Immunogenetics of drug-induced skin blistering disorders. Part II: Synthesis

The overall immunopathogenesis relevant to a large series of disorders caused by a drug or its associated hyperimmune condition is discussed based upon examining the genetics of severe drug-induced bullous skin problems (sporadic idiosyncratic adverse events including Stevens-Johnson syndrome and Toxic epidermal necrolysis). New results from an exemplar study on shared precipitating and perpetuating inner causes with other related disease phenotypes including aphtous stomatitis, Behcets, erythema multiforme, Hashimoto's thyroiditis, pemphigus, periodic fevers, Sweet's syndrome and drug-induced multisystem hypersensitivity are presented. A call for a collaborative, wider demographic profiling and deeper immunotyping in suggested future work is made.

Immunogenetics of drug-induced skin blistering disorders. Part I: Perspective

The overall immunopathogenesis relevant to a large series of disorders caused by a drug or its associated hyperimmune condition is discussed based upon the examination of the genetics of severe drug-induced bullous skin problems (sporadic idiosyncratic adverse events, including Stevens-Johnson syndrome and toxic epidermal necrolysis). An overarching pharmacogenetic schema is proposed. Immune cognition and early-effector processes are focused upon and a challenging synthesis around systems evolution is explained by a variety of projective analogies. Etiology, human leukocyte antigen-B, immune stability, clysiregulation, pharmacomimicry, viruses and an aggressive ethnically differentiated 'karmic' response are discussed.

Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children

Children with autistic spectrum disorders (ASDs) tend to suffer from severe gastrointestinal problems. Such symptoms may be due to a disruption of the indigenous gut flora promoting the overgrowth of potentially pathogenic micro-organisms. The faecal flora of patients with ASDs was studied and compared with those of two control groups (healthy siblings and unrelated healthy children). Faecal bacterial populations were assessed through the use of a culture-independent technique, fluorescence in situ hybridization, using oligonucleotide probes targeting predominant components of the gut flora. The faecal flora of ASD patients contained a higher incidence of the Clostridium histolyticum group (Clostridium clusters I and 11) of bacteria than that of healthy children. However, the non-autistic sibling group had an intermediate level of the C. histolyticum group, which was not significantly different from either of the other subject groups. Members of the C. histolyticum group are recognized toxin-producers and may contribute towards gut dysfunction, with their metabolic products also exerting systemic effects. Strategies to reduce clostridial population levels harboured by ASD patients or to improve their gut microflora profile through dietary modulation may help to alleviate gut disorders common in such patients.

Natural products as alternative treatments for metabolic bone disorders and for maintenance of bone health

Bone metabolism involves a complex balance between the deposition of matrix and mineralization and resorption. There is now good evidence that dietary components and herbal products can influence these processes, particularly by inhibiting bone resorption, thus having beneficial effects on the skeleton. For example, it has been reported that a number of common vegetables, including onion, garlic and parsley, can inhibit bone resorption in ovariectomized rats. Essential oils derived from sage, rosemary, thyme and other herbs inhibit osteoclast activity in vitro and in vitro and leading to an increase in bone mineral density. Soya, a rich source of isoflavones, has shown promising results and epidemiological evidence to support a use in maintaining bone health, and various traditional herbal formulae in Chinese and Ayurvedic medicine also have demonstrable effects in pharmacological models of osteoporosis. Recently, cannabinoids have been described as having positive effects on osteoblast differentiation, and the presence of cannabinoid receptors in bone tissue indicates a more complex role in bone metabolism than previously thought. The first part of this review briefly discusses normal bone metabolism and disorders caused by its disruption, with particular reference to osteoporosis and current pharmacological treatments. The effects of natural products on bone and connective tissue are then discussed, to include items of diet, herbal extracts and food supplements, with evidence for their efficacy outlined. Copyright (c) 2006 John Wiley & Sons, Ltd.

