Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-23T10:40:27.320Z Has data issue: false hasContentIssue false
  • English
  • Français

The effects of combined oxytocin and cognitive behavioral social skills training on social cognition in schizophrenia

Published online by Cambridge University Press:  05 September 2018

Gregory P. Strauss ,
Eric Granholm ,
Jason L. Holden ,
Ivan Ruiz ,
James M. Gold ,
Deanna L. Kelly  and
Robert W. Buchanan
Gregory P. Strauss*
Affiliation:
Department of Psychology, University of Georgia, Athens, GA, USA
Eric Granholm
Affiliation:
VA San Diego Healthcare System, Department of Psychiatry, University of California San Diego School of Medicine, San Diego, CA, USA
Jason L. Holden
Affiliation:
VA San Diego Healthcare System, Department of Psychiatry, University of California San Diego School of Medicine, San Diego, CA, USA
Ivan Ruiz
Affiliation:
Department of Psychology, University of Georgia, Athens, GA, USA VA San Diego Healthcare System, Department of Psychiatry, University of California San Diego School of Medicine, San Diego, CA, USA
James M. Gold
Affiliation:
Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA
Deanna L. Kelly
Affiliation:
Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA
Robert W. Buchanan
Affiliation:
Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA
*
Author for correspondence: Gregory P. Strauss, E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Individuals with schizophrenia have deficits in social cognition that are associated with poor functional outcome. Unfortunately, current treatments result in only modest improvement in social cognition. Oxytocin, a neuropeptide with pro-social effects, has significant benefits for social cognition in the general population. However, studies examining the efficacy of oxytocin in schizophrenia have yielded inconsistent results. One reason for inconsistency may be that oxytocin has typically not been combined with psychosocial interventions. It may be necessary for individuals with schizophrenia to receive concurrent psychosocial treatment while taking oxytocin to have the context needed to make gains in social cognitive skills.

Methods

The current study tested this hypothesis in a 24-week (48 session) double-blind, placebo-controlled trial that combined oxytocin and Cognitive-Behavioral Social Skills Training (CBSST), which included elements from Social Cognition and Interaction Training (SCIT). Participants included 62 outpatients diagnosed with schizophrenia (placebo n = 31; oxytocin n = 31) who received 36 IU BID, with supervised administration 45 min prior to sessions on CBSST group therapy days. Participants completed a battery of measures administered at 0, 12, and 24 weeks that assessed social cognition.

Results

CBSST generally failed to enhance social cognition from baseline to end of study, and there was no additive benefit of oxytocin beyond the effects of CBSST alone.

Conclusions

Findings suggest that combined CBSST and oxytocin had minimal benefit for social cognition, adding to the growing literature indicating null effects of oxytocin in multi-dose trials. Methodological and biological factors may contribute to inconsistent results across studies.

Keywords

Oxytocinpsychosissocial cognition
Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 10 , July 2019 , pp. 1731 - 1739
Copyright
Copyright © Cambridge University Press 2018 

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.)

References

Addington, D, Addington, J and Schissel, B (1990) A depression rating scale for schizophrenics. Schizophrenia Research 3, 247–251.Google Scholar
Adolphs, R (2009) The social brain: neural basis of social knowledge. Annual Review of Psychology 60, 693–716.Google Scholar
Andreasen, N (1982) The Scale for the Assessment of Negative Symptoms (SANS). Iowa City, Iowa: The University of Iowa.Google Scholar
Bakermans-Kranenburg, M and Van Ijzendoorn, M (2013) Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy. Translational Psychiatry 3, e258.Google Scholar
Baron-Cohen, S, Wheelwright, S, Hill, J, Raste, Y and Plumb, I (2001) The “reading the mind in the eyes” test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. The Journal of Child Psychology and Psychiatry and Allied Disciplines 42, 241–251.Google Scholar
Bartz, JA, Zaki, J, Bolger, N and Ochsner, KN (2011) Social effects of oxytocin in humans: context and person matter. Trends in Cognitive Sciences 15, 301–309.Google Scholar
Baumgartner, T, Heinrichs, M, Vonlanthen, A, Fischbacher, U and Fehr, E (2008) Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 58, 639–650.Google Scholar
Beckmann, H, Lang, RE and Gattaz, WF (1985) Vasopressin – oxytocin in cerebrospinal fluid of schizophrenic patients and normal controls. Psychoneuroendocrinology 10, 187–191.Google Scholar
Bethlehem, RA, van Honk, J, Auyeung, B and Baron-Cohen, S (2013) Oxytocin, brain physiology, and functional connectivity: a review of intranasal oxytocin fMRI studies. Psychoneuroendocrinology 38, 962–974.Google Scholar
Birchwood, M, Smith, J, Cochrane, R, Wetton, S and Copestake, S (1990) The social functioning scale. The development and validation of a new scale of social adjustment for use in family intervention programmes with schizophrenic patients. The British Journal of Psychiatry 157, 853–859.Google Scholar
Bradley, ER and Woolley, JD (2017) Oxytocin effects in schizophrenia: reconciling mixed findings and moving forward. Neuroscience & Biobehavioral Reviews 80, 36–56.Google Scholar
Brambilla, M, Cotelli, M, Manenti, R, Dagani, J, Sisti, D, Rocchi, M, Balestrieri, M, Pini, S, Raimondi, S and Saviotti, FM (2016) Oxytocin to modulate emotional processing in schizophrenia: a randomized, double-blind, cross-over clinical trial. European Neuropsychopharmacology 26, 1619–1628.Google Scholar
Bürkner, P-C, Williams, DR, Simmons, TC and Woolley, JD (2017) Intranasal oxytocin may improve high-level social cognition in schizophrenia, but not social cognition or neurocognition in general: a multilevel Bayesian meta-analysis. Schizophrenia Bulletin 43, 1291–1303.Google Scholar
Cacciotti-Saija, C, Langdon, R, Ward, PB, Hickie, IB, Scott, EM, Naismith, SL, Moore, L, Alvares, GA, Redoblado Hodge, MA and 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.Google Scholar
Churchland, PS and Winkielman, P (2012) Modulating social behavior with oxytocin: how does it work? What does it mean?. Hormones and Behavior 61, 392–399.Google Scholar
Davis, MC, Lee, J, Horan, WP, Clarke, AD, McGee, MR, Green, MF and Marder, SR (2013) Effects of single dose intranasal oxytocin on social cognition in schizophrenia. Schizophrenia Research 147, 393–397.Google Scholar
Davis, MC, Green, MF, Lee, J, Horan, WP, Senturk, D, Clarke, AD and Marder, SR (2014) Oxytocin-augmented social cognitive skills training in schizophrenia. Neuropsychopharmacology 39, 2070–2077.Google Scholar
Domes, G, Heinrichs, M, Michel, A, Berger, C and Herpertz, SC (2007) Oxytocin improves “mind-reading” in humans. Biological Psychiatry 61, 731–733.Google Scholar
First, MB, Spitzer, RL, Gibbon, M and Williams, JBW (2002) Structured Clinical Interview for DSM-IV-TR Axis 1 Disorders, Research Version, Patient Edition. (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute.Google Scholar
Fischer-Shofty, M, Brüne, M, Ebert, A, Shefet, D, Levkovitz, Y and Shamay-Tsoory, SG (2013) Improving social perception in schizophrenia: the role of oxytocin. Schizophrenia Research 146, 357–362.Google Scholar
Freeman, SM and Young, LJ (2016) Comparative perspectives on oxytocin and vasopressin receptor research in rodents and primates: translational implications. Journal of Neuroendocrinology 28.Google Scholar
Gibson, CM, Penn, DL, Smedley, KL, Leserman, J, Elliott, T and 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
Goldman, M, Marlow-O'Connor, M, Torres, I and Carter, CS (2008) Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits. Schizophrenia Research 98, 247–255.Google Scholar
Goldman, MB, Gomes, AM, Carter, CS and Lee, R (2011) Divergent effects of two different doses of intranasal oxytocin on facial affect discrimination in schizophrenic patients with and without polydipsia. Psychopharmacology (Berl) 216, 101–110.Google Scholar
Granholm, EL, McQuaid, JR and Holden, JL (2016) Cognitive-behavioral Social Skills Training for Schizophrenia: A Practical Treatment Guide. New York: Guilford Publications.Google Scholar
Green, MF, Penn, DL, Bentall, R, Carpenter, WT, Gaebel, W, Gur, RC, Kring, AM, Park, S, Silverstein, SM and Heinssen, R (2008) Social cognition in schizophrenia: an NIMH workshop on definitions, assessment, and research opportunities. Schizophrenia Bulletin 34, 1211–1220.Google Scholar
Guastella, AJ and MacLeod, C (2012) A critical review of the influence of oxytocin nasal spray on social cognition in humans: evidence and future directions. Hormones and Behavior 61, 410–418.Google Scholar
Guastella, AJ, Mitchell, PB and Dadds, MR (2008 a) Oxytocin increases gaze to the eye region of human faces. Biological Psychiatry 63, 3–5.Google Scholar
Guastella, AJ, Mitchell, PB and Mathews, F (2008 b) Oxytocin enhances the encoding of positive social memories in humans. Biological Psychiatry 64, 256–258.Google Scholar
Guastella, AJ, Howard, AL, Dadds, MR, Mitchell, P and Carson, DS (2009) A randomized controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety disorder. Psychoneuroendocrinology 34, 917–923.Google Scholar
Guastella, AJ, Ward, PB, Hickie, IB, Shahrestani, S, Hodge, MAR, Scott, EM and Langdon, R (2015) A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia. Schizophrenia Research 168, 628–633.Google Scholar
Guy, W (1976) ECDEU assessment Manual for Psychopharmacology. US Department of Health, and Welfare, pp. 534–537.Google Scholar
Horan, WP, Kern, RS, Shokat-Fadai, K, Sergi, MJ, Wynn, JK and Green, MF (2009) Social cognitive skills training in schizophrenia: an initial efficacy study of stabilized outpatients. Schizophrenia Research 107, 47–54.Google Scholar
Horta de Macedo, LRH, Zuardi, AW, Machado-de-Sousa, JP, Chagas, MHN and 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
Keech, B, Crowe, S and Hocking, DR (2018) Intranasal oxytocin, social cognition and neurodevelopmental disorders: a meta-analysis. Psychoneuroendocrinology 87, 9–19.Google Scholar
Kern, RS, Penn, DL, Lee, J, Horan, WP, Reise, SP, Ochsner, KN, Marder, SR and Green, MF (2013) Adapting social neuroscience measures for schizophrenia clinical trials, Part 2: trolling the depths of psychometric properties. Schizophrenia Bulletin 39, 1201–1210.Google Scholar
Kosfeld, M, Heinrichs, M, Zak, PJ, Fischbacher, U and Fehr, E (2005) Oxytocin increases trust in humans. Nature 435, 673–676.Google Scholar
Lee, MR, Wehring, HJ, McMahon, RP, Liu, F, Linthicum, J, Verbalis, JG, Buchanan, RW, Strauss, GP, Rubin, LH and Kelly, DL (2016) Relationship of plasma oxytocin levels to baseline symptoms and symptom changes during three weeks of daily oxytocin administration in people with schizophrenia. Schizophrenia Research 172, 165–168.Google Scholar
Leng, G and Ludwig, M (2016) Intranasal oxytocin: myths and delusions. Biological Psychiatry 79, 243–250.Google Scholar
Loughland, CM, Williams, LM and Gordon, E (2002) Visual scanpaths to positive and negative facial emotions in an outpatient schizophrenia sample. Schizophrenia Research 55, 159–170.Google Scholar
Luminet, O, Grynberg, D, Ruzette, N and Mikolajczak, M (2011) Personality-dependent effects of oxytocin: greater social benefits for high alexithymia scorers. Biological Psychology 87, 401–406.Google Scholar
Mancuso, F, Horan, WP, Kern, RS and Green, MF (2011) Social cognition in psychosis: multidimensional structure, clinical correlates, and relationship with functional outcome. Schizophrenia Research 125, 143–151.Google Scholar
Manning, M, Misicka, A, Olma, A, Bankowski, K, Stoev, S, Chini, B, Durroux, T, Mouillac, B, Corbani, M and Guillon, G (2012) Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. Journal of Neuroendocrinology 24, 609–628.Google Scholar
Marsh, AA, Henry, HY, Pine, DS and Blair, R (2010) Oxytocin improves specific recognition of positive facial expressions. Psychopharmacology 209, 225–232.Google Scholar
Matsumoto, D and Ekman, P (1995) Japanese and Caucasian Facial Expressions of Emotion (JACFEE) and Neutral Faces (JACNeuF).Google Scholar
Parker, KJ, Oztan, O, Libove, RA, Sumiyoshi, RD, Jackson, LP, Karhson, DS, Summers, JE, Hinman, KE, Motonaga, KS, Phillips, JM and Carson, DS (2017) Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proceedings of the National Academy of Sciences 114, 8119–8124.Google Scholar
Pedersen, CA, Gibson, CM, Rau, SW, Salimi, K, Smedley, KL, Casey, RL, Leserman, J, Jarskog, LF and 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
Penn, D and Combs, D (2000) Modification of affect perception deficits in schizophrenia. Schizophrenia Research 46, 217–229.Google Scholar
Penn, DL, Roberts, DL, Combs, D and Sterne, A (2007) Best practices: the development of the social cognition and interaction training program for schizophrenia spectrum disorders. Psychiatric Services 58, 449–451.Google Scholar
Pinkham, AE, Penn, DL, Perkins, DO and Lieberman, J (2003) Implications for the neural basis of social cognition for the study of schizophrenia. American Journal of Psychiatry 160, 815–824.Google Scholar
Quintana, DS (2018) Revisiting non-significant effects of intranasal oxytocin using equivalence testing. Psychoneuroendocrinology 87, 127–130.Google Scholar
Quintana, DS and Woolley, JD (2016) Intranasal oxytocin mechanisms can be better understood, but its effects on social cognition and behavior are not to be sniffed at. Biological Psychiatry 79, e49–e50.Google Scholar
Roberts, DL, Penn, DL and Combs, DR (2015) Social Cognition and Interaction Training (SCIT): Group Psychotherapy for Schizophrenia and Other Psychotic Disorders, Clinician Guide. New York: Oxford University Press.Google Scholar
Rubin, LH, Carter, CS, Drogos, L, Pournajafi-Nazarloo, H, Sweeney, JA and Maki, PM (2010) Peripheral oxytocin is associated with reduced symptom severity in schizophrenia. Schizophrenia Research 124, 13–21.Google Scholar
Rubin, LH, Carter, CS, Drogos, L, Jamadar, R, Pournajafi-Nazarloo, H, Sweeney, JA and Maki, PM (2011) Sex-specific associations between peripheral oxytocin and emotion perception in schizophrenia. Schizophrenia Research 130, 266–270.Google Scholar
Rubin, LH, Carter, CS, Bishop, JR, Pournajafi-Nazarloo, H, Harris, MS, Hill, SK, Reilly, JL and Sweeney, JA (2013) Peripheral vasopressin but not oxytocin relates to severity of acute psychosis in women with acutely-ill untreated first-episode psychosis. Schizophrenia Research 146, 138–143.Google Scholar
Rubin, LH, Carter, CS, Bishop, JR, Pournajafi-Nazarloo, H, Drogos, LL, Hill, SK, Ruocco, AC, Keedy, SK, Reilly, JL, Keshavan, MS, Pearlson, GD, Tamminga, CA, Gershon, ES and Sweeney, JA (2014) Reduced levels of vasopressin and reduced behavioral modulation of oxytocin in psychotic disorders. Schizophrenia Bulletin 40, 1374–1384.Google Scholar
Savaskan, E, Ehrhardt, R, Schulz, A, Walter, M and Schächinger, H (2008) Post-learning intranasal oxytocin modulates human memory for facial identity. Psychoneuroendocrinology 33, 368–374.Google Scholar
Shin, NY, Park, HY, Jung, WH, Park, JW, Yun, J-Y, Jang, JH, Kim, SN, Han, HJ, Kim, S-Y and Kang, D-H (2015) Effects of oxytocin on neural response to facial expressions in patients with schizophrenia. Neuropsychopharmacology 40, 1919–1927.Google Scholar
Strauss, GP, Keller, WR, Koenig, JI, Gold, JM, Frost, KH and Buchanan, RW (2015 a) Plasma oxytocin levels predict social cue recognition in individuals with schizophrenia. Schizophrenia Research 162, 47–51.Google Scholar
Strauss, GP, Keller, WR, Koenig, JI, Gold, JM, Ossenfort, KL and Buchanan, RW (2015 b) Plasma oxytocin levels predict olfactory identification and negative symptoms in individuals with schizophrenia. Schizophrenia Research 162, 57–61.Google Scholar
Strauss, GP, Keller, WR, Koenig, JI, Sullivan, SK, Gold, JM and Buchanan, RW (2015 c) Endogenous oxytocin levels are associated with the perception of emotion in dynamic body expressions in schizophrenia. Schizophrenia Research 162, 52–56.Google Scholar
Van't Wout, M and Sanfey, AG (2008) Friend or foe: the effect of implicit trustworthiness judgments in social decision-making. Cognition 108, 796–803.Google Scholar
Ventura, J, Lukoff, D, Nuechterlein, K, Liberman, R, Green, M and Shaner, A (1993) Brief Psychiatric Rating Scale (Expanded, Version 4.0). Los Angeles: UCLA Department of Psychiatry and Behavioural Sciences. Clinical Research Center for Schizophrenia and Psychiatric Rehabilitation.Google Scholar
Williams, LM, Loughland, CM, Green, MJ, Harris, AW and Gordon, E (2003) Emotion perception in schizophrenia: an eye movement study comparing the effectiveness of risperidone vs. Haloperidol. Psychiatry Research 120, 13–27.Google Scholar
Woolley, JD, Chuang, B, Lam, O, Lai, W, O'Donovan, A, Rankin, KP, Mathalon, DH and Vinogradov, S (2014) Oxytocin administration enhances controlled social cognition in patients with schizophrenia. Psychoneuroendocrinology 47, 116–125.Google Scholar
Woolley, J, Chuang, B, Fussell, C, Scherer, S, Biagianti, B, Fulford, D, Mathalon, D and Vinogradov, S (2017) Intranasal oxytocin increases facial expressivity, but not ratings of trustworthiness, in patients with schizophrenia and healthy controls. Psychological Medicine 47, 1311–1322.Google Scholar
Zaki, J, Bolger, N and Ochsner, K (2008) It takes two: the interpersonal nature of empathic accuracy. Psychological Science 19, 399–404.Google Scholar