Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series.

Psychiatric adverse drug reactions (ADRs) have been reported with statin use, but the literature regarding statin-associated mood/behavioral changes remains limited. We sought to elicit information germane to natural history and characteristics of central nervous system/behavioral changes in apparent connection with statin and/or cholesterol-lowering drug use, and delineate mechanisms that may bear on an association. Participants (and/or proxies) self-referred with behavioral and/or mood changes in apparent association with statins completed a survey eliciting cholesterol-lowering drug history, character and impact of behavioral/mood effect, time-course of onset and recovery in relation to drug use/modification, co-occurrence of recognized statin-associated ADRs, and factors relevant to ADR causality determination. Naranjo presumptive ADR causality criteria were assessed. Participants (n = 12) reported mood/behavior change that commenced following statin initiation and persisted or progressed with continued use. Reported problems included violent ideation, irritability, depression, and suicide. Problems resolved with drug discontinuation and recurred with rechallenge where attempted. Eight met presumptive criteria for "probable" or "definite" causality; others had additional factors not considered in Naranjo criteria that bear on casual likelihood. (1) Simvastatin 80 mg was followed in 5 days by irritability/depression culminating in suicide in a man in his 40s (Naranjo criteria: possible causality). (2) Simvastatin 10 mg was followed within 2 weeks by depression in a woman in her 50s (probable causality). (3) Atorvastatin 20 mg was followed in ~1 month by depression and irritability/aggression in a male in his 50s (probable causality). (4) Atorvastatin 10 mg was followed in several months by aggression/irritability and depression culminating in suicide in a man in his 40s (possible causality). (5) Fenofibrate + rosuvastatin (unknown dose), later combined with atorvastatin were followed in 1 month by aggression/irritability in a male in his 30s (probable causality). (6) Lovastatin (unknown dose and time-course to reaction) was followed by depression, dyscontrol of bipolar disorder, and suicide attempts in a male in his 40s (possible causality). (7) Atorvastatin 20 mg was followed within 2 weeks by cognitive compromise, and nightmares, depression, and anxiety culminating in suicide in a man in his teens (definite causality). (8) Simvastatin 10 mg was followed (time-course not recalled) by depression, aggression/irritability culminating in suicide in a man in his 60s (possible causality). (9) Simvastatin 20 mg then atorvastatin 10 mg were followed (time-course not provided) by irritability/aggression in a man in his 60s (definite causality). (10) Atorvastatin 10 then 20 then 40 mg were followed shortly after the dose increase by violent ideation and anxiety in a man in his 30s (probable causality). (11) Atorvastatin 20 mg and then simvastatin 20 mg were followed in 2 weeks by aggression/irritability in a man in his 50s (definite causality). (12) Lovastatin, rosuvastatin, atorvastatin, and simvastatin at varying doses were followed as quickly as 1 day by aggression, irritability, and violent ideation in a man in his 40s (definite causality). Most had risk factors for statin ADRs, and co-occurrence of other, recognized statin ADRs. ADRs had implications for marriages, careers, and safety of self and others. These observations support the potential for adverse mood and behavioral change in some individuals with statin use, extend the limited literature on such effects, and provide impetus for further investigation into these presumptive ADRs. Potential mechanisms are reviewed, including hypothesized mechanisms related to oxidative stress and bioenergetics

Physicians' Experiences as Patients with Statin Side Effects: A Case Series.

Physicians are among those prescribed statins and therefore, subject to potential statin adverse effects (AEs). There is little information on the impact of statin AEs on physicians affected by them. We sought to assess the character and impact of statin AEs occurring in physicians and retired physicians, and to ascertain whether/how personal experience of AEs moderated physicians' attitude toward statin use. Seven active or retired physicians from the United States communicated with the Statin Effects Study group regarding their personal experience of statin AEs. AE characteristics, experience with (their own) physicians, and impact of AE was ascertained. We inquired whether or how their experience altered their own attitude toward statins or statin AEs. Patient A: Atorvastatin 40 then 80 mg was followed by cognitive problems, neuropathy, and glucose intolerance in a Radiologist in his 50s (Naranjo criteria: probable causality). Patient B: Atorvastatin 10 mg was followed in 2 months by muscle weakness and myalgia in an Internist in his 40s (probable causality). Patient C: Atorvastatin, ezetimibe/simvastatin, rosuvastatin at varying doses was followed shortly after by irritability, myalgia, and fatigue in a Cardiac Surgeon in his 40s (probable causality). Patient D: Simvastatin 20 then 40 mg was followed in 4 years by mitochondriopathy, myopathy, neuropathy, and exercise intolerance in an Emergency Medicine physician in his 50s (definite causality). Patient E: Simvastatin 20 mg and niacin 1000 mg was followed in one month by muscle weakness and myalgia in a Physical Medicine and Rehabilitation physician in his 50s (probable causality). Patient F: Lovastatin 20 mg then simvastatin 20 mg, atorvastatin 20 mg, rosuvastatin 5 mg, niacin 20 mg and ezetimbe 10 mg was followed by muscle weakness and myalgia in an Obstetrician/Gynecologist in his 70s (definite causality). Patient G: Ezetimibe/simvastatin and atorvastatin (dose unavailable) was followed shortly after by cognitive problems in a Radiologist in her 80s (probable causality). Thus AEs affected multiple quality-of-life relevant domains, often in combination, encompassing muscle (N = 5), fatigue (N = 2), peripheral neuropathy (N = 2), cognitive (N = 2), dysglycemia (N = 1) and behavioral manifestations (N = 1). In five, the AEs affected the physician professionally. Five physicians experienced dismissive attitudes in some of their own healthcare encounters. One noted that his experience helped not only his own attention to statin AEs, but that of other physicians in his community. Several stated that their experience altered their understanding of and/or attitude toward statin AEs, and/or their view of settings in which statin use is warranted. Statin AEs can have profound impact in high functioning professionals with implications to the individual, their professional life, and those whom they serve professionally

Normal discrimination of spatial frequency and contrast across visual hemifields in left-onset Parkinson’s disease: evidence against perceptual hemifield biases

Individuals with Parkinson's disease (PD) with symptom onset on the left side of the body (LPD) show a mild type of left-sided visuospatial neglect, whereas those with right-onset (RPD) generally do not. The functional mechanisms underlying these observations are unknown. Two hypotheses are that the representation of left-space in LPD is either compressed or reduced in salience. We tested these hypotheses psychophysically. Participants were 31 non-demented adults with PD (15 LPD, 16 RPD) and 17 normal control adults (NC). The spatial compression hypothesis was tested by showing two sinusoidal gratings, side by side. One grating's spatial frequency (SF) was varied across trials, following a staircase procedure, whereas the comparison grating was held at a constant SF. While fixating on a central target, participants estimated the point at which they perceived the two gratings to be equal in SF. The reduced salience hypothesis was tested in a similar way, but by manipulating the contrast of the test grating rather than its SF. There were no significant differences between groups in the degree of bias across hemifields for SF discrimination or for contrast discrimination. Results did not support either the spatial compression hypothesis or the reduced salience hypothesis. Instead, they suggest that at this perceptual level, LPD do not have a systematically biased way of representing space in the left hemifield that differs from healthy individuals, nor do they perceive stimuli on the left as less salient than stimuli on the right. Neglect-like syndrome in LPD instead presumably arises from dysfunction of higher-order attention.Published versio

Dysregulation of visual motion inhibition in major depression

Individuals with depression show depleted concentrations of the inhibitory neurotransmitter GABA in occipital (visual) cortex, predicting weakened inhibition within their visual systems. Yet, visual inhibition in depression remains largely unexplored. To fill this gap, we examined the inhibitory process of centersurround suppression (CSS) of visual motion in depressed individuals. Perceptual performance in discriminating the direction of motion was measured as a function of stimulus presentation time and contrast in depressed individuals (n¼27) and controls (n¼22). CSS was operationalized as the accuracy difference between conditions using large (7.5°) and small (1.5°) grating stimuli. Both depressed and control participants displayed the expected advantage in accuracy for small stimuli at high contrast. A significant interaction emerged between subject group, contrast level and presentation time, indicating that alterations of CSS in depression were modulated by stimulus conditions. At high contrast, depressed individuals showed significantly greater CSS than controls at the 66 ms presentation time (where the effect peaked in both groups). The results' specificity and dependence on stimulus features such as contrast, size and presentation time suggest that they arise from changes in early visual processing, and are not the results of a generalized deficit or cognitive bias.Accepted versio

Relationship between hippocampal structure and memory function in elderly humans

With progressing age, the ability to recollect personal events declines, whereas familiarity-based memory remains relatively intact. It has been hypothesized that age-related hippocampal atrophy may contribute to this pattern because of its critical role for recollection in younger humans and after acute injury. Here, we show that hippocampal volume loss in healthy older persons correlates with gray matter loss (estimated with voxel-based morphometry) of the entire limbic system and shows no correlation with an electrophysiological (event-related potential [ERP]) index of recollection. Instead, it covaries with more substantial and less specific electrophysiological changes of stimulus processing. Age-related changes in another complementary structural measure, hippocampal diffusion, on the other hand, seemed to be more regionally selective and showed the expected correlation with the ERP index of recollection. Thus, hippocampal atrophy in older persons accompanies limbic atrophy, and its functional impact on memory is more fundamental than merely affecting recollection

Proportion Regulation in Globally Coupled Nonlinear Systems

As a model of proportion regulation in differentiation process of biological system, globally coupled activator-inhibitor systems are studied. Formation and destabilization of one and two cluster state are predicted analytically. Numerical simulations show that the proportion of units of clusters is chosen within a finite range and it is selected depend on the initial condition.Comment: 11 pages (revtex format) and 5 figures (PostScript)

Dual tasking in Parkinson's disease: cognitive consequences while walking

Published in final edited form as: Neuropsychology. 2017 September; 31(6): 613–623. doi:10.1037/neu0000331.OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) and exacerbate the functional limitations imposed by PD's hallmark motor symptoms, including impairments in walking. Though much research has addressed the effect of dual cognitive-locomotor tasks on walking, less is known about their effect on cognition. The purpose of this study was to investigate the relation between gait and executive function, with the hypothesis that dual tasking would exacerbate cognitive vulnerabilities in PD as well as being associated with gait disturbances. METHOD: Nineteen individuals with mild-moderate PD without dementia and 13 age- and education-matched normal control adults (NC) participated. Executive function (set-shifting) and walking were assessed singly and during dual tasking. RESULTS: Dual tasking had a significant effect on cognition (reduced set-shifting) and on walking (speed, stride length) for both PD and NC, and also on stride frequency for PD only. The impact of dual tasking on walking speed and stride frequency was significantly greater for PD than NC. Though the group by condition interaction was not significant, PD had fewer set-shifts than NC on dual task. Further, relative to NC, PD showed significantly greater variability in cognitive performance under dual tasking, whereas variability in motor performance remained unaffected by dual tasking. CONCLUSIONS: Dual tasking had a significantly greater effect in PD than in NC on cognition as well as on walking. The results suggest that assessment and treatment of PD should consider the cognitive as well as the gait components of PD-related deficits under dual-task conditions. (PsycINFO Database Record)

Artifacts with uneven sampling of red noise

The vast majority of sampling systems operate in a standard way: at each tick of a fixed-frequency master clock a digitizer reads out a voltage that corresponds to the value of some physical quantity and translates it into a bit pattern that is either transmitted, stored, or processed right away. Thus signal sampling at evenly spaced time intervals is the rule: however this is not always the case, and uneven sampling is sometimes unavoidable. While periodic or quasi-periodic uneven sampling of a deterministic signal can reasonably be expected to produce artifacts, it is much less obvious that the same happens with noise: here I show that this is indeed the case only for long-memory noise processes, i.e., power-law noises $1/f^\alpha$ with $\alpha > 2$. The resulting artifacts are usually a nuisance although they can be eliminated with a proper processing of the signal samples, but they could also be turned to advantage and used to encode information.Comment: 5 figure

Functional correlates of optic flow motion processing in Parkinson’s disease

The visual input created by the relative motion between an individual and the environment, also called optic flow, influences the sense of self-motion, postural orientation, veering of gait, and visuospatial cognition. An optic flow network comprising visual motion areas V6, V3A, and MT+, as well as visuo-vestibular areas including posterior insula vestibular cortex (PIVC) and cingulate sulcus visual area (CSv), has been described as uniquely selective for parsing egomotion depth cues in humans. Individuals with Parkinson’s disease (PD) have known behavioral deficits in optic flow perception and visuospatial cognition compared to age- and education-matched control adults (MC). The present study used functional magnetic resonance imaging (fMRI) to investigate neural correlates related to impaired optic flow perception in PD. We conducted fMRI on 40 non-demented participants (23 PD and 17 MC) during passive viewing of simulated optic flow motion and random motion. We hypothesized that compared to the MC group, PD participants would show abnormal neural activity in regions comprising this optic flow network. MC participants showed robust activation across all regions in the optic flow network, consistent with studies in young adults, suggesting intact optic flow perception at the neural level in healthy aging. PD participants showed diminished activity compared to MC particularly within visual motion area MT+ and the visuo-vestibular region CSv. Further, activation in visuo-vestibular region CSv was associated with disease severity. These findings suggest that behavioral reports of impaired optic flow perception and visuospatial performance may be a result of impaired neural processing within visual motion and visuo-vestibular regions in PD.Published versio

Models of Polaron Transport in Inorganic and Hybrid Organic-Inorganic Titanium Oxides

Polarons are a type of localized excess charge in materials and often form in transition metal oxides. The large effective mass and confined nature of polarons make them of fundamental interest for photochemical and electrochemical reactions. The most studied polaronic system is rutile TiO2 where electron addition results in small polaron formation through the reduction of Ti(IV) d0 to Ti(III) d1 centers. Using this model system, we perform a systematic analysis of the potential energy surface based on semiclassical Marcus theory parametrized from the first-principles potential energy landscape. We show that F-doped TiO2 only binds polaron weakly with effective dielectric screening after the second nearest neighbor. To tailor the polaron transport, we compare TiO2 to two metal-organic frameworks (MOFs): MIL-125 and ACM-1. The choice of MOF ligands and connectivity of the TiO6 octahedra largely vary the shape of the diabatic potential energy surface and the polaron mobility. Our models are applicable to other polaronic materials