Mark C. K. Yang

D-cycloserine does not enhance exposure-response prevention therapy in obsessive-compulsive disorder

Obsessive–compulsive disorder is a common, chronic, and oftentimes disabling disorder. The only established first-line treatments for obsessive–compulsive disorder are exposure and response prevention therapy and the serotonin reuptake inhibitors. Many patients do not experience complete symptom resolution with either modality and require augmentation approaches. Recent animal and clinical data suggest that D-cycloserine, a partial agonist that acts at the strychnine-insensitive glycine-recognition site of the N-methyl-D-aspartate receptor complex, may enhance extinction learning that occurs in exposure-based psychotherapies. Given this, this study examined if D-cycloserine (250 mg) enhances the overall efficacy and rate of change of exposure and response prevention therapy for adult obsessive–compulsive disorder. Participants were 24 adults meeting Diagnostic and Statistical Manual of Mental Disorders-IV criteria for obsessive–compulsive disorder. The study design was a randomized, double-blinded, placebo-controlled augmentation trial examining exposure and response prevention therapy+D-cycloserine versus exposure and response prevention therapy+placebo. All patients received 12 weekly sessions of exposure and response prevention treatment. The first session involved building a ritual hierarchy and providing psychoeducation about obsessive–compulsive disorder. The second session involved a practice exposure. Sessions 3–12 involved exposure and response prevention exercises. D-cycloserine or placebo (250 mg) was taken 4 h before every session. No significant group differences were found across outcome variables. The rate of improvement did not differ between groups. The present results fail to support the use of D-cycloserine with exposure and response prevention therapy for adult obsessive–compulsive disorder. As this study is the first to explore this question and a number of methodological issues must be considered when interpreting the findings, the conclusions that may be drawn from our results are limited.

A double-blind, placebo-controlled trial of olanzapine addition in fluoxetine-refractory obsessive-compulsive disorder

BACKGROUND One of the few combination approaches to the treatment of obsessive-compulsive disorder (OCD) with encouraging support is the addition of an antipsychotic to a serotonin reuptake inhibitor. METHODS The study consisted of a 6-week, placebo-controlled addition of olanzapine 5-10 mg (6.1 +/- 2.1 mg, mean +/- SD) to fluoxetine in OCD subjects who were partial or nonresponders to an 8-week, open-label fluoxetine trial (40 mg in 43 subjects, 20 mg in 1 subject). RESULTS Both the fluoxetine-plus-olanzapine (n = 22) and fluoxetine-plus-placebo (n = 22) groups improved significantly over 6 weeks [F(3,113) = 11.64, p <.0001] according to Yale-Brown Obsessive Compulsive Scale scores with repeated-measures analysis of variance; however, the treatment x time interaction was not significant for olanzapine versus placebo addition to fluoxetine. CONCLUSIONS These findings indicate no additional advantage of adding olanzapine for 6 weeks in OCD patients who have not had a satisfactory response to fluoxetine for 8 weeks, compared with extending the monotherapy trial.

Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics

BACKGROUND A subgroup of children with obsessive-compulsive and tic disorders are proposed to have an infectious trigger. The purpose of this study was to investigate the relationship between group A streptococcal titers and symptom fluctuations in children with a clinical course resembling that described for pediatric autoimmune neuropsychiatric disorders associated with streptococcus. METHODS Twenty-five children with obsessive-compulsive disorder and/or tic disorder were evaluated for neuropsychiatric severity and group A streptococcal antibody titers (streptolysin O, deoxyribonuclease B, and carbohydrate A) at 6-week intervals for > or = six consecutive evaluations (total visits=277). RESULTS Children with large symptom fluctuations (n=15) were compared with children without dramatic fluctuations (n=10). Co-movements of obsessive-compulsive/tic severity and group A streptococcal antibodies were assessed. In subjects with large symptom changes, positive correlations were found between streptococcal titers and obsessive-compulsive severity rating changes (p=.0130). These subjects were also more likely to have elevated group A streptococcal titers during the majority of observations (p=.001). Tic symptom exacerbations occurred more often in the fall/winter months than spring/summer months (p=.03). CONCLUSIONS Patients with marked obsessive-compulsive/tic symptom changes may be characterized by streptococcal titer elevations and exhibit evidence of seasonal tic exacerbations.

Chebyshev Inequality With Estimated Mean and Variance

Abstract Chebyshevs inequality is investigated when the population mean and variance are estimated from a sample. The necessary modification to the inequality is simple and is actually valid when (a) the population moments do not exist and (b) the sample is exchangeably distributed. The latter case would include, for example, a sample taken without replacement from a finite population and the independent and identically distributed case.

Energy Efficient Algorithms for the RFID Estimation Problem

RFID has been gaining popularity for inventory control, object tracking, and supply chain management in warehouses, retail stores, hospitals, etc. Periodically and automatically estimating the number of RFID tags deployed in a large area has many important applications in inventory management and theft detection. The prior work focuses on designing time-efficient algorithms that can estimate tens of thousands of tags in seconds. We observe that, for a RFID reader to access tags in a large area, active tags are likely to be used. These tags are batterypowered and use their own energy for information transmission. However, recharging batteries for tens of thousands of tags is laborious. Unlike the prior work, this paper studies the RFID estimation problem from the energy angle. Our goal is to reduce the amount of energy that is consumed by the tags during the estimation procedure. We design several energy-efficient probabilistic algorithms that iteratively refine a control parameter to optimize the information carried in the transmissions from the tags, such that both the number and the size of the transmissions are minimized.

Procedural learning and cognitive flexibility in a mouse model of restricted, repetitive behaviour

Restricted, repetitive behaviours (e.g., stereotypies, compulsions, rituals) in neurodevelopmental disorders have been linked to alterations in cortico-basal ganglia circuitry. Cognitive processes mediated by this circuitry (e.g., procedural learning, executive function) are likely to be impaired in individuals exhibiting high rates of repetitive behaviour. To test this hypothesis, we assessed both procedural learning and cognitive flexibility (reversal learning) using a T-maze task in deer mice (Peromyscus maniculatus) exhibiting various rates of repetitive behaviour (vertical jumping and backward somersaulting). These mice exhibited high rates of stereotypy when reared in standard rodent cages, and such behaviour was significantly attenuated by housing them in larger more complex environments. Mice reared in complex environments exhibited significantly better procedural and reversal learning than standard caged mice. Thus, early experience associated with the prevention and attenuation of stereotypy was associated with better striatally mediated learning and cognitive flexibility. Stereotypy score was significantly correlated with the number of errors made in reversal learning, and interacted with housing condition to affect overall cognitive performance. Our findings support the applicability of the deer mouse model of spontaneous stereotypy to a wider range of restricted, repetitive behaviour (e.g., insistence on sameness) typical of neurodevelopmental disorders.

Predictability analysis for an automated seizure prediction algorithm.

Epileptic seizures of mesial temporal origin are preceded by changes in signal properties detectable in the intracranial EEG. A series of computer algorithms designed to detect the changes in spatiotemporal dynamics of the EEG signals and to warn of impending seizures have been developed. In this study, we evaluated the performance of a novel adaptive threshold seizure warning algorithm (ATSWA), which detects the convergence in Short-Term Maximum Lyapunov Exponent (STLmax) values among critical intracranial EEG electrode sites, as a function of different seizure warning horizons (SWHs). The ATSWA algorithm was compared to two statistical based naïve prediction algorithms (periodic and random) that do not employ EEG information. For comparison purposes, three performance indices “area above ROC curve” (AAC), “predictability power” (PP) and “fraction of time under false warnings” (FTF) were defined and the effect of SWHs on these indices was evaluated. The results demonstrate that this EEG based seizure warning method performed significantly better (P < 0.05) than both naïve prediction schemes. Our results also show that the performance indexes are dependent on the length of the SWH. These results suggest that the EEG based analysis has the potential to be a useful tool for seizure warning.

Case series on the use of aripiprazole for Tourette syndrome

Characterized by multiple motor and phonic tics, Tourette syndrome (TS) is also associated with a constellation of comorbid disorders, including obsessive–compulsive symptoms that occur in 40–60% of patients. The pathophysiology of tics has been linked by many studies to specific cortical and basal ganglia changes and hypothesized to relate to dysregulation of dopamine responsive/dependent circuits (Jordan et al., 2004). Aripiprazole, a recently released atypical antipsychotic noted for its partial D2 agonist activity along with a low propensity for extrapyramidal effects, has been shown to be efficacious in reducing symptoms of schizophrenia in adults. The value of aripiprazole for treating neuropsychiatric disorders in children has not previously been reported. We present results of a retrospective chart review of six youth with TS and comorbid obsessive–compulsive disorder (OCD) who were treated for 12 wk with aripiprazole.

Open label aripiprazole in the treatment of youth with tic disorders.

BACKGROUND Primarily safe and efficacious treatments for chronic tic disorders are needed. Also needed are such treatments that target co-morbid conditions. Aripiprazole, a dopaminergic/serotonergic agent with partial agonist properties at the D2 dopamine receptor and 5-hydrdoxytryptamine 1A (5-HT(1A)) receptor and antagonist properties at the 5-HT(2A) receptor, holds promise in both regards. OBJECTIVE This was an open-label, flexible-dose study to evaluate the safety of aripiprazole in children and adolescents with a primary diagnosis of a chronic tic disorder with/without co-morbid disorder(s). METHOD Sixteen children (15 males) aged 8-17 years participated in the 6-week trial. Ratings for tic, obsessive compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and side effects were administered weekly. Baseline and exit laboratory measures, electrocardiograms (ECGs), weight, and height were obtained. RESULTS The average daily aripiprazole dose was 3.3 mg (range 1.25-7.5 mg). Significant pre-and posttreatment differences were ascertained for the Yale Global Tic Severity Scale motor (p < or = 0.0001), phonic (p < or = 0.0001), and total tic (p < or = 0.0001) scores. Results of other rating scales suggested significant improvements in co-morbid disorders as well, including OCD, ADHD, and depressive disorders. Although aripiprazole was well tolerated, increases in weight were found. CONCLUSION In this preliminary open-label trial, aripiprazole was a well-tolerated treatment for tics and co-morbid OCD and ADHD symptoms. Improvements in co-morbid conditions may be secondary to tic reduction or to specific to aripiprazole therapy; however, further study is warranted.

Hough transform modified by line connectivity and line thickness

A modified Hough transform based on a likelihood principle of connectivity and thickness is proposed for line detection. It makes short as well as thick line segments easier to detect in a noisy image. Certain desirable properties of the new method are justified by theory and simulations.