Harry McConnell

Difficult-to-treat pediatric obsessive-compulsive disorder: Feasibility and preliminary results of a randomized pilot trial of D-cycloserine-augmented behavior therapy

This study examined the feasibility and preliminary effectiveness of d‐cycloserine (DCS)–augmented cognitive behavioral therapy (CBT) for children and adolescents with difficult‐to‐treat Obsessive Compulsive Disorder, in a double‐blind randomized controlled pilot trial (RCT).

D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data

Importance Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, −3.62; 95% CI, −0.81 to −6.43; P = .01; d = −0.25) but not from pretreatment to midtreatment (mean difference, −1.66; 95% CI, −4.92 to 1.60; P = .32; d = −0.14) or from pretreatment to follow-up (mean difference, −2.98, 95% CI, −5.99 to 0.03; P = .05; d = −0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.

A topographical map of the causal network of mechanisms underlying the relationship between major depressive disorder and coronary heart disease

Objective: Major depressive disorder (MDD) and coronary heart disease (CHD) are both clinically important public health problems. Depression is linked with a higher incidence of ischaemic cardiac events and MDD is more prevalent in patients with CHD. No single comprehensive model has yet described the causal mechanisms linking MDD to CHD. Several key mechanisms have been put forward, comprising behavioural mechanisms, genetic mechanisms, dysregulation of immune mechanisms, coagulation abnormalities and vascular endothelial dysfunction, polyunsaturated omega-3 free fatty acid deficiency, and autonomic mechanisms. It has been suggested that these mechanisms form a network, which links MDD and CHD. The aim of this review is to examine the causal mechanisms underlying the relationship between MDD and CHD, with the aim of constructing a topological map of the causal network which describes the relationship between MDD and CHD. Methods: The search term ‘depression and heart disease’ was entered into an electronic multiple database search engine. Abstracts were screened for relevance and individually selected articles were collated. Results: This review introduces the first topological map of the causal network which describes the relationship between MDD and CHD. Conclusions: Viewing the causal pathways as an interdependent network presents a new paradigm in this field and provides fertile ground for further research. The causal network can be studied using the methodology of systems biology, which is briefly introduced. Future research should focus on the creation of a more comprehensive topological map of the causal network and the quantification of the activity between each node of the causal network.

Mind and Heart: Heart Rate Variability in Major Depressive Disorder and Coronary Heart Disease − a Review and Recommendations

Objective: There is a reciprocal association between major depressive disorder (MDD) and coronary heart disease (CHD). These conditions are linked by a causal network of mechanisms. This causal network should be quantitatively studied and it is hypothesised that the investigation of vagal function represents a promising starting point. Heart rate variability (HRV) has been used to investigate cardiac vagal control in the context of MDD and CHD. This review aims to examine the relationship of HRV to both MDD and CHD in the context of vagal function and to make recommendations for clinical practice and research. Methods: The search terms ‘heart rate variability’, ‘depression’ and ‘heart disease’ were entered into an electronic multiple database search engine. Abstracts were screened for their relevance and articles were individually selected and collated. Results: Decreased HRV is found in both MDD and CHD. Both diseases are theorised to disrupt autonomic control feedback loops on the heart and are linked to vagal function. Existing theories link vagal function to both mood and emotion as well as cardiac function. However, several factors can potentially confound HRV measures and would thus impact on a complete understanding of vagal mechanisms in the link between MDD and CHD. Conclusions: The quantitative investigation of vagal function using HRV represents a reasonable starting point in the study of the relationship between MDD and CHD. Many psychotropic and cardiac medications have effects on HRV, which may have clinical importance. Future studies of HRV in MDD and CHD should consider antidepressant medication, as well as anxiety, as potential confounders.

Brief intensive CBT for pediatric OCD with E-therapy maintenance

Cognitive behaviour therapy (CBT), incorporating exposure and response prevention (ERP), has received strong empirical support for the treatment of paediatric OCD, and moreover, is considered the first line treatment of choice (Geller & March, 2012). However, despite the availability of effective treatments for this chronic and debilitating disorder, only a small proportion of youth receive these evidence-based approaches. The present study aimed to examine the effectiveness of an intensive ERP-based treatment for youth OCD, using a multiple baseline controlled design. Children and youth (N=10; aged 11-16 years) with a primary diagnosis of OCD were randomly assigned to a 1- or 2-week baseline monitoring condition followed by the intervention. The efficacy of the intensive treatment, involving 1 session psychoeducation, 2-sessions ERP plus e-therapy maintenance was examined across parent- child- and clinician-rated measures at post-treatment and 6-month follow-up. Overall, there were significant reductions across time on almost all measures (except self-report anxiety), and moreover, the majority of the sample (80%) were considered reliably improved, and meeting clinically significant change. At post-treatment, 60% were in remission of symptoms, and at 6-month follow-up this increased to 70%. These findings provide strong support for intensive, time-limited approaches to ERP-based CBT for children and youth with OCD.

From Physiome to Pathome: A Systems Biology Model of Major Depressive Disorder and the Psycho-Immune-Neuroendocrine Network

This article introduces a systems biology model of the psycho-immune-neuroendocrine (PINE) network. It provides a comprehensive synthesis of the network of biological mechanisms which link major depressive disorder (MDD) with several diseases including hypertension, atherosclerosis, coronary heart disease (CHD), cerebrovascular accident (CVA) and type 2 diabetes. The first part of this article provides an overview of concepts such as the PINE physiome and pathome, as well as the application of a systems biology framework to explain the significant reciprocal associations of MDD with the above named medical illnesses. The second part describes the normal physiological pathways of immune mechanisms, the hypothalamic-pituitary-adrenal (HPA) axis, autonomic pathways and central nervous system function, which form the PINE physiome. The third section describes how homeostasis of the PINE physiome is disrupted by chronic stress, on a background of genetic and developmental diathesis factors, resulting in a network of pathophysiological pathways called the PINE pathome. MDD, CHD, type 2 diabetes, CVA, hypertension and atherosclerosis can act to maintain the PINE network in a stable pathological state. This article presents comprehensive topographical maps of both the PINE physiome and the PINE pathome. Implications of the model and the importance of adopting a systems approach to understanding the relationship between these diseases is discussed in the last section, including the possibility of novel treatments for MDD and areas of future research.

D-cycloserine-augmented one-session treatment of specific phobias in children and adolescents

D‐Cycloserine has potential to enhance exposure therapy outcomes. The current study presents a preliminary randomized, placebo‐controlled double‐blind pilot trial of DCS‐augmented one‐session treatment (OST) for youth (7–14 years) with specific phobia. A secondary aim of this pilot study was to explore the effects of youth age and within‐session fear reduction as potential moderators of DCS outcomes in order to generate hypotheses for a larger trial. It was hypothesized that DCS would be associated with greater improvements than placebo, that children (7–10 years) would have greater benefits than adolescents (11–14 years), and that DCS effects would be stronger for participants with the greater within‐session fear reduction during the OST.

A preprocessing tool for removing artifact from cardiac RR interval recordings using three-dimensional spatial distribution mapping

Artifact is common in cardiac RR interval data that is recorded for heart rate variability (HRV) analysis. A novel algorithm for artifact detection and interpolation in RR interval data is described. It is based on spatial distribution mapping of RR interval magnitude and relationships to adjacent values in three dimensions. The characteristics of normal physiological RR intervals and artifact intervals were established using 24-h recordings from 20 technician-assessed human cardiac recordings. The algorithm was incorporated into a preprocessing tool and validated using 30 artificial RR (ARR) interval data files, to which known quantities of artifact (0.5%, 1%, 2%, 3%, 5%, 7%, 10%) were added. The impact of preprocessing ARR files with 1% added artifact was also assessed using 10 time domain and frequency domain HRV metrics. The preprocessing tool was also used to preprocess 69 24-h human cardiac recordings. The tool was able to remove artifact from technician-assessed human cardiac recordings (sensitivity 0.84, SD = 0.09, specificity of 1.00, SD = 0.01) and artificial data files. The removal of artifact had a low impact on time domain and frequency domain HRV metrics (ranging from 0% to 2.5% change in values). This novel preprocessing tool can be used with human 24-h cardiac recordings to remove artifact while minimally affecting physiological data and therefore having a low impact on HRV measures of that data.

The sensitivity of 38 heart rate variability measures to the addition of artifact in human and artificial 24-hr cardiac recordings

Artifact is common in cardiac RR interval data derived from 24‐hr recordings and has a significant impact on heart rate variability (HRV) measures. However, the relative impact of progressively added artifact on a large group of commonly used HRV measures has not been assessed. This study compared the relative sensitivity of 38 commonly used HRV measures to artifact to determine which measures show the most change with increasing increments of artifact. A secondary aim was to ascertain whether short‐term and long‐term HRV measures, as groups, share similarities in their sensitivity to artifact.

The Impact of Methodology and Confounding Variables on the Association Between Major Depression and Coronary Heart Disease: Review and Recommendations

Background: A reciprocal association exists between Major Depressive Disorder (MDD) and Coronary Heart Disease (CHD). A quantitative evaluation of this association is necessary to identify potential areas of clinical intervention. However, the association is unclear because of methodological differences and confounders across studies. This review examines the impact of methodology and confounding variables on the magnitude of the relationship between MDD and CHD. Methods: The search terms “major depression AND coronary heart disease” were entered into an electronic multiple database search engine. Abstracts were screened for relevance and individually selected articles were collated. Results: Nine methodological issues and three confounders are identified, which have contributed to uncertainty in the quantitative relationship between MDD and CHD. More quantitative, prospective longitudinal studies are needed, which use standard definitions for MDD and CHD and define clear outcomes. Studies should clearly establish the temporal relationship between the onset of depressed mood and one or more adverse cardiac events, should use quantitative measures of depression which are treated as continuous data, and have frequent measures of mental state over time, correlated with measures of cardiac health. Study design should avoid confounding by considering demographic factors, cardiac risk factors and management of MDD in CHD patients. Conclusions: This review raises the need for a standardised methodology in future research, taking into account the biases and confounders listed. Adopting a consensus approach to methodology will facilitate the quantitative exploration of the causal network linking MDD and CHD.