Hostname: page-component-8448b6f56d-c4f8m Total loading time: 0 Render date: 2024-04-18T12:16:11.393Z Has data issue: false hasContentIssue false

The mediating role of depression in pathways linking positive and negative symptoms in schizophrenia. A longitudinal analysis using latent variable structural equation modelling

Published online by Cambridge University Press:  08 March 2019

Giuseppe Carrà
Affiliation:
Division of Psychiatry, University College London, 149 Tottenham Court Road, LondonW1T 7NF, UK Department of Medicine and Surgery, University of Milano Bicocca, Via Cadore 48, Monza20900, Italy
Cristina Crocamo*
Affiliation:
Department of Medicine and Surgery, University of Milano Bicocca, Via Cadore 48, Monza20900, Italy
Francesco Bartoli
Affiliation:
Department of Medicine and Surgery, University of Milano Bicocca, Via Cadore 48, Monza20900, Italy
Matthias Angermeyer
Affiliation:
Department of Psychiatry, University of Leipzig, Johannisallee 20, 04137 Leipzig, Germany
Traolach Brugha
Affiliation:
Department of Health Sciences, University of Leicester, College of Medicine, Biological Sciences and Psychology, University of Leicester, Centre for Medicine, University Road, LeicesterLE1 7RH, UK
Mondher Toumi
Affiliation:
Laboratoire de Santé Publique, Université de la Méditerranée, Marseille, France
Paul Bebbington
Affiliation:
Division of Psychiatry, University College London, 149 Tottenham Court Road, LondonW1T 7NF, UK
*
Author for correspondence: Cristina Crocamo, E-mail: cristina.crocamo@unimib.it

Abstract

Background

The interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms.

Methods

We analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months.

Results

We found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct.

Conclusions

Our findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

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, 247251.CrossRefGoogle ScholarPubMed
Addington, D, Addington, J, Maticka-Tyndale, E and Joyce, J (1992) Reliability and validity of a depression rating scale for schizophrenics. Schizophrenia Research 6, 201208.CrossRefGoogle ScholarPubMed
Addington, D, Addington, J and Atkinson, M (1996) A psychometric comparison of the Calgary depression scale for schizophrenia and the Hamilton depression rating scale. Schizophrenia Research 19, 205212.CrossRefGoogle ScholarPubMed
Andreasen, NC and Olsen, S (1982) Negative and positive symptoms in schizophrenia: definition and validation. Archives of General Psychiatry 30, 789794.CrossRefGoogle Scholar
Barch, DM, Pagliaccio, D and Luking, K (2016) Mechanisms underlying motivational deficits in psychopathology: similarities and differences in depression and schizophrenia. Current Topics in Behavioral Neurosciences 27, 411449.CrossRefGoogle Scholar
Barnes, TR, Schizophrenia Consensus Group of British Association for Psychopharmacology (2011) Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology 25, 567620.CrossRefGoogle ScholarPubMed
Barrowclough, C, Tarrier, N, Humphreys, L, Ward, J, Gregg, L and Andrews, B (2003) Self-esteem in schizophrenia: relationships between self-evaluation, family attitudes, and symptomatology. Journal of Abnormal Psychology 112, 9299.CrossRefGoogle ScholarPubMed
Bebbington, PE, Angermeyer, M, Azorin, JM, Brugha, T, Kilian, R, Johnson, S, Toumi, M, Kornfeld, A, EuroSC Research Group (2005) The European Schizophrenia Cohort (EuroSC): a naturalistic prognostic and economic study. Soc Psychiatry and Psychiatric Epidemiology 40, 707717.CrossRefGoogle ScholarPubMed
Best, MW, Gupta, M, Bowie, CR and Harvey, PD (2014) A longitudinal examination of the moderating effects of symptoms on the relationship between functional competence and real world functional performance in schizophrenia. Schizophrenia Research. Cognition 1, 9095.CrossRefGoogle Scholar
Birchwood, M, Iqbal, Z and Upthegrove, R (2005) Psychological pathways to depression in schizophrenia: studies in acute psychosis, post psychotic depression and auditory hallucinations. European Archives of Psychiatry and Clinical Neuroscience 255, 202212.CrossRefGoogle ScholarPubMed
Blanchard, JJ and Cohen, AS (2006) The structure of negative symptoms within schizophrenia: implications for assessment. Schizophrenia Bulletin 32, 238245.CrossRefGoogle ScholarPubMed
Bosanac, P and Castle, D (2012) Schizophrenia and depression. The Medical Journal of Australia 9, 3639.CrossRefGoogle Scholar
Brown, P, Waite, F and Freeman, D (2018) ‘Twisting the lion's tail’: manipulationist tests of causation for psychological mechanisms in the occurrence of delusions and hallucinations. Clinical Psychology Review. 2018 Dec 21. pii: S0272–7358(18)30104–1. doi: 10.1016/j.cpr.2018.12.003. [Epub ahead of print].Google ScholarPubMed
Buchanan, RW (2007) Persistent negative symptoms in schizophrenia: an overview. Schizophrenia Bulletin 33, 10131022.CrossRefGoogle ScholarPubMed
Buchanan, RW, Kreyenbuhl, J, Kelly, DL, Noel, JM, Boggs, DL, Fischer, BA, Himelhoch, S, Fang, B, Peterson, E, Aquino, PR, Keller, W, Schizophrenia Patient Outcomes Research Team (PORT) (2010) The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophrenia Bulletin 36, 7193.CrossRefGoogle ScholarPubMed
Carpenter, WT Jr, Heinrichs, DW and Wagman, AM (1988) Deficit and nondeficit forms of schizophrenia: the concept. The American Journal of Psychiatry 145, 578583.Google ScholarPubMed
Carrà, G, Johnson, S, Crocamo, C, Angermeyer, MC, Brugha, T, Azorin, JM, Toumi, M and Bebbington, P (2016) Psychosocial functioning, quality of life and clinical correlates of comorbid alcohol and drug dependence syndromes in people with schizophrenia across Europe. Psychiatry Research 239, 301307.CrossRefGoogle ScholarPubMed
Carrà, G, Crocamo, C, Angermeyer, M, Brugha, T, Toumi, M and Bebbington, P (2018) Positive and negative symptoms in schizophrenia: a longitudinal analysis using latent variable structural equation modelling. Schizophrenia Research [in press] doi: 10.1016/j.schres.2018.08.018.Google ScholarPubMed
