Skip to main content Accessibility help
Hostname: page-component-56f9d74cfd-p4n5r Total loading time: 0.289 Render date: 2022-06-25T09:22:56.845Z Has data issue: true Feature Flags: { "shouldUseShareProductTool": true, "shouldUseHypothesis": true, "isUnsiloEnabled": true, "useRatesEcommerce": false, "useNewApi": true }

The Differential Diagnosis of Pseudobulbar Affect (PBA): Distinguishing PBA Among Disorders of Mood and Affect

Published online by Cambridge University Press:  07 November 2014

David B. Arciniegas*
Dr. Arciniegas is director of the neuropsychiatry service and assistant professor in the Departments of Psychiatry and Neurology at, the University of Colorado School of Medicine in Denver, Colorado. He is a consultant to Avanir and Novartis, and has received grant/research support from Eisai, Forest, and Novartis.
Edward C. Lauterbach
Dr. Lauterbach is professor in the Departments of Psychiatry, Radiology, and Neurology at, the Mercer University School of Medicine in Macon, Georgia. He is a speaker for Forest, and receives grant/research support from Bristol-Myers Squibb.
Karen E. Anderson
Dr. Anderson is assistant professor in the Departments of Psychiatry and Neurology at, the University of Maryland School of Medicine in Baltimore, Maryland. She reports no affiliation with or financial interest in any organization that may pose a conflict of interest.
Tiffany W. Chow
Dr. Chow is assistant professor in the Department of Medicine, Division of Neurology at, the University of Toronto in Ontario, Canada. She reports no affiliation with or financial interest in any organization that may pose a conflict of interest.
Laura A. Flashman
Dr. Flashman is associate professor in the Department of Psychiatry at, Dartmouth Medical School in Lebanon, New Hampshire. She reports no affiliation with or financial interest in any organization that may pose a conflict of interest.
Robin A. Hurley
Dr. Hurley is a neuropsychiatrist for the Mental Health Service Line at the W.G. “Bill” Hefner Veterans Affairs Medical Center (Salisbury VAMC) in Salisbury, North Carolina. She reports no affiliation with or financial interest in any organization that may pose a conflict of interest.
Daniel I. Kaufer
Dr. Kaufer is associate professor in the Department of Neurology at, the University of North Carolina School of Medicine in Chapel Hill, North Carolina. He is a consultant to Bayer and Tap Holdings; is on the speaker's bureaus of Bayer, Eisai, and Pfizer; and receives grant/research support from Eisai and Pfizer.
Thomas W. McAllister
Dr. McAllister is professor and director of neuropsychiatry in the Department of Psychiatry at, Dartmouth Medical School in Lebanon, New Hampshire. He has received grant/research support from Novartis.
Alison Reeve
Dr. Reeve is associate professor in the Department of Psychiatry at, the University of New Mexico School of Medicine in Albuquerque, New Mexico. She is a consultant to Abbott.
Randolph B. Schiffer
Dr. Schiffer is professor and chairman of the Department of Neuropsychiatry and Behavioral Sciences at, the Texas Tech University Health Sciences Center in Lubbock, Texas. He is a consultant to, on the speaker's bureau of, and has received grant/research support from Avanir.
Jonathan M. Silver
Dr. Silver is clinical professor in the Department of Psychiatry at, the New York University School of Medicine in New York City. He is a consultant to Avanir and Novartis, and has received grant/research support from Novartis.
David B. Arciniegas, MD, Neuropsychiatry Service, University of Colorado School of Medicine, Campus Box C268-25, 4200 East Ninth Ave, Denver, CO 80211; Tel: 303-315-5365; Fax:, 303-315-5641; E-mail:,


This monograph summarizes the proceedings of a roundtable meeting convened to discuss pseudobulbar affect (PBA). Two didactic lectures were presented, followed by a moderated discussion among 11 participants. Post-meeting manuscript development synthesized didactic- and discussion-based content and incorporated additional material from the neuroscience literature. A conceptual framework with which to distinguish between disorders of mood and affect is presented first, and disorders of affect regulation are then reviewed briefly. A detailed description of the most common of these disorders, PBA, is the focus of the remainder of the monograph. The prevalence, putative neuranatomic and neurochemical bases of PBA are reviewed, and current and emerging methods of evaluation and treatment of persons with PBA are discussed. The material presented in this monograph will help clinicians better recognize, diagnose, and treat PBA, and will form a foundation for understanding and interpreting future studies of this condition.

Research Article
Copyright © Cambridge University Press 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


1.Dark, FL, McGrath, JJ, Ron, MA. Pathological laughing and crying. Aust N Z J Psychiatry. 1996;30(4):472479.CrossRefGoogle ScholarPubMed
2.Green, RL. Regulation of affect. Semin Clin Neuropsychiatry. 1998;3(3):195200.Google ScholarPubMed
3.Poeck, K. Pathological laughing and weeping in patients with progressive bulbar palsy. Ger Med Mon. 1969;14(8):394397.Google Scholar
4.Diagnostic and Statistical Manual of Mental Disorders. 3rd ed rev. Washington, DC: American Psychiatric Association; 1987.Google Scholar
5.Arciniegas, DB, Topkoff, J. The neuropsychiatry of pathologic affect: an approach to evaluation and treatment. Semin Clin Neuropsychiatry. 2000;5(4):290306.CrossRefGoogle ScholarPubMed
6.Wilson, SAK. Some problems in neurology. II. Pathological laughing and crying. J Neurol Psychopathol. 1924;4:299333.CrossRefGoogle Scholar
7.Poeck, K. Pathological laughter and crying. In: Fredericks, JAM, ed. Handbook of Clinical Neurology. Vol 45. Amsterdam, Netherlands: Elsevier Science Publishers; 1985.Google Scholar
8.Green, RL, Bernat, JL. Pathologic crying. In: Joseph, AB, Young, RR, eds. Movement disorders in Neurology and Neuropsychiatry. Oxford, UK: Blackwell Science, Inc; 1999.Google Scholar
9.Carota, A, Berney, A, Aybek, S, et al.A prospective study of predictors of poststroke depression. Neurology. 2005;64(3):428433.CrossRefGoogle ScholarPubMed
10.Woyshville, MJ, Lackamp, JM, Eisengart, JA, Gilliland, JA. On the meaning and measurement of affective instability: clues from chaos theory. Biol Psychiatry. 1999;45(3):261269.CrossRefGoogle ScholarPubMed
11.Moore, SR, Gresham, LS, Bromberg, MB, Kasarkis, EJ, Smith, RA. A self report measure of affective lability. J Neurol Neurosurg Psychiatry. 1997;63(1):8993.CrossRefGoogle ScholarPubMed
12.Feinstein, A, Feinstein, K, Gray, T, O'Connor, P. Prevalence and neurobehavioral correlates of pathological laughing and crying in multiple sclerosis. Arch Neurol. 1997;54(9):11161121.CrossRefGoogle ScholarPubMed
13.Green, RL, McAllister, TW, Bernat, JL. A study of crying in medically and surgically hospitalized patients. Am J Psychiatry. 1987;144(4):442447.Google ScholarPubMed
14.Berkovic, SF, Andermann, F. Pathological laughing. In: Joseph, AB, Young, RR, eds. Movement Disorders in Neurology and Neuropsychiatry. Oxford, UK: Blackwell Science, Inc; 1999.Google Scholar
15.Duchowny, MS. Pathological disorders of laughter. In: McGhee, PE, Goldstein, JH, eds. Handbook of Human Research. Vol II. New York, NY: Springer-Verlag; 1983.Google Scholar
16.Trimble, MR, Mendez, MF, Cummings, JL. Neuropsychiatric symptoms from the temporolimbic lobes. J Neuropsychiatry Clin Neurosci. 1997;9(3):429438.Google ScholarPubMed
17.Bucy, PC, Klüver, H. An anatomical investigation of the temporal lobe in the monkey (Macaca mulatta). J Comp Neurol. 1955;103(2):151251.CrossRefGoogle Scholar
18.Garg, RK, Misra, S, Verma, R. Pathological laughter as heralding manifestation of left middle cerebral artery territory infarct: case report and review of literature. Neurol India. 2000;48(4):388390.Google ScholarPubMed
19.Mukand, J, Kaplan, M, Senno, RG, Bishop, DS. Pathological crying and laughing: treatment with sertraline. Arch Phys Med Rehabil. 1996;77(12):13091311.CrossRefGoogle ScholarPubMed
20.Wild, B, Rodden, FA, Grodd, W, Ruch, W. Neural correlates of laughter and humour. Brain. 2003;126(Pt 10):21212138.CrossRefGoogle ScholarPubMed
21.Hopf, HC, Muller-Forell, W, Hopf, NJ. Localization of emotional and volitional facial paresis. Neurology. 1992;42(10):19181923.CrossRefGoogle ScholarPubMed
22.Munschauer, FE, Mador, MJ, Ahuja, A, Jacobs, L. Selective paralysis of voluntary but not limbically influenced automatic respiration. Arch Neurol. 1991;48(11):11901192.CrossRefGoogle Scholar
23.Arroyo, S, Lesser, RP, Gordon, B, et al.Mirth, laughter and gelastic seizures. Brain. 1993;116(Pt 4):757780.CrossRefGoogle ScholarPubMed
24.Foerster, O, Gagel, O. Ein Beltrag zur Frage der Bezlehungen psychischer Storungen Hirnstamm. Z ges Neurol Psychiatr. 1933;149:312.CrossRefGoogle Scholar
25.Bard, P. The neuro-humoral basis of emotional reactions. In: Murchison, C. Handbook of General Experimental Psychology. Worcester, MA: Clark University Press; 1934:264311.CrossRefGoogle Scholar
26.Hermann, C, Brown, IW. Palatal myoclonus: a reappraisal. J Neurol Sci. 1967;5:473492.CrossRefGoogle Scholar
27.Parvizi, J, Anderson, SW, Martin, CO, Damasio, H, Damasio, AR. Pathological laughter and crying: a link to the cerebellum. Brain. 2001;124(Pt 9):17081719.CrossRefGoogle ScholarPubMed
28.Riggs, JE, Schochet, SS Jr, Hogg, JP. Delayed diffuse upper motor neuron syndrome after compressive thoracic myelopathy. Mil Med. 1999;164(9):666668.CrossRefGoogle ScholarPubMed
29.Poeck, K. Pathological laughter and crying. In: Vinken, PJ, Bruyn, GW, Klawans, HV, eds. Handbook of Clinical Neurology. Vol 1 (45). Amsterdam, Netherlands: Elsevier; 1985:219225.Google Scholar
30.Lane, RD, Reiman, EM, Ahern, GL, Schwartz, GE, Davidson, RJ. Neuroanatomical correlates of happiness, sadness, and disgust. Am J Psychiatry. 1997;154(7):926933.Google ScholarPubMed
31.Martin, JH. Neuroanatomy Text and Atlas. New York, NY: Elsevier; 1989.Google Scholar
32.Andersen, G, Ingeman-Nielsen, M, Vestergaard, K, Riis, JO. Pathoanatomic correlation between poststroke pathological crying and damage to brain areas involved in serotonergic neurotransmission. Stroke. 1994;25(5):10501052.CrossRefGoogle ScholarPubMed
33.Brown, JW. Physiology and phylogenesis of emotional expression. Brain Res. 1967;5(1):114.CrossRefGoogle ScholarPubMed
34.Kelly, A, Beaton, LE, Magoun, HW. Midbrain mechanism for facio-vocal activity J Neurophysiol. 1946;8:181189.CrossRefGoogle Scholar
35.Holstege, G. The emotional motor system. Eur J Morphol. 1992;30(1):6779.Google ScholarPubMed
36.Ironside, R. Disorders oflaughter due to brain lesions. Brain. 1956;79(4):589609.CrossRefGoogle ScholarPubMed
37.McCullagh, S, Moore, M, Gawel, M, Feinstein, A. Pathological laughing and crying in amyotrophic lateral sclerosis: an association with prefrontal cognitive dysfunction. J Neurol Sci. 1999;169(1-2):4348.CrossRefGoogle ScholarPubMed
38.Kim, JS, Choi-Kwon, S. Poststroke depression and emotional incontinence: correlation with lesion location. Neurology. 2000;54(9):18051810.CrossRefGoogle ScholarPubMed
39.Okun, MS, Raju, DV, Walter, BL, et al.Pseudobulbar crying induced by stimulation in the region of the subthalamic nucleus. J Neurol Neurosurg Psychiatry. 2004; 75(6):921923.CrossRefGoogle ScholarPubMed
40.Schmahmann, JD, Ko, R, MacMore, J. The human basis pontis: motor syndromes and topographic organization. Brain. 2004;127(Pt 6):12691291.CrossRefGoogle ScholarPubMed
41.Kataoka, S, Hori, A, Shirakawa, T, Hirose, G. Paramedian pontine infarction. Neurological/topographical correlation. Stroke. 1997;28(4):809815.CrossRefGoogle ScholarPubMed
42.Achari, AN, Colover, J. Posterior fossa tumors with pathological laughter. JAMA. 1976;235(14):14691471.CrossRefGoogle ScholarPubMed
43.Doorenbos, DI, Haerer, AF, Payment, M, Clifton, ER. Stimulus-specific pathologic laughter: a case report with discrete unilateral localization. Neurology. 1993;43(1):229230.CrossRefGoogle ScholarPubMed
44.Lauterbach, EC, Price, ST, Spears, TE, Jackson, JG, Kirsh, AD. Serotonin responsive and nonresponsive diurnal depressive mood disorders and pathological affect in thalamic infarct associated with myoclonus and blepharospasm. Biol Psychiatry. 1994;35(7):488490.CrossRefGoogle ScholarPubMed
45.Kuzniecky, R, Guthrie, B, Mountz, J, et al.Intrinsic epileptogenesis of hypothalamic hamartomas in gelastic epilepsy. Ann Neurol. 1997;42(1):6067.CrossRefGoogle ScholarPubMed
46.Sackeim, HA, Greenberg, MS, Weiman, AL, Gur, RC, Hungerbuhler, JP, Geschwind, N. Hemispheric asymmetry in the expression of positive and negative emotions. Neurologic evidence. Arch Neurol. 1982;39(4):210218.CrossRefGoogle ScholarPubMed
47.Lauterbach, EC, Schweri, MM. Amelioration of pseudobulbar affect by fluoxetine: possible alteration of dopamine-related pathophysiology by a selective serotonin reuptake inhibitor. J Clin Psychopharmacol. 1991;11(6):392393.CrossRefGoogle ScholarPubMed
48.Brooks, BR, Thisted, RA, Appel, SH, et al.Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology. 2004;63(8):13641370.CrossRefGoogle ScholarPubMed
49.Derex, L, Ostrowsky, K, Nighoghossian, N, Trouillas, P. Severe pathological crying after left anterior choroidal artery infarct. Reversibility with paroxetine treatment. Stroke. 1997;28(7):14641466.CrossRefGoogle ScholarPubMed
50.Murai, T, Barthel, H, Berrouschot, J, Sorger, D, von Cramon, DY, Muller, U. Neuroimaging of serotonin transporters in post-stroke pathological crying. Psychiatry Res. 2003;123(3):207211.CrossRefGoogle ScholarPubMed
51.Klein, M, Musacchio, JM. High affinity dextromethorphan binding sites in guinea pig brain. Effect of sigma ligands and other agents. J Pharmacol Exp Ther. 1989;251(1):207215.Google ScholarPubMed
52.Tortella, FC, Pellicano, M, Bowery, NG. Dextromethorphan and neuromodulation: old drug coughs up new activities. Trends Pharmacol Sci. 1989;10(12):501507.CrossRefGoogle ScholarPubMed
53.Bermack, JE, Debonnel, G. The role of sigma receptors in depression. J Pharmacol Sci. 2005; 97(3):317336.CrossRefGoogle ScholarPubMed
54.Yamamoto, H, Yamamoto, T, Sagi, N, et al.Sigma ligands indirectly modulate the NMDA receptor-ion channel complex on intact neuronal cells via sigma 1 site. J Neurosci. 1995;15(1 Pt 2):731736.CrossRefGoogle ScholarPubMed
55.Rogawski, MA. Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents--toward an understanding of their favorable tolerability. Amino Acids. 2000;19(1):133149.CrossRefGoogle ScholarPubMed
56.Robinson, RG, Parikh, RM, Lipsey, JR, Starkstein, SE, Price, TR. Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study. Am J Psychiatry. 1993;150(2):286293.Google Scholar
57.Newsom-Davis, IC, Abrahams, S, Goldstein, LH, Leigh, PN. The emotional lability questionnaire: a new measure of emotional lability in amyotrophic lateral sclerosis. J Neurol Sci. 1999;169(1-2):2225.CrossRefGoogle ScholarPubMed
58.Harvey, PD, Greenberg, BR, Serper, MR. The affective lability scales: development, reliability, and validity. J Clin Psychol. 1989;45(5):786793.3.0.CO;2-P>CrossRefGoogle Scholar
59.Sloan, RL, Brown, KW, Pentland, B. Fluoxetine as a treatment for emotional lability after brain injury. Brain Inj. 1992; 6(4):315319.CrossRefGoogle ScholarPubMed
60.Smith, RA, Berg, JE, Pope, LE, Callahan, JD, Wynn, D, Thisted, RA. Validation of the CNS emotional lability scale for pseudobulbar affect (pathological laughing and crying) in multiple sclerosis patients. Mult Scler. 2004;10(6):679685.CrossRefGoogle Scholar
61.Szczudlik, A, Slowik, A, Tomik, B. The effect of amitriptyline on the pathological crying and other pseudobulbar signs. Neurol Neurochir Pol. 1995;29(5):663674.Google ScholarPubMed
62.Schiffer, RB, Herndon, RM, Rudick, RA. Treatment of pathologic laughing and weeping with amitriptyline. N Engl J Med. 1985;312(23):14801482.CrossRefGoogle Scholar
63.Andersen, G, Vestergaard, K, Riis, JO. Citalopram for post-stroke pathological crying. Lancet. 1993;342:837839.CrossRefGoogle ScholarPubMed
64.Lawson, IR, MacLeod, RD. The use of imipramine (“Tofranil”) and other psychotropic drugs in organic emotionalism. Br J Psychiatry. 1969;115(520):281285.CrossRefGoogle ScholarPubMed
65.Burns, A, Russell, E, Stratton-Powell, H, Tyrell, P, O'Neill, P, Baldwin, R. Sertraline in stroke-associated lability of mood. Int J Geriatr Psychiatry. 1999;14(8):681685.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
66.Nahas, Z, Arlinghaus, KA, Kotrla, KJ, Clearman, RR, George, MS. Rapid response of emotional incontinence to selective serotonin reuptake inhibitors. J Neuropsychiatry Clin Neurosci. 1998;10(4):453455.CrossRefGoogle ScholarPubMed
67.Müller, U, Murai, T, Bauer-Wittmund, T, von Cramon, DY. Paroxetine versus citalopram treatment of pathological crying after brain injury. Brain Inj. 1999;13(10):805811.CrossRefGoogle ScholarPubMed
68.Maurice, T, Urani, A, Phan, VL, Romieu, P. The interaction between neuroactive steroids and the sigma1 receptor function: behavioral consequences and therapeutic opportunities. Brain Res Brain Res Rev. 2001;37(1-3):116132.CrossRefGoogle ScholarPubMed
69.Choi, DW, Peters, S, Viseskul, V. Dextrorphan and levorphanol selectively block N-methyl-D-aspartate receptor-mediated neurotoxicity on cortical neurons. J Pharmacol Exp Ther. 1987;242(2):713720.Google ScholarPubMed
70.Chapman, AG, Meldrum, BS. Non-competitive N-methyl-D-aspartate antagonists protect against sound-induced seizures in DBA/2 mice. Eur J Pharmacol. 1989; 18;166(2):201211.CrossRefGoogle ScholarPubMed
71.Clement, HW, Grote, C, Svensson, L, Engel, J, Zofel, P, Wesemann, W. In vivo studies on the effects of memantine on dopamine metabolism in the striatum and n. accumbens of the rat. J Neural Transm Suppl. 1995;46:107–15.Google Scholar
72.Bubser, M, Keseberg, U, Notz, PK, Schmidt, WJ. Differential behavioural and neurochemical effects of competitive and non-competitive NMDA receptor antagonists in rats. Eur J Pharmacol. 1992; 8:229(1):7582.CrossRefGoogle ScholarPubMed
73.Moresco, RM, Volonte, MA, Messa, C, et al.New perspectives on neurochemical effects of amantadine in the brain of parkinsonian patients: a PET - [(11)C]raclopride study. J Neural Transm. 2002;109(10):12651274.CrossRefGoogle ScholarPubMed
74.Kim, HS, Park, IS, Lim, HK, Choi, HS. NMDA receptor antagonists enhance 5-HT2 receptor-mediated behavior, head-twitch response, in PCPA-treated mice. Arch Pharm Res. 1999;22(2):113118.CrossRefGoogle ScholarPubMed
75.Kim, HS, Park, IS, Park, WK. NMDA receptor antagonists enhance 5-HT2receptor-mediated behavior, head-twitch response, in mice. Life Sci. 1998;63(26):23052311.CrossRefGoogle ScholarPubMed
76.Meoni, P, Tortella, FC, Bowery, NG. An autoradiographic study of dextromethorphan high-affinity binding sites in rat brain: sodium-dependency and colocalization with paroxetine. Br J Pharmacol. 1997;120(7):12551262.CrossRefGoogle ScholarPubMed
77.Nemeroff, CB. Recent advances in the neurobiology of depression. Psychopharmacol Bull. 2002;36(Suppl 2):623.Google Scholar
78.Henn, FA, Vollmayr, B. Basic pathophysiological mechanisms in depression: what are they and how might they affect the course of the illness? Pharmacopsychiatry. 2004;37(suppl 2):S152156.CrossRefGoogle ScholarPubMed
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the or variations. ‘’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

The Differential Diagnosis of Pseudobulbar Affect (PBA): Distinguishing PBA Among Disorders of Mood and Affect
Available formats

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

The Differential Diagnosis of Pseudobulbar Affect (PBA): Distinguishing PBA Among Disorders of Mood and Affect
Available formats

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

The Differential Diagnosis of Pseudobulbar Affect (PBA): Distinguishing PBA Among Disorders of Mood and Affect
Available formats

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *