Вторичные негативные симптомы при шизофрении: клинико-психопатологические особенности и подходы к дифференциальной диагностике

Обоснование: вторичные негативные симптомы (ВНС) при шизофрении представляют собой важную клиническую проблему, обусловленную различными факторам, такими как депрессия, позитивные симптомы, когнитивные нарушения, побочные эффекты антипсихотиков, социальные и соматические причины. Дифференциальная диагностика этих расстройств остается сложной задачей из-за значительного клинического перекрытия и отсутствия унифицированных методов оценки.

Целью обзора литературы было изучение на основании анализа научных публикаций механизмов формирования ВНС, а также описание их клинико-психопатологических и динамических характеристик.

Материалы и методы: в нарративный обзор включены источники, найденные в базах данных Pubmed и eLibrary. В итоговый анализ вошли 93 публикации, соответствующие теме обзора.

Заключение: рассмотрены механизмы формирования вторичных негативных симптомов, их клинико-психопатологические и динамические особенности в зависимости от этиологии. Представлены ключевые дифференциально-диагностические критерии этих симптомов в зависимости от происхождения. Показано, что вторичные негативные симптомы могут быть обратимыми или частично обратимыми при устранении вторичных причин, что делает их важной мишенью для коррекционных мероприятий.

1. Correll CU, Schooler NR. Negative symptoms in schizophrenia: a review and clinical guide for recognition, assessment, and treatment. Neuropsychiatr Dis Treat. 2020;16:519–534. doi: 10.2147/NDT.S225643

2. Kirkpatrick B, Fenton WS, Carpenter WT Jr, Marder SR. The NIMH–MATRICS consensus statement on negative symptoms. Schizophr Bull. 2006;32(2):214–219. doi: 10.1093/schbul/sbj053

3. Незнанов НГ, Иванов МВ. Негативные и когнитивные расстройства при эндогенных психозах: диагностика, клиника, терапия. МЕДпресс-информ. 2021:320.

4. Смулевич АБ. Негативные расстройства в психопатологическом пространстве шизофрении. 2-е изд. МЕДпресс-информ. 2023:248 с ил. ISBN 978-5-907632-34-9.

5. Mosolov SN, Yaltonskaya PA. Primary and secondary negative symptoms in schizophrenia. Front Psychiatry. 2022;12:766692. doi: 10.3389/fpsyt.2021.766692

6. Kirschner M, Aleman A, Kaiser S. Secondary negative symptoms — a review of mechanisms, assessment and treatment. Schizophr Res. 2017;186:29–38. doi: 10.1016/j.schres.2016.05.003

7. Galderisi S, Mucci A, Dollfus S, Nordentoft M, Falkai P, Kaiser S, Giordano GM, Vandevelde A, Nielsen MØ, Glenthøj LB, Sabé M, Pezzella P, Bitter I, Gaebel W. EPA guidance on assessment of negative symptoms in schizophrenia. Eur Psychiatry. 2021;64(1):e23. doi: 10.1192/j.eurpsy.2021.11

8. Новицкий МА, Шнайдер НА, Насырова РФ. Частота встречаемости депрессивных расстройств у пациентов с шизофренией. Обозрение психиатрии и медицинской психологии им. ВМ Бехтерева. 2021;55(3):45–61. doi: 10.31363/2313-7053-2021-56-3-45-61

9. Demyttenaere K, Anthonis E, Acsai K, Correll CU. Depressive Symptoms and PANSS Symptom Dimensions in Patients With Predominant Negative Symptom Schizophrenia: A Network Analysis. Front Psychiatry. 2022;13:795866. Published 2022 Apr 25. doi: 10.3389/fpsyt.2022.795866

10. Dai J, Du X, Yin G, Zhang Y, Xia H, Li X, Cassidy R, Tong Q, Chen D, Teixeira AL, Zheng Y, Ning Y, Soares JC, He MX, Zhang XY. Prevalence, demographic and clinical features of comorbid depressive symptoms in drug naïve patients with schizophrenia presenting with first episode psychosis. Schizophr Res. 2018;193:182–187. doi: 10.1016/j.schres.2017.06.029

11. Paul NB, Strauss GP, Gates–Woodyatt JJ, Barchard KA, Allen DN. Two and five–factor models of negative symptoms in schizophrenia are differentially associated with trait affect, defeatist performance beliefs, and psychosocial functioning. Eur Arch Psychiatry Clin Neurosci. 2023;273(8):1715–1724. doi: 10.1007/s00406–022–01507–4

12. Krynicki CR, Upthegrove R, Deakin JFW, Barnes TRE. The relationship between negative symptoms and depression in schizophrenia: a systematic review. Acta Psychiatr Scand. 2018;137(5):380–390. doi: 10.1111/acps.12873

13. Hu N, Li W, Deng H, Song J, Yang H, Chai J, Huang W, Wang H, Zhou X, Zhang P, He S, Cui Y, Fan T, Li Y. The mediating role of negative symptoms in “secondary factors” determining social functioning in chronic schizophrenia. Front Psychiatry. 2023;14:1196760. doi: 10.3389/fpsyt.2023.1196760

14. Chen XJ, Wang DM, Zhou HX, Zhu RR, Tian Y, Du YX, Chen JJ, Chen DC, Wang L, Zhang XY. Association of depressive symptoms with cognitive impairment in patients with never–treated first–episode schizophrenia: Analysis of the Depression in Schizophrenia in China (DISC) study. Gen Hosp Psychiatry. 2021;71:108–113. doi: 10.1016/j.genhosppsych.2021.04.010

15. Upthegrove R, Marwaha S, Birchwood M. Depression and Schizophrenia: Cause, Consequence, or Trans–diagnostic Issue? Schizophr Bull. 2017;43(2):240–244. doi: 10.1093/schbul/sbw097

16. Belvederi Murri M, Respino M, Innamorati M, Cervetti A, Calcagno P, Pompili M, Lamis DA, Ghio L, Amore M. Is good insight associated with depression among patients with schizophrenia? Systematic review and meta–analysis. Schizophr Res. 2015;162(1–3):234–47. doi: 10.1016/j.schres.2015.01.003

17. Amore M, Murri MB, Calcagno P, Rocca P, Rossi A, Aguglia E, Bellomo A, Blasi G, Carpiniello B, Cuomo A, dell'Osso L, di Giannantonio M, Giordano GM, Marchesi C, Monteleone P, Montemagni C, Oldani L, Pompili M, Roncone R, Rossi R, Siracusano A, Vita A, Zeppegno P, Corso A, Arzani C, Galderisi S, Maj M. The association between insight and depressive symptoms in schizophrenia: undirected and Bayesian network analyses. Eur Psychiatry. 2020;63(1):1–21. doi: 10.1192/j.eurpsy.2020.45

18. An der Heiden W, Leber A, Häfner H. Negative symptoms and their association with depressive symptoms in the long-term course of schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2016;266(5):387–96. doi: 10.1007/s00406-016-0697-2

19. Addington D, Addington J, Atkinson M. A psychometric comparison of the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale. Schizophr Res. 1996;19:205–212. doi: 10.1016/0920–9964(95)00070–4

20. Artaloytia JF, Arango C, Lahti A, Sanz J, Pascual A, Cubero P, Prieto D, Palomo T. Negative signs and symptoms secondary to antipsychotics: a double– blind, randomized trial of a single dose of placebo, haloperidol, and risperidone in healthy volunteers. Am J Psychiatry. 2006;163(3):488–493. doi: 10.1176/APPI.AJP.163.3.488

21. Treen D, Savulich G, Mezquida G, García–Portilla MP, Toll A, García–Rizo C, García–Álvarez L, Bergé D, Bobes J, Bernardo M, Fernandez–Egea E, Mané A. In-fluence of secondary sources in the Brief Negative Symptom Scale. Schizophr Res. 2019;204:452–454. doi: 10.1016/j.schres.2018.10.004

22. Ali T, Sisay M, Tariku M, Mekuria AN, Desalew A. Antipsychotic–induced extrapyramidal side effects: a systematic review and meta–analysis of observational studies. PLoS One. 2021;16(9):e0257129. doi: 10.1371/journal.pone.0257129

23. Weng J, Zhang L, Yu W, Zhao N, Zhu B, Ye C, Zhang Z, Ma C, Li Y, Yu Y, Li H. Risk factors, clinical correlates, and social functions of Chinese schizophrenia patients with drug–induced parkinsonism: a cross–sectional analysis of a multicenter, observational, real–world, prospective cohort study. Front Pharmacol. 2023;14:1077607. doi: 10.3389/fphar.2023.1077607

24. Farreny A, Savill M, Priebe S. Correspondence between negative symptoms and potential sources of secondary negative symptoms over time. Eur Arch Psychiatry Clin Neurosci. 2018;268(6):603–609. doi: 10.1007/s00406-017-0813-y

25. De Pieri M, Berg X, Georgiadis F, Brakowski J, Burrer A, Sabé M, Kaliuzhna M, Vetter S, Seifritz E, Homan P, Kaiser S, Kirschner M. Negative symptoms and their associations with other clinical variables and working memory across the schizophrenia spectrum and bipolar disorder. Schizophr Bull Open. 2024;5(1):24. doi: 10.1093/schizbullopen/sgae024

26. Wolpe N, Chen S, Kirkpatrick B, Jones PB, Jenkins C, Cardinal RN, Fernandez–Egea E. Longitudinal effect of clozapine–associated sedation on motivation in schizophrenia: naturalistic longitudinal study. Br J Psychiatry. 2023;223(1):295–297. doi: 10.1192/bjp.2022.191

27. Ikemoto S, Yang C, Tan A. Basal ganglia circuit loops, dopamine and motivation: a review and inquiry. Behav Brain Res. 2015;290:17–31. doi: 10.1016/j.bbr.2015.04.018

28. Anwar S, Kay K. Hyperprolactinemia as a side effect of using antipsychotics in schizophrenic patients. Jurnal Psikiatri Surabaya. 2023;12(2):84–91. doi: 10.20473/jps.v12i2.23359

29. Stojkovic M, Radmanovic B, Jovanovic M, Janjic V, Muric N, Ristic DI. Risperidone induced hyperprolactinemia: from basic to clinical studies. Front Psychiatry. 2022;13:874705. doi: 10.3389/fpsyt.2022.874705

30. Galderisi S, Mucci A, Buchanan RW, Arango C. Negative symptoms of schizophrenia: new developments and unanswered research questions. Lancet Psychiatry. 2018;5(8):664–677. doi: 10.1016/S2215-0366(18)30050-6

31. Simpson GM, Angus JWS. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand. 1970;212(suppl 44):11–19. doi: 10.1111/j.1600-0447.1970.tb02066.x

32. Иванов МВ, Становая ВВ, Моритц АА, Теребова ПС. Методы коррекции эндокринных побочных эффектов антипсихотической терапии у больных шизофренией. В кн.: Диагностика и лечение психических и наркологических расстройств: современные подходы. Вып. 7. СПб.; 2024:480. ISBN 978-5-91258-527-2

33. Demyttenaere K, Leenaerts N, Acsai K, Sebe B, Laszlovszky I, Barabássy Á, Fonticoli L, Szatmári B, Earley W, Németh G, Correll CU. Disentangling the symptoms of schizophrenia: Network analysis in acute phase patients and in patients with predominant negative symptoms. Eur Psychiatry. 2021;65(1):e18. doi: 10.1192/j.eurpsy.2021.2241

34. Butcher I, Berry K, Haddock G. Understanding individuals' subjective experiences of negative symptoms of schizophrenia: A qualitative study. Br J Clin Psychol. 2020;59(3):319–334. doi: 10.1111/bjc.12248

35. Chen L, Johnston JA, Kinon BJ, Stauffer V, Succop P, Marques TR, Ascher-Svanum H. The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial. BMC Psychiatry. 2013;13:320. doi: 10.1186/1471-244x-13-320

36. Barnicot K, Michael C, Trione E, Lang S, Saunders T, Sharp M, Crawford MJ. Psychological interventions for acute psychiatric inpatients with schizophrenia–spectrum disorders: A systematic review and meta–analysis. Clin Psychol Rev. 2020;82:101929. doi: 10.1016/j.cpr.2020.101929

37. Harvey PD, Bosia M, Cavallaro R, Howes OD, Kahn RS, Leucht S, Müller DR, Penadés R, Vita A. Cognitive dysfunction in schizophrenia: an expert group paper on the current state of the art. Schizophr Res Cogn. 2022;29:100249. doi: 10.1016/j.scog.2022.100249

38. Vita A, Nibbio G, Barlati S. Conceptualization and characterization of “primary” and “secondary” cognitive impairment in schizophrenia. Psychiatry Res. 2024;340:116126. doi: 10.1016/j.psychres.2024.116126

39. Тумова МА, Степанова АА, Зазулина ЮС, Гусейнова ЗТ, Зайцева ММ, Дымент ИВ, Коцюбинский АП, Иванов МВ. Влияние антипсихотической и антихолинергической терапии на когнитивные функции у больных шизофренией. Журнал неврологии и психиатрии им. С.С. Корсакова. 2023;123(7):80-85. doi: 10.17116/jnevro202312307180

40. Baddeley AD, Hitch GJ, Allen RJ. From short–term store to multicomponent working memory: the role of the modal model. Mem Cognit. 2019;47(4):575– 588. doi: 10.3758/s13421-018-0878-5

41. Cooper JA, Barch DM, Reddy LF, Horan WP, Green MF, Treadway MT. Effortful goal–directed behavior in schizophrenia: computational subtypes and associations with cognition. J Abnorm Psychol. 2019;128(7):710–722. doi: 10.1037/abn0000443

42. Green MF, Horan WP, Lee J. Social cognition in schizophrenia. Nat Rev Neurosci. 2015;16(10):620–631. doi: 10.1038/nrn4005

43. Giordano GM, Pezzella P, Mucci A, Austin SF, Erfurth A, Glenthøj B, Hofer A, Hubenak J, Libiger J, Melle I, Nielsen MØ, Rybakowski JK, Wojciak P, Galderisi S and Sachs G. Negative symptoms and social cognition as mediators of the relationship between neurocognition and functional outcome in schizophrenia. Front Psychiatry. 2024;15:1333711. doi: 10.3389/fpsyt.2024.1333711

44. Lysaker PH, Dimaggio G, Carcione A, Procacci M, Buck KD, Davis LW, Nicolò G.. Metacognition and schizophrenia: the capacity for self–reflectivity as a predictor for prospective assessments of work performance over six months. Schizophr Res. 2010;122(1–3):124–130. doi: 10.1016/j.schres.2009.04.024

45. Lysaker PH, Chernov N, Moiseeva T, Sozinova M, Dmitryeva N, Alyoshin V, Faith LA, Karpenko O, Kostyuk G. Contrasting metacognitive profiles and their association with negative symptoms in groups with schizophrenia, early psychosis and depression in a Russian sample. Psychiatry Res. 2020;291:1131777. doi: 10.1016/j.psychres.2020.113177

46. Lo SB, Szuhany KL, Kredlow MA, Wolfe R, Mueser KT, McGurk SR. A confirmatory factor analysis of the MATRICS consensus cognitive battery in severe mental illness. Schizophr Res. 2016;175:79–84. doi: 10.1016/j.schres.2016.03.013

47. Keefe RS, Goldberg TE, Harvey PD, Gold JM, Poe MP, Coughenour L. The brief assessment of cognition in schizophrenia: reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophr Res. 2004;68:283–297. doi: 10.1016/j.schres.2003.09.011

48. Bryson G, Bell M, Lysaker P. Affect recognition in schizophrenia: a function of global impairment or a specific cognitive deficit. Psychiatry Res. 1997;71(2):105–113. doi: 10.1016/S01651781(97)00050-4

49. Vita A, Gaebel W, Mucci A, Sachs G, Erfurth A, Barlati S, Zanca F, Giordano GM, Birkedal Glenthøj L, Nordentoft M, Galderisi S. European Psychiatric Association guidance on assessment of cognitive impairment in schizophrenia. Eur Psychiatry. 2022;65(1):e58. doi: 10.1192/j.eurpsy.2022.2316

50. Strauss GP. A bioecosystem theory of negative symptoms in schizophrenia. Front Psychiatry. 2021;12:655471. doi: 10.3389/fpsyt.2021.655471

51. Samele C, van Os J, McKenzie K, Wright A, Gilvarry C, Manley C, Tattan T, Murray R. Does socioeconomic status predict course and outcome in patients with psychosis? Soc Psychiatry Psychiatr Epidemiol. 2001;36:573–581. doi: 10.1007/s127-001-8196-3

52. Thorup A, Petersen L, Jeppesen P, Øhlenschlaeger J, Christensen T, Krarup G, Jørgensen P, Nordentoft M. Social network among young adults with first–episode schizophrenia spectrum disorders. Soc Psychiatry Psychiatr Epidemiol. 2006;41:761–770. doi: 10.1007/s00127-06-0098-3

53. Герасимчук ЕС, Сорокин МЮ, Лутова НБ, Портениер СН, Горбунова ОВ. Роль негативного детского опыта и внутренней стигмы в формировании мотивации к лечению пациентов с психическими расстройствами. Научные результаты биомедицинских исследований. 2024;10(1):126–142. doi: 10.18413/2658-6533-2024-10-1-0-8

54. Sorokin MYu, Lutova NB, Bocharova MO, Khobeysh MA, Wied VD. Computational psychiatry approach to stigma subtyping in patients with mental disorders: explicit and implicit internalized stigma. Consortium Psychiatricum. 2023;4(3):CP6556. doi: 10.17816/cp6556

55. Tibber MS, Kirkbride JB, Mutsatsa S, Harrison I, Barnes TRE, Joyce EM, Huddy V. Are socioenvironmental factors associated with psychotic symptoms in people with first–episode psychosis? a cross– sectional study of a West London clinical sample. BMJ Open. 2019;9:e030448. doi: 10.1136/bmjopen-2019-030448

56. Borhade SR, Mishra KK, John S. A comparative study of internalized stigma in patients with schizophrenia and bipolar affective disorder in remission. Indian J Psychol Med. 2025;47(2):160–165. doi: 10.1177/02537176241240027

57. Grover S, Sahoo S, Chakrabarti S, Avasthi A. Association of internalized stigma and insight in patients with schizophrenia. Int J Cult Ment Health. 2017;11(3):338–350. doi: 10.1080/17542863.2017.1381750

58. Kumar KS, Vankar GK, Goyal AD, Sharma AS. Stigma and discrimination in patients with schizophrenia and bipolar mood disorder. Ann Indian Psychiatry. 2020;4(1):33–39. doi: 10.4103/aip.aip_49_19

59. Grant PM, Beck AT. Defeatist beliefs as a mediator of cognitive impairment, negative symptoms, and functioning in schizophrenia. Schizophr Bull. 2009;35(4):798–806. doi: 10.1093/schbul/sbn008

60. Anglin DM, Galea S, Bachman P. Going upstream to advance psychosis prevention and improve public health. JAMA Psychiatry. 2020;77(7):665–666. doi: 10.1001/jamapsychiatry.2020.0142

61. Karidi MV, Stefanis CN, Theleritis C, Tzedaki M, Rabavilas AD, Stefanis NC. Perceived social stigma, self–concept, and self–stigmatization of patient with schizophrenia. Compr Psychiatry. 2010;51(1):19–30. doi: 10.1016/j.comppsych.2009.01.001

62. Feldhaus T, Falke S, von Gruchalla L, Maisch B, Uhlmann C, Bock E, Lencer R. The impact of self–stigmatization on medication attitude in schizophrenia patients. Psychiatry Res. 2018;261:391–399. doi: 10.1016/j.psychres.2018.01.012

63. Oshima I, Mino Y, Inomata Y. Effects of environmental deprivation on negative symptoms of schizophrenia: a nationwide survey in Japan's psychiatric hospitals. Psychiatry Res. 2005;136(2–3):163–171. doi: 10.1016/j.psychres.2005.06.001

64. Zhang L, James SH, Strauss GP. Environmental resource reductions predict greater severity of negative symptoms in schizophrenia. Schizophr Res. 2023;261:94–99. doi: 10.1016/j.schres.2023.09.013

