The relevance of differential response to trauma in an animal model of posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder affects 20%-30% of those exposed. Clinical studies employ stringent inclusion-exclusion criteria, yet animal studies include the entire exposed population as the study population. We examined the effect of grouping prestressed rats according to magnitude of response on the statistical analysis of results. METHOD: Response magnitude to predator exposure was assessed and used to group the animals into "diagnostic" groups. Two extremes were studied (clearly "maladapted" and clearly "well adapted" rats) using arbitrarily selected cutoff behavioral criteria (CBC). The data for the middle group were discarded for reasons of clarity. Hypothalamic-pituitary-adrenal axis and heart-rate variability were analyzed for the entire exposed population and then according to the CBC. RESULTS: A single 10-min exposure to a predator caused fear-related behaviors in only 25.3% of exposed rats. Compared with control subjects and well-adapted exposed rats, maladapted rats exhibited significantly higher plasma corticosterone and corticotropin concentrations, increased sympathetic activity, diminished vagal tone, and increased sympathovagal balance. These differences surfaced only when data were analyzed according to CBC.Animals respond to stress heterogeneously, resembling humans. Overlooking this heterogeneity may obscure the results of data analysis. CONCLUSIONS: Animals can be divided into distinct groups according to magnitude of response and be studied accordingly.     

Validity of the clinical diagnostic criteria for vascular dementia: a critical review. Part II

This review is the second of a two-part series focusing on the validity of eight clinical criteria for vascular dementia. Sixteen studies were selected according to their purposes and quality of experimental design. The analysis revealed that criteria for vascular dementia are not interchangeable; the eight criteria sets yielded different sensitivity and specificity results, as well as marked variability in incidence, prevalence, and frequency rates. Although the State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) were the most sensitive and useful criteria in clinical settings and the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) were the most specific and useful criteria in research, all criteria shared similar flaws. A definition of the cognitive syndrome, associated vascular causes or lesions, and methods of assessment should be clearly specified in the future. Suggestions for improvement are made.     

Variability of ecological executive function in children and adolescents genetically at high risk for schizophrenia: a latent class analysis

Executive impairments have been observed both in patients with schizophrenia and in their unaffected first-degree relatives. Very few studies have investigated neurocognitive subgroups in unaffected first-degree relatives and in healthy participants using data-driven methods. The study included a high-risk group consisting of 100 unaffected young offspring and siblings of patients with schizophrenia and 198 healthy controls, all aged between 9 and 23 years. Executive function, victimization, and emotional and behavioral problems of participants were assessed by a series of self-report scales. Neurocognitive subgroups were investigated using latent class analysis of executive function measures. Four neurocognitive clusters were identified: a good performance cluster, a good self-control cluster, a low self-control cluster, and a severe impairment cluster. Participants in severe impaired executive function cluster reported a significantly higher level of victimization and had more prominent emotional and behavioral problems than the good performance cluster. Neurocognitive differences between high-risk young people and healthy controls were driven by individuals who have severe and global, rather than selective, executive deficits. Our results may provide clues to an explanation of the mechanisms behind executive impairments in young individuals at genetic risk and help to identify new targets for early interventions.

     

The influence of validity criteria on Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) test–retest reliability among high school athletes

Objective: Research findings to date on the stability of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) Composite scores have been inconsistent, requiring further investigation. The use of test validity criteria across these studies also has been inconsistent. Using multiple measures of stability, we examined test–retest reliability of repeated ImPACT baseline assessments in high school athletes across various validity criteria reported in previous studies. Method: A total of 1146 high school athletes completed baseline cognitive testing using the online ImPACT test battery at two time periods of approximately two-year intervals. No participant sustained a concussion between assessments. Five forms of validity criteria used in previous test–retest studies were applied to the data, and differences in reliability were compared. Results: Intraclass correlation coefficients (ICCs) ranged in composite scores from .47 (95% confidence interval, CI [.38, .54]) to .83 (95% CI [.81, .85]) and showed little change across a two-year interval for all five sets of validity criteria. Regression based methods (RBMs) examining the test–retest stability demonstrated a lack of significant change in composite scores across the two-year interval for all forms of validity criteria, with no cases falling outside the expected range of 90% confidence intervals. Conclusion: The application of more stringent validity criteria does not alter test–retest reliability, nor does it account for some of the variation observed across previously performed studies. As such, use of the ImPACT manual validity criteria should be utilized in the determination of test validity and in the individualized approach to concussion management. Potential future efforts to improve test–retest reliability are discussed.     

Factor versus cluster models of schizotypal traits. I: a comparison of unselected and highly schizotypal samples.

Factor analytic studies have long supported the division of schizophrenic symptoms into three relatively orthogonal factors: positive symptoms, negative symptoms, and disorders of relatedness/disorganization. Similarly, factor analyses of schizotypy often yield three factors: positive symptoms, negative symptoms, and social anxiety or disorganization. Recent cluster analyses, however, suggest that not all patients can be simply categorized according to these factors. Cluster analyses of schizotypal symptoms tend to result in clusters of individuals who are low in all factors, high in more than one factor, or high predominantly in one factor. The present study sought to compare factor and cluster models of schizotypal symptoms, as measured by the SPQ, PAS, and MIS, in unselected individuals and highly schizotypal individuals. Consistent with prior research, factor analysis of a large unselected undergraduate sample yielded three factors: "positive", "negative", and "disorganized." Factor analysis of schizotypal undergraduates produced the same three factors, plus a fourth designated "paranoid thinking." In contrast, cluster analysis of the unselected sample yielded four clusters ("low schizotypy", "average schizotypy", and "high schizotypy", plus "positive/disorganized"). Cluster analysis of the schizotypal subsample produced four clusters: "low schizotypy", "positive", "negative" and "high schizotypy."     

A prospective cohort study of childhood behavioral deviance and language abnormalities as predictors of adult schizophrenia

Language and behavioral deviance in early childhood in preschizophrenia individuals suggests that the pathologic processes predisposing to schizophrenia are present from early in life. However, the etiologic antecedents of such impairments, and the degree to which they predict adult schizophrenia, have not been conclusively demonstrated. To address this, we examined language and behavioral predictors of adult psychiatric outcome in a population cohort (72 individuals with schizophrenia or schizoaffective disorder, 63 of their unaffected siblings, and 7,941 with no diagnosis) evaluated prospectively with behavioral examinations and a speech and language evaluation at 8 months, 4 years, and 7 years of age. Psychiatric outcome was ascertained via adult treatment contacts, and diagnoses were made by chart review according to DSM-IV criteria. Social maladjustment at age 7 was found to predict adult schizophrenia, and focal deviant behaviors (e.g., echolalia, meaningless laughter) at ages 4 and 7 were significantly associated with both schizophrenia and sibling status. Unintelligible speech at age 7 was a highly significant predictor of adult schizophrenia (odds ratio = 12.7), and poor expressive language ability predicted both schizophrenia and unaffected sibling outcome. Early behavioral and language dysfunction did not differentially characterize preschizophrenia subjects with a history of fetal hypoxia or an early age of first treatment contact. Given that unaffected siblings show similar signs of deviance, such problems may indicate genotypic susceptibility to the disorder, or shared environmental influences, or both.     

Defining Recovery in Adult Bulimia Nervosa

To examine how different definitions of recovery lead to varying rates of recovery, maintenance of recovery, and relapse in bulimia nervosa (BN), end-of-treatment (EOT) and follow-up data were obtained from 96 adults with BN. Combining behavioral, physical, and psychological criteria led to recovery rates between 15.5% and 34.4% at EOT, though relapse was approximately 50%. Combining these criteria and requiring abstinence from binge eating and purging when defining recovery may lead to lower recovery rates than those found in previous studies; however, a strength of this definition is that individuals who meet this criteria have no remaining disordered behaviors or symptoms.     

Prospective investigation of a PTSD personality typology among individuals with personality disorders

This study investigated the replicability of a previously proposed personality typology of posttraumatic stress disorder (PTSD, and explored stability of cluster membership over a 6-month period. Participants with current PTSD (n = 156) were drawn from the Collaborative Longitudinal Personality Disorders Study (CLPS). The CLPS project tracked a large sample of individuals who met criteria for 1 of 4 target diagnoses (borderline, schizotypal, avoidant, and obsessive-compulsive) and a contrast group of individuals who met criteria for depression but no personality disorder. A cluster analysis using scales from the Schedule of Nonadaptive and Adaptive Personality yielded 3 clusters: "internalizing," "externalizing," and "low pathology." Using K-means cluster analysis, the results did not replicate previous work. Using Ward's method, the hypothesized 3-cluster structure was confirmed at baseline but did not demonstrate temporal stability at 6 months.     

A systematic review of cerebral hemodynamic responses to neural activation following stroke

The aim of this study was to systematically review CBF studies, assess their methodological quality, and identify trends in the association between task-related brain activation patterns and CBF changes in ischemic stroke (IS) patients. We searched the MEDLINE, EMBASE, CINAHL, and Web of Sciences databases for studies of functional recovery with quantification of CBF responses to brain activation paradigms after IS. Titles, abstracts and full text of articles were scrutinised according to pre-defined selection criteria. Two independent reviewers (AS, VH) undertook the methodological quality screening and data extraction of the included studies. Sixteen of the 1,521 identified studies were relevant. Studies showed weaknesses in key methodological criteria (e.g. population size, discussion of limitations), and only seven studies compared responses with a control population. Overall, there was no agreement between CBF responses in either the affected or unaffected hemisphere and prediction of post-IS recovery. Some studies have shown a higher CBF increase in the unaffected hemisphere when the affected hemisphere was stimulated compared to the healthy control responses. However, CBF responses in the affected hemisphere were inconsistent. Many post-IS CBF studies are of poor methodological quality, and do not demonstrate a consistent response post-IS or a relationship with recovery. Further longitudinal studies assessing the natural history of CBF responses to brain paradigms following IS should be undertaken to determine prognostic significance, and to inform future therapeutic strategies.     

The role of stress as a trigger for epileptic seizures: A narrative review of evidence from human and animal studies

Stress is one of the most frequently self‐identified seizure triggers in patients with epilepsy; however, most previous publications on stress and epilepsy have focused on the role of stress in the initial development of epilepsy. This narrative review explores the causal role of stress in triggering seizures in patients with existing epilepsy. Findings from human studies of psychological stress, as well as of physiologic stress responses in humans and animals, and evidence from nonpharmacologic interventions for epilepsy are considered. The evidence from human studies for stress as a trigger of epileptic seizures is inconclusive. Although retrospective self‐report studies show that stress is the most common patient‐perceived seizure precipitant, prospective studies have yielded mixed results and studies of life events suggest that stressful experiences only trigger seizures in certain individuals. There is limited evidence suggesting that autonomic arousal can precede seizures. Interventions designed to improve coping with stress reduce seizures in some individuals. Studies of physiologic stress using animal epilepsy models provide more convincing evidence. Exposure to exogenous and endogenous stress mediators has been found to increase epileptic activity in the brain and trigger overt seizures, especially after repeated exposure. In conclusion, stress is likely to exacerbate the susceptibility to epileptic seizures in a subgroup of individuals with epilepsy and may play a role in triggering “spontaneous” seizures. However, there is currently no strong evidence for a close link between stress and seizures in the majority of people with epilepsy, although animal research suggests that such links are likely. Further research is needed into the relationship between stress and seizures and into interventions designed to reduce perceived stress and improve quality of life with epilepsy.     

Comparisons of discrete-trial and normalized behavioral language intervention for young children with autism

This critical review examined a series of 10 controlled studies in which traditional operant behavioral procedures were compared with more recently developed normalized interventions for teaching language to young children with autism. Main characteristics of the older treatments include highly structured direct teaching sessions of discrete trials, teacher initiation, artificial reinforcers, and response shaping. Normalized interventions consist of loosely structured sessions of indirect teaching with everyday situations, child initiation, natural reinforcers, and liberal criteria for presentation of reinforcers. The main conclusion was that in all eight studies with language criterion responses, normalized language training was more effective than discrete-trial training. Furthermore, in both studies that assessed parental affect, normalized treatment yielded more positive affect than discrete-trial training.     

A principal components analysis of the Autism Diagnostic Interview-Revised

OBJECTIVE: To develop factors based on the Autism Diagnostic Interview-Revised (ADI-R) that index separate components of the autism phenotype that are genetically relevant and validated against standard measures of the constructs. METHOD: ADIs and ADI-Rs of 292 individuals with autism were subjected to a principal components analysis using VARCLUS. The resulting variable clusters were validated against standard measures. RESULTS: Six clusters of variables emerged: spoken language, social intent, compulsions, developmental milestones, savant skills and sensory aversions. Five of the factors were significantly correlated with the validating measures and had good internal consistency, face validity, and discriminant and construct validity. Most intraclass correlations between siblings were adequate for use in genetic studies. CONCLUSION: The ADI-R contains correlated clusters of variables that are valid, genetically relevant, and that can be used in a variety of studies.     

Latent class subtyping of attention-deficit/hyperactivity disorder and comorbid conditions

ObjectiveGenetic studies of attention-deficit/hyperactivity disorder (ADHD) generally use discrete DSM-IV subtypes to define diagnostic status. To improve correspondence between phenotypic variance and putative susceptibility genes, multivariate classification methods such as latent class analysis (LCA) have been proposed. The aim of this study was to perform LCA in a sample of 1,010 individuals from a nationwide recruitment of unilineal nuclear families with at least one child with ADHD and another child either affected or clearly unaffected.MethodLCA models containing one through 10 classes were fitted to data derived from all DSM-IV symptoms for ADHD, oppositional defiant disorder, and conduct disorder (CD), as well as seven items that screen for anxiety and depression from the National Initiative for Children's Healthcare Quality Vanderbilt Assessment Scale for Parents.ResultsWe replicated six to eight statistically significantly distinct clusters, similar to those described in other cross-cultural studies, mostly stable when comorbidities are included. For all age groups, anxiety and depression are strongly related to Inattentive and Combined types. Externalizing symptoms, especially CD, are strongly associated with the Combined type of ADHD. Oppositional defiant disorder symptoms in young children are associated with either conduct disorder or anxiety-related symptoms.ConclusionsMethods such as LCA allow inclusion of information about comorbidities to be quantitatively incorporated into genetic studies. LCA also permits incorporation of milder but still impairing phenotypes than are allowed using the DSM-IV. Such methods may be essential for analyses of large multicenter datasets and relevant for future clinical classifications. This population-based ADHD classification may help resolve the contradictory results presented in molecular genetic studies. J. Am. Acad. Child Adolesc. Psychiatry, 2008; 47(7):797–807.     

Behavioural laterality as a predictor of health in captive Caribbean flamingos (Phoenicopterus ruber): An exploratory analysis

The present study sought to explore the possibility that lateral behaviour in captive Caribbean flamingos (Phoenicopterus ruber) housed at the Philadelphia Zoo (Philadelphia, PA) could be used to predict a variety of physiological measures of health obtained via complete blood counts (CBC) and plasma biochemistry analyses that were performed as part of the flock's annual physical examination. Consistent with previous research, evidence of rightward lateral neck-resting preferences were obtained, no evidence was found for the existence of leg stance preferences, and neck-resting and leg stance preferences were shown to be unrelated. Both lateral neck-resting preferences and lateral support leg preference were shown to be related to a variety of measures from the CBC and plasma biochemistry analyses. While several general trends emerged in regards to the CBC variables, the relationships between the lateral behaviours and those variables generated via plasma biochemistry analyses proved to be fewer and somewhat less consistent. Birds with rightward neck-resting preferences and birds with leftward support leg preferences generally appeared to be healthier and less stressed according to the CBC measures; however, the validity of lateral leg stance preference as a predictor of health and wellbeing is questionable given the lack of statistically significant leg stance preferences.     

REM latency in depression: is there one best definition?

The concurrent validity of different definitions of REM latency has been tested by comparing the ability of each definition to discriminate between primary depressives (outpatients and inpatients) and normal controls. In outpatients the percentage of cases correctly identified ranged from 62.5% to 70.8%; in inpatients, from 64.6% to 70.8%. REM latency definitions with the least stringent sleep-onset criteria yielded the lowest specificity. In contrast, the range of sensitivities yielded by different definitions was narrower and not clearly affected by sleep-onset criterion or exclusion/inclusion of wakefulness between sleep onset and first REM period. Furthermore, different definitions of REM latency correlated equally well (p less than 0.01) with Hamilton depression ratings. The shorter REM latencies in both outpatients and inpatients were associated with a later time of NREM sleep onset than in controls, rather than with an earlier REM sleep-onset time.     

Mimicking human bipolar ion dysregulation models mania in rats

Psychiatric diseases in general, and bipolar illness in particular, are difficult to model in animals since the subjective nature of the core symptoms appears to preclude objective observation of behavioral changes. An adequate animal model of a psychiatric condition must fulfill three core criteria: share pathophysiological characteristics of the human condition (face validity), have similar behavioral manifestations as the human disease (construct validity), and improve with medications that improve the symptoms seen in afflicted humans (predictive validity). The ouabain model for bipolar illness mimics a widely reproduced biologic abnormality in mania: reduced sodium pump activity. An intracerebroventricular (ICV) administration of 5microL 10(-3)M ouabain induces motoric hyperactivity preventable by lithium, carbamazepine, and haloperidol. ICV ouabain may also produce environmentally dependent hypoactivity. The model, however, has not yet been examined for other potential manic behavior in rats such as reduced need for sleep, increased sexual activity, or increased irritability. While additional characterization of the model is required, the ouabain model for bipolar illness is the only available animal model that fulfills the three criteria for an adequate animal model for bipolar illness.     

Identification of Post-Traumatic Stress Disorder in Individuals with Autism Spectrum Disorder and Intellectual Disability: A Systematic Review

Introduction: autism spectrum disorder (ASD) and intellectual disability (ID) seem to influence the risk of and vulnerability to exposure to trauma and adverse events. While assessment of a psychiatric disorder in ASD and ID generally is challenging, identification of post-traumatic stress disorder (PTSD) seems particularly so, and knowledge does not seem easily accessible. Methods: This article provides a systematic review of studies describing trauma reactions in individuals with both ASD and ID, including studies involving any single case with the combination of ASD, ID, and PTSD. To systematically explore PTSD symptom presentation in the group, all reported symptoms from studies were assigned by DSM-5 criteria. Results: Eighteen studies met the inclusion criteria, eight group studies and 10 case studies. Assessment methodology in studies varied, as did the format of symptom report. DSM-5 criteria provided a useful framework for integrating findings across studies, indicating that PTSD may be identified in individuals with ASD and ID. However, symptoms involving alterations in arousal and negative alterations in thought and behavior seem more easily identified than symptoms of reexperiencing and avoidance. Conclusions: There is an urgent need to identify behavioral equivalents to PTSD symptoms in this group, making it possible to identify warning signs of trauma and abuse even if such incidents are not known to family or professional carers.