Perseveration and Shifting in Obsessive-Compulsive Disorder as a Function of Uncertainty, Punishment, and Serotonergic Medication

© 2023 The Author(s). Published by Elsevier Inc on behalf of the Society of Biological Psychiatry. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background The nature of cognitive flexibility deficits in obsessive-compulsive disorder (OCD), which historically have been tested with probabilistic reversal learning tasks, remains elusive. Here, a novel deterministic reversal task and inclusion of unmedicated patients in the study sample illuminated the role of fixed versus uncertain rules/contingencies and of serotonergic medication. Additionally, our understanding of probabilistic reversal was enhanced through theoretical computational modeling of cognitive flexibility in OCD. Methods We recruited 49 patients with OCD, 21 of whom were unmedicated, and 43 healthy control participants matched for age, IQ, and gender. Participants were tested on 2 tasks: a novel visuomotor deterministic reversal learning task with 3 reversals (feedback rewarding/punishing/neutral) measuring accuracy/perseveration and a 2-choice visual probabilistic reversal learning task with uncertain feedback and a single reversal measuring win-stay and lose-shift. Bayesian computational modeling provided measures of learning rate, reinforcement sensitivity, and stimulus stickiness. Results Unmedicated patients with OCD were impaired on the deterministic reversal task under punishment only at the first and third reversals compared with both control participants and medicated patients with OCD, who had no deficit. Perseverative errors were correlated with OCD severity. On the probabilistic reversal task, unmedicated patients were only impaired at reversal, whereas medicated patients were impaired at both the learning and reversal stages. Computational modeling showed that the overall change was reduced feedback sensitivity in both OCD groups. Conclusions Both perseveration and increased shifting can be observed in OCD, depending on test conditions including the predictability of reinforcement. Perseveration was related to clinical severity and remediated by serotonergic medication.Peer reviewe

Serotonin depletion amplifies distinct human social emotions as a function of individual differences in personality

Funder: Gates Cambridge Trust; doi: https://doi.org/10.13039/501100005370Abstract: Serotonin is involved in a wide range of mental capacities essential for navigating the social world, including emotion and impulse control. Much recent work on serotonin and social functioning has focused on decision-making. Here we investigated the influence of serotonin on human emotional reactions to social conflict. We used a novel computerised task that required mentally simulating social situations involving unjust harm and found that depleting the serotonin precursor tryptophan—in a double-blind randomised placebo-controlled design—enhanced emotional responses to the scenarios in a large sample of healthy volunteers (n = 73), and interacted with individual differences in trait personality to produce distinctive human emotions. Whereas guilt was preferentially elevated in highly empathic participants, annoyance was potentiated in those high in trait psychopathy, with medium to large effect sizes. Our findings show how individual differences in personality, when combined with fluctuations of serotonin, may produce diverse emotional phenotypes. This has implications for understanding vulnerability to psychopathology, determining who may be more sensitive to serotonin-modulating treatments, and casts new light on the functions of serotonin in emotional processing

Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans.

Funder: Gates Cambridge Trust; doi: https://doi.org/10.13039/501100005370Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Serotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.NIH

Community Health Centers: The Untapped Resource for Public Health and Medical Preparedness

This article appeared in Homeland Security Affairs (January 2009), v.5 no.1HSPD-21 was recently released to the public calling for a transformation in the national approach to public health and medical preparedness in the United States. The latest deliberations, as prioritized by this strategy, are to bolster the nation's ability to manage a public health crisis by stimulating improvements in the areas of biosurveillance, countermeasure distribution, mass casualty care, and community resilience -- the objective being to create a much more tightly integrated systems approach toward public health and medical preparedness. Community Health Centers (CHCs), by philosophic orientation, geographic location, and as publicly-funded entities, are well-positioned to provide medical services, education, and other human services to prevent, prepare for, respond to, mitigate, and recover from the public health impact of a bioterrorist event or other biological disease outbreak. Aggressive investment in CHCs and their emergency management programs serves a dual purpose that will (1) create greater social equity by reducing health disparities and make public health emergency management more accessible to special needs populations and (2) support many of the objectives identified in the Public Health and Medical Preparedness Strategy.Approved for public release; distribution is unlimited

Borehole dilution tests to measure leachate flow at a recirculation landfill

The recirculation and infiltration of leachate in landfills may be carried out to facilitate the flushing of contaminants and accelerate the stabilisation of waste. Flushing contaminants through recirculation relies on the movement of fluids through the landfill body to basal drains, which will predominantly be driven by gravity. Leachate recirculation and infiltration measures commenced at de Kragge II landfill (Bergen op Zoom, The Netherlands) in March 2018. Up to 90 m3/day of treated leachate is recirculated into the top of a 20 m deep, 5 ha landfill cell through 14 horizontal drains installed at the surface. Poor connectivity between the waste and the basal drainage system has resulted in saturated conditions forming in the lower 7-8 m of the landfill. Knowledge about the leachate flow within the waste body is essential for evaluating the success of the stabilisation measures. To investigate the flow regime within the saturated waste, 22 Single Borehole Dilution tests were carried out in 13 piezometers atdifferent depths, between 8.4 and 18.1 m below ground level, and locations across the landfill cell. Tests were repeated in a number of the piezometers to demonstrate repeatability. Flow was measured in all piezometers. Calculated Darcy flow velocities ranged between 0.01 and 1.02 m/day, with the highestvelocities measured in the deepest piezometers. Four tests were carried out in one nest of piezometers installed at different depths, with the leachate recirculation system switched off for two days prior to and during the test. Although flows were somewhat higher in two of the piezometers, it was not possible to conclude whether the infiltration of leachate significantly influences flow