Recent Onset Cases Research Articles

New clues to the elusive aetiology of nodding syndrome.

Nodding syndrome is a paediatric epileptic encephalopathy of unknown aetiology that affects children in impoverished communities of Eastern Africa subject to internal displacement. Set in southcentral South Sudan, where nodding syndrome first surfaced circa 1990, an important new study of recent-onset cases of nodding syndrome examined parasitic, bacterial, viral, immune-mediated, metabolic and nutritional factors associated with the brain disease. Infection with the nematode Mansonella perstans, but not with Onchocerca volvulus, was the most prominent finding in nodding syndrome cases versus controls. While M. perstans is unlikely to be causal of nodding syndrome, investigation of the freshwater habitats, where insect-to-human transmission of the filarial larvae takes place, may reveal a clue as to the aetiology of this neurodegenerative disease. The culpable environmental agent(s) must be able to induce neuroinflammation and tau pathology preferentially in infants and children.

Urbanicity and rates of untreated psychotic disorders in three diverse settings in the Global South.

Extensive evidence indicates that rates of psychotic disorder are elevated in more urban compared with less urban areas, but this evidence largely originates from Northern Europe. It is unclear whether the same association holds globally. This study examined the association between urban residence and rates of psychotic disorder in catchment areas in India (Kancheepuram, Tamil Nadu), Nigeria (Ibadan, Oyo), and Northern Trinidad. Comprehensive case detection systems were developed based on extensive pilot work to identify individuals aged 18-64 with previously untreated psychotic disorders residing in each catchment area (May 2018-April/May/July 2020). Area of residence and basic demographic details were collected for eligible cases. We compared rates of psychotic disorder in the more v. less urban administrative areas within each catchment area, based on all cases detected, and repeated these analyses while restricting to recent onset cases (<2 years/<5 years). We found evidence of higher overall rates of psychosis in more urban areas within the Trinidadian catchment area (IRR: 3.24, 95% CI 2.68-3.91), an inverse association in the Nigerian catchment area (IRR: 0.68, 95% CI 0.51-0.91) and no association in the Indian catchment area (IRR: 1.18, 95% CI 0.93-1.52). When restricting to recent onset cases, we found a modest positive association in the Indian catchment area. This study suggests that urbanicity is associated with higher rates of psychotic disorder in some but not all contexts outside of Northern Europe. Future studies should test candidate mechanisms that may underlie the associations observed, such as exposure to violence.

DeepMI: Deep multi-lead ECG fusion for identifying myocardial infarction and its occurrence-time

Myocardial Infarction (MI) has the highest mortality of all cardiovascular diseases (CVDs). Detection of MI and information regarding its occurrence-time in particular, would enable timely interventions that may improve patient outcomes, thereby reducing the global rise in CVD deaths. Electrocardiogram (ECG) recordings are currently used to screen MI patients. However, manual inspection of ECGs is time-consuming and prone to subjective bias. Machine learning methods have been adopted for automated ECG diagnosis, but most approaches require extraction of ECG beats or consider leads independently of one another. We propose an end-to-end deep learning approach, DeepMI, to classify MI from Normal cases as well as identifying the time-occurrence of MI (defined as Acute, Recent and Old), using a collection of fusion strategies on 12 ECG leads at data-, feature-, and decision-level. In order to minimise computational overhead, we employ transfer learning using existing computer vision networks. Moreover, we use recurrent neural networks to encode the longitudinal information inherent in ECGs. We validated DeepMI on a dataset collected from 17,381 patients, in which over 323,000 samples were extracted per ECG lead. We were able to classify Normal cases as well as Acute, Recent and Old onset cases of MI, with AUROCs of 96.7%, 82.9%, 68.6% and 73.8%, respectively. We have demonstrated a multi-lead fusion approach to detect the presence and occurrence-time of MI. Our end-to-end framework provides flexibility for different levels of multi-lead ECG fusion and performs feature extraction via transfer learning.

74-OR: Islet Autoantibodies in Youth with Diabetes from South Asia

The prevalence of diabetes in many South Asian countries is above 10%, but type 1 diabetes (T1D) is not fully characterized due to a lack of widespread access to islet autoantibody (IA) testing. Determining the prevalence of IA positivity in new and recent onset cases of childhood diabetes in these countries will allow for improved classification of diabetes and may impact treatment. We measured IA directed against glutamic acid decarboxylase 65 (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA) and zinc transporter 8 (ZnT8A) using fluid-phase radiobinding assays from dried blood spot eluents in children with diabetes from the Republic of Maldives (n=64), Bangladesh (n=103) and Pakistan (n=54). We compared the results to youth from our large diabetes Center in Colorado (n=132). South Asian children with clinically diagnosed T1D have a lower rate of positivity for each IA when compared to youth with T1D from Colorado (p<0.0001) (Figure). The majority of youth with T1D in each country were diagnosed at a young age, not overweight, and required insulin treatment. Interestingly, 52% of Bangladeshi youth are antibody negative (p<0.0001 compared to Colorado), yet 92% require insulin treatment, thus highlighting the need to investigate other forms of diabetes such as monogenic causes. Studying the phenotype of diabetes in youth across the globe provides an opportunity to dissect the heterogeneity within childhood onset diabetes.View largeDownload slideView largeDownload slide DisclosureK. Simmons: Other Relationship; Self; Provention Bio, Inc. E. M. Youngkin: None. A. Condie: None. A. Alkanani: None. K. Mcdaniel: None. L. Yu: None. G. D. Ogle: None. A. W. Michels: Stock/Shareholder; Self; IM Therapeutics.FundingNational Institutes of Health (K12DK094712-08)

0009 Anti-Streptococcal Antibodies in Chinese Patients with Type -1 Narcolepsy

Abstract Introduction Narcolepsy type 1 (NT1) is considered to be an autoimmune disease, and streptococcal infection may be an environmental trigger. However, previous studies from Asian narcolepsy patients did not reveal elevated anti-streptolysin O [ASO]. The aim is to investigate whether large sample Chinese patients with NT1 have an increase in antistreptococcal antibody titers. Methods A total of 214 narcolepsy patients and 360 healthy controls were recruited. All patients were DQB1*0602 positive with clear-cut cataplexy or had low CSF hypocretin-1. Participants were tested for ASO and anti DNAse B [ADB]. These patients were divided into five groups according to disease duration, including 29 patients less than 3 months; 25 from 3 months to 1 year; 40 from 1 to 3 years; 61 from 3 to 10 years and 59 patients over 10 years. Comparison was also made between children and adults with age matched controls, respectively. Results There were no significant differences between patients and healthy controls in regard to both ASO ≥ 200 IU (19.2% vs. 16.9%, p = 0.50) and ADB≥480IU (9.8% vs. 10.3%, p = 0.86). For children narcolepsy patients, ASO positive rates(19.8% vs. 18%, p = 0.68) and ADB positive rates(10.4% vs. 12%, p = 0.72) had no differences compared to age matched controls. And no difference was observed in adult narcolepsy patients either, with ASO positive rates (18.5% vs. 13.8%, p = 0.39) and ADB positive rates (9.3% vs. 5.3%, p = 0.42) compared to age matched controls, respectively. ASO (ADB) positive rates had no significant differences among different disease duration groups(p= 0.55, 0.9). Conclusion It is indicated that positive rates of ASO and ADB were not significantly different between Chinese patients with NT1 and healthy controls, including recent onset cases and children. Support The study was supported by the National Natural Science Foundation of China (No. 81420108002 and NO. 81570083)

Utility of the new Movement Disorder Society clinical diagnostic criteria for Parkinson's disease applied retrospectively in a large cohort study of recent onset cases

ObjectiveTo examine the utility of the new Movement Disorder Society (MDS) diagnostic criteria in a large cohort of Parkinson's disease (PD) patients. MethodsRecently diagnosed (<3.5 years) PD cases fulfilling United Kingdom (UK) brain bank criteria in Tracking Parkinson's, a UK multicenter prospective natural history study were assessed by retrospective application of the MDS criteria. ResultsIn 2000 cases, 1835 (91.7%) met MDS criteria for PD, either clinically established (n = 1261, 63.1%) or clinically probable (n = 574, 28.7%), leaving 165 (8.3%) not fulfilling criteria. Clinically established cases were significantly more likely to have limb rest tremor (89.3%), a good l-dopa response (79.5%), and olfactory loss (71.1%), than clinically probable cases (60.6%, 44.4%, and 34.5% respectively), but differences between probable PD and ‘not PD’ cases were less evident. In cases not fulfilling criteria, the mean MDS UPDRS3 score (25.1, SD 13.2) was significantly higher than in probable PD (22.3, SD 12.7, p = 0.016) but not established PD (22.9, SD 12.0, p = 0.066). The l-dopa equivalent daily dose of 341 mg (SD 261) in non-PD cases was significantly higher than in probable PD (250 mg, SD 214, p < 0.001) and established PD (308 mg, SD 199, p = 0.025). After 30 months' follow-up, 89.5% of clinically established cases at baseline remained as PD (established/probable), and 86.9% of those categorized as clinically probable at baseline remained as PD (established/probable). Cases not fulfilling PD criteria had more severe parkinsonism, in particular relating to postural instability, gait problems, and cognitive impairment. ConclusionOver 90% of cases clinically diagnosed as early PD fulfilled the MDS criteria for PD. Those not fulfilling criteria may have an atypical parkinsonian disorder or secondary parkinsonism that is not correctly identified by the UK Brain Bank criteria, but possibly by the new criteria.

Concepts of madness in diverse settings: a qualitative study from the INTREPID project.

BackgroundIn order to facilitate case identification of incident (untreated and recent onset) cases of psychosis and controls in three sites in India, Nigeria and Trinidad, we sought to understand how psychoses (or madness) were conceptualized locally. The evidence we gathered also contributes to a long history of research on concepts of madness in diverse settings.MethodsWe conducted focus group discussions and individual interviews to collect information about how informants in each site make sense of and respond to madness. A coding framework was developed and analyses of transcripts from the FGDs and interviews were conducted.ResultsAnalyses suggest the following: a) disturbed behaviors are the primary sign of madness; b) madness is attributed to a wide range of causes; and, c) responses to madness are dictated by cultural and pragmatic factors. These findings are congruent with similar research that has been conducted over the past 50 years.ConclusionsThe INTREPID research suggests that concepts about madness share similar features across diverse settings: a) terms for madness are often derived from a common understanding that involves disruptions in mental processes and capacities; b) madness is recognized mostly by disruptive behaviours or marked declines in functioning; c) causal attributions are varied; and, d) help-seeking is a complex process.

Continuous evolution of clinical phenotype in 578 Japanese patients with Behçet's disease: a retrospective observational study.

BackgroundIt has been suggested that the phenotypes of Behçet’s disease (BD) in Japan are changing. To ask whether the evolution of BD holds true in recent-onset cases in Japan, we performed a retrospective study.MethodsWe reviewed the records of 578 patients with BD who met the 1987 revised diagnostic criteria of the Behçet’s disease research committee of Japan. The patients were divided into three groups based on the date of disease onset. We compared the demography, clinical features, and treatments among them with or without adjustment for the observation period. Patients having oral ulcers, genital ulcers, regional skin involvement, and uveitis are categorized as having complete-type BD, and the associated factors were determined by univariate and multivariate logistic regression analyses.ResultsMale patients had a higher propensity for uveitis and central nervous system (CNS) involvement, whereas female patients had higher rates of genital ulcers and arthritis. We found a significant trend in reduction of complete-type, genital ulcer, HLA-B51 carriers, and increment of gastrointestinal BD over time. Multiple regression analysis identified HLA-B51 positivity, earlier date of disease onset, and younger age of onset as independently associated with complete-type BD. Although treatments had been also chronologically changed, the causative relationship between therapeutic agents and phenotypical changes was not determined from the study.ConclusionThe present study revealed that phenotypical evolution was characterized by decreased incidence of the complete type and increment of gastrointestinal involvement in Japanese patients with BD during the last 30 years.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1115-x) contains supplementary material, which is available to authorized users.

Tracking Parkinson's: Study Design and Baseline Patient Data.

Background:There is wide variation in the phenotypic expression of Parkinson’s disease (PD), which is driven by both genetic and epidemiological influences.Objectives:To define and explain variation in the clinical phenotype of PD, in relation to genotypic variation.Methods:Tracking Parkinson’s is a multicentre prospective longitudinal epidemiologic and biomarker study of PD. Patients attending specialist clinics in the United Kingdom with recent onset (<3.5 years) and young onset (diagnosed <50 years of age) PD were enrolled. Motor, non-motor and quality of life assessments were performed using validated scales. Cases are followed up 6 monthly up to 4.5 years for recent onset PD, and up to 1 year for young onset PD. We present here baseline clinical data from this large and demographically representative cohort.Results:2247 PD cases were recruited (1987 recent onset, 260 young onset). Recent onset cases had a mean (standard deviation, SD) age of 67.6 years (9.3) at study entry, 65.7% males, with disease duration 1.3 years (0.9), MDS-UPDRS 3 scores 22.9 (12.3), LEDD 295 mg/day (211) and PDQ-8 score 5.9 (4.8). Young onset cases were 53.5 years old (7.8) at study entry, 66.9% male, with disease duration 10.2 years (6.7), MDS-UPDRS 3 scores 27.4 (15.3), LEDD 926 mg/day (567) and PDQ-8 score 11.6 (6.1).Conclusions:We have established a large clinical PD cohort, consisting of young onset and recent onset cases, which is designed to evaluate variation in clinical expression, in relation to genetic influences, and which offers a platform for future imaging and biomarker research.

現在も発生する塗装工の鉛中毒

現在も発生する塗装工の鉛中毒

Islet inflammation in human type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is caused by the selective deletion of pancreatic β-cells in response to an assault mounted within the pancreas by infiltrating immune cells. However, this apparently clear and focussed annunciation conceals a stark reality in which the cellular and molecular events leading to β-cell loss remain poorly understood in humans. This reflects the difficulty of studying these processes in living individuals and the fact that, using pathological specimens, islet inflammation has been analysed in fewer than 200 recent-onset cases of T1DM worldwide, over the past century. Nevertheless, insights have been gained and the composition of the islet infiltrate is being disclosed. This is shown to be primarily lymphocytic in nature, with populations of both CD8+ and CD4+ T cells displaying an autoreactivity against specific islet antigenic peptides. The T cells are often accompanied by influent CD20+ B cells, although new data imply that the proportions of these individual cell types vary and that patients fall into at least two distinct categories having either a hyper-immune (CD20Hi) or a pauci-immune (CD20Lo) phenotype. The overall rate of β-cell decline appears to correlate with these two phenotypes such that hyper-immune patients lose β-cells more quickly and tend to develop disease at an earlier age than those with the pauci-immune profile. In this article, we review the evidence which underpins our current understanding of the aetiology of T1DM and highlight both the established features as well as areas of on-going ambiguity and debate.

Modelling the incidence and mortality of psychotic disorders: Data from the second Australian national survey of psychosis

The aim of this study was to model estimates related to (a) the incidence of psychotic disorders and (b) the mortality associated with these disorders based on a large, population-based prevalence study. Data were drawn from the second national survey of adults with psychotic disorders conducted in seven Australian catchment areas during March to December 2010. To generate incidence rate estimates, we identified recent onset cases recruited as part of the prevalence study and then imputed population-based incidence rates using a set of conservative assumptions. Similarly, for mortality rates, we identified individuals who had died after being identified as 'screen-positive' for psychosis, but prior to full clinical assessment. Using a set of conservative assumptions, we then used these estimates to infer population-based mortality rates. Based on our models, we estimated that the incidence rate for psychotic disorders was 28 cases per 100,000 population. The rate estimates were significantly higher in males than females, with an overall male:female ratio of 1.57:1. Incidence rate estimates peaked in the youngest age group (18-24 years). The adjusted mortality rate estimated during the whole period of observation was 12.5 per 1000 persons, with a standardised mortality ratio of 5.5. Using treated prevalence data and observed deaths with appropriate algorithms, we were able to impute incidence and mortality rates for psychotic disorders consistent with the published literature. While the second national survey of psychotic disorders was not designed to identify mortality, our estimates provide a stark reminder of the increased mortality associated with these disorders.

Emerging Effects of Early Environmental Factors over Genetic Background for Type 1 Diabetes Susceptibility: Evidence from a Nationwide Italian Twin Study

The incidence of type 1 diabetes has been increasing over time. We estimated the genetic and environmental components of type 1 diabetes susceptibility in a twin cohort of recent-onset cases to explore the sources of changing disease epidemiology. We linked the population-based Italian Twin Registry with 14803 type 1 diabetes records from 36 pediatric diabetes care centers throughout Italy, except Sardinia, and identified 173 diabetic twins. Patients were positive for at least one autoantibody to islet cell, glutamate decarboxylase, tyrosine phosphatase, insulin, or zinc transporter 8 and were insulin dependent since their diagnosis. Zygosity was determined by DNA genotyping or by questionnaire. We estimated proband-wise concordance, cotwin recurrence risk with Kaplan-Meier method, and genetic and environmental proportions of susceptibility variance by structural equation models. We recruited 104 diabetic twins (53 males) from 88 pairs (34 monozygotic, 54 dizygotic) and one triplet. The mean age at diagnosis was 8.1 yr (range 1.1-20.5 yr), and the median year of diagnosis was 2002. Proband-wise concordances were 45.5 and 16.4% in monozygotic and dizygotic pairs (P = 0.01). Recurrence risks in monozygotic and dizygotic cotwins were 37 and 12% after 10 yr from the proband's diagnosis (P = 0.005). Genetic contribution to type 1 diabetes susceptibility was 40% (95% confidence interval 8-78), and the shared and individual-specific environmental components were 51% (14-77) and 9% (4-19), respectively. In addition to the moderate genetic effects on type 1 diabetes susceptibility, our results draw attention to the substantial shared environmental effects, suggesting that exposures in fetal or early postnatal life may contribute to the increasing incidence of the disease.

Post-H1N1 Narcolepsy-Cataplexy

Post-H1N1 Narcolepsy-Cataplexy

Anti-Tribbles Homolog 2 (TRIB2) Autoantibodies in Narcolepsy are Associated with Recent Onset of Cataplexy

Recent studies have found increased autoantibodies against Tribbles homolog 2 (anti-TRIB2) and anti-streptolysin O (ASO) in narcolepsy. In this study, we replicated this finding with a primary focus on recent onset cases. Participants included (1) 90 cases with cataplexy, (2) 57 cases without cataplexy, and (3) 156 age-sex matched controls, including 73 human leukocyte antigen (HLA)-DQB1*0602 allele carriers. A radioligand binding assay was used to detect anti-TRIB2 antibodies. Anti-TRIB2 antibodies were prevalent in HLA-DQB1*0602 positive cases with cataplexy (25.0% of 76) and rare in cases without cataplexy (3.5% of 57, OR = 9.2, 95% CI = 2.5 - 33.5, P = 6.0 x 10(-4)) or controls (4.5% of 156, OR = 7.1, 95% CI = 3.1 - 16.2, P = 9.3 x 10(-6)). Anti-TRIB2 positivity in controls was not associated with DQB1*0602. In DQB1*0602 narcolepsy-cataplexy cases, the presence of anti-TRIB2 was associated with short disease duration (2.3 years from cataplexy onset), with 41.0% positive in this group (OR = 7.4 versus cases with onset > 2.3 years, 95% CI = 1.9- 28.5, P = 9.0 x 10(-4)). Anti-TRIB2 positivity in 39 DQB1*0602 positive recent onset cases was associated with increased ASO antibody (> 200 IU) (OR = 6.2, 95% CI = 1.6 - 24.6, P = 0.01), but did not correlate with age, gender, or body mass index. Anti-TRIB2 autoantibodies are strongly associated with narcolepsy close to cataplexy onset (< or = 2.3 years). Anti-TRIB2 was rarely found in cases without cataplexy or with distant onset.

Elevated Anti-Streptococcal Antibodies in Patients with Recent Narcolepsy Onset

Narcolepsy-cataplexy has long been thought to have an autoimmune origin. Although susceptibility to narcolepsy, like many autoimmune conditions, is largely genetically determined, environmental factors are involved based on the high discordance rate (approximately 75%) of monozygotic twins. This study evaluated whether Streptococcus pyogenes and Helicobacter pylori infections are triggers for narcolepsy. Retrospective, case-control. Sleep centers of general hospitals. 200 patients with narcolepsy/hypocretin deficiency, with a primary focus on recent onset cases and 200 age-matched healthy controls. All patients were DQB1*0602 positive with low CSF hypocretin-1 or had clear-cut cataplexy. Participants were tested for markers of immune response to beta hemolytic streptococcus (anti-streptolysin O [ASO]; anti DNAse B [ADB]) and Helicobacter pylori [Anti Hp IgG], two bacterial infections known to trigger autoimmunity. A general inflammatory marker, C-reactive protein (CRP), was also studied. When compared to controls, ASO and ADB titers were highest close to narcolepsy onset, and decreased with disease duration. For example, ASO > or = 200 IU (ADB > or = 480 IU) were found in 51% (45%) of 67 patients within 3 years of onset, compared to 19% (17%) of 67 age matched controls (OR = 4.3 [OR = 4.1], P < 0.0005) or 20% (15%) of 69 patients with long-standing disease (OR = 4.0 [OR = 4.8], P < 0.0005]. CRP (mean values) and Anti Hp IgG (% positive) did not differ from controls. Streptococcal infections are probably a significant environmental trigger for narcolepsy.

Reversibility of Antipsychotic Treatment–Related Diabetes in Patients With Schizophrenia

At present, antipsychotic drugs are not specifically referred to in the list of substances that can induce diabetes in the most recent American Diabetes Association guidelines (1), but there is a growing body of evidence that antipsychotic drugs might have diabetogenic properties (2,3). At present, there are no clear guidelines on what the best therapeutic strategies are when diabetes is detected during treatment with antipsychotics. Data from pharmacovigilance studies suggest that a significant proportion of recent-onset cases of diabetes can be reversed. Recent Belgian guidelines for screening and monitoring patients treated with antipsychotics propose a switch to an antipsychotic with a safer metabolic profile, but this …

Symptomatic and functional outcome of bipolar disorder in Butajira, Ethiopia

Background Limited information is available on the outcome of bipolar disorder in developing countries. Objective To describe the symptomatic and functional outcome of bipolar disorder. Methods The psychoses and affective disorder modules of the CIDI were used to screen 68,378 individuals by a door-to-door survey of a defined district in Ethiopia. In addition, key informants were used to identify individuals with probable major mental illnesses. SCAN interviews were completed at the second stage to confirm the diagnosis. A total of 315 cases of bipolar disorder were identified, of which 264 (69 recent-onset and 195 prevalent cases) were prospectively followed for a mean of 2.5 (range 1–4) years by baseline and annual clinical assessments using symptom rating scales. Functional dimensions of the SF-36 scale were used to describe functional outcome. Random coefficient analyses were used to evaluate potential correlates of outcome. Results The magnitudes of mania and depression symptoms were elevated at baseline but improved with follow-up, although the improvement was less marked for depression. Sociodemographic or clinical variables were not associated with the improvements in symptomatic outcome. Between 35% and 47% of the recent-onset cases had functional role restrictions, while 42–52% of long-standing cases had such restrictions during the follow-up years. Similarly, social and physical functioning deficits were also present in 52–86% and 35–47% of recent-onset and long-standing cases, respectively. The magnitude of depression and mania symptoms was associated with poor functional outcome, while male sex, rural residence and being married were associated with better functional outcome. Conclusion Although there were improvements in function with follow-up, between one-third and one-half of cases continued to have functional deficits.

Multimodal neuroimaging studies and neurodevelopment and neurodegeneration hypotheses of schizophrenia.

The interpretation of the huge number of results in schizophrenia research using neuroimaging is uncertain. However, the simultaneous use of complimentary data obtained with these techniques may yield more relevant information in this regard. In this paper we present a series of studies performed by our group in two schizophrenic samples with the use of structural (magnetic resonance imaging, MRI), functional [glucose positron emission tomography (PET) and N-acetyl-aspartate (NAA) magnetic resonance spectrocopy] and neurophysiological techniques (the P300 event-related potential). Transversal and longitudinal measurements were performed.The integrated vision of the results so obtained allows us to propose the hypothesis of a neurodevelopmentally determined state of prefrontal disinihibition, in which the degree of atrophy would directly relate to the metabolic rate. This state would already be present in the first stages of illness and could have neurotoxic consequences in the long term. This would explain the findings of an association between sulcal cerebrospinal fluid (CSF) and illness duration and decreased NAA levels in chronic but not in recent-onset cases. The prefrotnal disinhibition would overstimulate the limbic system and the hippocampus would become overactivated, the metabolic rate at this level being inversely related to P300 amplitude. Clozapine showed a more selective and intense action on that hyperactive metabolic tone than haloperidol.

Effect of temporomandibular disorder pain duration on facial expressions and verbal report of pain

This study investigated how specific expressive behaviors (verbal report of pain level and the frequency of emitting specific non-verbal facial expressions of pain) may change over the course of a chronic pain condition. Based on the concept of chronic pain behaviors, we hypothesized that both verbal and non-verbal behavior would increase with duration of pain. Thirty-six women with chronic temporomandibular disorder (TMD) pain (duration over 6 months) were compared with 35 recent onset cases (first episode, duration $ ̌ = 2 months). Subjects completed questionnaires assessing depression, anxiety, somatization, daily hassles and pain coping strategies. They were videotaped during a resting baseline and 2 painful conditions: experimental cold pressor pain and the clinically relevant pain of palpation of the masticatory muscles and temporomandibular joint; tapes were coded for facial expression using the Facial Action Coding System. Visual analog scale (VAS) ratings of the aversiveness and intensity of ongoing TMD pain were collected at baseline, and similar ratings of cold pressor and clinical examination pain were gathered after the painful stimulus. Recent onset and chronic cases did not differ on self-report measures of anxiety, depression, somatization or daily stress. Coping strategies were also similar, although chronic cases showed a greater tendency to catastrophize. Self-report measures of ambient facial pain, as well as the pain of clinical examination and cold pressor stimulation, revealed no significant differences between the 2 groups. In contrast, rates of pain facial expression were significantly higher for chronic cases under all conditions of the experiment, including baseline. The findings suggest that verbal and non-verbal expressions of pain may be differentially reinforced over the course of a chronic pain condition, such that non-verbal pain facial expressions become more frequent with time, while verbal reports of pain remain relatively constant.