Affective temperaments and neurocognitive functioning in bipolar disorder

Background: There is evidence that patients with bipolar disorder (BD) score higher on affective temperament ratings compared to healthy controls (HCs). Moreover, unaffected relatives demonstrate similar patterns as BD patients suggesting that such temperaments are related to the genetic risk for BD and may serve as endophenotypes for the disorder, It is unknown whether affective temperaments are associated with other core features of BD, such as impairments in neurocognition. This study examined the relationship between affective temperaments and neurocognition in patients with BD and in HCs. Methods: Temperaments were evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego, Auto-questionnaire version (TEMPS-A) in 64 patients with BD and 109 HCs. Neurocognitive functioning was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Correlational analyses between temperaments and cognition were conducted in BD and HC subjects. Results: Data suggest that affective temperaments and neurocognition are correlated. In BD higher ratings of cyclothymia and irritability were associated with better processing speed, working memory, reasoning and problem-solving. In the HC group, increased irritability was related to worse performance on measures of attention and social cognition. Limitations: Lack of functional outcome measures to evaluate the impact of temperaments and cognition on psychosocial functioning. It would be useful to test these findings on unaffected relatives of BD patients. Conclusions: Cyclothymic and irritable temperaments are correlated with specific aspects of neurocognition in BD. This study is among the few exploring the dimensional relationship between temperaments and cognition in BD, and provides preliminary evidence for future studies investigating the neural and genetic mechanisms underlying the association between these variables. (C) 2014 Elsevier By. All rights reserved

Independent modulation of engagement and connectivity of the facial network during affect processing by CACNA1C and ANK3 risk genes for bipolar disorder

IMPORTANCE: Genome-wide association studies (GWASs) indicate that single-nucleotide polymorphisms in the CACNA1C and ANK3 genes increase the risk for bipolar disorder (BD). The genes influence neuronal firing by modulating calcium and sodium channel functions, respectively. Both genes modulate γ-aminobutyric acid-transmitting interneuron function and can thus affect brain regional activation and interregional connectivity. OBJECTIVE: To determine whether the genetic risk for BD associated with 2 GWAS-supported risk single-nucleotide polymorphisms at CACNA1C rs1006737 and ANK3 rs10994336 is mediated through changes in regional activation and interregional connectivity of the facial affect-processing network. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional functional magnetic resonance imaging study at a research institute of 41 euthymic patients with BD and 46 healthy participants, all of British white descent. MAIN OUTCOMES AND MEASURES: Blood oxygen level-dependent signal and effective connectivity measures during the facial affect-processing task. RESULTS: In healthy carriers, both genetic risk variants were independently associated with increased regional engagement throughout the facial affect-processing network and increased effective connectivity between the visual and ventral prefrontal cortical regions. In contrast, BD carriers of either genetic risk variant exhibited pronounced reduction in ventral prefrontal cortical activation and visual-prefrontal effective connectivity. CONCLUSIONS AND RELEVANCE: Our data demonstrate that the effect of CACNA1C rs1006737 and ANK3 rs10994336 (or genetic variants in linkage disequilibrium) on the brain converges on the neural circuitry involved in affect processing and provides a mechanism linking BD to genome-wide genetic risk variants

Time Domain Regional Discriminants

The time and frequency domains are equivalent displays of seismic trace, information, though some qualities of the signal are more easily observed in one domain than the other. The relative frequency excitation of Lg, for instance, is most easily viewed in the frequency domain, but such waveform qualities as the sequence in which pulses arrive in the wave train or the sharpness of pulse onset are most easily studied in the time domain (Murphy and Bennett, 1982, Blandford, 1981). Because of the tremendous complexity of high frequency regional data, most attempts at using it for discrimination purposes have involved analysis of the frequency content of the various arrivals either through transforming selected windows or through multiple bandpass filtering. We report here on our initial attempts to explore the alternative and to discriminate events using those waveform characteristics most easily observed in the time domain. A second advantage of time domain analysis approaches is that they permit a deeper insight into the physical processes creating a seismic signal's character. For this reason, they can be more e3silv used to evaluate the transportabilty of a discriminant to varying geophysical and tectonic regimes. This is an especially important feature in the development of regional discriminants. The most prominent and successful spectral regional discriminants have been empirically developed. This means that they must be redeveloped and reverified in each new area. As we shall show in the following, through rigorous time domain analysis such features as regional depth phases can be identified and used to discriminate. Discriminants based on such simple physical features as source depth should be transportable anywhere. In work recently completed under the treaty verification program, we have proved that such time domain discriminants do exist. In analyzing a test discrimination data set from the western U. S., we have discovered that the onset of P_n is always very similar for explosions and that few earthquakes have this unique waveform character. This information can be constructed into a simple discrimination scheme by testing the correlation of observed P_n waveform onsets with average waveforms observed from explosions. High correlations indicate explosions and low correlations earthquakes. We have also discovered that the regional phase P_g is actually composed of a sequence of sub-arrivals which correspond to successively higher orders of reverberation in the crust. In realistic crust models, the depth phases play an important role in the waveshapes of these sub-arrivals. By selecting an appropriate frequency band to analyze, we have been able to accurately model this type of data from explosions in the western United States. Over the very relevant regional distance ranges of 200 to 600 km, it appears that a discrimination procedure very similar to the one which is known to work for P_n will also be effective for P_g. We are investigating whether similar discriminants can be constructed based on the phases S_n and S_g in areas where those phases are prominent arrivals

Time Domain Regional Discriminants

The time and frequency domains are equivalent displays of seismic trace, information, though some qualities of the signal are more easily observed in one domain than the other. The relative frequency excitation of Lg, for instance, is most easily viewed in the frequency domain, but such waveform qualities as the sequence in which pulses arrive in the wave train or the sharpness of pulse onset are most easily studied in the time domain (Murphy and Bennett, 1982, Blandford, 1981). Because of the tremendous complexity of high frequency regional data, most attempts at using it for discrimination purposes have involved analysis of the frequency content of the various arrivals either through transforming selected windows or through multiple bandpass filtering. We report here on our initial attempts to explore the alternative and to discriminate events using those waveform characteristics most easily observed in the time domain. A second advantage of time domain analysis approaches is that they permit a deeper insight into the physical processes creating a seismic signal's character. For this reason, they can be more e3silv used to evaluate the transportabilty of a discriminant to varying geophysical and tectonic regimes. This is an especially important feature in the development of regional discriminants. The most prominent and successful spectral regional discriminants have been empirically developed. This means that they must be redeveloped and reverified in each new area. As we shall show in the following, through rigorous time domain analysis such features as regional depth phases can be identified and used to discriminate. Discriminants based on such simple physical features as source depth should be transportable anywhere. In work recently completed under the treaty verification program, we have proved that such time domain discriminants do exist. In analyzing a test discrimination data set from the western U. S., we have discovered that the onset of P_n is always very similar for explosions and that few earthquakes have this unique waveform character. This information can be constructed into a simple discrimination scheme by testing the correlation of observed P_n waveform onsets with average waveforms observed from explosions. High correlations indicate explosions and low correlations earthquakes. We have also discovered that the regional phase P_g is actually composed of a sequence of sub-arrivals which correspond to successively higher orders of reverberation in the crust. In realistic crust models, the depth phases play an important role in the waveshapes of these sub-arrivals. By selecting an appropriate frequency band to analyze, we have been able to accurately model this type of data from explosions in the western United States. Over the very relevant regional distance ranges of 200 to 600 km, it appears that a discrimination procedure very similar to the one which is known to work for P_n will also be effective for P_g. We are investigating whether similar discriminants can be constructed based on the phases S_n and S_g in areas where those phases are prominent arrivals

Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications

Background. Recent data suggest trait-like neurocognitive impairments in bipolar disorder (BPD), with deficits about 1 S.D. below average, less severe than deficits noted in schizophrenia. The frequency of significant impairment in BPD is approximately 60%, with 40% of patients characterized as cognitively spared. This contrasts with a more homogeneous presentation in schizophrenia. It is not understood why some BPD patients develop deficits while others do not. Method. A total of 136 patients with BPD completed the MATRICS Consensus Cognitive Battery and data were entered into hierarchical cluster analyses to: (1) determine the optimal number of clusters (subgroups) that fit the sample; and (2) assign subjects to a specific cluster based on individual profiles. We then compared subgroups on several clinical factors and real-world community functioning. Results. Three distinct neurocognitive subgroups were found: (1) an intact group with performance comparable with healthy controls on all domains but with superior social cognition; (2) a selective impairment group with moderate deficits on processing speed, attention, verbal learning and social cognition and normal functioning in other domains; and (3) a global impairment group with severe deficits across all cognitive domains comparable with deficits in schizophrenia. Conclusions. These results suggest the presence of multiple cognitive subgroups in BPD with unique profiles and begin to address the relationships between these subgroups, several clinical factors and functional outcome. Next steps will include using these data to help guide future efforts to target these disabling symptoms with treatment

MATRICS cognitive consensus battery (MCCB) performance in children, adolescents, and young adults

Background: Neurodevelopmental models of schizophrenia suggest that cognitive deficits may be observed during childhood and adolescence, long before the onset of psychotic symptoms. Elucidating the trajectory of normal cognitive development during childhood and adolescence may therefore provide a basis for identifying specific abnormalities related to the development of schizophrenia. The MATRICS Consensus Cognitive Battery (MCCB), which was designed for use in clinical trials targeting cognitive deficits most common in schizophrenia, may provide a mechanism to understand this trajectory. To date, however, there is no performance data for the MCCB in healthy children and adolescents. The present study sought to establish performance data for the MCCB in healthy children, adolescents, and young adults. Methods: The MCCB was administered to a community sample of 190 healthy subjects between the ages of 8 and 23 years. All MCCB domain scores were converted to T-scores using sample means and standard deviations and were compared for significant performance differences between sex and age strata. Results: Analyses revealed age effects following quadratic trends in all MCCB domains, which is consistent with research showing a leveling off of childhood cognitive improvement upon approaching late adolescence. Sex effects after controlling for age only presented for one MCCB domain, with males exhibiting well-known spatial reasoning advantages. Conclusions: Utilizing this performance data may aid future research seeking to elucidate specific deficits that may be predictive of later development of SZ. (C) 2013 Elsevier B.V. All rights reserved

Age-associated alterations in corpus callosum white matter integrity in bipolar disorder assessed using probabilistic tractography

OBJECTIVES: Atypical age-associated changes in white matter integrity may play a role in the neurobiology of bipolar disorder, but no studies have examined the major white matter tracts using nonlinear statistical modeling across a wide age range in this disorder. The goal of this study was to identify possible deviations in the typical pattern of age-associated changes in white matter integrity in patients with bipolar disorder across the age range of 9-62 years. METHODS: Diffusion tensor imaging was performed in 57 (20 male and 37 female) patients with a diagnosis of bipolar disorder and 57 (20 male and 37 female) age- and sex-matched healthy volunteers. Mean diffusivity and fractional anisotropy were computed for the genu and splenium of the corpus callosum, two projection tracts, and five association tracts using probabilistic tractography. RESULTS: Overall, patients had lower fractional anisotropy and higher mean diffusivity compared to healthy volunteers across all tracts (while controlling for the effects of age and age2 ). In addition, there were greater age-associated increases in mean diffusivity in patients compared to healthy volunteers within the genu and splenium of the corpus callosum beginning in the second and third decades of life. CONCLUSIONS: Our findings provide evidence for alterations in the typical pattern of white matter development in patients with bipolar disorder compared to healthy volunteers. Changes in white matter development within the corpus callosum may lead to altered inter-hemispheric communication that is considered integral to the neurobiology of the disorder

Pollen-Mediated Gene Flow from Genetically Modified Herbicide Resistant Creeping Bentgrass

Approximately 162 ha of multiple experimental fields of creeping bentgrass (Agrostis stolonifera L.) genetically modified for resistance to Roundup ®herbicide, were planted in central Oregon in 2002. When the fields flowered for the first time in the summer of 2003, a unique opportunity was presented to evaluate methods to monitor potential pollen-mediated gene flow from the experimental GM crop fields to compatible sentinel and resident plants that were located in surrounding, primarily non-agronomic areas

Interaction Properties of the Periodic and Step-like Solutions of the Double-Sine-Gordon Equation

The periodic and step-like solutions of the double-Sine-Gordon equation are investigated, with different initial conditions and for various values of the potential parameter $\epsilon$. We plot energy and force diagrams, as functions of the inter-soliton distance for such solutions. This allows us to consider our system as an interacting many-body system in 1+1 dimension. We therefore plot state diagrams (pressure vs. average density) for step-like as well as periodic solutions. Step-like solutions are shown to behave similarly to their counterparts in the Sine-Gordon system. However, periodic solutions show a fundamentally different behavior as the parameter $\epsilon$ is increased. We show that two distinct phases of periodic solutions exist which exhibit manifestly different behavior. Response functions for these phases are shown to behave differently, joining at an apparent phase transition point.Comment: 17pages, 15 figure