Longitudinal risk factors for developing depressive symptoms in Parkinson's disease

BACKGROUND: Despite the established importance of identifying depression in Parkinson's disease, our understanding of the factors which place the Parkinson's disease patient at future risk of depression is limited. METHODS: Our sample consisted of 874 patients from two longitudinal cohorts, PPMI and PDBP, with median follow-up durations of 7 and 3 years respectively. Risk factors for depressive symptoms at baseline were determined using logistic regression. A Cox regression model was then used to identify baseline factors that predisposed the non-depressed patient to develop depressive symptoms that were sustained for at least one year, while adjusting for antidepressant use and cognitive impairment. Common predictors between the two cohorts were identified with a random-effects meta-analysis. RESULTS: We found in our analyses that the majority of baseline non-depressed patients would develop sustained depressive symptoms at least once during the course of the study. Probable REM sleep behavior disorder (pRBD), age, duration of diagnosis, impairment in daily activities, mild constipation, and antidepressant use were among the baseline risk factors for depression in either cohort. Our Cox regression model indicated that pRBD, impairment in daily activities, hyposmia, and mild constipation could serve as longitudinal predictors of sustained depressive symptoms. CONCLUSIONS: We identified several potential risk factors to aid physicians in the early detection of depression in Parkinson's disease patients. Our findings also underline the importance of adjusting for multiple covariates when analyzing risk factors for depression

A population scale analysis of rare SNCA variation in the UK Biobank

Parkinson's disease (PD) is a complex neurodegenerative disease with a variety of genetic and environmental factors contributing to disease. The SNCA gene encodes for the alpha-synuclein protein which plays a central role in PD, where aggregates of this protein are one of the pathological hallmarks of disease. Rare point mutations and copy number gains of the SNCA gene have been shown to cause autosomal dominant PD, and common DNA variants identified using Genome-Wide Association Studies (GWAS) are a moderate risk factor for PD. The UK Biobank is a large-scale population prospective study including ~500,000 individuals that has revolutionized human genetics. Here we assessed the frequency of SNCA variation in this cohort and identified 30 subjects carrying variants of interest including duplications (n = 6), deletions (n = 6) and large complex likely mosaic events (n = 18). No known pathogenic missense variants were identified. None of these subjects were reported to be a PD case, although it is possible that these individuals may develop PD at a later age, and whilst three had known prodromal features, these did not meet defined clinical criteria for being considered ‘prodromal’ cases. Seven of the 18 large complex carriers showed a history of blood based cancer. Overall, we identified copy number variants in the SNCA region in a large population based cohort without reported PD phenotype and symptoms. Putative mosaicism of the SNCA gene was identified, however, it is unclear whether it is associated with PD. These individuals are potential candidates for further investigation by performing SNCA RNA and protein expression studies, as well as promising clinical trial candidates to understand how duplication carriers potentially escape PD

Online Obsessive-Compulsive Disorder Treatment: Preliminary Results of the "OCD? Not Me!" Self-Guided Internet-Based Cognitive Behavioral Therapy Program for Young People

BACKGROUND: The development and evaluation of Internet-delivered cognitive behavioral therapy (iCBT) interventions provides a potential solution for current limitations in the acceptability, availability, and accessibility of mental health care for young people with obsessive-compulsive disorder (OCD). Preliminary results support the effectiveness of therapist-assisted iCBT for young people with OCD; however, no previous studies have examined the effectiveness of completely self-guided iCBT for OCD in young people. OBJECTIVE: We aimed to conduct a preliminary evaluation of the effectiveness of the OCD? Not Me! program for reducing OCD-related psychopathology in young people (12-18 years). This program is an eight-stage, completely self-guided iCBT treatment for OCD, which is based on exposure and response prevention. METHODS: These data were early and preliminary results of a longer study in which an open trial design is being used to evaluate the effectiveness of the OCD? Not Me! PROGRAM: Participants were required to have at least subclinical levels of OCD to be offered the online program. Participants with moderate-high suicide/self-harm risk or symptoms of eating disorder or psychosis were not offered the program. OCD symptoms and severity were measured at pre- and posttest, and at the beginning of each stage of the program. Data was analyzed using generalized linear mixed models. RESULTS: A total of 334 people were screened for inclusion in the study, with 132 participants aged 12 to 18 years providing data for the final analysis. Participants showed significant reductions in OCD symptoms (P<.001) and severity (P<.001) between pre- and posttest. CONCLUSIONS: These preliminary results suggest that fully automated iCBT holds promise as a way of increasing access to treatment for young people with OCD; however, further research needs to be conducted to replicate the results and to determine the feasibility of the program. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000152729; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363654 (Archived by WebCite at http://www.webcitation.org/ 6iD7EDFqH)

Moving from a Product-Based Economy to a Service-Based Economy for a More Sustainable Future

Traditionally, economic growth and prosperity have been linked with the availability, production and distribution of tangible goods as well as the ability of consumers to acquire such goods. Early evidence regarding this connection dates back to Adam Smith's Wealth of Nations (1776), in which any activity not resulting in the production of a tangible good is characterized as unproductive of any value." Since then, this coupling of economic value and material production has been prevalent in both developed and developing economies throughout the world. One unintended consequence of this coupling has been the exponential increase in the amount of solid waste being generated. The reason is that any production and consumption of material goods eventually generates the equivalent amount of (or even more) waste. Exacerbating this problem is the fact that, with today's manufacturing and supply chain management technologies, it has become cheaper to dispose and replace most products rather than to repair and reuse them. This has given rise to what some call a disposable society." To put things in perspective: In 2012 households in the U.K. generated approximately 22 thousand tons of waste, which amounted to 411 kg of waste generated per person (Department for Environment, Food & Rural Affairs, 2015). During the same time period, households in the U.S. generated 251 million tons of waste, which is equivalent to a person generating approximately 2 kg of waste every day (U.S. Environmental Protection Agency, 2012). Out of these 251 million tons of total waste generated, approximately 20% of the discarded items were categorized as durable goods. The disposal of durable goods is particularly worrisome because they are typically produced using material from non- renewable resources such as iron, minerals, and petroleum-based raw materials

Association of nail biting and psychiatric disorders in children and their parents in a psychiatrically referred sample of children

<p>Abstract</p> <p>Background</p> <p>Nail biting (NB) is a very common unwanted behavior. The majority of children are motivated to stop NB and have already tried to stop it, but are generally unsuccessful in doing so. It is a difficult behavior to modify or treat. The objective of this study was to investigate the prevalence of co-morbid psychiatric disorders in a clinical sample of children with NB who present at a child and adolescent mental healthcare outpatient clinic and the prevalence of psychiatric disorders in their parents.</p> <p>Method</p> <p>A consecutive sample of 450 referred children was examined for NB and 63 (14%) were found to have NB. The children and adolescents with nail biting and their parents were interviewed according to DSM-IV diagnostic criteria. They were also asked about lip biting, head banging, skin biting, and hair pulling behaviors.</p> <p>Results</p> <p>Nail biting is common amongst children and adolescents referred to a child and adolescent mental health clinic. The most common co-morbid psychiatric disorders in these children were attention deficit hyperactivity disorder (74.6%), oppositional defiant disorder (36%), separation anxiety disorder (20.6%), enuresis (15.6%), tic disorder (12.7%) and obsessive compulsive disorder (11.1%). The rates of major depressive disorder, mental retardation, and pervasive developmental disorder were 6.7%, 9.5%, 3.2%, respectively. There was no association between the age of onset of nail biting and the co-morbid psychiatric disorder. Severity and frequency of NB were not associated with any co-morbid psychiatric disorder. About 56.8% of the mothers and 45.9% of the fathers were suffering from at least one psychiatric disorder. The most common psychiatric disorder found in these parents was major depression.</p> <p>Conclusion</p> <p>Nail biting presents in a significant proportion of referrals to a mental healthcare clinic setting. Nail biting should be routinely looked for and asked for in the child and adolescent mental healthcare setting because it is common in a clinical population, easily visible in consultation and relatively unintrusive to ask about. If present, its detection can then be followed by looking for other more subtle stereotypic or self-mutilating behaviors.</p

The phenotype associated with a large deletion on MECP2

Multiplex ligation-dependent Probe Amplification (MLPA) has become available for the detection of a large deletion on the MECP2 gene allowing genetic confirmation of previously unconfirmed cases of clinical Rett syndrome. This study describes the phenotype of those with a large deletion and compares with those with other pathogenic MECP2 mutations. Individuals were ascertained from the Australian Rett Syndrome and InterRett databases with data sourced from family and clinician questionnaires, and two case studies were constructed from the longitudinal Australian data. Regression and survival analysis were used to compare severity and age of onset of symptoms in those with and without a large deletion. Data were available for 974 individuals including 51 with a large deletion and ages ranged from 1 year 4 months to 49 years (median 9 years). Those with a large deletion were more severely affected than those with other mutation types. Specifically, individuals with large deletions were less likely to have learned to walk (OR 0.42, 95% CI: 0.22–0.79, P=0.007) and to be currently walking (OR 0.53, 95% CI: 0.26–1.10, P=0.089), and were at higher odds of being in the most severe category of gross motor function (OR 1.84, 95% CI: 0.98–3.48, P=0.057) and epilepsy (OR 2.72, 95% CI: 1.38–5.37, P=0.004). They also developed epilepsy, scoliosis, hand stereotypies and abnormal breathing patterns at an earlier age. We have described the disorder profile associated with a large deletion from the largest sample to date and have found that the phenotype is severe with motor skills particularly affected

Are Child and Adolescent Responses to Placebo Higher in Major Depression than in Anxiety Disorders? A Systematic Review of Placebo-Controlled Trials

BACKGROUND: In a previous report, we hypothesized that responses to placebo were high in child and adolescent depression because of specific psychopathological factors associated with youth major depression. The purpose of this study was to compare the placebo response rates in pharmacological trials for major depressive disorder (MDD), obsessive compulsive disorder (OCD) and other anxiety disorders (AD-non-OCD). METHODOLOGY AND PRINCIPAL FINDINGS: We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalized disorders, restricting our review to double-blind studies including a placebo arm. Placebo response rates were pooled and compared according to diagnosis (MDD vs. OCD vs. AD-non-OCD), age (adolescent vs. child), and date of publication. From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication (mainly non-tricyclic antidepressants) involving youth with MDD, 7 pertaining to youth with OCD, and 10 pertaining to youth with other anxiety disorders (N = 2533 patients in placebo arms). As hypothesized, the placebo response rate was significantly higher in studies on MDD, than in those examining OCD and AD-non-OCD (49.6% [range: 17-90%] vs. 31% [range: 4-41%] vs. 39.6% [range: 9-53], respectively, ANOVA F = 7.1, p = 0.002). Children showed a higher stable placebo response within all three diagnoses than adolescents, though this difference was not significant. Finally, no significant effects were found with respect to the year of publication. CONCLUSION: MDD in children and adolescents appears to be more responsive to placebo than other internalized conditions, which highlights differential psychopathology

The Pediatric Obsessive-Compulsive Disorder Treatment Study II: rationale, design and methods

This paper presents the rationale, design, and methods of the Pediatric Obsessive-Compulsive Disorder Treatment Study II (POTS II), which investigates two different cognitive-behavior therapy (CBT) augmentation approaches in children and adolescents who have experienced a partial response to pharmacotherapy with a serotonin reuptake inhibitor for OCD. The two CBT approaches test a "single doctor" versus "dual doctor" model of service delivery. A specific goal was to develop and test an easily disseminated protocol whereby child psychiatrists would provide instructions in core CBT procedures recommended for pediatric OCD (e.g., hierarchy development, in vivo exposure homework) during routine medical management of OCD (I-CBT). The conventional "dual doctor" CBT protocol consists of 14 visits over 12 weeks involving: (1) psychoeducation, (2), cognitive training, (3) mapping OCD, and (4) exposure with response prevention (EX/RP). I-CBT is a 7-session version of CBT that does not include imaginal exposure or therapist-assisted EX/RP. In this study, we compared 12 weeks of medication management (MM) provided by a study psychiatrist (MM only) with two types of CBT augmentation: (1) the dual doctor model (MM+CBT); and (2) the single doctor model (MM+I-CBT). The design balanced elements of an efficacy study (e.g., random assignment, independent ratings) with effectiveness research aims (e.g., differences in specific SRI medications, dosages, treatment providers). The study is wrapping up recruitment of 140 youth ages 7–17 with a primary diagnosis of OCD. Independent evaluators (IEs) rated participants at weeks 0,4,8, and 12 during acute treatment and at 3,6, and 12 month follow-up visits