Skip to main content

Remission of depression in patients with schizophrenia and comorbid major depressive disorder: results from the FACE-SZ cohort

  • Guillaume Fond (a1), Laurent Boyer (a1), Fabrice Berna (a2), Ophélia Godin (a3), Ewa Bulzacka (a4), Méja Andrianarisoa (a4), Lore Brunel (a4), Bruno Aouizerate (a5), Delphine Capdevielle (a6), Isabelle Chereau (a7), Nathalie Coulon (a4), Thierry D'Amato (a8), Caroline Dubertret (a9), Julien Dubreucq (a10), Catherine Faget (a1), Sylvain Leignier (a11), Christophe Lançon (a1), Jasmina Mallet (a12), David Misdrahi (a13), Christine Passerieux (a14), Romain Rey (a15), Aurélie Schandrin (a16), Mathieu Urbach (a14), Pierre Vidailhet (a17), Marion Leboyer (a4), Franck Schürhoff (a4), Pierre-Michel Llorca (a18) and the FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a4) (a8) (a9) (a10) (a1) (a11) (a1) (a12) (a13) (a14) (a15) (a16) (a14) (a17) (a4) (a18)...

Major depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been strongly associated with impaired quality of life.


To determine the prevalence and associated factors of MDD and unremitted MDD in schizophrenia, to compare treated and non-treated MDD.


Participants were included in the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment. MDD was defined by a Calgary score ≥6. Non-remitted MDD was defined by current antidepressant treatment (unchanged for >8 weeks) and current Calgary score ≥6.


613 patients were included and 175 (28.5%) were identified with current MDD. MDD has been significantly associated with respectively paranoid delusion (odds ratio 1.8; P = 0.01), avolition (odds ratio 1.8; P = 0.02), blunted affect (odds ratio 1.7; P = 0.04) and benzodiazepine consumption (odds ratio 1.8; P = 0.02). Antidepressants were associated with lower depressive symptoms score (5.4 v. 9.5; P < 0.0001); however, 44.1% of treated patients remained in non-remittance MDD. Nonremitters were found to have more paranoid delusion (odds ratio 2.3; P = 0.009) and more current alcohol misuse disorder (odds ratio 4.8; P = 0.04). No antidepressant class or specific antipsychotic were associated with higher or lower response to antidepressant treatment. MDD was associated with Metabolic syndrome (31.4 v. 20.2%; P = 0.006) but not with increased C-reactive protein.


Antidepressant administration is associated with lower depressive symptom level in patients with schizophrenia and MDD. Paranoid delusions and alcohol misuse disorder should be specifically explored and treated in cases of non-remission under treatment. MetS may play a role in MDD onset and/or maintenance in patients with schizophrenia.

