Browsing by Author "Krystal, Andrew D"

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    Multifactorial determinants of the neurocognitive effects of electroconvulsive therapy.
    (J ECT, 2014-06) McClintock, Shawn M; Choi, Jimmy; Deng, Zhi-De; Appelbaum, Lawrence G; Krystal, Andrew D; Lisanby, Sarah H
    For many patients with neuropsychiatric illnesses, standard psychiatric treatments with mono or combination pharmacotherapy, psychotherapy, and transcranial magnetic stimulation are ineffective. For these patients with treatment-resistant neuropsychiatric illnesses, a main therapeutic option is electroconvulsive therapy (ECT). Decades of research have found ECT to be highly effective; however, it can also result in adverse neurocognitive effects. Specifically, ECT results in disorientation after each session, anterograde amnesia for recently learned information, and retrograde amnesia for previously learned information. Unfortunately, the neurocognitive effects and underlying mechanisms of action of ECT remain poorly understood. The purpose of this paper was to synthesize the multiple moderating and mediating factors that are thought to underlie the neurocognitive effects of ECT into a coherent model. Such factors include demographic and neuropsychological characteristics, neuropsychiatric symptoms, ECT technical parameters, and ECT-associated neurophysiological changes. Future research is warranted to evaluate and test this model, so that these findings may support the development of more refined clinical seizure therapy delivery approaches and efficacious cognitive remediation strategies to improve the use of this important and widely used intervention tool for neuropsychiatric diseases.
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    Sequential psychological and pharmacological therapies for comorbid and primary insomnia: study protocol for a randomized controlled trial.
    (Trials, 2016-03-03) Morin, Charles M; Edinger, Jack D; Krystal, Andrew D; Buysse, Daniel J; Beaulieu-Bonneau, Simon; Ivers, Hans
    BACKGROUND: Chronic insomnia is a prevalent disorder associated with significant psychosocial, health, and economic impacts. Cognitive behavioral therapies (CBTs) and benzodiazepine receptor agonist (BzRA) medications are the most widely supported therapeutic approaches for insomnia management. However, few investigations have directly compared their relative and combined benefits, and even fewer have tested the benefits of sequential treatment for those who do not respond to initial insomnia therapy. Moreover, insomnia treatment studies have been limited by small, highly screened study samples, fixed-dose, and fixed-agent pharmacotherapy strategies that do not represent usual clinical practices. This study will address these limitations. METHODS/DESIGN: This is a two-site randomized controlled trial, which will enroll 224 adults who meet the criteria for a chronic insomnia disorder with or without comorbid psychiatric disorders. Prospective participants will complete clinical assessments and polysomnography and then will be randomly assigned to first-stage therapy involving either behavioral therapy (BT) or zolpidem. Treatment outcomes will be assessed after 6 weeks, and treatment remitters will be followed for the next 12 months on maintenance therapy. Those not achieving remission will be offered randomization to a second, 6-week treatment, again involving either pharmacotherapy (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy (CT)). All participants will be re-evaluated 12 weeks after the protocol initiation and at 3-, 6-, 9-, and 12-month follow-ups. Insomnia remission, defined categorically as a score < 8 on the Insomnia Severity Index, a patient-reported outcome, will serve as the primary endpoint for treatment comparisons. Secondary outcomes will include sleep parameters derived from daily sleep diaries and from polysomnography, subjective measures of fatigue, mood, quality of life, and functional impairments; and measures of adverse events; dropout rates; and treatment acceptability. Centrally trained therapists will administer therapies according to manualized, albeit flexible, treatment algorithms. DISCUSSION: This clinical trial will provide new information about optimal treatment sequencing and will have direct implication for the development of clinical guidelines for managing chronic insomnia with and without comorbid psychiatric conditions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01651442 , Protocol version 4, 20 April 2011, registered 26 June 2012.
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    The relationship of sleep with temperature and metabolic rate in a hibernating primate.
    (PLoS One, 2013) Krystal, Andrew D; Schopler, Bobby; Kobbe, Susanne; Williams, Cathy; Rakatondrainibe, Hajanirina; Yoder, Anne D; Klopfer, Peter
    STUDY OBJECTIVES: It has long been suspected that sleep is important for regulating body temperature and metabolic-rate. Hibernation, a state of acute hypothermia and reduced metabolic-rate, offers a promising system for investigating those relationships. Prior studies in hibernating ground squirrels report that, although sleep occurs during hibernation, it manifests only as non-REM sleep, and only at relatively high temperatures. In our study, we report data on sleep during hibernation in a lemuriform primate, Cheirogaleus medius. As the only primate known to experience prolonged periods of hibernation and as an inhabitant of more temperate climates than ground squirrels, this animal serves as an alternative model for exploring sleep temperature/metabolism relationships that may be uniquely relevant to understanding human physiology. MEASUREMENTS AND RESULTS: We find that during hibernation, non-REM sleep is absent in Cheirogaleus. Rather, periods of REM sleep occur during periods of relatively high ambient temperature, a pattern opposite of that observed in ground squirrels. Like ground squirrels, however, EEG is marked by ultra-low voltage activity at relatively low metabolic-rates. CONCLUSIONS: These findings confirm a sleep-temperature/metabolism link, though they also suggest that the relationship of sleep stage with temperature/metabolism is flexible and may differ across species or mammalian orders. The absence of non-REM sleep suggests that during hibernation in Cheirogaleus, like in the ground squirrel, the otherwise universal non-REM sleep homeostatic response is greatly curtailed or absent. Lastly, ultra-low voltage EEG appears to be a cross-species marker for extremely low metabolic-rate, and, as such, may be an attractive target for research on hibernation induction.
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    The sleep effects of tiagabine on the first night of treatment predict post-traumatic stress disorder response at three weeks.
    (J Psychopharmacol, 2014-05) Krystal, Andrew D; Zhang, Wei; Davidson, Jonathan RT; Connor, Kathryn M
    INTRODUCTION: We sought to test the hypothesis that improvements in sleep might mediate treatment-related improvements in daytime symptoms of post-traumatic stress disorder (PTSD). We evaluated whether changes in sleep occurring on the first night of tiagabine (a gamma-amino butyric acid (GABA) reuptake inhibitor) administration predicted subsequent PTSD response. METHODS: This was an open-label three-week polysomnographic (PSG) study of nightly treatment with tiagabine dosing from 2-12 mg including 20 adults with PTSD with ≥30 min of self-reported and PSG wake time after sleep onset (WASO). RESULTS: A treatment night 1 decrease in self-reported and PSG WASO and an increase in slow-wave sleep (SWS) accounted for 94% of the variance in week 3 Short PTSD Rating Interview (SPRINT) score, the primary outcome measure (p<0.001). Increased night 1 SWS also accounted for 91% of the variance in Work/School Impairment and 45% of the variance in Social Life Impairment as measured with the Sheehan Disability Scale (p<0.001). These relationships were much stronger correlates of three-week outcome than three-week sleep effects. CONCLUSIONS: The initial sleep response to tiagabine may mediate or be an indicator of the subsequent PTSD response. The findings highlight the importance of sleep maintenance and SWS in the treatment of PTSD and also suggest a potential relationship between SWS and daytime function.