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The main aim of this study is to investigate the capacity of a number of variables from four dimensions (clinical, psychosocial, cognitive and genetic domains) to predict the antidepressant treatment outcome, and combined the predictors in one integrate regression model with the aim to investigate which predictor contributed most.
Methods
In a semi-naturalistic prospective cohort study with a total of 241 fully assessed MDD patients, decrease in HAM-D scores from baseline to after 6 weeks of treatment was used to measure the antidepressant treatment outcome.
Results
The clinical and psychosocial model (R2 = 0.451) showed that HAM-D scores at baseline and MMPI-2 scale paranoia was the best clinical and psychosocial predictor of treatment outcome respectively. The cognitive model (R2 = 0.502) revealed that combination of better performance on TMT-B test and worse performance on TOH and WAIS-R Digit Backward testes could predict decline in HAM-D scores. The genetics analysis only found median of percent improvement in HAM-D scores in G-allele of GR gene BclI polymorphism carriers (72.2%) was significant lower than that in non-G allele carriers (80.1%). The integrate model showed that three predictors, combination of HAM-D scores at baseline, MMPI-2 scale paranoia and TMT-B test, explained 57.1% of the variance.
Conclusion
Three markers, HAM-D scores at baseline, MMPI-2 scale paranoia and TMT-B test, might serve as predictor of antidepressant outcome in daily psychiatric practice.
Thirty-one accessions of Oryza glaberrima were evaluated to study the genetic variability, correlation, path, principal component analysis (PCA) and D2 analysis. Box plots depicted high estimates of variability for days to 50% flowering and grain yield per plant in Kharif 2016, plant height, productive tillers, panicle length and 1000 seed weight in Kharif 2017. Correlation studies revealed days to 50% flowering, plant height, panicle length, number of productive tillers, spikelets per panicle having a high direct positive association with grain yield, while path analysis identified the number of productive tillers having the maximum direct positive effect on grain yield. Days to 50% flowering via spikelets per panicle, productive tillers and plant height via spikelets per panicle exhibited high positive indirect effects on grain yield per plant. PCA showed that a cumulative variance of 54.752% from yield per plant, days to 50% flowering, spikelets per panicle and panicle length, contributing almost all the variation of traits while D2 analysis identified days to 50% flowering and grain yield per plant contributing maximum to the genetic diversity. Therefore, selection of accessions with more number of productive tillers and early maturity would be most suitable for yield improvement programme. The study has revealed the utility of African rice germplasm and its potential to utilize in the genetic improvement of indica rice varieties.
Association mapping (AM), an alternative method of quantitative trait loci (QTL) discovery, exploits historic linkage disequilibrium (LD) present in natural populations. AM is effective in self-pollinated crops such as Dolichos bean as LD extends over longer genomic distance driven-by low rate of recombination and thereby requiring fewer markers for exploring marker-traits associations. A core set of Dolichos bean germplasm consisting of 64 accessions was evaluated for nine quantitative traits (QTs) during 2014 and 2015 rainy seasons and genotyped using 234 simple sequence repeats (SSR) markers. Substantial diversity was observed among the core set accessions at loci controlling QTs and 95 of the 234 SSR markers were found polymorphic. The structure analysis and low magnitude of fixation indices suggested weak population structure, which in-turn indicated the low possibility of false discovery rates in the marker-QTs association. The marker allele's scores were regressed onto phenotypes at nine QTs following general linear model and mixed linear model for exploring marker-QTs associations. Significantly higher number of SSR markers was found associated with genomic regions controlling nine QTs. A few of the markers such as KT Dolichos (KTD) 200 for days to 50% flowering, KTD 273 for fresh pod yield per plant and KTD 130 for fresh pods per plant explained ≥10% of the trait variations. The study could also identify a few SSR markers such as KTD 273, KTD 271 and KTD 130 linked to multiple traits. These linked SSR markers are suggested for validation for their use in marker-assisted Dolichos bean improvement programmes.
