy controls. Enthesitis was observed in 3.4% of BD group and in 50% of SpA group. The patterns of eye involvement were different between these two groups. HLA-B27 was negative in all 49 patients of BD group, whereas it was positive in 67.9% of SpA group. The prevalence of HLA-B51 was 51.7% in BD group, and that in SpA group was 21.4%. One patient in BDSpA group was considered to have concurrent BD and ankylosing spondylitis (AS). Another patient was closer to AS, and the third to BD. Conclusively, it seems that BD could not be classified into the SpA complex.     

Claudin 6 Is a Positive Marker for Atypical Teratoid/Rhabdoid Tumors

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly aggressive pediatric brain tumors characterized by the presence of rhabdoid cells and negative immunostaining for INI1 (BAF47). Histogenesis is unknown and diagnosis can be challenging because of their extreme morphological and immunophenotypic heterogeneity. Currently no signature markers other than INI1 loss have been identified. To search for possible candidate proteins of interest in AT/RTs, Affymetrix GeneChip® microarrays were utilized to investigate nine AT/RTs vs. 124 other tumor samples. The most distinctive gene identified was claudin 6 ( CLDN6 ), a key component of tight junctions. CLDN6 showed moderate or higher mRNA expression in eight of nine AT/RTs, with little to no expression in 114 of 115 other tumors. Average expression was 38-fold higher in AT/RTs vs. other samples. Immunohistochemical (IHC) staining of 33 tumor specimens found positive membrane staining in seven of seven AT/RTs, and was negative in 26 of 27 other brain tumor samples. Notably, none of the 16 medulloblastomas/primitive neuroectodermal tumors showed IHC staining for CLDN6. IHC staining results closely matched the level of mRNA expression detected by microarray. CLDN6 may be a useful positive marker to help further identify AT/RTs for diagnostic and treatment purposes.     

Anticardiolipin and anti-beta2-glycoprotein I antibodies in Behcet's disease.

To investigate prevalence of anticardiolipin antibodies (aCL) in patients with Behcet''s disease (BD) and to determine whether they are related to anti-beta2-glycoprotein I antibodies (aGPI), we measured aCL and aGPI in 47 patients of BD and 14 patients of systemic lupus erythematosus (SLE). The levels of aCL and aGPI were determined by conventional enzyme immunoassay for both IgG and IgM classes. Twelve (25.5%) patients with BD were positive for IgG or IgM aCL and no patient was positive for aGPI. Eleven (78.6%) patients with SLE were also positive for aCL and among them, 8 (72.7%) patients were positive for aGPI. Positive IgG aCL patients with BD showed lower level of IgG aCL than those with SLE (15.7+/-7.3 vs 34.1+/-16.0 GPL, p<0.05). There was no relation between the presence of aCL in BD and either dinical activity or clinical features. In the patients with BD, aCL are found but it would not be associated with aGPI as they are in patients with SLE. In patients with BD, aCL seem to be authentic aCL unlike those in patients with SLE and may not be related with vascular complications in BD.     

HRP追踪技术对口虾蛄口胃神经系统的研究

采用神经节离体培养、HRP追踪技术对甲壳动物口虾蛄的口胃神经系统进行了初步研究。分别经侧胃神经、口胃神经和食道下神经对口虾蛄口胃神经系统的口胃神经节、食道神经节和食道旁神经节进行了追踪。经一侧的侧胃神经追踪时,可见大约8个阳性标记神经元位于口胃神经节远端胞体层的腹侧缘,中央神经纤维网也呈较强阳性反应;经口胃神经追踪时,口胃神经节胞体层可见5～6弱阳性标记胞体及阳性标记的神经纤维,食道神经节中可见2个胞体被标记,中央纤维网中也有较强的阳性标记末梢;经一侧食道下神经追踪时,食道神经节胞体层中可见4个阳性标记胞体及部分阳性纤维,而食道旁神经节中仅见阳性标记纤维存在于中央纤维网。以上结果表明:口胃神经节远端腹侧胞体层中的细胞发出突起后以长的分支进入侧胃神经支配胃部的运动,而短的分支则终止于口胃神经节中央纤维网。口胃神经节吻端的细胞突起经口胃神经与食道神经节建立联系。经侧胃神经和口胃神经追踪均未被标记的细胞应属于口胃神经节内的中间神经元。而食道神经节中的部分胞体发出突起进入食道旁神经节的纤维网与中枢神经系统发生联系,另一部分细胞发出突起沿口胃神经进入口胃神经节与此处的神经细胞形成联系,这两类细胞在食道神经节的纤维网中建立联系。     

Association of Transporter Associated with Antigen Processing Genes with Behçet's Disease in Japanese

Contribution of transporter associated with antigen processing (TAP) genes to the pathogenesis of Behçet's disease (BD) was studied. Restriction fragment length polymorphic analysis of TAP genes was carried out in 46 Japanese patients with BD and 95 healthy subjects. There were no significant differences in allele frequencies of TAP1 and TAP2 genes between whole patients with BD and control population. No significant differences in the frequencies of TAP alleles were observed, when patients of BD with complete type or incomplete type were compared with control population, respectively. An allele frequency of TAP2C was, however, slightly but significantly high in patients with BD who had symptom of erythema nodosum (24.1%) as compared to the control group (11.6%). [?p<0.05, RR=2.4]. The allele frequency of TAP2C was slightly high in HLA*B5101 positive patients with BD (28.6%) as compared to HLA*B5101 negative patients (10.9%), but the difference did not reach statistical significance. The absence of genotype TAP2B/C was observed in whole patients group, though it was present in control subjects (14.7%). [?p=0.003, RR=0.06]. A genotype frequency of TAP2C/H was high in patients with BD who had symptom of skin lesions (7.5%) as compared to the control group (0.0%). [?p=0.03, RR=15.4]. These results suggest the possibility that TAP molecule play some part in formation of skin lesion, such as erythema nodosum in BD in Japanese.     

Differences in beliefs about mood between people with and without bipolar disorder

Psychological models of bipolar disorder (BD), such as the self‐regulation model (SRM; Leventhal, Nerenz, & Steele, 1984), highlight the crucial role of beliefs about mood in relapse vulnerability. To date, no studies have directly compared these beliefs between people with and without BD. Based on the SRM, the current research examined beliefs about mood in people with and without BD and explored the impact of current affect on these beliefs. Fifty euthymic people with a diagnosis of BD and 50 controls were recruited through an online screening study, clinical services, and support organizations. Experience sampling methodology (ESM) was used to assess beliefs (according to the Brief Illness Perceptions Questionnaire; Broadbent, Petrie, Main, & Weinman, 2006) across a typical week of everyday life. Data were analysed using multilevel modelling. Forty‐two people with a diagnosis of BD and 50 controls were included in the analyses. Results indicated that the BD group reported less control over mood, a shorter duration of mood, and less understanding of mood and were more likely to report the cause of depressive symptoms as something internal, compared with controls. When controlling for current affect, the BD group also reported more positive consequences, made more internal attributions for hypomanic symptoms, and reported less concern about mood, compared with controls. Findings suggest important differences in beliefs about mood between people with and without BD that are not the result of current affect. These beliefs may be particularly important in understanding underlying vulnerability to future relapse into depression and/or mania.     

Implicit memory for emotional words is modulated by cardiac perception

In the present study we investigated the impact of viscero-sensory feedback on memory performance. Participants with good and poor perception of their heart activity were presented with positive, negative and neutral words while heart rate and skin conductance were measured. After a distractor task, participants were asked to complete primed and unprimed wordstems. Implicit memory performance was assessed in terms of accuracy of completion. In our study, participants with good cardiac perception completed significantly more wordstems of previously presented positive and negative words, whereas no group differences were found for wordstems of neutral words and physiological measures during encoding. Our findings document a substantial role of visceral feedback in implicit memory processes. They are in line with Damasio's somatic marker hypothesis stating that access to information about somatic processes facilitates cognitive processing.     

Goal relevance influences performance monitoring at the level of the FRN and P3 components

The feedback‐related negativity (FRN) provides a reliable ERP marker of performance monitoring (PM). It is usually larger for negative compared to positive feedback, and for unexpected relative to expected feedback. In two experiments, we assessed whether these effects could be modulated by goal relevance, defined as feedback informativeness (reliability) and/or impact on a person's goals. EEG (64‐channel) was recorded while 30 participants (in each experiment) performed a speeded go/no‐go task across blocks in which the feedback on task performance was deemed either relevant or not. At the ERP level, the FRN component was larger for (frequent) negative compared to (deviant) positive feedback exclusively when the feedback was relevant (Experiment 1). When the probability of positive and negative feedback was balanced (Experiment 2), this valence‐driven FRN effect was absent. However, across these two experiments, the FRN was always larger for irrelevant than relevant feedback. Moreover, the subsequent P300 component was larger for feedback in the relevant than the irrelevant blocks. This effect was valence unspecific in Experiment 1, while in Experiment 2 larger P3 amplitudes were recorded for negative than positive (relevant) feedback. Across the two experiments, a larger correct‐related negativity in the irrelevant than relevant context was also observed, suggesting that PM is flexible. These ERP findings indicate that goal relevance influences feedback (and response) processing during PM, with two nonoverlapping neurophysiological effects: It gates reward prediction error brain mechanisms (FRN effect), before enhancing subsequent motivational processes (P300 effect).     

Evaluation of BD Max StaphSR and BD Max MRSAXT Assays Using ESwab-Collected Specimens

The BD Max MRSAXT and the BD Max StaphSR assays were validated for the detection of methicillin-resistant Staphylococcus aureus (MRSA) in ESwab samples. In addition, the BD Max StaphSR assay was evaluated for its ability to detect and differentiate S. aureus and MRSA in the same sample. A total of 255 ESwab samples collected from the anterior nares of patients were tested by each of three BD Max assays, including the BD Max MRSA first-generation assay. The results were compared to those of direct and enrichment culture. Additionally, a challenge panel comprising 14 control strains was evaluated to determine the ability of these assays to correctly identify MRSA and also appropriately differentiate S. aureus by the BD Max StaphSR assay. Out of 255 clinical samples tested, 161 were negative and 30 were positive for MRSA, and 45 were positive for S. aureus (by BD Max StaphSR) and negative for MRSA by all three PCR assays and culture. Nineteen samples had discrepant results; all of them were retested by additional laboratory testing. All strains from the challenge panel were correctly identified or excluded by the BD Max MRSAXT and BD Max StaphSR assays. The results showed that the BD Max StaphSR and the BD MRSAXT assays have excellent sensitivity (94.3%) and specificity (97.7%) for detecting MRSA. The BD Max StaphSR assay demonstrated excellent sensitivity (96.4%) and specificity (93.6%) for detecting S. aureus.     

Direct Immunofluorescence in Beh?et's Disease: A Controlled Study with 108 Cases

Purpose

Behçet''s disease (BD) is a disease of unknown etiology, which has multisystemic involvement. This multisystemic involvement might be the clue for an autoimmune pathogenesis. In order to evaluate an autoimmune pathogenesis, we examined immunoreactans depositions in the skin of BD patients.

Materials and Methods

The skin samples of 108 BD patients (28 perilesional skin, 44 positive pathergy test site, 22 negative pathergy test site, 14 normal skin) were examined for the depositions of immunoglobulin (Ig)M, IgG, IgA, complement 3 (C₃), and fibrinogen (F) using direct immunofluorescence (DIF). The data were statistically compared to the DIF of 36 systemic lupus erythematosus (SLE) patients and 20 healthy controls using χ² Fisher exact test.

Results

Highly significant immunoreactans depositions were obtained in BD (deposition rates: IgM 70.3%, IgG 0%, IgA 20.3%, C₃ 62.9%, F 83.3%). The comparison with SLE revealed no differences in IgM, IgA, and C₃. However, IgG deposition was higher in SLE while F deposition was higher in BD. In both BD and SLE, the Ig depositions were highly significant when the data were compared with the healthy controls.

Conclusion

The significant deposition of immunoreactans in BD, especially in the negative pathergy and the normal skin sites, were observed. This study is the first controlled study revealing positive Ig depositions in BD, and it is expected to help us to reconsider the autoimmune pathogenesis in BD.     

Clinical Experience of Interferon Alfa-2a Treatment for Refractory Uveitis in Beh?et's Disease

Behçet''s disease (BD) involves multisystem vasculitis of unknown origin. Ocular manifestations of BD mostly include bilateral panuveitis and retinal vasculitis, which are very challenging to treat. Interferon alfa-2a (IFN) has been recently introduced for treating refractory Behçet uveitis, mainly in Germany and Turkey. Nonetheless, there is so far no consensus about the ideal treatment regimen of IFN for Behçet uveitis. We report our experience of IFN treatment in five Korean BD patients with refractory uveitis. All patients complained of oral ulcers; one patient had a positive pathergy test and 2 showed the presence of HLA-B51. Immunosuppressive agents used prior to IFN treatment included cyclosporine and methotrexate. The IFN treatment was commenced with a dose of 6-9 MIU/day for 7 days, adjusted according to individual ocular manifestations, tapered down to 3 MIU three times in a week, and then discontinued. All patients showed positive response to IFN treatment; 50% of them showed complete response without additional major ocular inflammation during the follow-up period. Other BD symptoms also improved after IFN treatment in most cases. After treatment, the relapse rate and the required dose of oral corticosteroid were decreased in most cases, showing a significant steroid-sparing effect. However, the visual acuity was not improved in most cases due to irreversible macular sequelae. Despite the small sample size of this study, we suggest that, in Korean patients, IFN is an effective treatment modality for BD uveitis as was observed in German and Turkish patients.     

Serum oxidant/antioxidant status in patients with Behçet's disease

The aims of this study were to assess whether the increased oxidative stress in affected tissues is reflected by serum lipid peroxidation and to check for alterations in serum levels of extracellular antioxidants and antioxidant enzyme activities in patients with Behcet's disease (BD). Serum malondialdehyde (MDA) and ceruloplasmin (Cp) levels and CuZn-superoxide dismutase (CuZn-SOD) and glutathione peroxidase (GSH-Px) activities were increased, while serum transferrin (Trf) levels were diminished in patients with active ocular BD (n = 19), inactive ocular BD (n=18), and nonocular BD (n=15), compared to healthy controls (n = 20). Serum MDA levels in patients with active ocular BD and nonocular BD were significantly higher than in the inactive ocular BD group. Patients with active ocular BD also had significantly higher serum Cu-Zn SOD activities, compared to the inactive ocular BD. Erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) levels were higher in patients with active ocular BD, inactive ocular BD, and nonocular BD, compared to the control group. In addition, patients with active ocular BD and nonocular BD had significantly higher ESR and serum CRP levels, compared to the inactive ocular BD group. Serum albumin concentrations showed no significant differences among the BD patients and controls. The authors speculate that in BD patients, serum superoxide radicals may be dismutated to H2O2 by increased CuZn-SOD activity and the conversion of H2O2 to hydroxyl radical may be enhanced by iron, owing to diminished serum Trf; these mechanisms may contribute to the increased serum lipid peroxidation.     

Methacholine inhalation challenge in young children: results of testing and follow-up

The diagnosis of asthma is often difficult in young children because their symptoms may not be typical and pulmonary function testing cannot be performed by the patient. We therefore performed methacholine inhalation challenges (MIC) in 24 patients 1 to 5.8 years of age in whom the diagnosis of asthma was uncertain. These patients had histories of recurrent respiratory symptoms for a mean duration of 2.4 years (range = 0.5 to 5.1) in the absence of other systemic diseases. Testing was done by either the 5-breath technique or 1-min inhalation via face mask until wheezing or coughing and retractions developed or a maximum methacholine concentration of 5 to 25 mg/mL was reached. Eighteen MIC were positive and six negative. The mean provocative dose was 3.0 mg/mL (range = 0.6 to 10). No patients suffered serious or delayed reactions and all symptoms reversed with inhaled bronchodilators (BD). During the MIC, the progression of symptoms often mimicked progression of those observed in the past and was useful in teaching the parents. Patients were followed for 0.5 to 3.8 years (mean = 2.3). All patients with a positive MIC have continued to have recurrent respiratory symptoms and require regular or intermittent BD. Only one patient with a negative MIC at 5 mg/mL has recurrent respiratory symptoms and requires daily BD 3 years after the initial evaluation. We conclude that MIC can safely be performed in young children in whom the diagnosis of asthma is uncertain. A positive MIC in this context demonstrates increased bronchial reactivity and is supportive of a clinical diagnosis of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)