Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [(18)F]dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.

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Direct brain infusion of glial cell line–derived neurotrophic factor in Parkinson disease

Background: Open access websites which deliver cognitive and behavioral interventions for anxiety and depression are characterised by poor adherence. We need to understand more about adherence in order to maximize the impact of Internet-based interventions on the disease burden associated with common mental disorders. Objective: The aims of this paper are to review briefly the adherence literature with respect to Internet interventions and to investigate the rates of dropout and compliance in randomized controlled trials of anxiety and depression Web studies. Methods: A systematic review of randomized controlled trials using Internet interventions for anxiety and depression was conducted, and data was collected on dropout and adherence, predictors of adherence, and reasons for dropout. Results: Relative to reported rates of dropout from open access sites, the present study found that the rates of attrition in randomized controlled trials were lower, ranging from approximately 1 - 50%. Predictors of adherence included disease severity, treatment length, and chronicity. Very few studies formally examined reasons for dropout, and most studies failed to use appropriate statistical techniques to analyze missing data. Conclusions: Dropout rates from randomized controlled trials of Web interventions are low relative to dropout from open access websites. The development of theoretical models of adherence is as important in the area of Internet intervention research as it is in the behavioral health literature. Disease-based factors in anxiety and depression need further investigation. [J Med Internet Res 2009;11(2):e13]

Adherence in internet interventions for anxiety and depression.

Child and adolescent patients may display mental health concerns within some contexts and not others (e.g., home vs. school). Thus, understanding the specific contexts in which patients display concerns may assist mental health professionals in tailoring treatments to patients’ needs. Consequently, clinical assessments often include reports from multiple informants who vary in the contexts in which they observe patients’ behavior (e.g., patients, parents, teachers). Previous meta-analyses indicate that informants’ reports correlate at low-to-moderate magnitudes. However, is it valid to interpret low correspondence among reports as indicating that patients display concerns in some contexts and not others? We meta-analyzed 341 studies published between 1989 and 2014 that reported cross-informant correspondence estimates, and observed low-to-moderate correspondence (mean internalizing: r = .25; mean externalizing: r = .30; mean overall: r = .28). Informant pair, mental health domain, and measurement method moderated magnitudes of correspondence. These robust findings have informed the development of concepts for interpreting multi-informant assessments, allowing researchers to draw specific predictions about the incremental and construct validity of these assessments. In turn, we critically evaluated research on the incremental and construct validity of the multi-informant approach to clinical child and adolescent assessment. In so doing, we identify crucial gaps in knowledge for future research, and provide recommendations for “best practices” in using and interpreting multi-informant assessments in clinical work and research. This article has important implications for developing personalized approaches to clinical assessment, with the goal of informing techniques for tailoring treatments to target the specific contexts where patients display concerns.

https://papers.ssrn.com/sol3/Delivery.cfm?abstractid=2632484

The Validity of the Multi-Informant Approach to Assessing Child and Adolescent Mental Health

Grounded in four theoretical positions-structural, cognitive, phenomenological, and ethical-the present review demonstrates the empirical evidence for the incremental validity of narrative identity as a cross-sectional indicator and prospective predictor of well-being, compared with other individual difference and situational variables. In doing so, we develop an organizational framework of four categories of narrative variables: (a) motivational themes, (b) affective themes, (c) themes of integrative meaning, and (d) structural elements. Using this framework, we detail empirical evidence supporting the incremental association between narrative identity and well-being, a case that is strongest for motivational, affective, and integrative meaning themes. These categories of themes serve as vital complimentary correlates and predictors of well-being, alongside commonly assessed variables such as dispositional personality traits. We then use the theoretically grounded review of the empirical literature to develop concrete areas of future research for the field.

https://journals.sagepub.com/doi/pdf/10.1177/1088868315585068

The Incremental Validity of Narrative Identity in Predicting Well-Being A Review of the Field and Recommendations for the Future

In response to rapidly growing rates of comorbidity among psychiatric disorders, clinical scientists have become interested in identifying transdiagnostic processes that can help explain dysfunction across diagnostic categories (e.g., Kring & Sloan, 2009). One factor that has received a great deal of attention is that of emotion regulation, namely, the ability to modulate the intensity and/or duration of emotional states (e.g., Cicchetti, Ackerman, & Izard, 1995; Gross, 1998). Recent theoretical and empirical work has begun to emphasize the role that emotion regulation plays in the temporal comorbidity between internalizing and externalizing conditions (e.g., Aldao & De Los Reyes, 2015; De Los Reyes & Aldao, 2015; Drabick & Kendall, 2010; Jarrett & Ollendick, 2008; Patrick & Hajcak, 2016). However, close inspection of this work reveals two very pertinent areas of growth: (a) this literature is characterized by mixed findings that are likely explained, in part, by methodological heterogeneity; and (b) emotion regulation tends to be studied in relatively narrow terms. To address these issues, we provide a series of recommendations for facilitating cross-study comparisons and leveraging multifaceted approaches to studying emotion regulation processes within a developmental psychopathology framework. We hope that our perspective can enhance the organization and growth of this very important area of inquiry, and ultimately result in more effective prevention and treatment programs.

P Sanders

Papers

Evidence based assessment.