65. Chai J, Liu F, Liu L, Hu N, Huang W, Wang H, Cui Y, Liu H, Li X and Li Y. The efficacy of homestyle rehabilitation on negative symptoms in chronic schizophrenia: a randomized controlled trial. Front Psychiatry. 2023;14:1138794. doi: 10.3389/fpsyt.2023.1138794

66. Abo El Ella EI, Hashim NZ, Elhabiby MM, Khalil SA, Shorab IM, Michael E. Negative symptoms and functioning in institutionalized versus outpatient schizophrenic patients. Middle East Curr Psychiatry. 2015;22(2):65–69. doi: 10.1097/01.XME.0000461674.43736.ac

67. Odgers CL, Caspi A, Russell MA, Sampson RJ, Arseneault L, Moffitt TE. Supportive parenting mediates neighborhood socioeconomic disparities in children's antisocial behavior from ages 5 to 12. Dev Psychopathol. 2012;24(3):705–721. doi: 10.1017/S0954579412000326

68. Valente TW, Palinkas LA, Czaja S, Chu KH, Brown CH. Social network analysis for program implementation. PLoS One. 2015;10(6):e0131712. doi: 10.1371/journal.pone.0131712

69. Margolese HC, Malchy L, Negrete JC, Tempier R, Gill K. Drug and alcohol use among patients with schizophrenia and related psychoses: levels and consequences. Schizophr Res. 2004;67(2–3):157–166. doi: 10.1016/s0920-9964(02)00523-6

70. Turkington A, Mulholland CC, Rushe TM, Anderson R, McCaul R, Barrett SL, Barr RS, Cooper SJ. Impact of persistent substance misuse on 1–year outcome in first– episode psychosis. Br J Psychiatry. 2009;195(3):242– 248. doi: 10.1192/bjp.bp.108.057471

71. Potvin S, Sepehry AA, Stip E. Meta–analysis of depressive symptoms in dual–diagnosis schizophrenia. Aust N Z J Psychiatry. 2007;41(10):792–799. doi: 10.1080/00048670701579041

72. Petersen SM, Toftdahl NG, Nordentoft M, Hjorthøj C. Schizophrenia is associated with increased risk of subsequent substance abuse diagnosis: A nation– wide population–based register study. Addiction. 2019;114(12):2217–2226. doi: 10.1111/add.14746

73. Brunette MF, Mueser KT, Babbin S, Meyer–Kalos P, Rosenheck R, Correll CU, Cather C, Robinson DG, Schooler NR, Penn DL, Addington J, Estroff SE, Gottlieb J, Glynn SM, Marcy P, Robinson J, Kane JM. Demographic and clinical correlates of substance use disorders in first episode psychosis. Schizophr Res. 2018;194:4–12. doi: 10.1016/j.schres.2017.06.039

74. Arranz B, Safont G, Corripio I, Ramirez N, Dueñas RM, Perez V, Alvarez E, San L. Substance Use in Patients With First–Episode Psychosis: Is Gender Relevant? J Dual Diagn. 2015;11(3–4):153–160. doi: 10.1080/15504263.2015.1113761

75. Archibald L, Brunette MF, Wallin DJ, Green AI. Alcohol Use Disorder and Schizophrenia or Schizoaffective Disorder. Alcohol Res. 2019;40(1):arcr.v40.1.06. doi: 10.35946/arcr.v40.1.06

76. Skumlien M, Langley C, Lawn W, Voon V, Curran HV, Roiser JP, Sahakian BJ. The acute and non–acute effects of cannabis on reward processing: A systematic review. Neurosci Biobehav Rev. 2021;130:512–528. doi: 10.1016/j.neubiorev.2021.09.008

77. Campbell RR, Lobo MK. Neurobiological mechanisms underlying psychostimulant use. Curr Opin Neurobiol. 2023;83:102786. doi: 10.1016/j.conb.2023.102786

78. Masroor A, Khorochkov A, Prieto J, Singh KB, Nnadozie MC, Abdal M, Shrestha N, Abe RAM, Mohammed L. Unraveling the Association Between Schizophrenia and Substance Use Disorder–Predictors, Mechanisms and Treatment Modifications: A Systematic Review. Cureus. 2021;13(7):e16722. doi: 10.7759/cureus.16722

79. Garland EL. Mindful Positive Emotion Regulation as a Treatment for Addiction: From Hedonic Pleasure to Self–Transcendent Meaning. Curr Opin Behav Sci. 2021;39:168–177. doi: 10.1016/j.cobeha.2021.03.019

80. Oud MJ, Meyboom–de Jong B. Somatic diseases in patients with schizophrenia in general practice: their prevalence and health care. BMC Fam Pract. 2009;10:32. doi: 10.1186/1471–2296–10–32

81. Chen YL, Pan CH, Chang CK, Chen PH, Chang HM, Tai MH, Su SS, Tsai SY, Chen CC, Kuo CJ. Physical Illnesses Before Diagnosed as Schizophrenia: A Nationwide Case–Control Study. Schizophr Bull. 2020;46(4):785– 794. doi: 10.1093/schbul/sbaa009

82. Oprya Y, Pustovoyt M, Biesieda Y, Kozishkurt Y. Pecularities of Mental Pathology at Psychiatric Patient With the Comorbid Somatic Disorders. J Educ Health Sport 2021;11(5):348–355. doi: 10.12775/JEHS.2021.11.05.037

83. Dayan CM, Panicker V. Hypothyroidism and depression. Eur Thyroid J. 2013;2(3):168–179. doi: 10.1159/000353777

84. Karami N, Kazeminia M, Karami A, Salimi Y, Ziapour A, Janjani P.Global prevalence of depression, anxiety, and stress in cardiac patients: A systematic review and meta–analysis. J Affect Disord. 2023;324:175– 189. doi: 10.1016/j.jad.2022.12.055

85. Lee TY, Jo HJ. Differential diagnosis and comorbid physical illness of schizophrenia. J Korean Med Assoc. 2021;64(8):551–558. doi: 10.5124/jkma.2021.64.8.551

86. Engels G, Francke AL, van Meijel B, Douma JG, de Kam H, Wesselink W, Houtjes W, Scherder EJ. Clinical pain in schizophrenia: a systematic review. J Pain. 2014;15(5):457–467. doi: 10.1016/j.jpain.2013.11.005

87. Lévesque M, Potvin S, Marchand S, Stip E, Grignon S, Pierre L, Lipp O, Goffaux P. Pain perception in schizophrenia: evidence of a specific pain response profile. Pain Med. 2012;13(12):1571–1579. doi: 10.1111/j.1526-4637.2012.01505.x

88. Girard M, Plansont B, Bonnabau H, Malauzat D. Experimental pain hypersensitivity in schizophrenic patients. Clin J Pain. 2011;27(9):790–795. doi: 10.1097/ajp.0b013e31821d904c

89. Stubbs B, Thompson T, Acaster S, Vancampfort D, Gaughran F, Correll CU. Decreased pain sensitivity among people with schizophrenia: a meta– analysis of experimental pain induction studies. Pain. 2015;156(11):2121–2131. doi: 10.1097/j.pain.0000000000000304

90. Jochum T, Letzsch A, Greiner W, et al. Influence of antipsychotic medication on pain perception in schizophrenia. Psychiatry Res. 2006;142(2–3):151– 156. doi: 10.1016/j.psychres.2005.09.004

91. Kokurcan A, Atbasoglu EC. Differential Diagnosis of Schizophrenia: Psychotic Symptoms in Neurodevelopmental Disorders and Psychotic Disorders due to other Medical Conditions. Turk Psikiyatri Derg. 2015;26(4):279–290. PMID: 26731025

92. Strauss GP, Gold JM. A Psychometric Comparison of the Clinical Assessment Interview for Negative Symptoms and the Brief Negative Symptom Scale. Schizophr Bull. 2016;42(6):1384–1394. doi: 10.1093/schbul/sbw046

93. Kirkpatrick B, Strauss GP, Nguyen L, Fischer BA, Daniel DG, Cienfuegos A, Marder SR. The brief negative symptom scale: psychometric properties. Schizophr Bull. 2011;37(2):300–305. doi: 10.1093/schbul/sbq059