An online survey to understand the needs of caregivers of family members with 22q11 deletion syndrome.

BACKGROUND: Most individuals with 22q11.2 deletion syndrome (22q11DS) have multi-system and lifelong needs requiring substantial support. Their primary caregivers are usually family members who dedicate lifelong time and effort to their role. The pressures of their roles can negatively impact caregivers' psychosocial well-being, suggesting a need for additional support for this community who currently have no specialised interventions available. METHOD: This online study surveyed 103 caregivers of family members with 22q11DS to determine the barriers to accessing support that they faced, the kind of support they would value and whether an online intervention could meet their needs. RESULTS: The caregivers indicated that a brief online intervention focused on teaching practical skills and connecting them with a peer network of support would be most valuable. CONCLUSIONS: Future studies are planned that will build on these results by designing and testing online interventions tailored to this community.

Genetic effects influencing risk for major depressive disorder in China and Europe.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Systematic review of childhood and adolescent risk and prognostic factors for persistent abdominal pain.

This review aimed to identify childhood and adolescence risk and prognostic factors associated with onset and persistence of persistent abdominal pain and related disability and assess quality of the evidence. While findings suggest a possible role for negative emotional symptoms and parental mental health as risk and prognostic factors for onset and persistence of persistent abdominal pain, the evidence is of poor quality overall and nonexistent when it comes to prognostic factors associated with disability. CONCLUSION: Further research is needed to increase confidence in existing evidence and to explore new factors. This research will inform prevention.

A computational analysis of flanker interference in depression.

BACKGROUND: Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study. METHOD: One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials). RESULTS: Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = -0.28, p = 0.007). CONCLUSIONS: Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.

The effect of pain on involuntary and voluntary capture of attention.

BACKGROUND: There is converging evidence for the notion that pain affects a broad range of attentional domains. This study investigated the influence of pain on the involuntary capture of attention as indexed by the P3a component in the event-related potential derived from the electroencephalogram. METHODS: Participants performed in an auditory oddball task in a pain-free and a pain condition during which they submerged a hand in cold water. Novel, infrequent and unexpected auditory stimuli were presented randomly in a series of frequent standard and infrequent target tones. P3a and P3b amplitudes were observed to novel, unexpected and target-related stimuli, respectively. RESULTS: Both electrophysiological components were characterized by reduced amplitudes in the pain compared with the pain-free condition. Hit rate and reaction time to target stimuli did not differ between the two conditions presumably because the experimental task was not difficult enough to exceed attentional capacities under pain conditions. CONCLUSIONS: These results indicate that voluntary attention serving the maintenance and control of ongoing information processing (reflected by the P3b amplitude) is impaired by pain. In addition, the involuntary capture of attention and orientation to novel, unexpected information (measured by the P3a) is also impaired by pain. Thus, neurophysiological measures examined in this study support the theoretical positions proposing that pain can reduce attentional processing capacity. These findings have potentially important implications at the theoretical level for our understanding of the interplay of pain and cognition, and at the therapeutic level for the clinical treatment of individuals experiencing ongoing pain.

Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies.

We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1636 screened controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS data sets: STAR*D, Genetics of Recurrent Early-onset Depression and the publicly available Genetic Association Information Network-MDD data set. These data sets, totaling 3957 cases and 3428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500 K, and Perlegen). For each of 2.4 million HapMap II single-nucleotide polymorphisms (SNPs), using genotyped data where available and imputed data otherwise, single-SNP association tests were carried out in each sample with correction for ancestry-informative principal components. The strongest evidence for association in the meta-analysis was observed for intronic SNPs in ATP6V1B2 (P=6.78 x 10⁻7), SP4 (P=7.68 x 10⁻7) and GRM7 (P=1.11 x 10⁻6). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N=2191 cases), and separately for males and females. Several of the best findings were supported primarily by evidence from narrow cases or from either males or females. On the basis of previous biological evidence, we consider GRM7 a strong MDD candidate gene. Larger samples will be required to determine whether any common SNPs are significantly associated with MDD.

Feeding grape seed extract to horses: effects on health, intake and digestion.

A feeding trial involving four Thoroughbred race horses was undertaken to establish whether inclusion of grape seed extract (GSE) in the diet of horses undergoing mild exercise had any effects on their general health, intake and digestion. Supplementation with GSE had no effect on either feed or water intake of the horses and the supplement was readily palatable to the horses at all levels of inclusion. Feeding GSE caused no adverse effects in terms of animal health (temperature, pulse and respirations rates), and there were some positive effects related to a presumed alteration in fermentation in the hindgut. Feeding GSE increased faecal pH, changing from acid faeces (pH 6.6) when no GSE was fed to neutral faeces (pH 7.0) when 150 mg GSE/kg body weight (BW) was fed. In addition, blood glucose concentrations were significantly (P < 0.05) decreased when GSE was fed at 100 and 150 mg/kg BW (5.50 ± 0.26 and 5.32 ± 0.72 mmol/l, respectively) compared with the control diet (5.77 ± 0.31 mmol/l). The actual mechanisms causing these alterations are yet to be elucidated, but could have important implications for the prevention of acidosis.

Working out the kinks: testing the feasibility of an electronic pain diary for adolescents with arthritis.

BACKGROUND: Current approaches to evaluating pain in children with chronic arthritis suffer from methodological problems. A real-time data capture approach using electronic diaries has been proposed as a new standard for pain measurement. However, there is limited information available regarding the development and feasibility of this approach in children. OBJECTIVES: The aim of the present study was to pilot test the e-Ouch electronic pain diary in terms of compliance and acceptability in adolescents with arthritis to further refine the prototype. METHODS: A descriptive study design -- with two iterative phases of testing, modifying the prototype and retesting -- was used. A purposive sample of 13 adolescents with mild to severe pain and disability was drawn from a large rheumatology clinic in a university-affiliated pediatric tertiary care centre in Canada over a four-week period in December 2004. Participants were signalled with an alarm to use the diary three times per day for a two-week period. Adolescents completed an electronic diary acceptability questionnaire. RESULTS: Overall mean compliance rates for phases 1 and 2 were 72.9% and 70.5%, respectively. Compliance was affected by the timing of data collection and technical difficulties. Children rated the diary as highly acceptable and easy to use. Phase 1 testing revealed aspects of the software program that affected compliance, which were subsequently altered and tested in phase 2. No further technical difficulties arose in phase 2 testing. CONCLUSIONS: Feasibility testing is a crucial first step in the development of electronic pain measures before use in clinical and research practice.

A review of systematic reviews on pain interventions in hospitalized infants.

BACKGROUND: Hospitalized infants undergo multiple, repeated painful procedures. Despite continued efforts to prevent procedural pain and improve pain management, clinical guidelines and standards frequently do not reflect the highest quality evidence from systematic reviews. OBJECTIVE: To critically appraise all systematic reviews on the effectiveness of procedural pain interventions in hospitalized infants. METHODS: A structured review was conducted on published systematic reviews and meta-analyses of pharmacological and nonpharmacological interventions of acute procedural pain in hospitalized infants. Searches were completed in the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, CINAHL and PsycINFO. Two reviewers independently selected articles for review and rated the methodological quality of the included reviews using a validated seven-point quality assessment measure. Any discrepancies were resolved by a third reviewer. RESULTS: Of 1469 potential systematic reviews on interventions for painful procedures in hospitalized infants, 11 high-quality reviews were included in the analysis. Pharmacological interventions supported by research evidence included premedication for intubation, dorsal penile nerve block and EMLA (AstraZeneca Canada, Inc) for circumcision, and sucrose for single painful procedures. Non-nutritive sucking, swaddling, holding, touching, positioning, facilitative tucking, breast feeding and supplemental breast milk were nonpharmacological interventions supported for procedural pain. CONCLUSION: There is a growing number of high-quality reviews supporting procedural pain management in infants. Ongoing research of single, repeated and combined pharmacological and nonpharmacological interventions is required to provide the highest quality evidence to clinicians for decision-making on optimal pain management.

Sex differences in parent and child pain ratings during an experimental child pain task.

Research in the field of pediatric pain has largely ignored the role of fathers in their children's pain experiences. The first objective of the present study was to examine the effect of the presence of mothers versus fathers on children's subjective ratings, facial expressions and physiological responses to acute pain. The second objective was to examine whether child and parent sex influence parents' proxy ratings of their children's pain. The final objective was to compare levels of agreement between mothers' and fathers' assessments of their children's pain. Participants included 73 children (37 boys, 36 girls), four to 12 years of age, along with 32 fathers and 41 mothers. Children undertook the cold pressor pain task while observed by one of their parents. During the task, the children's heart rates and facial expressions were recorded. Children provided self-reports and parents provided proxy reports of child pain intensity using the seven-point Faces Pain Scale. Neither child nor parent sex had a significant impact on children's subjective reports, facial expressions or heart rates in response to acute pain. Fathers gave their sons higher pain ratings than their daughters, whereas mothers' ratings of their sons' and daughters' pain did not differ. Kappa statistics and t tests revealed that fathers tended to be more accurate judges of their children's pain than mothers. Overall, this research highlights the importance of examining both parent and child sex differences in pediatric pain research.

Atypical depression: current status and relevance to melancholia.

OBJECTIVE: The Diagnostic and Statistical Manual, Fourth Edition (DSM-IV, 1994) included atypical features as an illness specifier for major depression and dysthymia. We asked whether subsequent literature supported its validity and addressed the relationship between depression with atypical features and melancholia. METHOD: Literature review focusing on studies addressing the validity of atypical depression, supplemented by the authors' previously unpublished data. RESULTS: Most studies support the discriminant validity of depression with atypical features relative to melancholia and depression having neither melancholic nor atypical features. However, studies addressing illness course suggest that criteria for depression with atypical features define a heterogeneous patient population. CONCLUSION: DSM-IV criteria for depression with atypical features define a valid, but heterogeneous disorder. Criteria including age of onset and chronicity may define a more homogeneous group that is distinct from both melancholia and other depressed patients.

Pain's impact on adaptive functioning.

BACKGROUND: Pain interferes with the functioning of typical children, but no study has examined its effect on children with pre-existing intellectual disabilities (ID). METHODS: Caregivers of 63 children observed their children for 2-h periods and recorded in 1-week diaries: pain presence, cause, intensity and duration. Caregivers also recorded the children's performance of pre-existing skills during each period. Proportion of skills displayed when pain was present and absent was compared. Fifty caregivers completed a second set of observations when pain was present and absent. RESULTS: Comparison of the first set of observations indicated children displayed significantly more abilities (64%) when pain-free (Pain-Free Day 1), than when pain was present (54%; Pain Day 1). Children displayed 64% of their possible abilities during Pain-Free Day 2, but only 53% during Pain Day 2. Pain impacted all areas of function (communication, daily living, social and motor skills). Children's physical and demographic characteristics did not moderate the impact of pain on function, but functioning of children with more severe ID was most impacted by pain. CONCLUSIONS: Children perform fewer adaptive skills when pain is present. This could affect long-term functioning as well, through reduced practice of skills.

Psychological interventions for needle-related procedural pain and distress in children and adolescents.

BACKGROUND: Needle-related procedures are a common source of pain and distress for children. Several psychological (cognitive-behavioral) interventions to help manage or reduce pain and distress are available; however, a previous comprehensive systematic review of the efficacy of these interventions has not been conducted. OBJECTIVES: To assess the efficacy of cognitive-behavioral psychological interventions for needle-related procedural pain and distress in children and adolescents. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4, 2005), MEDLINE (1966 to 2005), PsycINFO (1887 to 2005), EMBASE (1974 to 2005), the Cumulative Index to Nursing and Allied Health Literature (1982 to 2005), Web of Science (1980 to 2005), and Dissertation-Abstracts International (1980 to 2005). We also searched citation lists and contacted researchers via various electronic list-servers and via email requests. SELECTION CRITERIA: Participants included children and adolescents aged two to 19 years undergoing needle-related procedures. Only randomized controlled trials (RCTs) with at least five participants in each study arm comparing a psychological intervention group with a control or comparison group were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. Included studies were coded for quality using the Oxford Quality Scale devised by Jadad and colleagues. Standardized mean differences with 95% confidence intervals were computed for all analyses using RevMan 4.0 software. MAIN RESULTS: Twenty eight trials with 1951 participants were included. Together, these studies included 1039 participants in treatment conditions and 951 in control conditions. The most commonly studied needle-procedures were immunizations and injections. The largest effect sizes for treatment improvement over control conditions exist for distraction (on self-reported pain, SMD -0.24 (95% CI -0.45 to -0.04), combined cognitive-behavioral interventions--reduced other-reported distress (SMD -0.88, 95% CI -1.65 to -0.12; and behavioral measures of distress (SMD -0.67, 95% CI -0.95 to -0.38) with hypnosis being the most promising--self-reported pain (SMD -1.47, 95% CI -2.67 to -0.27), with promising but limited evidence for the efficacy of numerous other psychological interventions, such as information/preparation, nurse coaching plus distraction, parent positioning plus distraction, and distraction plus suggestion. AUTHORS' CONCLUSIONS: Overall, there is preliminary evidence that a variety of cognitive-behavioral interventions can be used with children and adolescents to successfully manage or reduce pain and distress associated with needle-related procedures. However, many of the included studies received lower quality scores because they failed to describe the randomization procedure and participant withdrawals or drop-outs from the study. Further RCTs need to be conducted, particularly for the many interventions for which we could not locate any trials.

Investigation of serotonin-related genes in antidepressant response.

In this study, we sought out to test the hypothesis that genetic factors may influence antidepressant response to fluoxetine. The investigation focused on seven candidate genes in the serotonergic pathway involved in the synthesis, transport, recognition, and degradation of serotonin. Our clinical sample consisted of 96 subjects with unipolar major depression treated with fluoxetine with response variables assessed after a 12-week trial. Patient data were also collected to investigate the pattern of drug response. Using a high-throughput single-nucleotide polymorphism (SNP) genotyping platform and capillary electrophoresis, we genotyped patients at 110 SNPs and four repeat polymorphisms located in seven candidate genes (HTR1A, HTR2A, HTR2C, MAOA, SLC6A4, TPH1, and TPH2). Statistical tests performed included single-locus and haplotype association tests, and linkage disequilibrium (LD) estimation. Little evidence of population stratification was observed in the sample with 20 random SNPs using a genomic control procedure. Our most intriguing result involved three SNPs in the TPH1 gene and one SNP in the SLC6A4 gene, which show significant single-locus association when response to fluoxetine is compared to nonresponse (P=0.02-0.04). All odds ratios indicated an increased risk of not responding to fluoxetine. In the specific response vs nonspecific and nonresponse comparison, three SNPs in the TPH2 gene (P=0.02-0.04) were positively associated and one SNP in the HTR2A gene (P=0.02) was negatively associated. When comparing specific response to nonspecific response, we found significant negative associations in three SNPs in the HTR2A gene (P=0.001-0.03) and two SNPs in the MAOA gene (P=0.03-0.05). We observed variable, although strong LD, in each gene and unexpectedly low numbers of estimated haplotypes, formed from tagged SNPs. Significant haplotype associations were found in all but the HTR1A and HTR2C genes. Although these data should be interpreted cautiously due to the small sample size, these results implicate TPH1 and SLC6A4 in general response, and HTR2A, TPH2, and MAOA in the specificity of response to fluoxetine. Intriguingly, we observe that a number of the less frequent alleles of many of the SNP markers were associated with the nonresponse and nonspecific phenotypes.

Assessing self-help issues for patients with prostate cancer, interstitial cystitis, erectile dysfunction and urinary diversion.

OBJECTIVE: To determine the prevalence of self-help (which is widely available and can assist clinicians to educate and empower patients) for several urological diseases. PATIENTS AND METHODS: Using a structured interview, the prevalence of self-help use and awareness was assessed in patients with prostate cancer, interstitial cystitis, erectile dysfunction and urinary diversion. Patients were also asked to report levels of support and information they required and to specify how well these needs were being met. Consecutive patients (120, 30 from each group) were recruited from an outpatient urology clinic in a tertiary-care health centre. RESULTS: Patients with interstitial cystitis and erectile dysfunction reported having the greatest need but were least satisfied with the level of support and information they currently receive. Inversely, patients with prostate cancer reported having the least need and were most satisfied. Excluding brochures, the use and awareness of self-help were low in all groups but most patients claimed they would use many types of self-help if they were available. Many patients are not directed to self-help resources by their urologist or family physician. CONCLUSION: Most patients would like to use more self-help but many do not. The low percentage of patients referred to self-help by their physician probably contributes to, or causes, this problem. It is important for clinicians to encourage and refer patients to specific resources to ensure that the patient receives accurate and pertinent information. As most patients read brochures it is logical to use them to provide basic information and to direct them to other more sophisticated forms of self-help. We have used urology patients as a model but consider that many of our findings could be applied to other medical and surgical specialties.

The disruptive effect of chronic pain on mismatch negativity.

OBJECTIVE: To investigate the effect of chronic pain on processes that generate the mismatch negativity (MMN). METHODS: Twelve participants with a diagnosis of chronic intractable pain were tested before and after pain treatment. During testing, event-related potentials were recorded while participants performed tasks of varying difficulty. RESULTS: The amplitude of the MMN was found to be greater following a nerve block procedure compared to MMN amplitude when participants were experiencing chronic pain. This effect was found to occur in the MMN for difficult-to-detect tones elicited while participants were performing a simultaneous cognitively demanding visual task. MMN amplitude was found to be greater with attention to difficult-to-detect deviants during pain but not in no pain conditions. CONCLUSIONS: These results provide an electrophysiological correlate of previous findings that high levels of pain disrupt cognition during the performance of demanding tasks.

Somatization as a predictor of medication discontinuation due to adverse events.

Medication discontinuation due to intolerable side-effects remains a significant clinical problem in the treatment of depression. We were unable to locate studies which found predictors of medication cessation due to side-effects. We posited that an identifiable subgroup of medically healthy, depressed adults who discontinued medication because of adverse events would have higher pre-treatment somatic symptoms than patients who completed a course of treatment. The sample (n =940) was drawn from a series of double-blind, placebo-controlled studies of antidepressants (imipramine, phenelelzine, L-deprenyl, mianserin and desipramine). Within the medication group, side-effect dropouts had more somatic symptoms than study completers and those who discontinued treatment for miscellaneous reasons. Within the placebo-treated group, the small number of subject who discontinued treated because of side-effects precluded valid statistical analyses, but the findings were in the same direction as those in the medication group. Clearly, further research is required to determine whether these results, obtained from a series of university-based clinical trials with healthy subjects, are generalizable to patients with significant comorbid medical and/or psychiatric disorders, treated with newer antidepressants agents in a general clinical practice setting.