Cole, DA and Maxwell, SE (2003) Testing mediational models with longitudinal data: questions and tips in the use of structural equation modeling. Journal of Abnormal Psychology 112, 558577.CrossRefGoogle ScholarPubMed
Crow, TJ (1980) Positive and negative schizophrenic symptoms and the role of dopamine. The British Journal of Psychiatry 137, 383386.CrossRefGoogle ScholarPubMed
Cuthbert, BN and Kozak, MJ (2013) Constructing constructs for psychopathology: the NIMH research domain criteria. Journal of Abnormal Psychology 122, 928937.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Nelson, B, Valmaggia, L, Yung, AR and McGuire, PK (2014) Comorbid depressive and anxiety disorders in 509 individuals with an at-risk mental state: impact on psychopathology and transition to psychosis. Schizophrenia Bulletin 40, 120131.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Papanastasiou, E, Stahl, D, Rocchetti, M, Carpenter, W, Shergill, S and McGuire, P (2015) Treatments of negative symptoms in schizophrenia: meta-analysis of 168 randomized placebo-controlled trials. Schizophrenia Bulletin 41, 892899.CrossRefGoogle ScholarPubMed
Helfer, B, Samara, MT, Huhn, M, Klupp, E, Leucht, C, Zhu, Y, Engel, RR and Leucht, S (2016) Efficacy and safety of antidepressants added to antipsychotics for schizophrenia: a systematic review and meta-analysis. The American Journal of Psychiatry 173, 876886.CrossRefGoogle ScholarPubMed
Hu, L and Bentler, PM (1999) Cutoff criteria for fit indexes in covariance structure analysis: conventional criteria versus new alternatives. Structural Equation Modeling: A Multidisciplinary Journal 6, 155.CrossRefGoogle Scholar
Kay, SR (1990) Positive-negative symptom assessment in schizophrenia:psychometric issues and scale comparison. Psychiatric Quarterly 61, 163178.CrossRefGoogle ScholarPubMed
Kay, SR, Opler, LA and Lindenmayer, JP (1989) The positive and Negative Syndrome Scale (PANSS): rationale and standardisation. The British Journal of Psychiatry. Supplement 155, 5967.CrossRefGoogle Scholar
Kenny, DA (2005) Cross-lagged panel design. In Everitt, BS and Howell, DC (eds), Encyclopedia of Statistics in Behavioral Science, vol. 1. New York: John Wiley & Sons, pp. 450451.Google Scholar
Kirkpatrick, B, Fenton, WS, Carpenter, WT Jr. and Marder, SR (2006) The NIMH-MATRICS consensus statement on negative symptoms. Schizophrenia Bulletin 32, 214219.CrossRefGoogle ScholarPubMed
Kring, AM and Barch, DM (2014) The motivation and pleasure dimension of negative symptoms: neural substrates and behavioral outputs. European Neuropsychopharmacology 24, 725736.CrossRefGoogle ScholarPubMed
Krynicki, CR, Upthegrove, R, Deakin, JFW and Barnes, TRE (2018) The relationship between negative symptoms and depression in schizophrenia: a systematic review. Acta Psychiatrica Scandinavica 137, 380390.CrossRefGoogle ScholarPubMed
Kuipers, J, Moffa, G, Kuipers, E, Freeman, D and Bebbington, P (2019) Links between psychotic and neurotic symptoms in the general population: an analysis of longitudinal British National Survey data using Directed Acyclic Graphs. Psychological Medicine 49, 388395.CrossRefGoogle ScholarPubMed
Lehman, AF, Lieberman, JA, Dixon, LB, McGlashan, TH, Miller, AL, Perkins, DO and Kreyenbuhl, J, American Psychiatric Association; Steering Committee on Practice Guidelines (2004) Practice guideline for the treatment of patients with schizophrenia, second edition. The American Journal of Psychiatry 161(2 Suppl), 156.Google ScholarPubMed
Leucht, S, Arbter, D, Engel, RR, Kissling, W and Davis, JM (2009) How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials. Molecular Psychiatry 14, 429447.CrossRefGoogle ScholarPubMed
Liu, WH, Wang, LZ, Shang, HR, Shen, Y, Li, Z, Cheung, EF and Chan, RC (2014) The influence of anhedonia on feedback negativity in major depressive disorder. Neuropsychologia 53, 213220.CrossRefGoogle ScholarPubMed
Lockhart, G, MacKinnon, DP and Ohlrich, V (2011) Mediation analysis in psychosomatic medicine research. Psychosomatic Medicine 73, 2943.CrossRefGoogle ScholarPubMed
Mao, YM and Zhang, MD (2015) Augmentation with antidepressants in schizophrenia treatment: benefit or risk. Neuropsychiatric Disease and Treatment 11, 701713.Google ScholarPubMed
Marwaha, S, Broome, MR, Bebbington, PE, Kuipers, E and Freeman, D (2014) Mood instability and psychosis: analyses of British national survey data. Schizophrenia Bulletin 40, 269277.CrossRefGoogle ScholarPubMed
Maxwell, SE and Cole, DA (2007) Bias in cross-sectional analyses of longitudinal mediation. Psychological Methods 12, 2344.CrossRefGoogle ScholarPubMed
Mehl, S, Werner, D and Lincoln, TM (2015) Does Cognitive Behavior Therapy for psychosis (CBTp) show a sustainable effect on delusions? A meta-analysis. Frontiers in Psychology 6, 1450.CrossRefGoogle ScholarPubMed
Millan, MJ, Fone, K, Steckler, T and Horan, WP (2014) Negative symptoms of schizophrenia: clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment. European Neuropsychopharmacology 24, 645692.CrossRefGoogle ScholarPubMed
Müller, MJ, Brening, H, Gensch, C, Klinga, J, Kienzle, B and Müller, KM (2005) The Calgary Depression Rating Scale for schizophrenia in a healthy control group: psychometric properties and reference values. Journal of Affective Disorders 88, 6974.CrossRefGoogle Scholar
Muthén, LK and Muthén, BO (2017) Mplus User's Guide. 1998–2017. Los Angeles, CA: Muthén and Muthén.Google Scholar
NICE - National Institute for Health and Care Excellence (2014) Psychosis and Schizophrenia: Treatment and Management. London: National Institute for Health and Care Excellence. (http://guidance.nice.org.uk/CG178). Accessed 24 September 2018.Google Scholar
Norman, RM, Malla, AK, Cortese, L and Diaz, F (1996) A study of the interrelationship between and comparative interrater reliability of the SAPS, SANS and PANSS. Schizophrenia Research 19, 7385.CrossRefGoogle ScholarPubMed
Pogue-Geile, MF and Harrow, M (1984) Negative and positive symptoms in schizophrenia and depression: a followup. Schizophrenia Bulletin 10, 371387.CrossRefGoogle ScholarPubMed
Quattrone, D, Di Forti, M, Gayer-Anderson, C, Ferraro, L, Jongsma, HE, Tripoli, G, La Cascia, C, La Barbera, D, Tarricone, I, Berardi, D, Szöke, A, Arango, C, Lasalvia, A, Tortelli, A, Llorca, PM, de Haan, L, Velthorst, E, Bobes, J, Bernardo, M, Sanjuán, J, Santos, JL, Arrojo, M, Del-Ben, CM, Menezes, PR, Selten, JP, EU-GEI WP2 Group, Jones, PB, Kirkbride, JB, Richards, AL, O'Donovan, MC, Sham, PC, Vassos, E, Rutten, BP, van Os, J, Morgan, C, Lewis, CM, Murray, RM and Reininghaus, U (2018) Transdiagnostic dimensions of psychopathology at first episode psychosis: findings from the multinational EU-GEI study. Psychological Medicine 114. doi: 10.1017/S0033291718002131. [Epub ahead of print].Google ScholarPubMed
Sandhu, A, Ives, J, Birchwood, M and Upthegrove, R (2013) The subjective experience and phenomenology of depression following first episode psychosis: a qualitative study using photo-elicitation. Journal of Affective Disorders 149, 166174.CrossRefGoogle ScholarPubMed
Sarkar, S, Hillner, K and Velligan, DI (2015) Conceptualization and treatment of negative symptoms in schizophrenia. World Journal of Psychiatry 5, 352361.CrossRefGoogle Scholar
Sax, KW, Strakowski, SM, Keck, PE Jr., Upadhyaya, VH, West, SA and McElroy, SL (1996) Relationships among negative, positive, and depressive symptoms in schizophrenia and psychotic depression. The British Journal of Psychiatry 168, 6871.CrossRefGoogle ScholarPubMed
Spitzer, RL, Williams, JB, Gibbon, M and First, MB (1992) The structured clinical interview for DSM-III-R (SCID).I: history, rationale, and description. Archives of General Psychiatry 49, 624629.CrossRefGoogle ScholarPubMed
Strauss, GP, Sandt, AR, Catalano, LT and Allen, DN (2012) Negative symptoms and depression predict lower psychological well-being in individuals with schizophrenia. Comprehensive Psychiatry 53, 11371144.CrossRefGoogle ScholarPubMed
Upthegrove, R, Birchwood, M, Ross, K, Brunett, K, McCollum, R and Jones, L (2010) The evolution of depression and suicidality in first episode psychosis. Acta Psychiatrica Scandinavica 122, 211218.CrossRefGoogle ScholarPubMed
Upthegrove, R, Marwaha, S and Birchwood, M (2017) Depression and schizophrenia: cause, consequence, or trans-diagnostic issue? Schizophrenia Bulletin 43, 240244.Google ScholarPubMed
WHO - World Health Organization (1992) SCAN: Schedule for Clinical Assessment in Neuropsychiatry. Geneva: WHO Press.Google Scholar
Yung, AR, Buckby, JA, Cosgrave, EM, Killackey, EJ, Baker, K, Cotton, SM and McGorry, PD (2007) Association between psychotic experiences and depression in a clinical sample over 6 months. Schizophrenia Research 91, 246253.CrossRefGoogle Scholar