This study was conducted to characterize new plant type (NPT) traits among 650 genetically diverse rice genotypes of tropical japonica and indica and to establish an initial core set for NPT traits. Analysis of variance revealed highly significant differences among the genotypes for all the traits assessed except flag length and width and leaf angles. Dendrogram categorized the genotypes into five distinct duration groups. Genotypes viz., Pumphamah, IRGC5097, IRGC37015, IRGC43741, IRGC50448, IRGC53089, IRGC39111, IRGC18021, Haorei Machang, IRGC44069, IRGC8269, Thangmoi, IRGC33130 and IRGC29772 were identified as possessing strong culm. Long panicles with a length of more than 35 cm were found in IRGC8269, IRGC9147, IRGC14694, IRGC19642, IRGC27435, IRGC39111, IRGC31051, IRGC26011and IRGC25892. Ideal leaf angle of NPT genotypes of 5°, 10° and 20° of flag leaf, 1st and 2nd leaves was not found in any genotype but with a combination of 5°, 10° and 10° was observed in IRGC63102 and IRGC66644. NPT flag leaf length and width of 50 and 2 cm, respectively, was seen in ‘Kemenya Kepeu’ and ‘IRGC29772’. High grain number of more than 350 was observed in IRGC53089, IRGC31063 and Azhoghi. A total of 72 genotypes were found with a combination of one or more ideal plant type traits of which, hierarchical cluster analysis based on genetic distances selected 32 as NPT core set. This core set will serve as an ideal genetic resource for breeding programs aimed at NPT development.
Outpatient parenteral antimicrobial therapy (OPAT) programmes facilitate hospital discharge, but patients remain at risk of complications and consequent healthcare utilisation (HCU). Here we elucidated the incidence of and risk factors associated with HCU in OPAT patients. This was a retrospective, single-centre, case–control study of adult patients discharged on OPAT. Cases (n = 63) and controls (n = 126) were patients that did or did not utilise the healthcare system within 60 days. Characteristics associated with HCU in bivariate analysis (P ≤ 0.2) were included in a multivariable logistic regression model. Variables were retained in the final model if they were independently (P < 0.05) associated with 60-day HCU. Among all study patients, the mean age was 55 ± 16, 65% were men, and wound infection (22%) and cellulitis (14%) were common diagnoses. The cumulative incidence of 60-day unplanned HCU was 27% with a disproportionately higher incidence in the first 30 days (21%). A statin at discharge (adjusted odds ratios (aOR) 0.23, 95% confidence intervals (CIs) 0.09–0.57), number of prior admissions in past 12 months (aOR 1.48, 95% CIs 1.05–2.10), and a sepsis diagnosis (aOR 4.62, 95% CIs 1.23–17.3) were independently associated with HCU. HCU was most commonly due to non-infection related complications (44%) and worsening primary infection (31%). There are multiple risk factors for HCU in OPAT patients, and formal OPAT clinics may help to risk stratify and target the highest risk groups.
Although dementia has been described in ancient texts over many centuries (e.g., “Be kind to your father, even if his mind fail him.” – Old Testament: Sirach 3:12), our knowledge of its underlying causes is little more than a century old. Alzheimer published his now famous case study only 110 years ago, and our modern understanding of the disease that bears his name, and its neuropsychological consequences, really only began to accelerate in the 1980s. Since then we have witnessed an explosion of basic and translational research into the causes, characterizations, and possible treatments for Alzheimer’s disease (AD) and other dementias. We review this lineage of work beginning with Alzheimer’s own writings and drawings, then jump to the modern era beginning in the 1970s and early 1980s and provide a sampling of neuropsychological and other contextual work from each ensuing decade. During the 1980s our field began its foundational studies of profiling the neuropsychological deficits associated with AD and its differentiation from other dementias (e.g., cortical vs. subcortical dementias). The 1990s continued these efforts and began to identify the specific cognitive mechanisms affected by various neuropathologic substrates. The 2000s ushered in a focus on the study of prodromal stages of neurodegenerative disease before the full-blown dementia syndrome (i.e., mild cognitive impairment). The current decade has seen the rise of imaging and other biomarkers to characterize preclinical disease before the development of significant cognitive decline. Finally, we suggest future directions and predictions for dementia-related research and potential therapeutic interventions. (JINS, 2017, 23, 818–831)
