Psychopharmacology

, Volume 200, Issue 2, pp 261–272

Effect of risperidone versus haloperidol on emotional responding in schizophrenic patients

  • E. Fakra
  • S. Khalfa
  • D. Da Fonseca
  • N. Besnier
  • P. Delaveau
  • J. M. Azorin
  • O. Blin
Original Investigation

Abstract

Rationale

Studies on emotional processing report that schizophrenic patients present a specific pattern of emotional responding that usually includes deficits in emotional expressiveness, increased feelings of unpleasant emotion but decreased feelings of pleasant emotion, and increased physiological reactivity. However, studies have rarely controlled the nature of antipsychotic medication. Yet, the influence of these drugs on emotional response is uncertain and could vary depending on their pharmacological profile.

Objective

This prospective and randomized study aimed to compare the effects of an atypical antipsychotic, risperidone, to a typical one, haloperidol, on patients’ emotional responding during an emotional induction task.

Materials and methods

Twenty-five schizophrenic patients underwent two emotional and clinical evaluations: one before treatment initiation and a second 4 weeks after. Emotional states of fear, sadness, anger, joy, and disgust were induced, as well as a neutral baseline state. Video recordings of patients during the induction task allowed for assessment of emotional expressiveness. Self-reports and measures of skin conductance and heart rate were performed to determine both subjective and physiological reactions to emotional experience.

Results

Compared to haloperidol, risperidone did not reduce patients’ facial expressiveness, decreased physiological reactivity, and decreased experience of unpleasant emotion but maintained experience of pleasant emotion. Emotional expressiveness was negatively correlated to parkisonism.

Conclusions

Our preliminary results suggest that atypical antipsychotics allow for better-adapted patterns of emotional responding than typical ones do. We suggest that this effect is due to reduced striatal D2 blockade, therefore, attenuating akinesia, coupled with increased 5HT and DA levels in prefrontal cortex, which improves emotional regulation.

Keywords

Schizophrenia Antipsychotic agents Emotion Facial expressions Emotional experience Physiological responses Serotonin Dopamine Prefrontal cortex 

