Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

<b>Background</b><p></p> It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.<p></p> <b>Methods</b><p></p> Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.<p></p> <b>Results</b><p></p> There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p < 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.<p></p> <b>Conclusions</b><p></p> Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes

Landmark Recognition in Alzheimer’s Dementia: Spared Implicit Memory for Objects Relevant for Navigation

Contains fulltext : 97074.pdf (publisher's version ) (Open Access)BACKGROUND: In spatial navigation, landmark recognition is crucial. Specifically, memory for objects placed at decision points on a route is relevant. Previous fMRI research in healthy adults showed higher medial-temporal lobe (MTL) activation for objects placed at decision points compared to non-decision points, even at an implicit level. Since there is evidence that implicit learning is intact in amnesic patients, the current study examined memory for objects relevant for navigation in patients with Alzheimer's dementia (AD). METHODOLOGY/PRINCIPAL FINDINGS: 21 AD patients participated with MTL atrophy assessed on MRI (mean MMSE = 21.2, SD = 4.0), as well as 20 age- and education-matched non-demented controls. All participants watched a 5-min video showing a route through a virtual museum with 20 objects placed at intersections (decision points) and 20 at simple turns (non-decision points). The instruction was to pay attention to the toys (half of the objects) for which they were supposedly tested later. Subsequently, a recognition test followed with the 40 previously presented objects among 40 distracter items (both toys and non-toys). Results showed a better performance for the non-toy objects placed at decision points than non-decision points, both for AD patients and controls. CONCLUSION/SIGNIFICANCE: Our findings indicate that AD patients with MTL damage have implicit memory for object information relevant for navigation. No decision point effect was found for the attended items. Possibly, focusing attention on the items occurred at the cost of the context information in AD, whereas the controls performed at an optimal level due to intact memory function.5 p

A structured review of reasons for ecstasy use and related behaviours: pointers for future research

Abstract Background While the health risks of using ecstasy warrant intervention development, a recent meta-analysis of determinants of ecstasy use identified a number of lacunae in the literature. Specifically, no studies were included that address behaviours other than 'using ecstasy' (e.g. 'trying out ecstasy' or 'ceasing ecstasy use'). However, because meta-analyses aim to integrate study results quantitatively, the resulting rigid exclusion criteria cause many studies to be discarded on the basis of their qualitative methodology. Such qualitative studies may nonetheless provide valuable insights to guide future research. To provide an overview of these insights regarding ecstasy use, the current study summarizes and combines what is known from qualitative and exploratory quantitative literature on ecstasy use. Methods The databases PsycINFO and MedLine were searched for publications reporting reasons for ecstasy use and related behaviour, and the results were structured and discussed per behaviour and compared over behaviours. Results Two main categories of reasons were found. The first category comprised reasons to start using ecstasy, use ecstasy, use ecstasy more often, and refrain from ceasing ecstasy use. The second category comprised reasons to refrain from starting to use ecstasy, use less ecstasy, and cease using ecstasy. Reasons for related behaviours within each of these two categories appear to differ, but not as substantially as between the two categories. A large number of reasons that were not yet explored in quantitative research emerged. Conclusion The current summary and combination of exploratory studies yields useful lists of reasons for each behaviour. Before these lists can inform interventions, however, they beg quantitative verification. Also, similarity of determinant configurations of different behaviours can be assessed by addressing determinants of several behaviours in one study. Another important finding is that meta-analytical integration of the literature may overlook important findings and implications. Thus, qualitative reviews remain useful instruments in setting the research agenda.</p

Careers in ecstasy use: do ecstasy users cease of their own accord? Implications for intervention development

<p>Abstract</p> <p>Background</p> <p>Ecstasy (MDMA, 3, 4-methylenodioxymethamphetamine) use is widespread in the Netherlands, with a lifetime prevalence of 4.3%, and two-thirds of dance party visitors being ecstasy users. However, research into Dutch ecstasy use patterns is lacking. In addition, recent studies suggest that ecstasy users cease their use automatically, which implies that interventions would do better to better focus on the promotion of harm reduction strategies than on inducing cessation. The current study addresses this process of ecstasy cessation.</p> <p>Methods</p> <p>32 participants from the Dutch dance scene were interviewed, and the results were systematically analysed using NVivo.</p> <p>Results</p> <p>Most ecstasy users had started to use out of curiosity. During use, users applied a host of harm reduction strategies, albeit inconsistently and sometimes incorrectly. Most users appeared to cease ecstasy use automatically because of loss of interest or changing life circumstances (e.g. a new job or relationship).</p> <p>Conclusion</p> <p>It appears that cessation of ecstasy use is largely determined by environmental variables and not by health concerns. This supports the idea that health promotion resources are better spent in trying to promote consistent and correct application of harm reduction practices than in trying to induce cessation.</p

Effect of the G72 (DAOA) putative risk haplotype on cognitive functions in healthy subjects

<p>Abstract</p> <p>Background</p> <p>In the last years, several susceptibility genes for psychiatric disorders have been identified, among others <it>G72 </it>(also named D-amino acid oxidase activator, DAOA). Typically, the high-risk variant of a vulnerability gene is associated with decreased cognitive functions already in healthy individuals. In a recent study however, a positive effect of the high-risk variant of <it>G72 </it>on verbal working memory was reported. In the present study, we therefore examined the relationship between <it>G72 </it>genotype status and a broad range of cognitive functions in 423 healthy individuals.</p> <p>Methods</p> <p>The <it>G72 </it>carrier status was assessed by the two single nucleotide polymorphisms (SNPs) M23 and M24. Subjects were divided into three risk groups (low, intermediate and high risk).</p> <p>Results</p> <p><it>G72 </it>status influenced a number of cognitive functions, such as verbal working memory, attention, and, at a trend level, spatial working memory and executive functions. Interestingly, the high-risk allele carriers scored better than one or even both other groups.</p> <p>Conclusion</p> <p>Our data show that the putative high-risk haplotype (i.e. homozygote C/C-allele carriers in SNP M23 and homozygote T/T-allele carriers in SNP M24) is in healthy individuals not necessarily associated with worse performance in cognitive functions, but even with better performance in some domains. Further work is required to identify the mechanisms of <it>G72 </it>on brain functions.</p

Learning and Memory Alterations Are Associated with Hippocampal N-acetylaspartate in a Rat Model of Depression as Measured by 1H-MRS

It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS), to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA) in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume

Optimizing Preprocessing and Analysis Pipelines for Single-Subject fMRI: 2. Interactions with ICA, PCA, Task Contrast and Inter-Subject Heterogeneity

A variety of preprocessing techniques are available to correct subject-dependant artifacts in fMRI, caused by head motion and physiological noise. Although it has been established that the chosen preprocessing steps (or “pipeline”) may significantly affect fMRI results, it is not well understood how preprocessing choices interact with other parts of the fMRI experimental design. In this study, we examine how two experimental factors interact with preprocessing: between-subject heterogeneity, and strength of task contrast. Two levels of cognitive contrast were examined in an fMRI adaptation of the Trail-Making Test, with data from young, healthy adults. The importance of standard preprocessing with motion correction, physiological noise correction, motion parameter regression and temporal detrending were examined for the two task contrasts. We also tested subspace estimation using Principal Component Analysis (PCA), and Independent Component Analysis (ICA). Results were obtained for Penalized Discriminant Analysis, and model performance quantified with reproducibility (R) and prediction metrics (P). Simulation methods were also used to test for potential biases from individual-subject optimization. Our results demonstrate that (1) individual pipeline optimization is not significantly more biased than fixed preprocessing. In addition, (2) when applying a fixed pipeline across all subjects, the task contrast significantly affects pipeline performance; in particular, the effects of PCA and ICA models vary with contrast, and are not by themselves optimal preprocessing steps. Also, (3) selecting the optimal pipeline for each subject improves within-subject (P,R) and between-subject overlap, with the weaker cognitive contrast being more sensitive to pipeline optimization. These results demonstrate that sensitivity of fMRI results is influenced not only by preprocessing choices, but also by interactions with other experimental design factors. This paper outlines a quantitative procedure to denoise data that would otherwise be discarded due to artifact; this is particularly relevant for weak signal contrasts in single-subject, small-sample and clinical datasets

Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebocontrolled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.TW Weickert, D Weinberg, R Lenroot, SV Catts, R Wells, A Vercammen, M O, Donnell, C Galletly, D Liu, R Balzan, B Short, D Pellen, J Curtis, VJ Carr, J Kulkarni, PR Schofield and CS Weicker