Physicians

Department / Division
Psychiatry / Psychiatry-Outpatient

Address
DUMC 3309
Durham, NC 27710

Appointment Telephone
919-681-8742

Office Telephone
919-681-8742

Fax Telephone
919-681-8744

Training

• MD, Duke University School of Medicine, 1987

Residency

• Psychiatry, Duke University Medical Center, 1987-1991
• Clinical Research Methodology, Duke University Medical Center, 1991-1993

Fellowship

• Clinical Neurophysiology, Duke University Medical Center, 1992-1994

Clinical Interests
Sleep and affective disorders

Research Interests
My research is focused on better understanding the pathophysiology of sleep disorders and mood disorders and developing improved treatments for these conditions.  My primary research tools are: electroencepahlography (EEG), polysomnography (PSG), computer signal analysis and modeling, functional magnetic resonance imaging (fMRI), and positron emission tomograophy (PET).  Nearly all of my projects have been carried out with humans, however, projects are ongoing with gene knock-out models in mice, and lemurs in collaboration with the Duke Primate Center.  A few representative current studies are: 1) Defining physiologic (EEG, PSG, PET, fMRI) correlates of sleep complaints and subtyping insomnia on the basis of the associated pathophysiology, 2) Studying the relationship of EEG data recorded during non-REM sleep, daytime function, and insomnia treatment response, 3) Developing new pharmacologic and non-pharmacologic treatments for insomnia, 4) Studying the relationship of natural sleep and hibernation-like phenomena (torpor), 5) Predicting depression treatment response on the basis of pre-treatment EEG and structural MRI data.

Industry Relationships and Collaborations (What's this?)

This physician (or a member of their immediate family) has a working relationship (i.e. consulting, research, and/or educational services) with the companies listed below. These relations have been reported to the health system leadership and, when appropriate, management plans are in place to address potential conflicts.

• Abbott Laboratories
• Actelion Pharmaceuticals Ltd.
• American Academy of Sleep Medicine
• Arena Pharmaceuticals
• Astellas Pharma Inc.
• AstraZeneca
• Bristol-Myers Squibb
• Cephalon, Inc.
• Eisai Pharmaceuticals
• GlaxoSmithKline
• Kingsdown, Inc.
• MECTA Corp
• Medtronic Inc.
• Merck & Co. USA (not assoc'd with Merck KGaA)
• Pfizer Inc.
• Philips Medical Systems
• Sanofi-Aventis
• Somaxon Pharmaceuticals, Inc.
• Sunovion
• Takeda Pharmaceutical Co. Ltd.
• Transoral Pharmaceuticals

Representative Publications
, Ancoli-Israel S, Benca RM, Edinger JD, Krystal AD, Mendelson W, Moldofsky H, Petrie J, Roth T, Walsh JK, Winkelman J. Panel Discussion: Changing How We Think About Insomnia. J Clin Psychiatry. 2004 Aug;65(Supplement 8):44-46. (2004) Abstract

Krystal AD. The changing perspective on chronic insomnia management. J Clin Psychiatry. 2004 Aug;65 Suppl 8:20-5. (2004) Abstract

Singh J, Zarate CA Jr, Krystal AD. Case report: Successful riluzole augmentation therapy in treatment-resistant bipolar depression following the development of rash with lamotrigine. Psychopharmacology (Berl). 2004 Apr;173(1-2):227-8. (2004) Abstract

Edinger JD, Krystal AD. Subtyping primary insomnia: is sleep state misperception a distinct clinical entity? Sleep Med Rev. 2003 Jun;7(3):203-14. (2003) Abstract

Krystal AD, Walsh JK, Laska E, Caron J, Amato DA, Wessel TC, Roth T. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep. 2003 Nov 1;26(7):793-9. (2003) Abstract

Krystal AD, Weiner RD, Dean MD, Lindahl VH, Tramontozzi III LA, Falcone G, Coffey CE. Comparison of Seizure Duration, Ictal EEG, and Cognitive Effects of Ketamine and Methohexital Anesthesia With ECT. J Neuropsychiatry Clin Neurosci. 2003 Winter;15(1):27-34. (2003) Abstract

Krystal AD. Insomnia in women. Clin Cornerstone. 2003;5(3):41-50. (2003) Abstract

Krystal AD, Edinger JD, Wohlgemuth WK, Marsh GR. NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes. Sleep. 2002 Sep 15;25(6):630-40. (2002) Abstract

Prado R, West M, Krystal AD  Multichannel electroencephalographic analyses via dynamic regression models with time-varying lag-lead structure J. Royal Statistical Society C-APP Part I. 2001;50: 95-109. (2001)

Krystal AD, Dean MD, Weiner RD, Tramontozzi LA 3rd, Connor KM, Lindahl VH, Massie RW. ECT stimulus intensity: are present ECT devices too limited? Am J Psychiatry. 2000 Jun;157(6):963-7. (2000) Abstract

Krystal AD, Holsinger T, Weiner RD, Coffey CE. Prediction of the utility of a switch from unilateral to bilateral ECT in the elderly using treatment 2 ictal EEG indices. J ECT. 2000 Dec;16(4):327-37. (2000) Abstract

Krystal AD, Weiner RD, Lindahl V, Massie R. The development and retrospective testing of an electroencephalographic seizure quality-based stimulus dosing paradigm with ECT. J ECT. 2000 Dec;16(4):338-49. (2000) Abstract

Krystal AD, West M, Prado R, Greenside H, Zoldi S, Weiner RD. EEG effects of ECT: implications for rTMS. Depress Anxiety. 2000;12(3):157-65. (2000) Abstract

Zoldi SM, Krystal A, Greenside HS. Stationarity and redundancy of multichannel EEG data recorded during generalized tonic-clonic seizures. Brain Topogr. 2000 Spring;12(3):187-200. (2000) Abstract

Asnis GM, Chakraburtty A, DuBoff EA, Krystal A, Londborg PD, Rosenberg R, Roth-Schechter B, Scharf MB, Walsh JK. Zolpidem for persistent insomnia in SSRI-treated depressed patients. J Clin Psychiatry. 1999 Oct;60(10):668-76. (1999) Abstract

Krystal AD, Prado R, West M. New methods of time series analysis of non-stationary EEG data: eigenstructure decompositions of time varying autoregressions. Clin Neurophysiol. 1999 Dec;110(12):2197-206. (1999) Abstract

Krystal AD, Weiner RD. EEG correlates of the response to ECT: a possible antidepressant role of brain-derived neurotrophic factor. J ECT. 1999 Mar;15(1):27-38. (1999) Abstract

West, M. Prado, R. and Krystal, A.  Evaluation and comparison of EEG traces: Latent structure in non-staionary time series.  Journal of the American Statistical Association, 94:375-387, 1999. (1999)

Krystal AD, Coffey CE, Weiner RD, Holsinger T. Changes in seizure threshold over the course of electroconvulsive therapy affect therapeutic response and are detected by ictal EEG ratings. J Neuropsychiatry Clin Neurosci. 1998 Spring;10(2):178-86. (1998) Abstract

Krystal AD, Greenside HS. Low-dimensional chaos in bipolar disorder? Arch Gen Psychiatry. 1998 Mar;55(3):275-6. (1998) Abstract

Krystal AD, Watts BV, Weiner RD, Moore S, Steffens DC, Lindahl V. The use of flumazenil in the anxious and benzodiazepine-dependent ECT patient. J ECT. 1998 Mar;14(1):5-14. (1998) Abstract

Krystal AD. The clinical utility of ictal EEG seizure adequacy models. Psychiatric Annals 1:30- 35, 1998. (1998)

Krystal, A.D., (member of the U.S. Modafinil in Narcolepsy Study Group). HLA-DQB1*0602 homozygosity increases relative risk for narcolepsy but not disease severity in two ethnic groups. Tissue Antigens 51:96-100, 1998. (1998)

Krystal, A.D., (member of the U.S. Modafinil in Narcolepsy Study Group). Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Annals of Neurology 43:88-97, 1998. (1998)

Krystal, A.D., Edinger, J., Wohlgemuth, W., Marsh, G.R. Sleep in peri-menopausal and post- menopausal women. Sleep Medicine Reviews, 2:243-253, 1998. (1998)

Krystal, A.D., Zoldi, S., Greenside, H., Prado, R., West, M., Weiner, R. The effects of ECT on the EEG: implicatons for rTMS. Progress in Neuro-Psychopharmacology & Biological Psychiatry, in press. (1998)

Edinger, J.D., Fins, A.I., Goeke, J.M., McMillan, D.K., Gersh, T.L., Krystal, A.D., McCall, W.V. The empirical identification of insomnia subtypes: A cluster analytic approach. Sleep (in press). (1997)

Krystal AD, Coffey CE. Neuropsychiatric considerations in the use of electroconvulsive therapy. J Neuropsychiatry Clin Neurosci. 1997 Spring;9(2):283-92. (1997) Abstract

Krystal AD, Zaidman C, Greenside HS, Weiner RD, Coffey CE. The largest Lyapunov exponent of the EEG during ECT seizures as a measure of ECT seizure adequacy. Electroencephalogr Clin Neurophysiol. 1997 Dec;103(6):599-606. (1997) Abstract

Krystal, A.D. The clinical utility of ictal EEG seizure adequacy models. Psychiatric Annals, 1:30-35, 1998. (1997)

Krystal, A.D., Coffey, C.E. Neuropsychiatric considerations in the use of Electroconvulsive Therapy. Journal of Neuropsychiatry and Clinical Neurosciences 9:283-292, 1997. (1997)

Krystal, A.D., Greenside, H.S. Low Dimensional Chaos in Bipolar Disorders? (Letter to the Editor) Arch. Gen. Psychiatry (in press). (1997)

Krystal, A.D., Zaidman, C., Greenside, H.S., Weiner, R.D., Coffey, C.E. The largest Lyapunov exponent of the EEG during ECT seizures as a measure of therapeutic adequacy. Electroencephalography and Clinical Neurophysiology 103:599-606, 1997. (1997)

Edinger JD, Fins AI, Goeke JM, McMillan DK, Gersh TL, Krystal AD, McCall WV. The empirical identification of insomnia subtypes: a cluster analytic approach. Sleep. 1996 Jun;19(5):398-411. (1996) Abstract

Krystal AD, Greenside HS, Weiner RD, Gassert D. A comparison of EEG signal dynamics in waking, after anesthesia induction and during electroconvulsive therapy seizures. Electroencephalogr Clin Neurophysiol. 1996 Aug;99(2):129-40. (1996) Abstract

Krystal AD, Weiner RD, Coffey CE, McCall WV. Effect of ECT treatment number on the ictal EEG. Psychiatry Res. 1996 May 17;62(2):179-89. (1996) Abstract

Krystal AD, Weiner RD, Gassert D, McCall WV, Coffey CE, Sibert T, Holsinger T. The relative ability of three ictal EEG frequency bands to differentiate ECT seizures on the basis of electrode placement, stimulus intensity, and therapeutic response. Convuls Ther. 1996 Mar;12(1):13-24. (1996) Abstract

Krystal, A.D., Coffey, C.E., Weiner, R.D., Holsinger, T. Changes in seizure threshold over the ECTcourse affect therapeutic response and are detected by ictal EEG ratings. (1996)

Krystal, A.D., Greenside, H.S., Weiner, R.D., Gassert, D. A comparison of EEG signal dynamics in waking, after anesthesia induction and during ECT seizures. Electroencephalography and Clinical Neurophysiology 99:129-140, 1996. (1996)

Coffey CE, Lucke J, Weiner RD, Krystal AD, Aque M. Seizure threshold in electroconvulsive therapy (ECT) II. The anticonvulsant effect of ECT. Biol Psychiatry. 1995 Jun 1;37(11):777-88. (1995) Abstract

Coffey CE, Lucke J, Weiner RD, Krystal AD, Aque M. Seizure threshold in electroconvulsive therapy: I. Initial seizure threshold. Biol Psychiatry. 1995 May 15;37(10):713-20. (1995) Abstract

Edinger JD, Erwin CW, Fins AI, Marsh GR, Krystal AD. Ambulatory cassette polysomnography: findings from a large cohort of drug-free insomnia patients. J Clin Neurophysiol. 1995 May;12(3):302-9. (1995) Abstract

Krystal AD, Weiner RD, Coffey CE. The ictal EEG as a marker of adequate stimulus intensity with unilateral ECT. J Neuropsychiatry Clin Neurosci. 1995 Summer;7(3):295-303. (1995) Abstract

Krystal AD, Weiner RD. ECT seizure duration: reliability of manual and computer-automated determinations. Convuls Ther. 1995 Sep;11(3):158-69. (1995) Abstract

Krystal, A.D., Weiner, R.D., Coffey, C.E. The ictal EEG as a marker of adequate stimulus intensity with unilateral ECT. J. Neuropsychiatr. and Clin. Neurosciences 7:295-303, 1995. (1995)

Krystal AD, Weiner RD, McCall WV, Shelp F, Arias R, Smith P: The effects of ECT stimulus dose and electrode placement on the ictal electroencehpalogram: An intraindividual crossover study. Biological Psychiatry 34: 759-767, 1993. (1994)

Krystal AD, Weiner RD. ECT seizure therapeutic adequacy. Convuls Ther. 1994 Jun;10(2):153-64. (1994) Abstract

Krystal AD, Weiner RD: Low frequency ictal EEG activity and ECT therapeutic impact. Convulsive Therapy 9: 220-224, 1993. (1994)

McCall WV, Edinger JD, Krystal AD, Marsh GR: Ambulatory polysomnogrophic differences in healthy and insomniac older men. Ambulatory monitoring 6: 135-140, 1993. (1994)

Weiner RD, Krystal AD. The present use of electroconvulsive therapy. Annu Rev Med. 1994;45:273-81. (1994) Abstract

Weiner RD, Krystal AD: EEG monitoring of ECT seizures. In (ed Coffey CE), The Clinical Science of Electroconvulsive Therapy. Washington DC: American Psychiatric Press, Inc., pp 93-109, 1993. (1994)

Krystal AD, Weiner RD, McCall WV, Shelp FE, Arias R, Smith P. The effects of ECT stimulus dose and electrode placement on the ictal electroencephalogram: an intraindividual crossover study. Biol Psychiatry. 1993 Dec 1;34(11):759-67. (1993) Abstract

Krystal AD, Weiner RD, Coffey CE, Smith P, Arias R, Moffett E. EEG evidence of more "intense" seizure activity with bilateral ECT. Biol Psychiatry. 1992 Mar 15;31(6):617-21. (1992) Abstract

McCall WV, Erwin CW, Edinger JD, Krystal AD, Marsh GR. Ambulatory polysomnography: technical aspects and normative values. J Clin Neurophysiol. 1992 Jan;9(1):68-77. (1992) Abstract

Weiner RD, Krystal AD, Coffey CE, Smith P. The electrophysiology of ECT: relevance to mechanism of action. Clin Neuropharmacol. 1992;15 Suppl 1 Pt A:671A-672A. (1992) Abstract

Weiner RD, Coffey CE, Krystal AD. The monitoring and management of electrically induced seizures. Psychiatr Clin North Am. 1991 Dec;14(4):845-69. (1991) Abstract

Krystal A, Krishnan KR, Raitiere M, Poland R, Ritchie JC, Dunnick NR, Hanada K, Nemeroff CB. Differential diagnosis and pathophysiology of Cushing's syndrome and primary affective disorder. J Neuropsychiatry Clin Neurosci. 1990 Winter;2(1):34-43. (1990) Abstract

Krystal AD, McEvoy JP. Shared features of neuroleptic malignant syndrome and alcohol abuse complications. J Clin Psychiatry. 1990 Dec;51(12):523. (1990) Abstract