References

  1. Aalto S, Wallius E, Naatanen P, Hiltunen J, Metsahonkala L, Sipila H, Karlsson H (2005) Regression analysis utilizing subjective evaluation of emotional experience in PET studies on emotions. Brain Res Brain Res Protoc 15:142–154PubMedCrossRefGoogle Scholar
  2. Aleman A, Kahn RS (2005) Strange feelings: do amygdala abnormalities dysregulate the emotional brain in schizophrenia? Prog Neurobiol 77:283–298PubMedGoogle Scholar
  3. Audet MC, Goulet S, Dore FY (2007) Enhanced anxiety follows withdrawal from subchronic exposure to phencyclidine in rats. Behav Brain Res 176:358–361PubMedCrossRefGoogle Scholar
  4. Berenbaum H, Oltmanns TF (1992) Emotional experience and expression in schizophrenia and depression. J Abnorm Psychol 101:37–44PubMedCrossRefGoogle Scholar
  5. Breier A (1995) Serotonin, schizophrenia and antipsychotic drug action. Schizophr Res 14:187–202PubMedCrossRefGoogle Scholar
  6. Burbridge JA, Larsen RJ, Barch DM (2005) Affective reactivity in language: the role of psychophysiological arousal. Emotion 5:145–153PubMedCrossRefGoogle Scholar
  7. Casey DE (2004) Pathophysiology of antipsychotic drug-induced movement disorders. J Clin Psychiatry 65 Suppl 9:25–28Google Scholar
  8. Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Kirshner MA, Bies RR, Kapur S, Gharabawi G (2006) A model of anticholinergic activity of atypical antipsychotic medications. Schizophr Res 88:63–72PubMedCrossRefGoogle Scholar
  9. Chouinard G, Ross-Chouinard A, Annable L, Jones B (1980) The extra-pyramidal symptom rating scale. Can J Neurol Sci 7:233Google Scholar
  10. Davidson RJ, Putnam KM, Larson CL (2000) Dysfunction in the neural circuitry of emotion regulation—a possible prelude to violence. Science 289:591–594PubMedCrossRefGoogle Scholar
  11. de Haan L, van Bruggen M, Lavalaye J, Booij J, Dingemans PM, Linszen D (2003) Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study. Am J Psychiatry 160:303–309PubMedCrossRefGoogle Scholar
  12. de Millas W, Lambert M, Naber D (2006) The impact of subjective well-being under neuroleptic treatment on compliance and remission. Dialogues Clin Neurosci 8:131–136PubMedGoogle Scholar
  13. Delay J, Deniker P (1956) Chlorpromazine and neuroleptic treatments in psychiatry. J Clin Exp Psychopathol 17:19–24PubMedGoogle Scholar
  14. DSM-IV-TR (2000) Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text Revised (DSM-IV-TR). In: Association AP (ed), Washington, DC, pp 803–805Google Scholar
  15. Dworkin RH, Clark SC, Amador XF, Gorman JM (1996) Does affective blunting in schizophrenia reflect affective deficit or neuromotor dysfunction? Schizophr Res 20:301–306PubMedCrossRefGoogle Scholar
  16. Earnst KS, Kring AM (1999) Emotional responding in deficit and non-deficit schizophrenia. Psychiatry Res 88:191–207PubMedCrossRefGoogle Scholar
  17. Earnst KS, Kring AM, Kadar MA, Salem JE, Shepard DA, Loosen PT (1996) Facial expression in schizophrenia. Biol Psychiatry 40:556–558PubMedCrossRefGoogle Scholar
  18. Fahrenberg J (1988) Psychophysiological processes. In: Nesselroade JR, Cattell RB (eds) Handbook of multivariate experimental psychology, 2nd edn. Plenum, New York, pp 867–914Google Scholar
  19. Fakra E, Salgado-Pineda P, Besnier N, Azorin JM, Blin O (2007) Risperidone versus haloperidol for facial affect recognition in schizophrenia: findings from a randomised study. World J Biol Psychiatry 10:1–10Google Scholar
  20. First MB, Spitzer RL, Gibbon M, Williams JBW (1994) Structured Clinical Interview for DSM-IV—Patient Version. Biometrics Research Department, New York State Psychiatric Institute, New YorkGoogle Scholar
  21. Flack WF Jr, Cavallaro LA, Laird JD, Miller DR (1997) Accurate encoding and decoding of emotional facial expressions in schizophrenia. Psychiatry 60:197–210PubMedGoogle Scholar
  22. Fleischhacker WW, Rabinowitz J, Kemmler G, Eerdekens M, Mehnert A (2005) Perceived functioning, well-being and psychiatric symptoms in patients with stable schizophrenia treated with long-acting risperidone for 1 year. Br J Psychiatry 187:131–136PubMedCrossRefGoogle Scholar
  23. Fowles DC, Christie MJ, Edelberg R, Grings WW, Lykken DT, Venables PH (1981) Committee report. Publication recommendations for electrodermal measurements. Psychophysiology 18:232–239PubMedCrossRefGoogle Scholar
  24. Gaebel W, Wolwer W (1992) Facial expression and emotional face recognition in schizophrenia and depression. Eur Arch Psychiatry Clin Neurosci 242:46–52PubMedCrossRefGoogle Scholar
  25. Gaebel W, Wolwer W (2004) Facial expressivity in the course of schizophrenia and depression. Eur Arch Psychiatry Clin Neurosci 254:335–342PubMedCrossRefGoogle Scholar
  26. Garcia C, Philippot P, Lacarelle B, Valli M, Rime B, Bruguerolle B, Blin O (1997) Effects of lorazepam on film-induced differentiated emotions in healthy volunteers. Fundam Clin Pharmacol 11:466–475PubMedGoogle Scholar
  27. Gerrards-Hesse A, Spies K, Hesse FW (1994) Experimental inductions of emotional states and their effectiveness: a review. Br J Psychol 85:55–78Google Scholar
  28. Grace AA (2006) Disruption of cortical–limbic interaction as a substrate for comorbidity. Neurotox Res 10:93–101PubMedGoogle Scholar
  29. Green MF, Nuechterlein KH, Satz P (1989) The relationship of symptomatology and medication to electrodermal activity in schizophrenia. Psychophysiology 26:148–157PubMedCrossRefGoogle Scholar
  30. Gross J, Levenson R (1995) Emotion elicitation using films. Cogn Emot 9:87–108CrossRefGoogle Scholar
  31. Heerey EA, Gold JM (2007) Patients with schizophrenia demonstrate dissociation between affective experience and motivated behavior. J Abnorm Psychol 116:268–278PubMedCrossRefGoogle Scholar
  32. Hempel RJ, Tulen JH, van Beveren NJ, Mulder PG, Hengeveld MW (2007) Subjective and physiological responses to emotion-eliciting pictures in male schizophrenic patients. Int J Psychophysiol 64:174–183PubMedCrossRefGoogle Scholar
  33. Hertel P, Nomikos GG, Iurlo M, Svensson TH (1996) Risperidone: regional effects in vivo on release and metabolism of dopamine and serotonin in the rat brain. Psychopharmacology (Berl) 124:74–86CrossRefGoogle Scholar
  34. Ichikawa J, Kuroki T, Dai J, Meltzer HY (1998) Effect of antipsychotic drugs on extracellular serotonin levels in rat medial prefrontal cortex and nucleus accumbens. Eur J Pharmacol 351:163–171PubMedCrossRefGoogle Scholar
  35. Izard CE (1972) Patterns of emotions: a new analysis of anxiety and depression. Academic, New YorkGoogle Scholar
  36. Izard CE, Libero DZ, Putnam P, Haynes OM (1993) Stability of emotion experiences and their relations to traits of personality. J Pers Soc Psychol 64:847–860PubMedCrossRefGoogle Scholar
  37. Kane JM, Leucht S, Carpenter D, Docherty JP (2003) Expert consensus guideline series. Optimizing pharmacologic treatment of psychotic disorders. Introduction: methods, commentary, and summary. J Clin Psychiatry 64(Suppl 12):5–19PubMedGoogle Scholar
  38. Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276PubMedGoogle Scholar
  39. Kemp AH, Gray MA, Silberstein RB, Armstrong SM, Nathan PJ (2004) Augmentation of serotonin enhances pleasant and suppresses unpleasant cortical electrophysiological responses to visual emotional stimuli in humans. Neuroimage 22:1084–1096PubMedCrossRefGoogle Scholar
  40. Knable MB, Weinberger DR (1997) Dopamine, the prefrontal cortex and schizophrenia. J Psychopharmacol 11:123–131PubMedCrossRefGoogle Scholar
  41. Knutson B, Wolkowitz OM, Cole SW, Chan T, Moore EA, Johnson RC, Terpstra J, Turner RA, Reus VI (1998) Selective alteration of personality and social behavior by serotonergic intervention. Am J Psychiatry 155:373–379PubMedGoogle Scholar
  42. Kornreich C, Philippot P, Verpoorten C, Dan B, Baert I, Le Bon O, Verbanck P, Pelc I (1998) Alcoholism and emotional reactivity: more heterogeneous film-induced emotional response in newly detoxified alcoholics compared to controls—a preliminary study. Addict Behav 23:413–418PubMedCrossRefGoogle Scholar
  43. Kring AM, Earnst KS (1999) Stability of emotional responding in schizophrenia. Behav ther 30:373–388CrossRefGoogle Scholar
  44. Kring AM, Neale JM (1996) Do schizophrenic patients show a disjunctive relationship among expressive, experiential, and psychophysiological components of emotion? J Abnorm Psychol 105:249–257PubMedCrossRefGoogle Scholar
  45. Kring AM, Kerr SL, Smith DA, Neale JM (1993) Flat affect in schizophrenia does not reflect diminished subjective experience of emotion. J Abnorm Psychol 102:507–517PubMedCrossRefGoogle Scholar
  46. Lane RD, McRae K (2004) Neural substrates of conscious emotional experience: a cognitive-neuroscientific perspective. In: Beauregard M (ed) Consciousness, emotional self-regulation and the brain. John Benjamins, Amsterdam, The Netherlands, pp 87–122Google Scholar
  47. Lang PJ (1979) A bio-informational theory of emotional imagery. Psychophysiology 16:495–512PubMedCrossRefGoogle Scholar
  48. Lang PJ, Bradley MM, Cuthbert BN (1998) Emotion and motivation: measuring affective perception. J Clin Neurophysiol 15:397–408PubMedCrossRefGoogle Scholar
  49. Leucht S, Pitschel-Walz G, Abraham D, Kissling W (1999) Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr Res 35:51–68PubMedCrossRefGoogle Scholar
  50. Levesque J, Joanette Y, Mensour B, Beaudoin G, Leroux JM, Bourgouin P, Beauregard M (2003) Neural correlates of sad feelings in healthy girls. Neuroscience 121:545–551PubMedCrossRefGoogle Scholar
  51. Marder SR (2005) Subjective experiences on antipsychotic medications: synthesis and conclusions. Acta Psychiatr Scand 111:43–46CrossRefGoogle Scholar
  52. McGrath J, Scheldt S, Welham J, Clair A (1997) Performance on tests sensitive to impaired executive ability in schizophrenia, mania and well controls: acute and subacute phases. Schizophr Res 26:127–137PubMedCrossRefGoogle Scholar
  53. McGrath J, Chapple B, Wright M (2001) Working memory in schizophrenia and mania: correlation with symptoms during the acute and subacute phases. Acta Psychiatr Scand 103:181–188PubMedCrossRefGoogle Scholar
  54. Micallef J, Tardieu S, Gentile S, Fakra E, Jouve E, Sambuc R, Blin O (2003) Effects of a subanaesthetic dose of ketamine on emotional and behavioral state in healthy subjects. Neurophysiol Clin 33:138–147PubMedCrossRefGoogle Scholar
  55. Mueck-Weymann M, Rechlin T, Ehrengut F, Rauh R, Acker J, Dittmann RW, Czekalla J, Joraschky P, Musselman D (2002) Effects of olanzapine and clozapine upon pulse rate variability. Depress Anxiety 16:93–99PubMedCrossRefGoogle Scholar
  56. Nieoullon A, Coquerel A (2003) Dopamine: a key regulator to adapt action, emotion, motivation and cognition. Curr Opin Neurol 16(Suppl 2):S3–S9PubMedCrossRefGoogle Scholar
  57. Ochsner KN, Bunge SA, Gross JJ, Gabrieli JD (2002) Rethinking feelings: an FMRI study of the cognitive regulation of emotion. J Cogn Neurosci 14:1215–1229PubMedCrossRefGoogle Scholar
  58. Ouss L, Carton S, Jouvent R, Widlocher D (1990) French translation and validation of Izard’s differential emotion scale. Study of the verbal qualification of emotions. Encephale 16:453–458PubMedGoogle Scholar
  59. Phan KL, Fitzgerald DA, Nathan PJ, Moore GJ, Uhde TW, Tancer ME (2005) Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study. Biol Psychiatry 57:210–219PubMedCrossRefGoogle Scholar
  60. Philippot P (1993) Inducing and assessing differentiated emotion feeling states in the laboratory. Cogn Emot 7:171–173CrossRefGoogle Scholar
  61. Rao ML, Moller HJ (1994) Biochemical findings of negative symptoms in schizophrenia and their putative relevance to pharmacologic treatment. A review. Neuropsychobiology 30:160–172PubMedCrossRefGoogle Scholar
  62. Schneider F, Ellgring H, Friedrich J, Fus I, Beyer T, Heimann H, Himer W (1992) The effects of neuroleptics on facial action in schizophrenic patients. Pharmacopsychiatry 25:233–239PubMedCrossRefGoogle Scholar
  63. Schnur DB (1990) Effects of neuroleptics on electrodermal activity in schizophrenic patients: a review. Psychopharmacology (Berl) 102:429–437CrossRefGoogle Scholar
  64. Schooler NR, Kane JM (1982) Research diagnoses for tardive dyskinesia. Arch Gen Psychiatry 39:486–487PubMedGoogle Scholar
  65. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl) 124:57–73CrossRefGoogle Scholar
  66. Song F (1997) Risperidone in the treatment of schizophrenia: a meta-analysis of randomized controlled trials. J Psychopharmacol 11:65–71PubMedCrossRefGoogle Scholar
  67. Tremeau F (2006) A review of emotion deficits in schizophrenia. Dialogues Clin Neurosci 8:59–70PubMedGoogle Scholar
  68. Westermann R, Spies K, Stahl G, Hesse FW (1996) Relative effectiveness and validity of mood induction procedures: a meta-analysis. Eur J Soc Psychol 26:557–580CrossRefGoogle Scholar
  69. Williams LM, Das P, Harris AW, Liddell BB, Brammer MJ, Olivieri G, Skerrett D, Phillips ML, David AS, Peduto A, Gordon E (2004) Dysregulation of arousal and amygdala–prefrontal systems in paranoid schizophrenia. Am J Psychiatry 161:480–489PubMedCrossRefGoogle Scholar
  70. Williams LM, Das P, Liddell BJ, Olivieri G, Peduto AS, David AS, Gordon E, Harris AW (2007) Fronto-limbic and autonomic disjunctions to negative emotion distinguish schizophrenia subtypes. Psychiatry Res 155:29–44PubMedCrossRefGoogle Scholar
  71. Zahn TP, Pickar D, van Kammen DP (2001) Neuroleptic effects on autonomic activity in schizophrenia: between-group and within-subject paradigms and comparisons with controls. Schizophr Bull 27:503–515PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • E. Fakra
    • 1
    • 2
  • S. Khalfa
    • 1
  • D. Da Fonseca
    • 3
  • N. Besnier
    • 2
  • P. Delaveau
    • 1
  • J. M. Azorin
    • 2
  • O. Blin
    • 1
  1. 1.CIC-UPCET et Pharmacologie Clinique, Hôpital de la TimoneUMR CNRS 6193 Institut des Neurosciences Cognitives de la MéditerranéeMarseilleFrance
  2. 2.SHU PsychiatrieHôpital Ste. MargueriteMarseilleFrance
  3. 3.SHU Pédo-PsychiatrieHôpital Ste. MargueriteMarseilleFrance

Personalised recommendations