Neural, physiological, and psychological markers of appetitive conditioning in anorexia nervosa: a study protocol

Stuart B Murray, Tomislav D Zbozinek, Michelle Craske, Reza Tadayonnejad, Michael Strober, Ausaf A Bari, John P O'Doherty, Jamie D Feusner, Stuart B Murray, Tomislav D Zbozinek, Michelle Craske, Reza Tadayonnejad, Michael Strober, Ausaf A Bari, John P O'Doherty, Jamie D Feusner

Abstract

Background: Anorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations-a critical component of hedonic responding-has never been studied in AN.

Methods: This multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12-22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired.

Discussion: This study will be the first to interrogate appetitive conditioning in AN-a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward.

Trial registration: Pending.

Intended registry: Clinicaltrials.gov.

Keywords: Anorexia nervosa; Appetitive conditioning; Eating disorders; Reward; fMRI.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
A An overview of the 2-day appetitive conditioning paradigm, the temporal sequencing of task phases, and the overall timing parameters of each phase. B represents an overview of cue sequencing for the acquisition phase, when the CS+ is paired with the US, and C represents an overview of cue sequencing for the habituation, extinction, recovery, and reinstatement phases, when the CS+ is presented without the US
Fig. 2
Fig. 2
Schedule of enrollment, interventions, and assessments. *Recommended content can be displayed using various schematic formats. See SPIRIT 2013 Explanation and Elaboration for examples from protocols. **List specific timepoints in this row

References

    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 5. Arlington, VA: American Psychiatric Association; 2013.
    1. Arcelus J, Mitchell AJ, Wales J, Nielsen S. Mortality rates in patients with anorexia nervosa and other eating disorders: a meta-analysis of 36 studies. Arch Gen Psychiatry. 2011;68:724–731. doi: 10.1001/archgenpsychiatry.2011.74.
    1. Mitchell JE, Crow S. Medical complications of anorexia nervosa and bulimia nervosa. Curr Opin Psychiatry. 2006;19:438–443. doi: 10.1097/01.yco.0000228768.79097.3e.
    1. Vos T, Mathers CD. The burden of mental disorders: a comparison of methods between the Australian burden of disease studies and the global burden of disease study. Bull World Health Organ. 2000;78:427–438.
    1. Whiteford HA, Ferrari AJ, Degenhardt L, Feigin V, Vos T. The global burden of mental, neurological and substance use disorders: an analysis from the global burden of disease study. PLoS ONE. 2010;10:e0116820. doi: 10.1371/journal.pone.0116820.
    1. Murray SB, Quintana DS, Loeb KL, Griffiths S, Le Grange D. Treatment outcomes for anorexia nervosa: a systematic review and meta-analysis of randomized controlled trials. Psychol Med. 2019;49:535–544. doi: 10.1017/S0033291718002088.
    1. Watson HJ, Bulik CM. Update on the treatment of anorexia nervosa: review of clinical trials, practice guidelines and emerging interventions. Psychol Med. 2013;43:2477–2500. doi: 10.1017/S0033291712002620.
    1. Fichter MM, Quadflieg N, Crosby RD, Koch S. Long-term outcome of anorexia nervosa: results from a large clinical longitudinal study. Int J Eat Disord. 2017;50:1018–1030. doi: 10.1002/eat.22736.
    1. Kringelbach ML. Food for thought: hedonic experience beyond homeostasis in the human brain. Neuroscience. 2004;126:807–819. doi: 10.1016/j.neuroscience.2004.04.035.
    1. Kaye WH, Fudge JL, Paulus M. New insights into symptoms and neurocircuit function of anorexia nervosa. Nat Rev Neurosci. 2009;10:573–584. doi: 10.1038/nrn2682.
    1. Kaye WH, Wierenga CE, Bailer UF, Simmons AN, Bischoff-Grethe A. Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa. Trends Neurosci. 2013;36:110–120. doi: 10.1016/j.tins.2013.01.003.
    1. Cowdrey FA, Finlayson G, Park RJ. Liking compared with wanting for high- and low-calorie foods in anorexia nervosa: aberrant food reward even after weight restoration. Am J Clin Nutr. 2013;97:463–470. doi: 10.3945/ajcn.112.046011.
    1. Jiang T, Soussignan R, Rigaud D, Schaal B. Pleasure for visual and olfactory stimuli evoking energy-dense foods is decreased in anorexia nervosa. Psychiatry Res. 2010;180:42–47. doi: 10.1016/j.psychres.2010.04.041.
    1. Anderson LM, Crow SJ, Peterson CB. The impact of meal consumption on emotion among individuals with eating disorders. Eat Weight Disord Stud Anorex Bulim Obes. 2013;19:347–354. doi: 10.1007/s40519-013-0084-1.
    1. Bruch H. The golden cage: the enigma of anorexia nervosa. Harvard University Press; 1978.
    1. Bruch H. Conversations with anorexics: a compassionate and hopeful journey through the therapeutic process. Oxford: Basic Books; 1994.
    1. Boehm I, Flohr L, Steding J, Holzapfel L, Seitz J, Roessner V, et al. The trajectory of anhedonic and depressive symptoms in anorexia nervosa: a longitudinal and cross-sectional approach. Eur Eat Disord Rev. 2018;26:69–74. doi: 10.1002/erv.2565.
    1. Harrison A, Mountford VA, Tchanturia K. Social anhedonia and work and social functioning in the acute and recovered phases of eating disorders. Psychiatry Res. 2014;218:187–194. doi: 10.1016/j.psychres.2014.04.007.
    1. Pinheiro AP, Raney TJ, Thornton LM, Fichter MM, Berrettini WH, Goldman D, et al. Sexual functioning in women with eating disorders. Int J Eat Disord. 2009;43:123–129.
    1. Gonidakis F, Kravvariti V, Varsou E. Sexual function of women suffering from anorexia nervosa and bulimia nervosa. J Sex Marital Ther. 2015;41:368–378. doi: 10.1080/0092623X.2014.915904.
    1. Anderluh MB, Tchanturia K, Rabe-Hesketh S, Treasure J. Childhood obsessive-compulsive personality traits in adult women with eating disorders: defining a broader eating disorder phenotype. Am J Psychiatry. 2003;160:242–247. doi: 10.1176/appi.ajp.160.2.242.
    1. Soussignan R, Jiang T, Rigaud D, Royet JP, Schaal B. Subliminal fear priming potentiates negative facial reactions to food pictures in women with anorexia nervosa. Psychol Med. 2010;40:503–514. doi: 10.1017/S0033291709990377.
    1. Soussignan R, Schaal B, Rigaud D, Royet JP, Jiang T. Hedonic reactivity to visual and olfactory cues: rapid facial electromyographic reactions are altered in anorexia nervosa. Biol Psychol. 2011;86:265–272. doi: 10.1016/j.biopsycho.2010.12.007.
    1. Cardi V, Di Matteo R, Corfield F, Treasure J. Social reward and rejection sensitivity in eating disorders: an investigation of attentional bias and early experiences. World J Biol Psychiatry. 2013;14:622–633. doi: 10.3109/15622975.2012.665479.
    1. Watson KK, Werling DM, Zucker NL, Platt ML. Altered social reward and attention in anorexia nervosa. Front Psychol. 2010;1:36. doi: 10.3389/fpsyg.2010.00036.
    1. Cardi V, Corfield F, Leppanen J, Rhind C, Deriziotis S, Hadjimichalis A, et al. Emotional processing, recognition, empathy and evoked facial expression in eating disorders: an experimental study to map deficits in social cognition. PLoS ONE. 2015;10:e0133827. doi: 10.1371/journal.pone.0133827.
    1. Davies H, Schmidt U, Tchanturia K. Emotional facial expression in women recovered from anorexia nervosa. BMC Psychiatry. 2013;13:291. doi: 10.1186/1471-244X-13-291.
    1. Kaye WH, Frank GK, McConaha C. Altered dopamine activity after recovery from restricting-type anorexia nervosa. Neuropsychopharmacology. 1999;21:503–506. doi: 10.1016/S0893-133X(99)00053-6.
    1. Frank GK, Bailer UF, Henry SE, Drevets W, Meltzer CC, Price JC, et al. Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [11c]raclopride. Biol Psychiatry. 2005;58:908–912. doi: 10.1016/j.biopsych.2005.05.003.
    1. Frank GK, Shott ME, Hagman JO, Mittal VA. Alterations in brain structures related to taste reward circuitry in ill and recovered anorexia nervosa and in bulimia nervosa. Am J Psychiatry. 2013;170:1152–1160. doi: 10.1176/appi.ajp.2013.12101294.
    1. Titova OE, Hjorth OC, Schiöth HB, Brooks SJ. Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions: a meta-analysis of VBM studies. BMC Psychiatry. 2013;13:110. doi: 10.1186/1471-244X-13-110.
    1. Cha J, Ide JS, Bowman FD, Simpson HB, Posner J, Steinglass JE. Abnormal reward circuitry in anorexia nervosa: a longitudinal, multimodal MRI study. Hum Brain Mapp. 2016;37:3835–3846. doi: 10.1002/hbm.23279.
    1. Via E, Zalesky A, Sánchez I, Forcano L, Harrison BJ, Pujol J, et al. Disruption of brain white matter microstructure in women with anorexia nervosa. J Psychiatry Neurosci. 2014;39:367–375. doi: 10.1503/jpn.130135.
    1. Jiang T, Soussignan R, Carrier E, Royet JP. Dysfunction of the mesolimbic circuit to food odors in women with anorexia and bulimia nervosa: a fMRI Study. Front Hum Neurosci. 2019;13:117. doi: 10.3389/fnhum.2019.00117.
    1. Brooks SJ, O’Daly OG, Uher R, Friederich HC, Giampietro V, Brammer M, et al. Differential neural responses to food images in women with bulimia versus anorexia nervosa. PLoS ONE. 2011;6:e22259. doi: 10.1371/journal.pone.0022259.
    1. Holsen L, Lawson EA, Blum J, Ko E, Makris N, Fazeli PK, et al. Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa. J Psychiatry Neurosci. 2012;37:322–332. doi: 10.1503/jpn.110156.
    1. McFadden KL, Tregellas JR, Shott ME, Frank GKW. Reduced salience and default mode network activity in women with anorexia nervosa. J Psychiatry Neurosci. 2014;39:178–188. doi: 10.1503/jpn.130046.
    1. Oberndorfer TA, Frank GKW, Simmons AN, Wagner A, McCurdy D, Fudge JL, et al. Altered insula response to sweet taste processing after recovery from anorexia and bulimia nervosa. Am J Psychiatry. 2013;170:1143–1151. doi: 10.1176/appi.ajp.2013.11111745.
    1. Cowdrey FA, Park RJ, Harmer CJ, McCabe C. Increased neural processing of rewarding and aversive food stimuli in recovered anorexia nervosa. Biol Psychiat. 2011;70:736–743. doi: 10.1016/j.biopsych.2011.05.028.
    1. Vocks S, Busch M, Grönemeyer D, Schulte D, Herpertz S, Suchan B. Neural correlates of viewing photographs of one’s own body and another woman’s body in anorexia and bulimia nervosa: an fMRI study. J Psychiatry Neurosci. 2010;35:163–176. doi: 10.1503/jpn.090048.
    1. Kerr KL, Moseman SE, Avery JA, Bodurka J, Simmons WK. Influence of visceral interoceptive experience on the brain’s response to food images in anorexia nervosa. Psychosom Med. 2017;79:777–784. doi: 10.1097/PSY.0000000000000486.
    1. Uher R, Brammer MJ, Murphy T, Campbell IC, Ng VW, Williams SCR, et al. Recovery and chronicity in anorexia nervosa: brain activity associated with differential outcomes. Biol Psychiatty. 2003;54:934–942. doi: 10.1016/S0006-3223(03)00172-0.
    1. Uher R, Murphy T, Brammer MJ, Dalgleish T, Phillips ML, Ng VW, et al. Medial prefrontal cortex activity associated with symptom provocation in eating disorders. Am J Psychiatry. 2004;161:1238–1246. doi: 10.1176/appi.ajp.161.7.1238.
    1. Wagner A, Aizenstein H, Venkatraman VK, Fudge J, May JC, Mazurkewicz L, et al. Altered reward processing in women recovered from anorexia nervosa. Am J Psychiatry. 2007;164:1842–1849. doi: 10.1176/appi.ajp.2007.07040575.
    1. Steinglass JE, Lempert KM, Choo T-H, Kimeldorf MB, Wall M, Walsh BT, et al. Temporal discounting across three psychiatric disorders: anorexia nervosa, obsessive compulsive disorder, and social anxiety disorder. Depress Anxiety. 2017;34:463–470. doi: 10.1002/da.22586.
    1. Serpell L, Treasure J, Teasdale J, Sullivan V. Anorexia nervosa: friend or foe? Int J Eat Disord. 1999;25:177–186. doi: 10.1002/(SICI)1098-108X(199903)25:2<177::AID-EAT7>;2-D.
    1. Brotsky SR, Giles D. Inside the “pro-ana” community: a covert online participant observation. Eat Disord. 2007;15:93–109. doi: 10.1080/10640260701190600.
    1. Fladung A-K, Grön G, Grammer K, Gerrnberger B, Schilly E, Grasteit S, et al. A neural signature of anorexia nervosa in the ventral striatal reward system. Am J Psychiatry. 2010;167:206–212. doi: 10.1176/appi.ajp.2009.09010071.
    1. Fladung A-K, Schulze UME, Schöll F, Bauer K, Grön G. Role of the ventral striatum in developing anorexia nervosa. Transl Psychiatry. 2013;3:e315. doi: 10.1038/tp.2013.88.
    1. Holsen LM, Lawson EA, Christensen K, Klibanski A, Goldstein JM. Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa. Psychiatry Res. 2014;223:94–103. doi: 10.1016/j.pscychresns.2014.04.015.
    1. Haynos AF, Lavender JM, Nelson J, Crow SJ, Peterson CB. Moving towards specificity: a systematic review of cue features associated with reward and punishment in anorexia nervosa. Clin Psychol Rev. 2020;79:101872. doi: 10.1016/j.cpr.2020.101872.
    1. Frank GKW, DeGuzman MC, Shott ME, Laudenslager ML, Rossi B, Pryor T. Association of brain reward learning response with harm avoidance, weight gain, and hypothalamic effective connectivity in adolescent anorexia nervosa. JAMA Psychiat. 2018;75:1071–1080. doi: 10.1001/jamapsychiatry.2018.2151.
    1. Monteleone AM, Monteleone P, Esposito F, Prinster A, Volpe U, Canton E, et al. Altered processing of rewarding and aversive basic taste stimuli in symptomatic women with anorexia nervosa and bulimia nervosa: an fMRI study. J Psychiatry Res. 2017;90:94–101. doi: 10.1016/j.jpsychires.2017.02.013.
    1. Steding J, Boehm I, King JA, Geisler D, Ritschel F, Seidel M, et al. Goal-directed vs. habitual instrumental behavior during reward processing in anorexia nervosa: an fMRI study. Sci Rep. 2019;9:13529. doi: 10.1038/s41598-019-49884-6.
    1. Pike KM. Long-term course of anorexia nervosa: response, relapse, remission, and recovery. Clin Psychol Rev. 1998;18:447–475. doi: 10.1016/S0272-7358(98)00014-2.
    1. Schebendach JE, Mayer LE, Devlin MJ, Attia E, Contento IR, Wolf RL, et al. Dietary energy density and diet variety as predictors of outcome in anorexia nervosa. Am J Clin Nutr. 2008;87:810–816. doi: 10.1093/ajcn/87.4.810.
    1. Carter JC, Blackmore E, Sutandar-Pinnock K, Woodside B. Relapse in anorexia nervosa: a survival analysis. Psychol Med. 2004;4:671–679. doi: 10.1017/S0033291703001168.
    1. Martin-Soelch C, Linthicum J, Ernst M. Appetitive conditioning: neural bases and implications for psychopathology. Neurosci Biobehav Rev. 2007;31:426–440. doi: 10.1016/j.neubiorev.2006.11.002.
    1. Watson HJ, Yilmaz Z, Thornton LM, Hübel C, Coleman JRI, Gaspar HA, et al. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nat Genet. 2019;51:1207–1214. doi: 10.1038/s41588-019-0439-2.
    1. Drevets WC. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol. 2001;11:240–249. doi: 10.1016/S0959-4388(00)00203-8.
    1. Carr KD. Chronic food restriction: enhancing effects on drug reward and striatal cell signaling. Physiol Behav. 2007;91:459–472. doi: 10.1016/j.physbeh.2006.09.021.
    1. Carr KD, Tsimberg Y, Berman Y, Yamamoto N. Evidence of increased dopamine receptor signaling in food-restricted rats. Neuroscience. 2003;119:1157–1167. doi: 10.1016/S0306-4522(03)00227-6.
    1. Avena NM, Rada P, Hoebel BG. Underweight rats have enhanced dopamine release and blunted acetylcholine response in the nucleus accumbens while bingeing on sucrose. Neuroscience. 2008;156:865–871. doi: 10.1016/j.neuroscience.2008.08.017.
    1. Oinio V, Bäckström P, Uhari-Väänänen J, Raasmaja A, Piepponen P, Kiianmaa K, et al. Dopaminergic modulation of reward-guided decision making in alcohol-preferring AA rats. Behav Brain Res. 2017;326:87–95. doi: 10.1016/j.bbr.2017.03.007.
    1. Frank GKW, DeGuzman MC, Shott ME. Motivation to eat and not to eat—the psychobiological conflict in anorexia nervosa. Physiol Behav. 2019;206:185–190. doi: 10.1016/j.physbeh.2019.04.007.
    1. DeGuzman M, Shott ME, Yang TT, Riederer J, Frank GKW. Association of elevated reward prediction error response with weight gain in adolescent anorexia nervosa. Am J Psychiatry. 2017;174:557–565. doi: 10.1176/appi.ajp.2016.16060671.
    1. Bernardoni F, King JA, Geisler D, Stein E, Jaite C, Nätsch D, et al. Weight restoration therapy rapidly reverses cortical thinning in anorexia nervosa: a longitudinal study. Neuroimage. 2016;130:214–222. doi: 10.1016/j.neuroimage.2016.02.003.
    1. Dalla C, Shors TJ. Sex differences in learning processes of classical and operant conditioning. Physiol Behav. 2009;97:229–238. doi: 10.1016/j.physbeh.2009.02.035.
    1. Tapia León I, Kruse O, Stalder T, Stark R, Klucken T. Neural correlates of subjective CS/UCS association in appetitive conditioning. Hum Brain Mapp. 2018;39:1637–1646. doi: 10.1002/hbm.23940.
    1. Lock J, Le Grange D, Agras WS, Fitzpatrick KK, Jo B, Accurso E, et al. Can adaptive treatment improve outcomes in family-based therapy for adolescents with anorexia nervosa? feasibility and treatment effects of a multi-site treatment study. Behav Res Ther. 2015;73:90–95. doi: 10.1016/j.brat.2015.07.015.
    1. Fairburn CG, Cooper Z. The eating disorder examination. In: Fairburn CG, Wilson GT, editors. Binge eating: nature, assessment & treatment. New York: Guilford Press; 1993. pp. 317–360.
    1. Parsons CE, Young KS, Craske MG, Stein AL, Kringelbach ML. Introducing the oxford vocal (OxVoc) sounds database: a validated set of non-acted affective sounds from human infants, adults, and domestic animals. Front Psychol. 2014;5:562.
    1. Riem MME, Ijzendoorn MHV, Tops M, Boksem MAS, Rombouts SARB, Kranenburg-Bakermans MJ. No laughing matter: intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter. Neuropsychopharmacology. 2012;37:1257–1266. doi: 10.1038/npp.2011.313.
    1. Brown LA, LeBeau RT, Chat KY, Craske MG. Associative learning versus fear habituation as predictors of long-term extinction retention. Cogn Emot. 2017;31:687–698. doi: 10.1080/02699931.2016.1158695.
    1. Staples-Bradley LK, Treanor M, Craske MG. Discrimination between safe and unsafe stimuli mediates the relationship between trait anxiety and return of fear. Cogn Emot. 2018;32:167–173. doi: 10.1080/02699931.2016.1265485.
    1. Pietrock C, Ebrahimi C, Katthagen TM, Koch SP, Heinz A, Rothkirch M, et al. Pupil dilation as an implicit measure of appetitive Pavlovian learning. Psychophysiology. 2019;56:e13463. doi: 10.1111/psyp.13463.
    1. Murphy PR, O’Connell RG, O’Sullivan M, Robertson IH, Balsters JH. Pupil diameter covaries with BOLD activity in human locus coeruleus. Hum Brain Mapp. 2014;35:4140–4154. doi: 10.1002/hbm.22466.
    1. Joshi S, Li Y, Kalwani RM, Gold JI. Relationships between pupil diameter and neuronal activity in the locus coeruleus, colliculi, and cingulate cortex. Neuron. 2016;89:221–234. doi: 10.1016/j.neuron.2015.11.028.
    1. Bouret S, Sara SJ. Reward expectation, orientation of attention and locus coeruleus-medial frontal cortex interplay during learning. Eur J Neurosci. 2004;20:791–802. doi: 10.1111/j.1460-9568.2004.03526.x.
    1. Hoeks B, Levelt WJM. Pupillary dilation as a measure of attention: a quantitative system analysis. Behav Res Methods Instrum Comput. 1993;25:16–26. doi: 10.3758/BF03204445.
    1. Esteban O, Markiewicz CJ, Blair RW, Moodie CA, Isik AI, Erramuzpe A, et al. fMRIPrep: a robust preprocessing pipeline for functional MRI. Nat Methods. 2019;16:111–116. doi: 10.1038/s41592-018-0235-4.
    1. Pauli WM, Nili AN, Tyszka JM. A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei. Sci Data. 2018;5:180063. doi: 10.1038/sdata.2018.63.
    1. Sheehan DV, Sheehan KH, Shytle RD, Janavs J, Bannon Y, Rogers JE, et al. Reliability and validity of the Mini-International Neuropsychiatric Interview for children and adolescents (MINI-KID) J Clin Psychiatry. 2010;71:313–326. doi: 10.4088/JCP.09m05305whi.
    1. Carver CS, White TL. Behavioural inhibition, behavioural activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J Pers Soc Psychol. 1994;67:319–333. doi: 10.1037/0022-3514.67.2.319.
    1. Lovibond PF, Lovibond SH. The structure of the negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. Behav Res Ther. 1995;33:335–343. doi: 10.1016/0005-7967(94)00075-U.
    1. Mahmoud JSR, Hall LA, Staten R. The psychometric properties of the 21-item Depression Anxiety and Stress Scale (DASS-21) among a sample of young adults. South Online J Nurs Res. 2010;10:21–34.
    1. Spielberger CD, Gorsuch RL, Lushene RE. STAI manual for the State-Trait Anxiety Inventory. Palo Alto: Consulting Psychologists Press; 1970.
    1. Kaye WH, Bulik CM, Thornton L, Barbarich N, Masters K. Comorbidity of anxiety disorders with anorexia and bulimia nervosa. Am J Psychiatry. 2004;161:2215–2221. doi: 10.1176/appi.ajp.161.12.2215.
    1. Grillon C, Ameli R, Foot M, Davis M. Fear-potentiated startle: relationship to the level of state/trait anxiety in healthy subjects. Biol Psychiatry. 1993;33:566–574. doi: 10.1016/0006-3223(93)90094-T.
    1. Paulus PC, Castegnetti G, Bach DR. Modeling event-related heart period responses. Psychophysiology. 2016;53:837–846. doi: 10.1111/psyp.12622.
    1. Hayes AF. Partial, conditional, and moderated moderated mediation: Quantification, inference, and interpretation. Commun Monogr. 2018;85:4–40. doi: 10.1080/03637751.2017.1352100.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere