Parent-reported subjective complaints in children using antiepileptic drugs: what do they mean?

We used a parent-completed 20-item "side effect scale" quantifying complaints that parents perceive to be caused by antiepileptic drugs (AEDs) in 108 children with active epilepsy. We studied the associations between parent-reported complaints, severity of seizures, and restrictions due to epilepsy, and clinical data including number and AED load. In 85% of the children at least one complaint was reported, in less than 20% complaints were perceived as a substantial problem. In a multivariate analysis, there was no significant relationship between the "side effect scale" score and AED load, or the number of AEDs. However, complaints were associated with parent-reported frequency and severity of seizures. We conclude that the adverse effects of seizures or parental concern about the severity and intractability of seizures in their children may have influenced the reported complaints.     

Models of community treatments in schizophrenia: do they travel?

OBJECTIVE: To explore the stability of conclusions from mental health services research across differing care systems. Contradictory results in different countries for similar studies of programmes for patients with schizophrenia have usually been attributed to poor replication. This paper explores whether these differing results can illuminate aspects of schizophrenia by examining the interaction of the disorder with the care context as an alternative explanation. METHOD: The findings of a large UK random controlled trial of intensive case management with such patients is compared to previous UK and US studies. RESULTS: Reduction of case-load size of psychotic patients did not significantly reduce their need for hospitalization in the context of locally available co-ordinated care. CONCLUSION: There is more to be gained in understanding complex disorders such as schizophrenia by interpreting the impact of context on treatment study outcomes than by simply dismissing contradictory findings as failures of implementation of either research or clinical practice.     

Meta-analysis of associations between human brain volume and intelligence differences: How strong are they and what do they mean?

Positive associations between human intelligence and brain size have been suspected for more than 150 years. Nowadays, modern non-invasive measures of in vivo brain volume (Magnetic Resonance Imaging) make it possible to reliably assess associations with IQ. By means of a systematic review of published studies and unpublished results obtained by personal communications with researchers, we identified 88 studies examining effect sizes of 148 healthy and clinical mixed-sex samples (>8000 individuals). Our results showed significant positive associations of brain volume and IQ (r = .24, R² = .06) that generalize over age (children vs. adults), IQ domain (full-scale, performance, and verbal IQ), and sex. Application of a number of methods for detection of publication bias indicates that strong and positive correlation coefficients have been reported frequently in the literature whilst small and non-significant associations appear to have been often omitted from reports. We show that the strength of the positive association of brain volume and IQ has been overestimated in the literature, but remains robust even when accounting for different types of dissemination bias, although reported effects have been declining over time. While it is tempting to interpret this association in the context of human cognitive evolution and species differences in brain size and cognitive ability, we show that it is not warranted to interpret brain size as an isomorphic proxy of human intelligence differences.     

Recovery-based practice: do we know what we mean or mean what we know?

The concept of recovery is now widely promoted as the guiding principle for the provision of mental health services in Australia and overseas. While there is increasing pressure on service providers to ensure that services are recovery oriented, the way in which recovery-based practice is operationalized at the coalface presents a number of challenges. These are discussed in the context of five key questions that address (i) the appropriateness of recovery as a focus for service delivery, (ii) the distinction between recovery as a process and an outcome, (iii) the assessment of recovery initiatives, (iv) the alignment of recovery with current service delivery models, and (v) the risks associated with recovery-based practice. It is argued that these questions provide a framework for a debate that must extend beyond patients and providers of mental health services to the broader public, whose attitudes will ultimately determine the possibilities and limits of recovery-oriented practice.     

Genetics in schizophrenia: where are we and what next?

Understanding the genetic basis of schizophrenia continues to be major challenge. The research done during the last two decades has provided several candidate genes which unfortunately have not been consistently replicated across or within a population. The recent genome-wide association studies (GWAS) and copy number variation (CNV) studies have provided important evidence suggesting a role of both common and rare large CNVs in schizophrenia genesis. The burden of rare copy number variations appears to be increased in schizophrenia patients. A consistent observation among the GWAS studies is the association with schizophrenia of genetic markers in the major histocompatibility complex (6p22.1)-containing genes including NOTCH4 and histone protein loci. Molecular genetic studies are also demonstrating that there is more overlap between the susceptibility genes for schizophrenia and bipolar disorder than previously suspected. In this review we summarize the major findings of the past decade and suggest areas of future research.     

Adult-onset leukodystrophies from respiratory chain disorders: do they exist?

Respiratory chain disorders (RCDs) have been included in the differential diagnosis of adult-onset leukodystrophies. Here, we first report a 32-year-old female with an atypical, adult-onset, non-syndromic RCD due to a mitochondrial DNA deletion and manifesting as complicated ataxia. A ‘leukodystrophic’ pattern was found on brain MRI, but it was neither isolated nor predominant because of the presence of overt basal ganglia and infratentorial lesions, which led us to the proper diagnosis. Subsequently, we evaluated our series of patients with RCDs in order to verify whether a ‘leukodystrophic’ pattern with little or no involvement of deep grey structures and brainstem may be found in adult-onset RCDs, as reported in children. Among 52 patients with adult-onset RCDs, no case with a ‘leukodystrophic’ pattern was found, apart from three cases with a classical phenotype of mitochondrial neurogastrointestinal encephalopathy. In addition, no case of RCDs was found among six cases of adult-onset leukodystrophy of unknown origin and at least one feature suggestive of mitochondrial disease. The review of the literature was in agreement with these findings. Thus, we provide evidence that, unlike in children, RCDs should not be included in the differential diagnosis of adult-onset leukodystrophies, except when there are additional MRI findings or clinical features which unequivocally point towards a mitochondrial disorder.     

Placebo-controlled trials in schizophrenia: are they ethical? Are they necessary?

The current controversy as to the proper role of the placebo control in the evaluation of new treatments for schizophrenia requires an analysis that is sensitive to both ethical and scientific issues. Clinical equipoise, widely regarded as the moral foundation of the randomized controlled trial (RCT), requires the use of best available treatment as the control in RCT. Scientific criticisms of the use of an active control are examined and none present an insuperable barrier to the use of an active control. Indeed, scrutiny of the most recent argument for the use of placebo controls, 'assay sensitivity', suggests that the use of placebo may be the cause of the problem pointed to. Scientific, regulatory, ethical and legal advantages of the use of an active control are described. While the use of a placebo control may be acceptable in carefully defined circumstances, in most cases the use of an active control in schizophrenia research is ethically and scientifically preferable.     

Do people with schizophrenia comprehend what they read?

Although people with schizophrenia appear to be able to read aloud, their reading comprehension has been little tested. This study asks, Do people with schizophrenia have deficits in reading comprehension compared with well controls and, if so, what are the type and severity of those deficits? The reading comprehension of 30 people with chronic schizophrenia was compared with a group of 30 people without a psychiatric diagnosis. The groups were matched for sex and age and had similar intelligence scores. The Reading Comprehension Battery for Aphasia (RCBA) was used to obtain a profile of reading comprehension skills, and intelligence was estimated using the National Adult Reading Test. Schizophrenia subjects took significantly longer to complete the RCBA and obtained significantly poorer scores than did controls on the RCBA total and on all but one RCBA subtest. Although these findings could have serious implications for the presentation of written material such as consent and information forms, further research is needed to determine how these deficits impact on functional reading and whether or not they can be addressed.     

Pregnancy registries: What do they mean to clinical practice?

Multiple surveillance pregnancy registries have been established in order to better understand the effects of antiepileptic drugs (AEDs) on pregnancy. These registries are either hospital based, population based, or pharmaceutical based and are primarily focused on the potential teratogenicity of AEDs. The main outcome variable for most of these registries is the risk of major congenital malformations. Registries also gather data on other aspects of pregnancy, including seizure control. The methodology of the registries varies. They have different populations, ascertainment strategies, follow-up, and reporting criteria. These differences limit the ability to allow direct comparisons. Overall, the registry data suggest that the overwhelming majority of women with epilepsy treated with AEDs will have normal, healthy babies. A second consistent finding is that valproate, particularly at higher doses, is associated with a higher risk of major congenital malformations than other AEDs.     

Old age psychiatrists: what do they find stressful?

Objective. To examine the main sources of stress for practising old age psychiatrists. Design. Postal survey. Setting. Old age psychiatry services in England and Wales. Participants. Old age psychiatrists on the list held by the Section of Old Age Psychiatry, Royal College of Psychiatrists. Main outcome measures. Number and nature of stresses identified by respondents. Main results. One hundred and thirty-eight old age psychiatrists identified a mean of 5.1 stresses per respondent, which fell into seven broad categories: changes within the health service, community care changes, personal, management-related, resource-related, related to time pressures, overwork and others. Conclusions. Unavoidable stresses were rarely listed. Most were related to work overload and organizational structure and climate. More research is needed on stress in other areas of psychiatry, ways to minimize/prevent stress and how to optimize the balance between work and home life. © 1997 John Wiley & Sons, Ltd.