Effects of acute tryptophan depletion on executive function in healthy male volunteers

BACKGROUND: Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT) levels using the method of acute tryptophan depletion (ATD). METHODS: Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood. RESULTS: Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P < 0.001). ATD selectively improved motor speed/ attention on the Trails A test (P = 0.027), with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests. CONCLUSIONS: The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions

The neural substrate of positive bias in spontaneous emotional processing

Even in the presence of negative information, healthy human beings display an optimistic tendency when thinking of past success and future chances, giving a positive bias to everyday's cognition. The tendency to actively select positive thoughts suggests the existence of a mechanism to exclude negative content, raising the issue of its dependence on mechanisms like those of effortful control. Using perfusion imaging, we examined how brain activations differed according to whether participants were left to prefer positive thoughts spontaneously, or followed an explicit instruction to the same effect, finding a widespread dissociation of brain perfusion patterns. Under spontaneous processing of emotional material, recruitment of areas associated with effortful attention, such as the dorsolateral prefrontal cortex, was reduced relative to instructed avoidance of negative material (F(1,58) = 26.24, p = 0.047, corrected). Under spontaneous avoidance perfusion increments were observed in several areas that were deactivated by the task, including the perigenual medial prefrontal cortex. Furthermore, individual differences in executive capacity were not associated with positive bias. These findings suggest that spontaneous positive cognitive emotion regulation in health may result from processes that, while actively suppressing emotionally salient information, differ from those associated with effortful and directed control

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging

Mercury Spikes Indicate a Volcanic Trigger for the Late Ordovician Mass Extinction Event: An Example from a Deep Shelf of the Peri-Baltic Region.

The Late Ordovician mass extinction (LOME) was the second largest Phanerozoic crisis, but its cause remains elusive. Several triggering mechanisms have been proposed over the years, including bioevolutionary events, oceanographic changes, and geotectonic processes. Here, we report the presence of Hg spikes in the Zbrza PIG-1 borehole from the Upper Ordovician deep shelf sections of the peri-Baltic region. A strong positive anomaly in the lower late Katian (Hg/TOC = 2537.3 ppb/wt%) was noted. No correlation between Hg and TOC (R² = 0.07) was distinguished in the Hirnantian, although several positive anomalies were found. Because the Hg/Mo ratio showed trends very similar to those of Hg/TOC, it seems likely that TOC values reflect the redox conditions. In order to evaluate the role of anoxia in levels of Hg enrichment several redox indicators were measured. These showed that the elevated mercury values in the Hirnantian are not caused by anoxia/euxinia because euxinic biomarkers (maleimides and aryl isoprenoids) are present in very low abundance and pyrite framboids are absent. In total, positive Hg/TOC anomalies occur in the lower late Katian, at the Katian - Hirnantian boundary, and in the late Hirnantian. The lack of a strong Hg/TOC correlation, Ni enrichments, and the absence of 'anoxic indicators' (no biomarkers, no framboids, low Mo concentration) at these levels, supports the interpretation that Hg enrichment is due to enhanced environmental loading. We conclude that our Hg and Hg/TOC values were associated with volcanic pulses which triggered the massive environmental changes resulting in the Late Ordovician mass extinction

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging