Skip to main content Accessibility help

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

  • J. D. Woolley (a1) (a2), B. Chuang (a1) (a2), C. Fussell (a1) (a2), S. Scherer (a3), B. Biagianti (a2), D. Fulford (a4), D. H. Mathalon (a1) (a2) and S. Vinogradov (a1) (a2)...



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.


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).


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).


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.


Corresponding author

*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:


Hide All
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, 35233532.
Adolphs, R, Tranel, D, Damasio, AR (1998). The human amygdala in social judgment. Nature 393, 470474.
Aghevli, MA, Blanchard, JJ, Horan, WP (2003). The expression and experience of emotion in schizophrenia: a study of social interactions. Psychiatry Research 119, 261270.
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, 255262.
Anticevic, A, Repovs, G, Barch, DM (2012). Emotion effects on attention, amygdala activation, and functional connectivity in schizophrenia. Schizophrenia Bulletin 38, 967980.
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, 719727.
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, 747754.
Barraza, JA, Zak, PJ (2009). Empathy toward strangers triggers oxytocin release and subsequent generosity. Annals of the New York Academy of Sciences 1167, 182189.
Berenbaum, H, Oltmanns, TF (1992). Emotional experience and expression in schizophrenia and depression. Journal of Abnormal Psychology 101, 3744.
Blanchard, JJ, Cohen, AS (2006). The structure of negative symptoms within schizophrenia: implications for assessment. Schizophrenia Bulletin 32, 238245.
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.
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, 483493.
Cohen, AS, Alpert, M, Nienow, TM, Dinzeo, TJ, Docherty, NM (2008). Computerized measurement of negative symptoms in schizophrenia. Journal of Psychiatry Research 42, 827836.
Cohen, AS, Minor, KS (2010). Emotional experience in patients with schizophrenia revisited: meta-analysis of laboratory studies. Schizophrenia Bulletin 36, 143150.
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, 237241.
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, 158164.
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, 6775.
Ekman, P, Friesen, WV (1976). Measuring facial movement. Environmental Psychology and Nonverbal Behavior 1, 5675.
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, 678680.
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, 222233.
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.
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, 116126.
Gamer, M, Büchel, C (2012). Oxytocin specifically enhances valence-dependent parasympathetic responses. Psychoneuroendocrinology 37, 8793.
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, 261265.
Green, MF (2016). Impact of cognitive and social cognitive impairment on functional outcomes in patients with schizophrenia. Journal of Clinical Psychiatry 77 (Suppl. 2), 811.
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, 279287.
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, 13561366.
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, 98107.
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, 125128.
Kay, SR, Fiszbein, A, Opler, LA (1987). The Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.
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, 1148911493.
Kosfeld, M, Heinrichs, M, Zak, PJ, Fischbacher, U, Fehr, E (2005). Oxytocin increases trust in humans. Nature 435, 673676.
Kring, AM, Elis, O (2013). Emotion deficits in people with schizophrenia. Annual Review of Clinical Psychology 9, 409433.
Kring, AM, Moran, EK (2008). Emotional response deficits in schizophrenia: insights from affective science. Schizophrenia Bulletin 34, 819834.
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.
Kring, AM, Sloan, DM (2007). The Facial Expression Coding System (FACES): development, validation, and utility. Psychological Assessment 19, 210224.
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.
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, 6068.
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, 18331844.
Lukoff, D, Liberman, RP, Nuechterlein, KH (1986). Symptom monitoring in the rehabilitation of schizophrenic patients. Schizophrenia Bulletin 12, 578602.
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, H2269H2276.
Narum, SR (2006). Beyond Bonferroni: less conservative analyses for conservation genetics. Conservation Genetics 7, 783787.
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, 13131319.
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, 5053.
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.
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, 164175.
Repantis, D, Laisney, O, Heuser, I (2010). Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacological Research 61, 473481.
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, 648658.
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, 433453.
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, 19191927.
Shrout, PE, Fleiss, JL (1979). Intraclass correlations: uses in assessing rater reliability. Psychological Bulletin 86, 420428.
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, 255260.
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, 301308.
Taylor, SF, Phan, KL, Decker, LR, Liberzon, I (2003). Subjective rating of emotionally salient stimuli modulates neural activity. NeuroImage 18, 650659.
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, 92101.
Tsapakis, EM, Dimopoulou, T, Tarazi, FI (2015). Clinical management of negative symptoms of schizophrenia: an update. Pharmacology and Therapeutics 153, 135147.
Walker, EF, Grimes, KE, Davis, DM, Smith, AJ (1993). Childhood precursors of schizophrenia: facial expressions of emotion. American Journal of Psychiatry 150, 16541660.
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), S130S131.
Winston, JS, Strange, BA, O'Doherty, J, Dolan, RJ (2002). Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nature Neuroscience 5, 277283.
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, 278281.
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, 116125.


Type Description Title
Supplementary materials

Woolley supplementary material
Woolley supplementary material 1

 Word (205 KB)
205 KB


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed