Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder: A Randomized Clinical Trial

Importance Evidence is lacking for viable treatment options for patients with difficult-to-treat obsessive-compulsive disorder (OCD). It has been suggested that D-cycloserine (DCS) could potentiate the effect of exposure and response prevention (ERP) treatment, but the hypothesis has not been tested among patients with difficult-to-treat OCD. Objective To evaluate whether DCS potentiates the effect of concentrated ERP among patients with difficult-to-treat OCD. Design, Setting, and Participants The study was a randomized placebo-controlled triple-masked study with a 12-month follow-up. Participants were adult outpatients with difficult-to-treat OCD. A total of 220 potential participants were referred, of whom 36 did not meet inclusion criteria and 21 declined to participate. Patients had either relapsed after (n = 100) or not responded to (n = 63) previous ERP treatment. A total of 9 specialized OCD teams within the public health care system in Norway participated, giving national coverage. An expert team of therapists from the coordinating site delivered treatment. Inclusion of patients started in January 2016 and ended in August 2017. Data analysis was conducted February to September 2019. Interventions All patients received individual, concentrated ERP treatment delivered during 4 consecutive days in a group setting (the Bergen 4-day treatment format) combined with 100 mg DCS, 250 mg DCS, or placebo. Main outcomes and Measures Change in symptoms of OCD and change in diagnostic status. Secondary outcomes measures included self-reported symptoms of OCD, anxiety, depression, and quality of life. Results The total sample of 163 patients had a mean (SD) age of 34.5 (10.9) years, and most were women (117 [71.8%]). They had experienced OCD for a mean (SD) of 16.2 (10.2) years. A total of 65 patients (39.9%) were randomized to receive 100 mg DCS, 67 (41.1%) to 250 mg of DCS, and 31 (19.0%) to placebo. Overall, 91 (56.5%) achieved remission at posttreatment, while 70 (47.9%) did so at the 12-month follow-up. There was no significant difference in remission rates among groups. There was a significant reduction in symptoms at 12 months, and within-group effect sizes ranged from 3.01 (95% CI, 2.38-3.63) for the group receiving 250 mg DCS to 3.49 (95% CI, 2.78-4.18) for the group receiving 100 mg DCS (all P < .001). However, there was no significant effect of treatment group compared with placebo in obsessive-compulsive symptoms (250 mg group at posttreatment: d = 0.33; 95% CI, −0.10 to 0.76; 100 mg group at posttreatment: d = 0.36; 95% CI, −0.08 to 0.79), symptoms of depression and anxiety (eg, Patient Health Questionnaire–9 score among 250 mg group at 12-month follow-up: d = 0.30; 95% CI, −0.17 to 0.76; Generalized Anxiety Disorder–7 score among 100 mg group at 12-month follow-up: d = 0.27; 95% CI, −0.19 to 0.73), and well-being (250 mg group: d = 0.10; 95% CI, −0.42 to 0.63; 100 mg group: d = 0.34; 95% CI, −0.19 to 0.86). No serious adverse effects were reported. Conclusions and Relevance In this study, DCS did not potentiate ERP treatment effect, but concentrated ERP treatment was associated with improvement. Trial Registration ClinicalTrials.gov identifier: NCT02656342publishedVersio

The importance of the altricial – precocial spectrum for social complexity in mammals and birds:A review

Various types of long-term stable relationships that individuals uphold, including cooperation and competition between group members, define social complexity in vertebrates. Numerous life history, physiological and cognitive traits have been shown to affect, or to be affected by, such social relationships. As such, differences in developmental modes, i.e. the ‘altricial-precocial’ spectrum, may play an important role in understanding the interspecific variation in occurrence of social interactions, but to what extent this is the case is unclear because the role of the developmental mode has not been studied directly in across-species studies of sociality. In other words, although there are studies on the effects of developmental mode on brain size, on the effects of brain size on cognition, and on the effects of cognition on social complexity, there are no studies directly investigating the link between developmental mode and social complexity. This is surprising because developmental differences play a significant role in the evolution of, for example, brain size, which is in turn considered an essential building block with respect to social complexity. Here, we compiled an overview of studies on various aspects of the complexity of social systems in altricial and precocial mammals and birds. Although systematic studies are scarce and do not allow for a quantitative comparison, we show that several forms of social relationships and cognitive abilities occur in species along the entire developmental spectrum. Based on the existing evidence it seems that differences in developmental modes play a minor role in whether or not individuals or species are able to meet the cognitive capabilities and requirements for maintaining complex social relationships. Given the scarcity of comparative studies and potential subtle differences, however, we suggest that future studies should consider developmental differences to determine whether our finding is general or whether some of the vast variation in social complexity across species can be explained by developmental mode. This would allow a more detailed assessment of the relative importance of developmental mode in the evolution of vertebrate social systems

Prediction value of genetic and neuromarkers in blood and liquor in patients with severe traumatic brain injury

Background: Severe traumatic brain injury (sTBI) is the most common cause of mortality in young adults. sTBI induces variable brain damage, invisible in Computer Tomographic scans early post-trauma. Further, neurology is difficult to evaluate in sedated patients. Therefore, biochemical neuromarkers (BNMs) in blood or cerebrospinal fluid (CSF) may be valuable tools to both evaluate trauma and to prognosticate patient outcome. Aims: The aim of the thesis was to evaluate if concentrations of the BNMs; Glial Fibrillary Acid Protein (GFAP, CSF, study IV), Neurofilament light (NFL, CSF, study IV), Tau (CSF, study II), β-amyloid (1-42) and amyloid precursor-proteins (CSF & plasma, study I) were enhanced after a sTBI. Further, we investigated if these levels were correlated to outcome, neurology and patient ability of daily living 1-year post-trauma. Finally, we explored if patient-genotype, specifically Apolipoprotein E, (gene APOE), influenced 1-year outcome in sTBI-patients, (plasma, study III). Methods: Patients were consecutively included if; aged ≥7 years, < 9 in Glasgow Coma Scale, receiving an indwelling ventricular catheter allowing CSF sampling), were artificially ventilated and admitted to the Neurointensive care unit (NICU) within 48h post-trauma. NICU-care was performed according to a standardized protocol. CSF samples were collected on days 0-4, 6, 8 and once on days 11-18. Surviving patients were assessed at 1-year evaluating; 1) outcome by Glasgow Outcome Scale (GOS), 2. neurology and 3. activities of daily living. NFL, GFAP, Tau, β-amyloid (1-42) and amyloid precursor-proteins were all analyzed by ELISAmethods. APOE genotyping was performed by polymerase chain reaction & solidphase mini-sequencing. Results: During the inclusion period, patients (n=28-96) were included into studies IIV for CSF and /or blood sampling. Study I; β-amyloid (1-42) and amyloid precursor-proteins increased from day 0 until day 11 in the CSF, but not in plasma. In study II we found enhanced levels of CSF-Tau on days 2-3 correlated to mortality (GOS 1) at 1-year. In study III we found that patients with APOE allele 4 had worse outcome (GOS) at 1-year. Finally, in paper IV we found increased CSF levels of GFAP and NFL both correlating to outcome (GOS) at 1-year. Conclusions; In this thesis we have found in sTBI-patients that genetic and BNMs in the plasma and/or CSF correlate to outcome at 1 -year post-trauma. The result may be clinically applicable to prognosticate outcome and influence treatment paradigms in these patients

Event-related potentials when identifying or color-naming threatening schematic stimuli in spider phobic and non-phobic individuals

<p>Abstract</p> <p>Background</p> <p>Previous studies revealed increased parietal late positive potentials (LPPs) in response to spider pictures in spider phobic individuals. This study searched for basic features of fear-relevant stimuli by investigating whether schematic spider images are sufficient to evoke differential behavioral as well as differential early and late ERP responses in spider phobic, social phobic (as a clinical control group), and non-phobic control participants.</p> <p>Methods</p> <p>Behavioral and electrophysiological correlates of the processing of schematic spider and flower images were investigated while participants performed a color (emotional Stroop) and an object identification task. Stimuli were schematic pictures of spiders and flowers matched with respect to constituting visual elements.</p> <p>Results</p> <p>Consistent with previous studies using photographic spider pictures, spider phobic persons showed enhanced LPPs when identifying schematic spiders compared to schematic flowers. In addition, spider phobic individuals showed generally faster responses than the control groups. This effect was interpreted as evidence for an increased general behavioral hypervigilance in this anxiety disorder group. Furthermore, both phobic groups showed enhanced P100 amplitudes compared to controls, which was interpreted as evidence for an increased (cortical) hypervigilance for incoming stimuli in phobic patients in general. Finally, all groups showed faster identification of and larger N170 amplitudes in response to schematic spider than flower pictures. This may reflect either a general advantage for fear-relevant compared to neutral stimuli, or might be due to a higher level of expertise in processing schematic spiders as compared to the more artificially looking flower stimuli.</p> <p>Conclusion</p> <p>Results suggest that schematic spiders are sufficient to prompt differential responses in spider-fearful and spider-non-fearful persons in late ERP components. Early ERP components, on the other hand, seem to be modified by anxiety status per se, which is consistent with recent theories on general hypervigilance in the anxiety disorder spectrum.</p