Cannabis use has been linked to impairments in neuropsychological functioning across a large and continually expanding body of research. Yet insight into underlying causal relations remains limited due to the historically cross-sectional nature of studies in this area. Recently, however, studies have begun to use more informative design strategies to delineate these associations. The aim of this article is to provide a critical evaluation and review of research that uses longitudinal designs to examine the link between cannabis use and neuropsychological functioning. In summarizing the primary findings across these studies, this review suggests that cannabis use leads to neuropsychological decline. However, across most studies, these associations were modest, were present only for the group with the heaviest cannabis use, and were often attenuated (or no longer significant) after controlling for potential confounding variables. Future studies with neuropsychological data before and after initiation of cannabis use, along with careful measurement and control of “shared risk factors” between cannabis use and poorer neuropsychological outcomes, are needed to better understand who, and under what conditions, is most vulnerable to cannabis-associated neuropsychological decline. (JINS, 2017, 23, 893–902)
Hemispheric asymmetry is commonly viewed as a dual system, unique to humans, with the two sides of the human brain in complementary roles. To the contrary, modern research shows that cerebral and behavioral asymmetries are widespread in the animal kingdom, and that the concept of duality is an oversimplification. The brain has many networks serving different functions; these are differentially lateralized, and involve many genes. Unlike the asymmetries of the internal organs, brain asymmetry is variable, with a significant minority of the population showing reversed asymmetries or the absence of asymmetry. This variability may underlie the divisions of labor and the specializations that sustain social life. (JINS, 2017, 23, 710–718)
An ambition of depression biomarker research is to augment psychometric and cognitive assessment of clinically relevant phenomena with neural measures. Although such applications have been slow to arrive, we observe a steady evolution of the idea and anticipate emerging technologies with some optimism. To highlight critical themes and innovations in depression biomarker research, we take as our point of reference a specific research narrative. We begin with an early model of frontal-limbic dysfunction, which represents a conceptual shift from localized pathology to understanding symptoms as an emergent property of distributed networks. Over the decades, this model accommodates perspectives from neurology, psychiatry, clinical, and cognitive neuroscience, and preserves past insight as more complex methods become available. We also track the expanding mission of brain biomarker research: from the development of diagnostic tools to treatment selection algorithms, measures of neurocognitive functioning and novel targets for neuromodulation. To conclude, we draw from this particular research narrative future directions for biomarker research. We emphasize integration of measurement modalities to describe dynamic change in domain-general networks, and we speculate that a brain-based framework for psychiatric problems may dissolve classical diagnostic and disciplinary boundaries. (JINS, 2017, 23, 870–880)
Common bean (Phaseolus vulgaris L.) is the most important food legume for human consumption. Drought stress is the major abiotic stress limitation of bean yields in smallholder farming systems worldwide. The current work aimed to determine the role of enhanced photosynthate mobilization to improve adaptation to intermittent and terminal drought stress and to identify a few key adaptive traits that can be used for developing drought-resistant genotypes. Field studies were conducted over three seasons at Centro Internacional de Agricultura Tropical, Palmira, Colombia to determine genotypic differences in adaptation to intermittent (two seasons) and terminal (one season) drought stress compared with irrigated conditions. A set of 36 genotypes, including 33 common bean, two wild bean and one cowpea were evaluated using a 6 × 6 lattice design under irrigated and rainfed field conditions. Three common bean elite lines (NCB 226, SEN 56, SER 125) were identified with superior levels of adaptation to both intermittent and terminal drought stress conditions. The greater performance of these lines under drought stress was associated with their ability to remobilize photosynthate to increase grain yield based on higher values of harvest index, pod harvest index, leaf area index and canopy biomass. Two wild bean germplasm accessions (G 19902, G 24390) showed very poor adaptation to both types of drought stress. One small-seeded black line (NCB 226) was superior in combining greater values of canopy biomass with greater ability to mobilize photosynthates to grain under both types of drought stress. Two small-seeded red lines (SER 78, SER 125) seem to combine the desirable traits of enhanced mobilization of photosynthates to seed with effective use of water through canopy cooling under terminal drought stress. Pod harvest index showed significant positive association with grain yield under both types of drought stress and this trait can be used by breeders as an additional selection method to grain yield in evaluation of breeding populations for both types of drought stress.
Objectives: White matter (WM) integrity within the mesial temporal lobe (MTL) is important for episodic memory (EM) functioning. The current study investigated the ability of diffusion tensor imaging (DTI) in MTL WM tracts to predict 3-year changes in EM performance in healthy elders at disproportionately higher genetic risk for Alzheimer’s disease (AD). Methods: Fifty-one cognitively intact elders (52% with family history (FH) of dementia and 33% possessing an Apolipoprotein E ε4 allelle) were administered the Rey Auditory Verbal Learning Test (RAVLT) at study entry and at 3-year follow-up. DTI scanning, conducted at study entry, examined fractional anisotropy and mean, radial and axial diffusion within three MTL WM tracts: uncinate fasciculus (UNC), cingulate-hippocampal (CHG), and fornix-stria terminalis (FxS). Correlations were performed between residualized change scores computed from RAVLT trials 1–5, immediate recall, and delayed recall scores and baseline DTI measures; MTL gray matter (GM) and WM volumes; demographics; and AD genetic and metabolic risk factors. Results: Higher MTL mean and axial diffusivity at baseline significantly predicted 3-year changes in EM, whereas baseline MTL GM and WM volumes, FH, and metabolic risk factors did not. Both ε4 status and DTI correlated with change in immediate recall. Conclusions: Longitudinal EM changes in cognitively intact, healthy elders can be predicted by disruption of the MTL WM microstructure. These results are derived from a sample with a disproportionately higher genetic risk for AD, suggesting that the observed WM disruption in MTL pathways may be related to early neuropathological changes associated with the preclinical stage of AD. (JINS, 2016, 22, 1005–1015)
Fast photometric observations of a nova-like variable KR Aurigae and the intermediate polar BG CMi (3A0729+103) were made in the B and U bands during 1984–89 to study pulsations in them. The light curves of KR Aur show large amplitude quasi-periodic pulsations with periods in the range 500–800s which can be ascribed to inhomogeneities in the accretion disc. The light curves of the X-ray emitting intermediate polar BG CMi show variable amplitude pulsations with 913s period. From the times of maxima of the pulsations obtained from observations over the period 1984–1989, the pulsation period is derived to be 0.010572966 ± 8 days and the spin-up rate to be (−5.7 ± 0.5) × 10−11 ss−1. The spin-up rate is consistent with the pulsating source being a white dwarf and not a neutron star.
Objectives: Individuals with major depressive disorder (MDD) demonstrate poorer learning and memory skills relative to never-depressed comparisons (NDC). Previous studies report decreased volume and disrupted function of frontal lobes and hippocampi in MDD during memory challenge. However, it has been difficult to dissociate contributions of short-term memory and executive functioning to memory difficulties from those that might be attributable to long-term memory deficits. Methods: Adult males (MDD, n=19; NDC, n=22) and females (MDD, n=23; NDC, n=19) performed the Semantic List Learning Task (SLLT) during functional magnetic resonance imaging. The SLLT Encoding condition consists of 15 lists, each containing 14 words. After each list, a Distractor condition occurs, followed by cued Silent Rehearsal instructions. Post-scan recall and recognition were collected. Groups were compared using block (Encoding-Silent Rehearsal) and event-related (Words Recalled) models. Results: MDD displayed lower recall relative to NDC. NDC displayed greater activation in several temporal, frontal, and parietal regions, for both Encoding-Silent Rehearsal and the Words Recalled analyses. Groups also differed in activation patterns in regions of the Papez circuit in planned analyses. The majority of activation differences were not related to performance, presence of medications, presence of comorbid anxiety disorder, or decreased gray matter volume in MDD. Conclusions: Adults with MDD exhibit memory difficulties during a task designed to reduce the contribution of individual variability from short-term memory and executive functioning processes, parallel with decreased activation in memory and executive functioning circuits. Ecologically valid long-term memory tasks are imperative for uncovering neural correlates of memory performance deficits in adults with MDD. (JINS, 2016, 22, 412–425)
Objectives: Individuals with chronic traumatic brain injury (TBI) often show detrimental deficits in higher order cognitive functions requiring coordination of multiple brain networks. Although assessing TBI-related deficits in higher order cognition in the context of network dysfunction is promising, few studies have systematically investigated altered interactions among multiple networks in chronic TBI. Method: We characterized disrupted resting-state functional connectivity of the default mode network (DMN), dorsal attention network (DAN), and frontoparietal control network (FPCN) whose interactions are required for internally and externally focused goal-directed cognition in chronic TBI. Specifically, we compared the network interactions of 40 chronic TBI individuals (8 years post-injury on average) with those of 17 healthy individuals matched for gender, age, and years of education. Results: The network-based statistic (NBS) on DMN-DAN-FPCN connectivity of these groups revealed statistically significant (pNBS<.05; |Z|>2.58) reductions in within-DMN, within-FPCN, DMN-DAN, and DMN-FPCN connectivity of the TBI group over healthy controls. Importantly, such disruptions occurred prominently in between-network connectivity. Subsequent analyses further exhibited the disrupted connectivity patterns of the chronic TBI group occurring preferentially in long-range and inter-hemispheric connectivity of DMN-DAN-FPCN. Most importantly, graph-theoretic analysis demonstrated relative reductions in global, local and cost efficiency (p<.05) as a consequence of the network disruption patterns in the TBI group. Conclusion: Our findings suggest that assessing multiple networks-of-interest simultaneously will allow us to better understand deficits in goal-directed cognition and other higher order cognitive phenomena in chronic TBI. Future research will be needed to better understand the behavioral consequences related to these network disruptions. (JINS, 2016, 22, 263–279)
Objectives: Cognitive impairment is common in Parkinson’s disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. Methods: We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. Results: PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson’s disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. Conclusions: Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson’s disease. (JINS, 2016, 22, 205–215)
Objectives: The purpose of this study was to assess whether age-related differences in white matter microstructure are associated with altered task-related connectivity during episodic recognition. Methods: Using functional magnetic resonance imaging and diffusion tensor imaging from 282 cognitively healthy middle-to-late aged adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention, we investigated whether fractional anisotropy (FA) within white matter regions known to decline with age was associated with task-related connectivity within the recognition network. Results: There was a positive relationship between fornix FA and memory performance, both of which negatively correlated with age. Psychophysiological interaction analyses revealed that higher fornix FA was associated with increased task-related connectivity amongst the hippocampus, caudate, precuneus, middle occipital gyrus, and middle frontal gyrus. In addition, better task performance was associated with increased task-related connectivity between the posterior cingulate gyrus, middle frontal gyrus, cuneus, and hippocampus. Conclusions: The findings indicate that age has a negative effect on white matter microstructure, which in turn has a negative impact on memory performance. However, fornix microstructure did not significantly mediate the effect of age on performance. Of interest, dynamic functional connectivity was associated with better memory performance. The results of the psychophysiological interaction analysis further revealed that alterations in fornix microstructure explain–at least in part–connectivity among cortical regions in the recognition memory network. Our results may further elucidate the relationship between structural connectivity, neural function, and cognition. (JINS, 2016, 22, 191–204)
A growing body of literature has explored the influence of physical activity on brain structure and function. While the mechanisms of this relationship remain largely speculative, recent research suggests that one of the effects of physical exercise is an increase in synaptic long-term potentiation (LTP). This has not yet been explored directly in humans due to the difficulty of measuring LTP non-invasively. However, we have previously established that LTP-like changes in visual-evoked potentials (VEPs) can be measured in humans. Here, we investigated whether physical fitness status affects the degree of visual sensory LTP. Using a self-report measure of physical activity, participants were split into two groups: a high-activity group, and a low-activity group. LTP was measured and compared between the two groups using the previously established electroencephalography-LTP paradigm, which assesses the degree to which the N1b component of the VEP elicited by a sine grating is potentiated (enhanced) following a rapid “tetanic” presentation of that grating. Both groups demonstrated increased negativity in the amplitude of the N1b component of the VEP immediately after presentation of the visual “tetanus,” indicating potentiation. However, after a 30-min rest period, the N1b for the high-activity group remained potentiated while the N1b for the low-activity group returned to baseline. This study presents the first evidence for the impact of self-reported levels of physical activity on LTP in humans, and sheds light on potential neurological mechanisms underlying the relationship between physical fitness and cognition. (JINS, 2015, 21, 831–840)
The effects of acute aerobic exercise on cognitive functions in humans have been the subject of much investigation; however, these studies are limited by several factors, including a lack of randomized controlled designs, focus on only a single cognitive function, and testing during or shortly after exercise. Using a randomized controlled design, the present study asked how a single bout of aerobic exercise affects a range of frontal- and medial temporal lobe-dependent cognitive functions and how long these effects last. We randomly assigned 85 subjects to either a vigorous intensity acute aerobic exercise group or a video watching control group. All subjects completed a battery of cognitive tasks both before and 30, 60, 90, or 120 min after the intervention. This battery included the Hopkins Verbal Learning Test-Revised, the Modified Benton Visual Retention Test, the Stroop Color and Word Test, the Symbol Digit Modalities Test, the Digit Span Test, the Trail Making Test, and the Controlled Oral Word Association Test. Based on these measures, composite scores were formed to independently assess prefrontal cortex- and hippocampal-dependent cognition. A three-way mixed Analysis of Variance was used to determine whether differences existed between groups in the change in cognitive function from pre- to post-intervention testing. Acute exercise improved prefrontal cortex- but not hippocampal-dependent functioning, with no differences found between delay groups. Vigorous acute aerobic exercise has beneficial effects on prefrontal cortex-dependent cognition and these effects can last for up to 2 hr after exercise. (JINS, 2015, 21, 791–801)
The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841–850)