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Using Multivariate Statistics

Meta-analyses were conducted on 14 separate risk factors for posttraumatic stress disorder (PTSD), and the moderating effects of various sample and study characteristics, including civilian/military status, were examined. Three categories of risk factor emerged: Factors such as gender, age at trauma, and race that predicted PTSD in some populations but not in others; factors such as education, previous trauma, and general childhood adversity that predicted PTSD more consistently but to a varying extent according to the populations studied and the methods used; and factors such as psychiatric history, reported childhood abuse, and family psychiatric history that had more uniform predictive effects. Individually, the effect size of all the risk factors was modest, but factors operating during or after the trauma, such as trauma severity, lack of social support, and additional life stress, had somewhat stronger effects than pretrauma factors.

Meta-analysis of risk factors for posttraumatic stress disorder in trauma-exposed adults.

The reverse transcription polymerase chain reaction (RT-PCR) is the most sensitive method for the detection of low-abundance mRNA, often obtained from limited tissue samples. However, it is a complex technique, there are substantial problems associated with its true sensitivity, reproducibility and specificity and, as a quantitative method, it suffers from the problems inherent in PCR. The recent introduction of fluorescence-based kinetic RT-PCR procedures significantly simplifies the process of producing reproducible quantification of mRNAs and promises to overcome these limitations. Nevertheless, their successful application depends on a clear understanding of the practical problems, and careful experimental design, application and validation remain essential for accurate quantitative measurements of transcription. This review discusses the technical aspects involved, contrasts conventional and kinetic RT-PCR methods for quantitating gene expression and compares the different kinetic RT-PCR systems. It illustrates the usefulness of these assays by demonstrating the significantly different levels of transcription between individuals of the housekeeping gene family, glyceraldehyde-3-phosphate-dehydrogenase (GAPDH).

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Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays.

A review of 2,647 studies of posttraumatic stress disorder (PTSD) yielded 476 potential candidates for a meta-analysis of predictors of PTSD or of its symptoms. From these, 68 studies met criteria for inclusion in a meta-analysis of 7 predictors: (a) prior trauma, (b) prior psychological adjustment, (c) family history of psychopathology, (d) perceived life threat during the trauma, (e) posttrauma social support, (f) peritraumatic emotional responses, and (g) peritraumatic dissociation. All yielded significant effect sizes, with family history, prior trauma, and prior adjustment the smallest (weighted r = .17) and peritraumatic dissociation the largest (weighted r = .35). The results suggest that peritraumatic psychological processes, not prior characteristics, are the strongest predictors of PTSD.

Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis.

Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

The expression of two cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3), has been investigated in MLA-144 cells before and after induction with phorbol 12-myristate 13-acetate. We describe an adaptation of the polymerase chain reaction (PCR) for highly accurate quantitation of mRNA or DNA from a small number of cells. Aliquots of the PCR mixture containing cDNA copies of the RNA to be assayed were added to serial dilutions of a competitor DNA fragment that differed from the cDNA of interest by having either a small intron or a mutated internal restriction enzyme site. Therefore, the same primers were used to coamplify the unknown and the competitor. The ratio of products remains constant through the amplification and can be readily quantitated. In unstimulated cells, no GM-CSF or IL-3 mRNA could be detected. However, with appropriate induction, mRNA for both cytokines was detected and quantitated in as few as 200 cells. Competitive PCR was also used to accurately quantitate the copy number of the human GM-CSF gene in normal human cells, in a clonal population of cells from a patient with 5q- syndrome, and in a human-hamster cell line known to have only one copy of the human GM-CSF gene.

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Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction

There is considerable evidence that children and adolescents with autistic spectrum disorders (ASD) are at increased risk of anxiety and anxiety disorders. However, it is less clear which of the specific DSM-IV anxiety disorders occur most in this population. The present study used meta-analytic techniques to help clarify this issue. A systematic review of the literature identified 31 studies involving 2,121 young people (aged <18 years) with ASD, and where the presence of anxiety disorder was assessed using standardized questionnaires or diagnostic interviews. Across studies, 39.6% of young people with ASD had at least one comorbid DSM-IV anxiety disorder, the most frequent being specific phobia (29.8%) followed by OCD (17.4%) and social anxiety disorder (16.6%). Associations were found between the specific anxiety disorders and ASD subtype, age, IQ, and assessment method (questionnaire versus interview). Implications for the identification and treatment of anxiety in young people with ASD are discussed.

/pdf/anxiety-disorders-in-children-and-adolescents-with-autistic-1x21lq410c.pdf

Anxiety disorders in children and adolescents with autistic spectrum disorders: a meta-analysis

An affective, somatic, and memory check-list of symptoms was administered to subjects who had no personal experience or knowledge of head injury. Subjects indicated their current experiences of symptoms, then imagined having sustained a mild head injury in a motor vehicle accident, and endorsed symptoms they expected to experience six months after the injury. The checklist of symptoms was also administered to a group of patients with head injuries for comparison. Imaginary concussion reliably showed expectations in controls of a coherent cluster of symptoms virtually identical to the postconcussion syndrome reported by patients with head trauma. Patients consistently underestimated the premorbid prevalence of these symptoms compared with the base rate in controls. Symptom expectations appear to share as much variance with postconcussion syndrome as head injury itself. An aetiological role is suggested.

https://jnnp.bmj.com/content/jnnp/55/3/200.full.pdf

Symptoms following mild head injury: expectation as aetiology.

Objective: To evaluate course and outcome of DSM-Ill-R anxiety disorders prospectively in clinically referred children. Method: Children were blindly and repeatedly assessed with a structured diagnostic interview over a 3- to 4-year period to determine recovery from anxiety disorder and development of new psychiatric disorders. Both psychopathological (attention-deficit hyperactivity disorder, n = 50) and never psychiatrically ill (NPI, n = 83) controls served as comparison groups for children with anxiety disorders (n = 84). Results: The majority of children (82%) were free from their intake anxiety disorders by the end of the follow-up. Relapse of these anxiety disorders after remission was rare (8%). During follow-up, anxious children were more likely to develop new psychiatric disorders (30%), primarily new anxiety disorders (l6%), than were NPI children (1 1% and 2%, respectively), but not psychopathological controls (42% and lo%, respectively). Conclusions: Overall, results suggest a favorable outcome with respect to diagnostic status for clinically referred children with anxiety disorders. However, these children may be at risk for new psychiatric disorders over time. J. Am. Prior to 1980, anxiety disorders in children and adolescents had been relatively ignored in terms of scientific inquiry. One reason for this was the widely held notion that fears and worries during childhood were transitory in nature and thus did not constitute an important or compelling area for investigation. With the arrival of DSM-III (American Psychiatric Association, 1980), childhood anxiety disorders gained a prominent position in our diagnostic nomenclature. The improvements in the diagnostic criteria that accompanied this revision led to increased attention to childhood anxiety disorders from the research community. Anxiety disorders now are recognized to be among the most prevalent of childhood disorders (Bernstein and Borchardt, 199 l), with anxious children manifesting levels of symptom severity and impairment akin to adult anxiety disorders (Last, 1993). Moreover, retrospective studies of children and adults suggest that childhood anxiety

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A Prospective Study of Childhood Anxiety Disorders

The Children's Revised Impact of Event Scale (CRIES) is a brief child-friendly measure designed to screen children at risk for Posttraumatic Stress Disorder (PTSD). It has good face and construct validity, a stable factor structure, correlates well with other indices of distress, and has been used to screen very large samples of at-risk-children following a wide range of traumatic events. However, few studies have examined the scale's validity against a structured diagnostic interview based on the DSM-IV criteria for PTSD. In the present study, the CRIES and the PTSD section of the Anxiety Disorders Interview Schedule-Child and Parent Version (ADIS-CP) were administered to a sample of children and adolescents (n=63) recruited from hospital accident and emergency rooms and the validity of the CRIES as a screening tool evaluated. Cutoff scores were chosen from this sample with a low base-rate of PTSD (11.1%) to maximize sensitivity and minimize the likelihood that children with a diagnosis of PTSD would fail to be identified. Cutoff scores were then cross-validated in a sample of 52 clinically referred children who had a high base-rate of PTSD (67.3%). A cutoff score of 30 on the CRIES-13 and a cutoff score of 17 on the CRIES-8 maximized sensitivity and specificity, minimized the rate of false negatives, and correctly classified 75-83% of the children in the two samples. The CRIES-8 (which lacks any arousal items) worked as efficiently as the CRIES-13 (which includes arousal items) in correctly classifying children with and without PTSD. Results are discussed in light of the current literature and of the need for further development of effective screens for children at-risk of developing PTSD.

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Sean Perrin

Papers

Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction

Anxiety disorders in children and adolescents with autistic spectrum disorders: a meta-analysis

Symptoms following mild head injury: expectation as aetiology.

A Prospective Study of Childhood Anxiety Disorders

The Children’s Revised Impact of Event Scale (CRIES): Validity as a screening instrument for PTSD.