Childhood emotional abuse and neglect as predictors of psychological and physical symptoms in women presenting to a primary care practice

Objective: There were two aims to this study: first to examine whether emotional abuse and neglect are significant predictors of psychological and somatic symptoms, and lifetime trauma exposure in women presenting to a primary care practice, and second to examine the strength of these relationships after controlling for the effects of other types of childhood abuse and trauma. Method: Two-hundred and five women completed the Childhood Trauma Questionnaire (Bernstein et al., 1994), Trauma History Questionnaire (Green, 1996), the Symptom Checklist-revised (Derogatis, 1997), and the Revised Civilian Mississippi Scale for posttraumatic stress disorder (Norris & Perilla, 1996) when presenting to their primary care physician for a visit. Hierarchical multiple regression analyses were conducted to examine unique contributions of emotional abuse and neglect variables on symptom measures while controlling for childhood sexual and physical abuse and lifetime trauma exposure. Results: A history of emotional abuse and neglect was associated with increased anxiety, depression, posttraumatic stress and physical symptoms, as well as lifetime trauma exposure. Physical and sexual abuse and lifetime trauma were also significant predictors of physical and psychological symptoms. Hierarchical multiple regressions demonstrated that emotional abuse and neglect predicted symptomatology in these women even when controlling for other types of abuse and lifetime trauma exposure. Conclusions: Long-standing behavioral consequences may arise as a result of childhood emotional abuse and neglect, specifically, poorer emotional and physical functioning, and vulnerability to further trauma exposure. (C) 2003 Elsevier Ltd. All rights reserved.

Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample

Objective: Autism spectrum disorders are now recognized to occur in up to 1% of the population and to be a major public health concern because of their early onset, lifelong persistence, and high levels of associated impairment. Little is known about the associated psychiatric disorders that may contribute to impairment. We identify the rates and type of psychiatric comorbidity associated with ASDs and explore the associations with variables identified as risk factors for child psychiatric disorders. Method: A subgroup of 112 ten- to 14-year old children from a population-derived cohort was assessed for other child psychiatric disorders (3 months' prevalence) through parent interview using the Child and Adolescent Psychiatric Assessment. DSM-IV diagnoses for childhood anxiety disorders, depressive disorders, oppositional defiant and conduct disorders, attention-deficit/hyperactivity disorder, tic disorders, trichotillomania, enuresis, and encopresis were identified. Results: Seventy percent of participants had at least one comorbid disorder and 41% had two or more. The most common diagnoses were social anxiety disorder (29.2%, 95% confidence interval [CI)] 13.2-45.1), attention-deficit/hyperactivity disorder (28.2%, 95% CI 13.3-43.0), and oppositional defiant disorder (28.1%, 95% CI 13.9-42.2). Of those with attention/deficit/hyperactivity disorder, 84% received a second comorbid diagnosis. There were few associations between putative risk factors and psychiatric disorder. Conclusions: Psychiatric disorders are common and frequently multiple in children with autism spectrum disorders. They may provide targets for intervention and should be routinely evaluated in the clinical assessment of this group.

Effect of psychological treatment on attentional bias in eating disorders

Objective: The aims of these studies were (a) to investigate the relationship between attentional bias and eating disorders and (b) examine the impact of psychological treatment on attentional bias. Method: The first study compared performance on a pictorial dot probe of 82 female patients with clinical eating disorders and 44 healthy female controls. The second study compared the performance of 31 patients with eating disorder on the same task before and after receiving 20 weeks of standardized cognitive behavior therapy. Twenty-four patients with eating disorder served as wait-list controls. Results: With the exception of neutral shape stimuli, attentional biases for eating, shape, and weight stimuli were greater in the patient sample than the healthy controls. The second study found that attentional biases significantly reduced after active treatment only. Conclusion: Attentional biases may be an expression of the eating disorder. The question of whether such biases warrant specific intervention requires further investigation. (C) 2008 by Wiley Periodicals, Inc.

Attentional bias in eating disorders

Objective: To examine the relationship between eating disorders and attentional biases. Method: The first study comprised 23 female patients with clinical eating disorders, women with high levels of anxiety (n = 19), and three female normal control groups comprising low (n = 31), moderate (n = 21), or high levels of shape concern (n 23). The second study comprised 82 women with clinical eating disorders and 44 healthy controls. All participants completed measures of eating disorder psychopathology and completed a modified pictorial dot-probe task. Results: In the first study, biases were found for negative eating and neutral weight pictures, and for positive eating pictures in women with eating disorders; these biases were greater than those found in anxious and normal controls. The second study replicated these findings and biases were also found for negative and neutral shape stimuli. Conclusion: It is concluded that future research should establish whether such biases warrant specific therapeutic interventions. (c) 2007 by Wiley Periodicals, Inc.

Children's representation of family mealtime in the context of maternal eating disorders

Background Recent research provides evidence for specific disturbance in feeding and growth in children of mothers with eating disorders. Aim To investigate the impact of maternal eating disorders during the post-natal year on the internal world of children, as expressed in children's representations of self and their mother in pretend mealtime play at 5 years of age. Methods Children of mothers with eating disorders (n = 33) and a comparison group (n = 24) were videotaped enacting a family mealtime in pretend play. Specific classes of children's play representations were coded blind to group membership. Univariate analyses compared the groups on representations of mother and self. Logistic regression explored factors predicting pretend play representations. Results Positive representations of the mother expressed as feeding, eating or body shape themes were more frequent in the index group. There were no other significant group differences in representations. In a logistic regression analysis, current maternal eating psychopathology was the principal predictor of these positive maternal representations. Marital criticism was associated with negative representations of the mother. Conclusions These findings suggest that maternal eating disorders may influence the development of a child's internal world, such that they are more preoccupied with maternal eating concerns. However, more extensive research on larger samples is required to replicate these preliminary findings.

The development of anxiety disorders in childhood: an integrative review

We present an integrative review of the development of child anxiety, drawing on a number of strands of research. Family aggregation and genetic studies indicate raised vulnerability to anxiety in offspring of adults with the disorder (e.g. the temperamental style of behavioural inhibition, or information processing biases). Environmental factors are also important; these include adverse life events and exposure to negative information or modelling. Parents are likely to be key, although not unique, sources of such influences, particularly if they are anxious themselves. Some parenting behaviours associated with child anxiety, such as overprotection, may be elicited by child characteristics, especially in the context of parental anxiety, and these may serve to maintain child disorder. Emerging evidence emphasizes the importance of taking the nature of child and parental anxiety into account, of constructing assessments and interventions that are both disorder specific, and of considering bidirectional influences.

Neural response to emotional prosody in schizophrenia and in bipolar affective disorder

Background Evidence suggests a reversal of the normal left-lateralised response to speech in schizophrenia. Aims To test the brain's response to emotional prosody in schizophrenia and bipolar disorder. Method BOLD contrast functional magnetic resonance imaging of subjects while they passively listened or attended to sentences that differed in emotional prosody Results Patients with schizophrenia exhibited normal right-lateralisation of the passive response to 'pure' emotional prosody and relative left-lateralisation of the response to unfiltered emotional prosody When attending to emotional prosody, patients with schizophrenia activated the left insula more than healthy controls. When listening passively, patients with bipolar disorder demonstrated less activation of the bilateral superior temporal gyri in response to pure emotional prosody, and greater activation of the left superior temporal gyrus in response to unfiltered emotional prosody In both passive experiments, the patient groups activated different lateral temporal lobe regions. Conclusions Patients with schizophrenia and bipolar disorder may display some left-lateralisation of the normal right-lateralised temporal lobe response to emotional prosody. Declaration of interest R.M. received a studentship from Neuraxis,, and funding from the Neuroscience and Psychiatry Unit, University of Manchester.

The neural response to emotional prosody, as revealed by functional magnetic resonance imaging

Prosody is an important feature of language, comprising intonation, loudness, and tempo. Emotional prosodic processing forms an integral part of our social interactions. The main aim of this study was to use bold contrast fMRI to clarify the normal functional neuroanatomy of emotional prosody, in passive and active contexts. Subjects performed six separate scanning studies, within which two different conditions were contrasted: (1) "pure" emotional prosody versus rest; (2) congruent emotional prosody versus 'neutral' sentences; (3) congruent emotional prosody versus rest; (4) incongruent emotional prosody versus rest; (5) congruent versus incongruent emotional prosody; and (6) an active experiment in which subjects were instructed to either attend to the emotion conveyed by semantic content or that conveyed by tone of voice. Data resulting from these contrasts were analysed using SPM99. Passive listening to emotional prosody consistently activated the lateral temporal lobe (superior and/or middle temporal gyri). This temporal lobe response was relatively right-lateralised with or without semantic information. Both the separate and direct comparisons of congruent and incongruent emotional prosody revealed that subjects used fewer brain regions to process incongruent emotional prosody than congruent. The neural response to attention to semantics, was left lateralised, and recruited an extensive network not activated by attention to emotional prosody. Attention to emotional prosody modulated the response to speech, and induced right-lateralised activity, including the middle temporal gyrus. In confirming the results of lesion and neuropsychological studies, the current study emphasises the importance of the right hemisphere in the processing of emotional prosody, specifically the lateral temporal lobes. (C) 2003 Elsevier Science Ltd. All rights reserved.

Decoding emotional prosody in Parkinson's disease and its potential neuropsychological basis

Parkinson's disease patients may have difficulty decoding prosodic emotion cues. These data suggest that the basal ganglia are involved, but may reflect dorsolateral prefrontal cortex dysfunction. An auditory emotional n-back task and cognitive n-back task were administered to 33 patients and 33 older adult controls, as were an auditory emotional Stroop task and cognitive Stroop task. No deficit was observed on the emotion decoding tasks; this did not alter with increased frontal lobe load. However, on the cognitive tasks, patients performed worse than older adult controls, suggesting that cognitive deficits may be more prominent. The impact of frontal lobe dysfunction on prosodic emotion cue decoding may only become apparent once frontal lobe pathology rises above a threshold.

fMRI delineation of working memory for emotional prosody in the brain: commonalities with the lexico-semantic emotion network

Decoding emotional prosody is crucial for successful social interactions, and continuous monitoring of emotional intent via prosody requires working memory. It has been proposed by Ross and others that emotional prosody cognitions in the right hemisphere are organized in an analogous fashion to propositional language functions in the left hemisphere. This study aimed to test the applicability of this model in the context of prefrontal cortex working memory functions. BOLD response data were therefore collected during performance of two emotional working memory tasks by participants undergoing fMRI. In the prosody task, participants identified the emotion conveyed in pre-recorded sentences, and working memory load was manipulated in the style of an N-back task. In the matched lexico-semantic task, participants identified the emotion conveyed by sentence content. Block-design neuroimaging data were analyzed parametrically with SPM5. At first, working memory for emotional prosody appeared to be right-lateralized in the PFC, however, further analyses revealed that it shared much bilateral prefrontal functional neuroanatomy with working memory for lexico-semantic emotion. Supplementary separate analyses of males and females suggested that these language functions were less bilateral in females, but their inclusion did not alter the direction of laterality. It is concluded that Ross et al.'s model is not applicable to prefrontal cortex working memory functions, that evidence that working memory cannot be subdivided in prefrontal cortex according to material type is increased, and that incidental working memory demands may explain the frontal lobe involvement in emotional prosody comprehension as revealed by neuroimaging studies. (c) 2007 Elsevier Inc. All rights reserved.

Age-related decline in the ability to decode emotional prosody: primary or secondary phenomenon?

Emotion processing deficits can cause catastrophic damage to a person's ability to interact socially. While it is known that older adults have difficulty identifying facial emotions, it is still not clear whether this difficulty extends to identification of the emotion conveyed by prosody. This study investigated whether the ability of older adults to decode emotional prosody falls below that of young adults after controlling for loss of hearing sensitivity and key features of cognitive ageing. Apart from frontal lobe load, only verbal IQ was associated with the age-related reduction in performance displayed by older participants, but a notable deficit existed after controlling for its effects. It is concluded that older adults may indeed have difficulty deducing the emotion conveyed by prosody, and that while this difficulty can be exaggerated by some aspects of cognitive ageing, it is primary in origin.