Declaration of interest


Corresponding author
Correspondence: Guillaume Fond, MD, PhD, Aix-Marseille Universite, Faculté de Médecine - Secteur Timone, EA 3279: Centre d'Etude et de Recherche sur les Services de Santé et la Qualité de vie, 27 Boulevard Jean Moulin, 13005 Marseille, France. Email:
Hide All
1Andrianarisoa, M, Boyer, L, Godin, O, Brunel, L, Bulzacka, E, Aouizerate, B, et al. Childhood trauma, depression and negative symptoms are independently associated with impaired quality of life in schizophrenia. Results from the national FACE-SZ cohort. Schizophr Res 2017; 185: 173–81.
2Buckley, PF, Miller, BJ, Lehrer, DS, Castle, DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009; 35: 383402.
3Vorontsova, N, Garety, P, Freeman, D. Cognitive factors maintaining persecutory delusions in psychosis: the contribution of depression. J Abnorm Psychol 2013; 122: 1121–31.
4Godin, O, Leboyer, M, Gaman, A, Aouizerate, B, Berna, F, Brunel, L, et al. Metabolic syndrome, abdominal obesity and hyperuricemia in schizophrenia: results from the FACE-SZ cohort. Schizophr Res 2015; 168: 388–94.
5Bulzacka, E, Boyer, L, Schürhoff, F, Godin, O, Berna, F, Brunel, L, et al. Chronic peripheral inflammation is associated with cognitive impairment in schizophrenia: results from the multicentric FACE-SZ dataset. Schizophr Bull 2016; 42: 1290–302.
6Addington, DE, Mohamed, S, Rosenheck, RA, Davis, SM, Stroup, TS, McEvoy, JP, et al. Impact of second-generation antipsychotics and perphenazine on depressive symptoms in a randomized trial of treatment for chronic schizophrenia. J Clin Psychiatry 2011; 72: 7580.
7Rey, R, D'Amato, T, Boyer, L, Brunel, L, Aouizerate, B, Berna, F, et al. Nicotine dependence is associated with depression and childhood trauma in smokers with schizophrenia: results from the FACE-SZ dataset. Eur Arch Psychiatry Clin Neurosci 2017; 267: 567–77.
8Taylor, M, Perera, U. NICE CG178 psychosis and schizophrenia in adults: treatment and management – an evidence-based guideline? Br J Psychiatry 2015; 206: 357–9.
9Gregory, A, Mallikarjun, P, Upthegrove, R. Treatment of depression in schizophrenia: systematic review and meta-analysis. Br J Psychiatry 2017; 211: 198204.
10Helfer, B, Samara, MT, Huhn, M, Klupp, E, Leucht, C, Zhu, Y, et al. Efficacy and safety of antidepressants added to antipsychotics for schizophrenia: a systematic review and meta-analysis. Am J Psychiatry 2016; 173: 876–86.
11Godin, O, Leboyer, M, Schürhoff, F, Boyer, L, Andrianarisoa, M, Brunel, L, et al. Predictors of rapid high weight gain in schizophrenia: longitudinal analysis of the French FACE-SZ cohort. J Psychiatr Res 2017; 94: 62–9.
12Fond, G, Godin, O, Brunel, L, Aouizerate, B, Berna, F, Bulzacka, E, et al. Peripheral sub-inflammation is associated with antidepressant consumption in schizophrenia. Results from the multi-center FACE-SZ data set. J Affect Disord 2016; 191: 209–15.
13Faugere, M, Micoulaud-Franchi, J-A, Faget-Agius, C, Lançon, C, Cermolacce, M, Richieri, R. High C-reactive protein levels are associated with depressive symptoms in schizophrenia. J Affect Disord 2018; 225: 671–5.
14Schürhoff, F, Fond, G, Berna, F, Bulzacka, E, Vilain, J, Capdevielle, D, et al. A national network of schizophrenia expert centres: an innovative tool to bridge the research-practice gap. Eur Psychiatry 2015; 30: 728–35.
15American Psychiatric Association. APA (2000) Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Text revised. American Psychiatric Association, 2000.
16Addington, D, Addington, J, Maticka-Tyndale, E, Joyce, J. Reliability and validity of a depression rating scale for schizophrenics. Schizophr Res 1992; 6: 201–8.
17Lançon, C, Auquier, P, Reine, G, Bernard, D, Toumi, M. Study of the concurrent validity of the Calgary Depression Scale for Schizophrenics (CDSS). J Affect Disord 2000; 58: 107–15.
18Kay, SR, Fiszbein, A, Opler, LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13: 261–76.
19First, MB, Spitzer, RL, Gibbon, M, and Williams, JJBW. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute, 2002.
20Birchwood, M, Smith, J, Drury, V, Healy, J, Macmillan, F, Slade, M. A self-report insight scale for psychosis: reliability, validity and sensitivity to change. Acta Psychiatr Scand 1994; 89: 62–7.
21Cleary, SD, Bhatty, S, Broussard, B, Cristofaro, SL, Wan, CR, Compton, MT. Measuring insight through patient self-report: an in-depth analysis of the factor structure of the Birchwood Insight Scale. Psychiatry Res 2014; 216: 263–8.
22Leucht, S, Samara, M, Heres, S, Patel, MX, Woods, SW, Davis, JM. Dose equivalents for second-generation antipsychotics: the minimum effective dose method. Schizophr Bull 2014; 40: 314–26.
23Alberti, KGMM, Zimmet, P, Shaw, J. Metabolic syndrome—a new world-wide definition. A consensus statement from the international diabetes federation. Diabet Med 2006; 23: 469–80.
24Bender, R, Lange, S. Adjusting for multiple testing—when and how? J Clin Epidemiol 2001; 54: 343–9.
25Ventriglio, A, Gentile, A, Bonfitto, I, Stella, E, Mari, M, Steardo, L, et al. Suicide in the early stage of schizophrenia. Front Psychiatry 2016; 7: 116.
26Hutton, P, Kelly, J, Lowens, I, Taylor, PJ, Tai, S. Self-attacking and self-reassurance in persecutory delusions: a comparison of healthy, depressed and paranoid individuals. Psychiatry Res 2013; 205: 127–36.
27Thewissen, V, Bentall, RP, Oorschot, M, A Campo, J, van Lierop, T, van Os, J, et al. Emotions, self-esteem, and paranoid episodes: an experience sampling study. Br J Clin Psychol 2011; 50: 178–95.
28Fowler, D, Hodgekins, J, Garety, P, Freeman, D, Kuipers, E, Dunn, G, et al. Negative cognition, depressed mood, and paranoia: a longitudinal pathway analysis using structural equation modeling. Schizophr Bull 2012; 38: 1063–73.
29Bentall, RP, Rowse, G, Rouse, G, Kinderman, P, Blackwood, N, Howard, R, et al. Paranoid delusions in schizophrenia spectrum disorders and depression: the transdiagnostic role of expectations of negative events and negative self-esteem. J Nerv Ment Dis 2008; 196: 375–83.
30Freeman, D, Pugh, K, Dunn, G, Evans, N, Sheaves, B, Waite, F, et al. An early phase II randomised controlled trial testing the effect on persecutory delusions of using CBT to reduce negative cognitions about the self: the potential benefits of enhancing self confidence. Schizophr Res 2014; 160: 186–92.
31Hutton, P, Morrison, AP, Wardle, M, Wells, A. Metacognitive therapy in treatment-resistant psychosis: a multiple-baseline study. Behav Cogn Psychother 2014; 42: 166–85.
32Foulds, JA, Adamson, SJ, Boden, JM, Williman, JA, Mulder, RT. Depression in patients with alcohol use disorders: systematic review and meta-analysis of outcomes for independent and substance-induced disorders. J Affect Disord 2015; 185: 4759.
33Lejoyeux, M, Lehert, P. Alcohol-use disorders and depression: results from individual patient data meta-analysis of the acamprosate-controlled studies. Alcohol Alcohol 2011; 46: 61–7.
34Lee, SB, Chung, S, Lee, H, Seo, JS. The mutual relationship between men's drinking and depression: a 4-year longitudinal analysis. Alcohol Alcohol 2018, in press.
35Bilevicius, E, Single, A, Bristow, LA, Foot, M, Ellery, M, Keough, MT, et al. Shame mediates the relationship between depression and addictive behaviours. Addict Behav 2018; 82: 94100.
36Koskinen, J, Löhönen, J, Koponen, H, Isohanni, M, Miettunen, J. Prevalence of alcohol use disorders in schizophrenia--a systematic review and meta-analysis. Acta Psychiatr Scand 2009; 120: 8596.
37Maslov, B, Marcinko, D, Milicevic, R, Babić, D, Dordević, V, Jakovljević, M. Metabolic syndrome, anxiety, depression and suicidal tendencies in post-traumatic stress disorder and schizophrenic patients. Coll Antropol 2009; 33(Suppl 2): 710.
38Saatcioglu, O, Kalkan, M, Fistikci, N, Erek, S, Kilic, KC. Relationship between metabolic syndrome and clinical features, and its personal-social performance in patients with schizophrenia. Psychiatr Q 2016; 87: 265–80.
39Suttajit, S, Pilakanta, S. Prevalence of metabolic syndrome and its association withdepression in patients with schizophrenia. Neuropsychiatr Dis Treat 2013; 9: 941–6.
40Kucerova, J, Babinska, Z, Horska, K, Kotolova, H. The common pathophysiology underlying the metabolic syndrome, schizophrenia and depression. A review. Biomed Pap Med Fac Univ Palacky Olomouc Czechoslov 2015; 159: 208–14.
41Birkenhäger, TK, Moleman, P, Nolen, WA. Benzodiazepines for depression? A review of the literature. Int Clin Psychopharmacol 1995; 10: 181–95.
42Boldrini, M, Butt, TH, Santiago, AN, Tamir, H, Dwork, AJ, Rosoklija, GB, et al. Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders. Int J Neuropsychopharmacol 2014; 17: 1923–33.
43Wu, X, Castrén, E. Co-treatment with diazepam prevents the effects of fluoxetine on the proliferation and survival of hippocampal dentate granule cells. Biol Psychiatry 2009; 66: 58.
44Fond, G, Berna, F, Boyer, L, Godin, O, Brunel, L, Andrianarisoa, M, et al. Benzodiazepine long-term administration is associated with impaired attention/working memory in schizophrenia: results from the national multicentre FACE-SZ data set. Eur Arch Psychiatry Clin Neurosci 2018; 268: 1726.
45Fond, G, Boyer, L, Favez, M, Brunel, L, Aouizerate, B, Berna, F, et al. Medication and aggressiveness in real-world schizophrenia. Results from the FACE-SZ dataset. Psychopharmacology (Berl) 2016; 233: 571–8.
46Sussman, N. Anxiolytic antidepressant augmentation. J Clin Psychiatry 1998; 59(Suppl 5): 42–8; discussion 49–50.
47Grigoriadis, S, Seeman, MV. The role of estrogen in schizophrenia: implications for schizophrenia practice guidelines for women. Can J Psychiatry 2002; 47: 437–42.
48Tedeschi, GJ, Cummins, SE, Anderson, CM, Anthenelli, RM, Zhuang, Y-L, Zhu, S-H. Smokers with self-reported mental health conditions: a case for screening in the context of tobacco cessation services. PLoS One 2016; 11: e0159127.
49Parikh, V, Kutlu, MG, Gould, TJ. nAChR dysfunction as a common substrate for schizophrenia and comorbid nicotine addiction: current trends and perspectives. Schizophr Res 2016; 171: 115.
50Schefft, C, Kilarski, LL, Bschor, T, Köhler, S. Efficacy of adding nutritional supplements in unipolar depression: a systematic review and meta-analysis. Eur Neuropsychopharmacol 2017; 27: 1090–109.
51Rossell, SL, Francis, PS, Galletly, C, Harris, A, Siskind, D, Berk, M, et al. N-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms. BMC Psychiatry 2016; 16: 320.
52Firth, J, Carney, R, Stubbs, B, Teasdale, SB, Vancampfort, D, Ward, PB, et al. Nutritional deficiencies and clinical correlates in first-episode psychosis: a systematic review and meta-analysis. Schizophr Bull 2017, in press.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
Type Description Title
Supplementary materials

Fond et al. supplementary material
Fond et al. supplementary material 1

 Word (45 KB)
45 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

Remission of depression in patients with schizophrenia and comorbid major depressive disorder: results from the FACE-SZ cohort

  • Guillaume Fond (a1), Laurent Boyer (a1), Fabrice Berna (a2), Ophélia Godin (a3), Ewa Bulzacka (a4), Méja Andrianarisoa (a4), Lore Brunel (a4), Bruno Aouizerate (a5), Delphine Capdevielle (a6), Isabelle Chereau (a7), Nathalie Coulon (a4), Thierry D'Amato (a8), Caroline Dubertret (a9), Julien Dubreucq (a10), Catherine Faget (a1), Sylvain Leignier (a11), Christophe Lançon (a1), Jasmina Mallet (a12), David Misdrahi (a13), Christine Passerieux (a14), Romain Rey (a15), Aurélie Schandrin (a16), Mathieu Urbach (a14), Pierre Vidailhet (a17), Marion Leboyer (a4), Franck Schürhoff (a4), Pierre-Michel Llorca (a18) and the FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a4) (a8) (a9) (a10) (a1) (a11) (a1) (a12) (a13) (a14) (a15) (a16) (a14) (a17) (a4) (a18)...
Submit a response


No eLetters have been published for this article.


Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *