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Intranasal oxytocin increases facial expressivity, but not ratings of trustworthiness, in patients with schizophrenia and healthy controls

Published online by Cambridge University Press:  16 January 2017

J. D. Woolley ,
B. Chuang ,
C. Fussell ,
S. Scherer ,
B. Biagianti ,
D. Fulford ,
D. H. Mathalon  and
S. Vinogradov
J. D. Woolley*
Affiliation:
Department of Psychiatry, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA
B. Chuang
Affiliation:
Department of Psychiatry, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA
C. Fussell
Affiliation:
Department of Psychiatry, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA
S. Scherer
Affiliation:
Institute for Creative Technologies, University of Southern California, Los Angeles, CA, USA
B. Biagianti
Affiliation:
Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA
D. Fulford
Affiliation:
Departments of Occupational Therapy and Psychological & Brain Sciences, Boston University, Boston, MA, USA
D. H. Mathalon
Affiliation:
Department of Psychiatry, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA
S. Vinogradov
Affiliation:
Department of Psychiatry, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA
*
*Address for correspondence: J. Woolley, M.D./Ph.D., Department of Psychiatry, University of California San Francisco, 4150 Clement Street, 116C-1, San Francisco, CA 94121, USA. (Email: [email protected])
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Abstract

Background

Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population.

Method

We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants’ facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES).

Results

While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z = −2.33, p = 0.02) and at trend level in healthy controls (Z = −1.87, p = 0.06).

Conclusions

These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.

Keywords

Blunted affectfacial expressivityoxytocinschizophreniasocial cognitiontrustworthiness
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 7 , May 2017 , pp. 1311 - 1322
Copyright
Copyright © Cambridge University Press 2017 

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References

Abu-Akel, A, Fischer-Shofty, M, Levkovitz, Y, Decety, J, Shamay-Tsoory, S (2014). The role of oxytocin in empathy to the pain of conflictual out-group members among patients with schizophrenia. Psychological Medicine 44, 3523–3532.CrossRefGoogle Scholar
Adolphs, R, Tranel, D, Damasio, AR (1998). The human amygdala in social judgment. Nature 393, 470–474.CrossRefGoogle ScholarPubMed
Aghevli, MA, Blanchard, JJ, Horan, WP (2003). The expression and experience of emotion in schizophrenia: a study of social interactions. Psychiatry Research 119, 261–270.Google Scholar
Andreasen, NC, Pressler, M, Nopoulos, P, Miller, D, Ho, BC (2010). Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs. Biological Psychiatry 67, 255–262.CrossRefGoogle ScholarPubMed
Anticevic, A, Repovs, G, Barch, DM (2012). Emotion effects on attention, amygdala activation, and functional connectivity in schizophrenia. Schizophrenia Bulletin 38, 967–980.CrossRefGoogle ScholarPubMed
Baas, D, Aleman, A, Vink, M, Ramsey, NF, De Haan, EH, Kahn, RS (2008 a). Evidence of altered cortical and amygdala activation during social decision-making in schizophrenia. NeuroImage 40, 719–727.CrossRefGoogle ScholarPubMed
Baas, D, Van't Wout, M, Aleman, A, Kahn, R (2008 b). Social judgement in clinically stable patients with schizophrenia and healthy relatives: behavioural evidence of social brain dysfunction. Psychological Medicine 38, 747–754.Google Scholar
Barraza, JA, Zak, PJ (2009). Empathy toward strangers triggers oxytocin release and subsequent generosity. Annals of the New York Academy of Sciences 1167, 182–189.Google Scholar
Berenbaum, H, Oltmanns, TF (1992). Emotional experience and expression in schizophrenia and depression. Journal of Abnormal Psychology 101, 37–44.Google Scholar
Blanchard, JJ, Cohen, AS (2006). The structure of negative symptoms within schizophrenia: implications for assessment. Schizophrenia Bulletin 32, 238–245.Google Scholar
Busnelli, M, Dagani, J, Girolamo, G, Balestrieri, M, Pini, S, Saviotti, FM, Scocco, P, Sisti, D, Rocchi, M, Chini, B (2016). Unaltered oxytocin and vasopressin plasma levels in patients with schizophrenia after 4 months of daily treatment with intranasal oxytocin. Journal of Neuroendocrinology 28. Published online 25 April 2016. doi:10.1111/jne.12359.CrossRefGoogle ScholarPubMed
Cacciotti-Saija, C, Langdon, R, Ward, PB, Hickie, IB, Scott, EM, Naismith, SL, Moore, L, Alvares, GA, Redoblado, Hod ge, MA, Guastella, AJ (2015). A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis. Schizophrenia Bulletin 41, 483–493.CrossRefGoogle ScholarPubMed
Cohen, AS, Alpert, M, Nienow, TM, Dinzeo, TJ, Docherty, NM (2008). Computerized measurement of negative symptoms in schizophrenia. Journal of Psychiatry Research 42, 827–836.CrossRefGoogle ScholarPubMed
Cohen, AS, Minor, KS (2010). Emotional experience in patients with schizophrenia revisited: meta-analysis of laboratory studies. Schizophrenia Bulletin 36, 143–150.Google Scholar
Couture, SM, Penn, DL, Addington, J, Woods, SW, Perkins, DO (2008). Assessment of social judgments and complex mental states in the early phases of psychosis. Schizophrenia Research 100, 237–241.Google Scholar
Dagani, J, Sisti, D, Abelli, M, Di Paolo, L, Pini, S, Raimondi, S, Rocchi, MB, Saviotti, FM, Scocco, P, Totaro, S, Balestrieri, M, de Girolamo, G (2016). Do we need oxytocin to treat schizophrenia? A randomized clinical trial. Schizophrenia Research 172, 158–164.CrossRefGoogle ScholarPubMed
Eckert, SL, Diamond, PM, Miller, AL, Velligan, DI, Funderburg, LG, True, JE (1996). A comparison of instrument sensitivity to negative symptom change. Psychiatry Research 63, 67–75.CrossRefGoogle ScholarPubMed
Ekman, P, Friesen, WV (1976). Measuring facial movement. Environmental Psychology and Nonverbal Behavior 1, 56–75.CrossRefGoogle Scholar
Feifel, D, Macdonald, K, Nguyen, A, Cobb, P, Warlan, H, Galangue, B, Minassian, A, Becker, O, Cooper, J, Perry, W, Lefebvre, M, Gonzales, J, Hadley, A (2010). Adjunctive intranasal oxytocin reduces symptoms in schizophrenia patients. Biological Psychiatry 68, 678–680.Google Scholar
Feifel, D, Shilling, PD, Macdonald, K (2016). A review of oxytocin's effects on the positive, negative, and cognitive domains of schizophrenia. Biological Psychiatry 79, 222–233.Google Scholar
First, MB, Gibbon, M, Spitzer, RL, Williams, JBW (2002). Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Research Version, Patient Edition (SCID-I/P). New York State Psychiatric Institute: New York.Google Scholar
Foussias, G, Siddiqui, I, Fervaha, G, Agid, O, Remington, G (2015). Dissecting negative symptoms in schizophrenia: opportunities for translation into new treatments. Journal of Psychopharmacology 29, 116–126.Google Scholar
Gamer, M, Büchel, C (2012). Oxytocin specifically enhances valence-dependent parasympathetic responses. Psychoneuroendocrinology 37, 87–93.CrossRefGoogle ScholarPubMed
Gibson, CM, Penn, DL, Smedley, KL, Leserman, J, Elliott, T, Pedersen, CA (2014). A pilot six-week randomized controlled trial of oxytocin on social cognition and social skills in schizophrenia. Schizophrenia Research 156, 261–265.Google Scholar
Green, MF (2016). Impact of cognitive and social cognitive impairment on functional outcomes in patients with schizophrenia. Journal of Clinical Psychiatry 77 (Suppl. 2), 8–11.CrossRefGoogle ScholarPubMed
Gur, RE, Kohler, CG, Ragland, JD, Siegel, SJ, Lesko, K, Bilker, WB, Gur, RC (2006). Flat affect in schizophrenia: relation to emotion processing and neurocognitive measures. Schizophrenia Bulletin 32, 279–287.Google Scholar
Gur, RE, Loughead, J, Kohler, CG, Elliott, MA, Lesko, K, Ruparel, K, Wolf, DH, Bilker, WB, Gur, RC (2007). Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia. Archives of General Psychiatry 64, 1356–1366.CrossRefGoogle ScholarPubMed
Hooker, CI, Tully, LM, Verosky, SC, Fisher, M, Holland, C, Vinogradov, S (2011). Can I trust you? Negative affective priming influences social judgments in schizophrenia. Journal of Abnormal Psychology 120, 98–107.Google Scholar
Horta de Macedo, LR, Zuardi, AW, Machado-De-Sousa, JP, Chagas, MH, Hallak, JE (2014). Oxytocin does not improve performance of patients with schizophrenia and healthy volunteers in a facial emotion matching task. Psychiatry Research 220, 125–128.Google Scholar
Kay, SR, Fiszbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.CrossRefGoogle ScholarPubMed
Kirsch, P, Esslinger, C, Chen, Q, Mier, D, Lis, S, Siddhanti, S, Gruppe, H, Mattay, VS, Gallhofer, B, Meyer-Lindenberg, A (2005). Oxytocin modulates neural circuitry for social cognition and fear in humans. Journal of Neuroscience 25, 11489–11493.CrossRefGoogle ScholarPubMed
Kosfeld, M, Heinrichs, M, Zak, PJ, Fischbacher, U, Fehr, E (2005). Oxytocin increases trust in humans. Nature 435, 673–676.Google Scholar
Kring, AM, Elis, O (2013). Emotion deficits in people with schizophrenia. Annual Review of Clinical Psychology 9, 409–433.Google Scholar
Kring, AM, Moran, EK (2008). Emotional response deficits in schizophrenia: insights from affective science. Schizophrenia Bulletin 34, 819–834.Google Scholar
Kring, AM, Neale, JM (1996). Do schizophrenic patients show a disjunctive relationship among expressive, experiential, and psychophysiological components of emotion? Journal of Abnormal Psychology 105, 249–257.Google Scholar
Kring, AM, Sloan, DM (2007). The Facial Expression Coding System (FACES): development, validation, and utility. Psychological Assessment 19, 210–224.CrossRefGoogle ScholarPubMed
Kring, AM, Smith, DA, Neale, JM (1994). Individual differences in dispositional expressiveness: development and validation of the emotional expressivity scale. Journal of Personality and Social Psychology 66, 934–949.CrossRefGoogle ScholarPubMed
Lambert, B, Declerck, CH, Boone, C (2014). Oxytocin does not make a face appear more trustworthy but improves the accuracy of trustworthiness judgments. Psychoneuroendocrinology 40, 60–68.Google Scholar
Lepage, M, Sergerie, K, Benoit, A, Czechowska, Y, Dickie, E, Armony, JL (2011). Emotional face processing and flat affect in schizophrenia: functional and structural neural correlates. Psychological Medicine 41, 1833–1844.Google Scholar
Lukoff, D, Liberman, RP, Nuechterlein, KH (1986). Symptom monitoring in the rehabilitation of schizophrenic patients. Schizophrenia Bulletin 12, 578–602.CrossRefGoogle ScholarPubMed
Michelini, LC, Marcelo, MC, Amico, J, Morris, M (2003). Oxytocinergic regulation of cardiovascular function: studies in oxytocin-deficient mice. American Journal of Physiology – Heart and Circulatory Physiology 284, H2269–H2276.CrossRefGoogle ScholarPubMed
Narum, SR (2006). Beyond Bonferroni: less conservative analyses for conservation genetics. Conservation Genetics 7, 783–787.Google Scholar
Norman, GJ, Cacioppo, JT, Morris, JS, Karelina, K, Malarkey, WB, Devries, AC, Berntson, GG (2011). Selective influences of oxytocin on the evaluative processing of social stimuli. Journal of Psychopharmacology 25, 1313–1319.Google Scholar
Pedersen, CA, Gibson, CM, Rau, SW, Salimi, K, Smedley, KL, Casey, RL, Leserman, J, Jarskog, LF, Penn, DL (2011). Intranasal oxytocin reduces psychotic symptoms and improves theory of mind and social perception in schizophrenia. Schizophrenia Research 132, 50–53.Google Scholar
Peterman, JS, Bekele, E, Bian, D, Sarkar, N, Park, S (2015). Complexities of emotional responses to social and non-social affective stimuli in schizophrenia. Frontiers in Psychology 6, 320.CrossRefGoogle ScholarPubMed
Pinkham, AE, Hopfinger, JB, Pelphrey, KA, Piven, J, Penn, DL (2008). Neural bases for impaired social cognition in schizophrenia and autism spectrum disorders. Schizophrenia Research 99, 164–175.Google Scholar
Repantis, D, Laisney, O, Heuser, I (2010). Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacological Research 61, 473–481.Google Scholar
Scherer, S, Stratou, G, Lucas, G, Mahmoud, M, Boberg, J, Gratch, J, Morency, L-P (2014). Automatic audiovisual behavior descriptors for psychological disorder analysis. Image and Vision Computing 32, 648–658.Google Scholar
Serretti, A, Calati, R, Goracci, A, Di Simplicio, M, Castrogiovanni, P, De Ronchi, D (2010). Antidepressants in healthy subjects: what are the psychotropic/psychological effects? European Neuropsychopharmacology 20, 433–453.CrossRefGoogle ScholarPubMed
Shin, NY, Park, HY, Jung, WH, Park, JW, Yun, JY, Jang, JH, Kim, SN, Han, HJ, Kim, SY, Kang, DH, Kwon, JS (2015). Effects of oxytocin on neural response to facial expressions in patients with schizophrenia. Neuropsychopharmacology 40, 1919–1927.Google Scholar
Shrout, PE, Fleiss, JL (1979). Intraclass correlations: uses in assessing rater reliability. Psychological Bulletin 86, 420–428.Google Scholar
Sripada, CS, Phan, KL, Labuschagne, I, Welsh, R, Nathan, PJ, Wood, AG (2013). Oxytocin enhances resting-state connectivity between amygdala and medial frontal cortex. International Journal of Neuropsychopharmacology 16, 255–260.CrossRefGoogle ScholarPubMed
Sweet, LH, Primeau, M, Fichtner, CG, Lutz, G (1998). Dissociation of affect recognition and mood state from blunting in patients with schizophrenia. Psychiatry Research 81, 301–308.Google Scholar
Taylor, SF, Phan, KL, Decker, LR, Liberzon, I (2003). Subjective rating of emotionally salient stimuli modulates neural activity. NeuroImage 18, 650–659.Google Scholar
Tremeau, F, Malaspina, D, Duval, F, Correa, H, Hager-Budny, M, Coin-Bariou, L, Macher, JP, Gorman, JM (2005). Facial expressiveness in patients with schizophrenia compared to depressed patients and nonpatient comparison subjects. American Journal of Psychiatry 162, 92–101.CrossRefGoogle ScholarPubMed
Tsapakis, EM, Dimopoulou, T, Tarazi, FI (2015). Clinical management of negative symptoms of schizophrenia: an update. Pharmacology and Therapeutics 153, 135–147.Google Scholar
Walker, EF, Grimes, KE, Davis, DM, Smith, AJ (1993). Childhood precursors of schizophrenia: facial expressions of emotion. American Journal of Psychiatry 150, 1654–1660.Google Scholar
Weiser, M, Saporta, L, Levi, L, Feldman, R (2015). S.13.03 RCT administering oxytocin for schizophrenia, a three week add-on study. European Neuropsychopharmacology 25 (Suppl. 2), S130–S131.Google Scholar
Winston, JS, Strange, BA, O'Doherty, J, Dolan, RJ (2002). Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nature Neuroscience 5, 277–283.Google Scholar
Wolf, K, Mass, R, Kiefer, F, Eckert, K, Stritzky, AV, Haasen, C, Wiedemann, K, Naber, D (2005). The influence of olanzapine versus risperidone on facial expression of emotions in schizophrenia – preliminary results of a facial electromyogram study. Journal of Clinical Psychopharmacology 25, 278–281.Google Scholar
Woolley, JD, Chuang, B, Lam, O, Lai, W, O'Donovan, A, Rankin, KP, Mathalon, DH, Vinogradov, S (2014). Oxytocin administration enhances controlled social cognition in patients with schizophrenia. Psychoneuroendocrinology 47, 116–125.Google Scholar
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