Gabapentin treatment for bipolar disorders

OBJECTIVE: To review the effectiveness data on the use of gabapentin in bipolar disorders. DATA SOURCES: Clinical literature was accessed through MEDLINE (January 1985–November 2000). Key search terms included gabapentin, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: Bipolar disorder is a complex condition that can be difficult to treat effectively. Mood stabilizers are increasingly being used to manage bipolar disorder. Studies that used gabapentin in bipolar disorders are evaluated. CONCLUSIONS: From the data presented, gabapentin cannot be recommended for treatment of bipolar disorder. Further studies are required to determine whether gabapentin has any role in the management of bipolar disorder.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

Species differential regulation of COX2 can be described by an NFκB-dependent logic AND gate

Cyclooxygenase 2 (COX2), a key regulatory enzyme of the prostaglandin/eicosanoid pathway, is an important target for anti-inflammatory therapy. It is highly induced by pro-inflammatory cytokines in a Nuclear factor kappa B (NFκB)-dependent manner. However, the mechanisms determining the amplitude and dynamics of this important pro-inflammatory event are poorly understood. Furthermore, there is significant difference between human and mouse COX2 expression in response to the inflammatory stimulus tumor necrosis factor alpha (TNFα). Here, we report the presence of a molecular logic AND gate composed of two NFκB response elements (NREs) which controls the expression of human COX2 in a switch-like manner. Combining quantitative kinetic modeling and thermostatistical analysis followed by experimental validation in iterative cycles, we show that the human COX2 expression machinery regulated by NFκB displays features of a logic AND gate. We propose that this provides a digital, noise-filtering mechanism for a tighter control of expression in response to TNFα, such that a threshold level of NFκB activation is required before the promoter becomes active and initiates transcription. This NFκB-regulated AND gate is absent in the mouse COX2 promoter, most likely contributing to its differential graded response in promoter activity and protein expression to TNFα. Our data suggest that the NFκB-regulated AND gate acts as a novel mechanism for controlling the expression of human COX2 to TNFα, and its absence in the mouse COX2 provides the foundation for further studies on understanding species-specific differential gene regulation.

Influence of light exposure during early life on the age of onset of bipolar disorder

Background: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. Methods: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4N and 70.7N, and 1.2S and 41.3S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. Results: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. Conclusions: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.

Correlates of depression in bipolar disorder

We analyse time series from 100 patients with bipolar disorder for correlates of depression symptoms. As the sampling interval is non-uniform, we quantify the extent of missing and irregular data using new measures of compliance and continuity. We find that uniformity of response is negatively correlated with the standard deviation of sleep ratings (ρ = -0.26, p = 0.01). To investigate the correlation structure of the time series themselves, we apply the Edelson-Krolik method for correlation estimation. We examine the correlation between depression symptoms for a subset of patients and find that self-reported measures of sleep and appetite/weight show a lower average correlation than other symptoms. Using surrogate time series as a reference dataset, we find no evidence that depression is correlated between patients, though we note a possible loss of information from sparse sampling. © 2013 The Author(s).

Clinical guidelines on long-term pharmacotherapy for bipolar disorder in children and adolescents

Bipolar disorder is a severe affective disorder which can present in adolescence, or sometimes earlier, and often requires a pharmacotherapeutic approach. The phenomenology of bipolar disorder in children and adolescents appears to differ from that of adult patients, prompting the need for specific pharmacotherapy guidelines for long-term management in this patient population. Current treatment guidelines were mainly developed based on evidence from studies in adult patients, highlighting the requirement for further research into the pharmacotherapy of children and adolescents with bipolar disorder. This review compares and critically analyzes the available guidelines, discussing the recommended medication classes, their mechanisms of action, side effect profiles and evidence base

Assessing personal financial management in patients with bipolar disorder and its relation to impulsivity and response inhibition

Introduction: Impulsivity and risk-taking behaviours are reported in bipolar disorder (BD). We examined whether financial management skills are related to impulsivity in patients with BD. Methods: We assessed financial management skills using the Executive Personal Finance Scale (EPFS), impulsivity using the Barratt Impulsiveness Scale (BIS) and response inhibition using an emotional go/no-go task in bipolar individuals (N = 21) and healthy controls (HC; N = 23). Results: Patients had fewer financial management skills and higher levels of impulsivity than HC. In patients and controls, increased impulsivity was associated with poorer personal financial management. Patients and HC performed equally on the emotional go/no-go task. Higher BIS scores were associated with faster reaction times in HC. In patients, however, higher BIS scores were associated with slower reaction times, possibly indicating compensatory cognitive strategies to counter increased impulsivity. Conclusions: Patients with BD may have reduced abilities to manage personal finances, when compared against healthy participants. Difficulty with personal finance management may arise in part as a result of increased levels of impulsivity. Patients may learn to compensate for increased impulsivity by modulating response times in our experimental situations although whether such compensatory strategies generalize to real-world situations is unknown.

Managing bipolar depression:a therapeutic challenge?

Most people with bipolar disorder first seek treatment for depressive rather than manic symptoms. However, effective management of bipolar depression remains a challenge. In this review, Celia Feetam highlights how bipolar depression differs from unipolar depression both in its characteristics and in the approach to its treatment. © 2011 John Wiley & Sons, Ltd.

Assessment of social cognition in bipolar disorder

Background: Impairment in social cognition may contribute to deficits in social functioning in patients with bipolar disorder (BD). In this study, a complex social cognition task was administered during a neuroimaging session. The behavioral and neural correlates of social cogniton in patients with BD were compared to healthy comparison (HC) subjects. Methods: The task was administered to 25 HC and 25 patients with depression scores ranging from euthymic to depressed at the time of assessment. The task required participants to evaluate situations that were “enhancing” or “threatening” to self-esteem, directed at both oneself, and at other people. For instance, self-esteem enhancing scenarios involved vignettes of activities such as receiving praise during a sports game, while a threatening scenario involved, for example, receiving criticism at a party. Participants were then required to evaluate characters in the scenarios on the basis of positive (“kind”) or negative (“mean”) descriptors. Evaluations were classified from extremely negative to extremely positive. The frequencies of behavioral responses were analyzed using chi-square tests and fMRI data were analyzed using Statistical Parametric Mapping software. Results: Patients differed significantly from HCs in their evaluation of threatening scenarios, directed at both oneself and at other people (p<0.001). Patients had a lower proportion of responses in the neutral category, and more responses in the positive and negative categories, relative to HCs. Neuroimaging results reveal differential patterns of prefrontal-cortical and limbic-subcortical activation in BDs throughout the task [p<0.05 (unc.)]. Conclusions: Findings will contribute to understanding difficulty in interpersonal functioning in patients with BD.

Internet use by patients with bipolar disorder:results from an international multisite survey

There is considerable international interest in online education of patients with bipolar disorder, yet little understanding of how patients use the Internet and other sources to seek information. 1171 patients with bipolar disorder diagnosis in 17 countries completed a paper-based, anonymous survey. 81% of the patients used the Internet, a percentage similar to the general public. Older age, less education, and challenges in country telecommunications infrastructure and demographics decreased the odds of using the Internet. About 78% of the Internet users looked online for information on bipolar disorder or 63% of the total sample. More years of education in relation to the country mean, and feeling very confident about managing life decreased the odds of seeking information on bipolar disorder online, while having attended support groups increased the odds. Patients who looked online for information on bipolar disorder consulted medical professionals plus a mean of 2.3 other information sources such as books, physician handouts, and others with bipolar disorder. Patients not using the Internet consulted medical professionals plus a mean of 1.6 other information sources. The percentage of patients with bipolar disorder who use the Internet is about the same as the general public. Other information sources remain important.

Field programmable gate array based target detection and gesture recognition

The move from Standard Definition (SD) to High Definition (HD) represents a six times increases in data, which needs to be processed. With expanding resolutions and evolving compression, there is a need for high performance with flexible architectures to allow for quick upgrade ability. The technology advances in image display resolutions, advanced compression techniques, and video intelligence. Software implementation of these systems can attain accuracy with tradeoffs among processing performance (to achieve specified frame rates, working on large image data sets), power and cost constraints. There is a need for new architectures to be in pace with the fast innovations in video and imaging. It contains dedicated hardware implementation of the pixel and frame rate processes on Field Programmable Gate Array (FPGA) to achieve the real-time performance. ^ The following outlines the contributions of the dissertation. (1) We develop a target detection system by applying a novel running average mean threshold (RAMT) approach to globalize the threshold required for background subtraction. This approach adapts the threshold automatically to different environments (indoor and outdoor) and different targets (humans and vehicles). For low power consumption and better performance, we design the complete system on FPGA. (2) We introduce a safe distance factor and develop an algorithm for occlusion occurrence detection during target tracking. A novel mean-threshold is calculated by motion-position analysis. (3) A new strategy for gesture recognition is developed using Combinational Neural Networks (CNN) based on a tree structure. Analysis of the method is done on American Sign Language (ASL) gestures. We introduce novel point of interests approach to reduce the feature vector size and gradient threshold approach for accurate classification. (4) We design a gesture recognition system using a hardware/ software co-simulation neural network for high speed and low memory storage requirements provided by the FPGA. We develop an innovative maximum distant algorithm which uses only 0.39% of the image as the feature vector to train and test the system design. Database set gestures involved in different applications may vary. Therefore, it is highly essential to keep the feature vector as low as possible while maintaining the same accuracy and performance^

System-on-a-Chip (SoC) based hardware acceleration in Register Transfer Level (RTL) design

Today, modern System-on-a-Chip (SoC) systems have grown rapidly due to the increased processing power, while maintaining the size of the hardware circuit. The number of transistors on a chip continues to increase, but current SoC designs may not be able to exploit the potential performance, especially with energy consumption and chip area becoming two major concerns. Traditional SoC designs usually separate software and hardware. Thus, the process of improving the system performance is a complicated task for both software and hardware designers. The aim of this research is to develop hardware acceleration workflow for software applications. Thus, system performance can be improved with constraints of energy consumption and on-chip resource costs. The characteristics of software applications can be identified by using profiling tools. Hardware acceleration can have significant performance improvement for highly mathematical calculations or repeated functions. The performance of SoC systems can then be improved, if the hardware acceleration method is used to accelerate the element that incurs performance overheads. The concepts mentioned in this study can be easily applied to a variety of sophisticated software applications. The contributions of SoC-based hardware acceleration in the hardware-software co-design platform include the following: (1) Software profiling methods are applied to H.264 Coder-Decoder (CODEC) core. The hotspot function of aimed application is identified by using critical attributes such as cycles per loop, loop rounds, etc. (2) Hardware acceleration method based on Field-Programmable Gate Array (FPGA) is used to resolve system bottlenecks and improve system performance. The identified hotspot function is then converted to a hardware accelerator and mapped onto the hardware platform. Two types of hardware acceleration methods – central bus design and co-processor design, are implemented for comparison in the proposed architecture. (3) System specifications, such as performance, energy consumption, and resource costs, are measured and analyzed. The trade-off of these three factors is compared and balanced. Different hardware accelerators are implemented and evaluated based on system requirements. 4) The system verification platform is designed based on Integrated Circuit (IC) workflow. Hardware optimization techniques are used for higher performance and less resource costs. Experimental results show that the proposed hardware acceleration workflow for software applications is an efficient technique. The system can reach 2.8X performance improvements and save 31.84% energy consumption by applying the Bus-IP design. The Co-processor design can have 7.9X performance and save 75.85% energy consumption.

Noise in gallium nitride-based quantum well structures used for nanometer devices in the frequency range 1 Hz--3 Mhz and temperature range 77K--324K

Electronic noise has been investigated in AlxGa1−x N/GaN Modulation-Doped Field Effect Transistors (MODFETs) of submicron dimensions, grown for us by MBE (Molecular Beam Epitaxy) techniques at Virginia Commonwealth University by Dr. H. Morkoç and coworkers. Some 20 devices were grown on a GaN substrate, four of which have leads bonded to source (S), drain (D), and gate (G) pads, respectively. Conduction takes place in the quasi-2D layer of the junction (xy plane) which is perpendicular to the quantum well (z-direction) of average triangular width ∼3 nm. A non-doped intrinsic buffer layer of ∼5 nm separates the Si-doped donors in the AlxGa1−xN layer from the 2D-transistor plane, which affords a very high electron mobility, thus enabling high-speed devices. Since all contacts (S, D, and G) must reach through the AlxGa1−xN layer to connect internally to the 2D plane, parallel conduction through this layer is a feature of all modulation-doped devices. While the shunting effect may account for no more than a few percent of the current IDS, it is responsible for most excess noise, over and above thermal noise of the device. ^ The excess noise has been analyzed as a sum of Lorentzian spectra and 1/f noise. The Lorentzian noise has been ascribed to trapping of the carriers in the AlxGa1−xN layer. A detailed, multitrapping generation-recombination noise theory is presented, which shows that an exponential relationship exists for the time constants obtained from the spectral components as a function of 1/kT. The trap depths have been obtained from Arrhenius plots of log (τT2) vs. 1000/T. Comparison with previous noise results for GaAs devices shows that: (a) many more trapping levels are present in these nitride-based devices; (b) the traps are deeper (farther below the conduction band) than for GaAs. Furthermore, the magnitude of the noise is strongly dependent on the level of depletion of the AlxGa1−xN donor layer, which can be altered by a negative or positive gate bias VGS. ^ Altogether, these frontier nitride-based devices are promising for bluish light optoelectronic devices and lasers; however, the noise, though well understood, indicates that the purity of the constituent layers should be greatly improved for future technological applications. ^

System to predict bipolar disorder crises analysing massive data

Durante el desarrollo del proyecto he aprendido sobre Big Data, Android y MongoDB mientras que ayudaba a desarrollar un sistema para la predicción de las crisis del trastorno bipolar mediante el análisis masivo de información de diversas fuentes. En concreto hice una parte teórica sobre bases de datos NoSQL, Streaming Spark y Redes Neuronales y después diseñé y configuré una base de datos MongoDB para el proyecto del trastorno bipolar. También aprendí sobre Android y diseñé y desarrollé una aplicación de móvil en Android para recoger datos para usarlos como entrada en el sistema de predicción de crisis. Una vez terminado el desarrollo de la aplicación también llevé a cabo una evaluación con usuarios.

Thermal stability study of AlGaN/GaN MOS-HEMTs using Gd2O3 as gate dielectric

Thermal stability of AlGaN/GaN MOS-HEMTs and -diodes using Gd_(2)O_(3) are investigated by means of different thermal cycles and storage tests up to 500ºC for one week. IV DC and pulsed characteristics of the devices before and after the processes are evaluated and compared with conventional HEMTs. Results show that the devices with Gd_(2)O_(3) dielectric layer have lower leakage current and a more stable behavior during thermal treatment processes compared with conventional devices. In fact, an excellent on/off ratio of about 108 and a stable V_(t) is observed after storage at high temperature. The beneficial effects of Gd_(2)O_(3) on trapping effects of MOS-HEMTs are also dis-cussed.