Dynamics of views on different aspects of schizophrenia (Narrative Literature Review)


Как известно, шизофрения остается во многом неясным психическим расстройством, являющимся значительным социальным и экономическим бременем. Поэтому  обзоры литературы, охватывающие основные аспекты этиологии, диагностики и диагностических ошибок в разные временные периоды, представляются актуальными.  В статье приведены  данные анализа более 200 отечественных и зарубежных работ по указанным аспектам шизофрении, преимущественно за последние 10 лет, а также имеющих важное историческое значение. Обзор литературы по вопросам этиологии и диагностики шизофрении может способствовать вниманию ученых к тем или иным результатам исследований на новом концептуальном и методическом этапе. При этом качественные изменения в понимании шизофрении и расстройств шизофренического спектра способствуют развитию инновационных технологий в психиатрии, что важно для науки и практики данной дисциплины.

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 “Is  schizophrenia the price of human brain evolution?”    

          Introduction                                                                       (P. Khaitovich)

         Research on schizophrenia is difficult to capture in its completeness. It never stops, having begun in the process of the formation of psychiatry as a science. Over the course of two centuries, the understanding of this disease has deepened, but many studies are contradictory, and there are concepts to which scientists return after decades. This is due to the development of scientific methods, different psychiatric schools, the integration of clinical and biological psychiatry and concerns the etiology of schizophrenia and an increase in the optimality of diagnostic approaches and criteria. Distinguishing schizophrenia from other mental disorders has long been a major source of diagnostic discrepancies and errors, with great medical, social and economic implications. In this case, both the pathomorphosis of schizophrenia and changes in the boundaries of the dichotomous division of the mental state and behavior into "norm and not norm", as well as the attitude of society to psychiatry can play an important role.

         Thus, an analytical review of literary sources on the problems of etiology, views on the diagnosis of schizophrenia and its difficulties seems to be quite relevant. Naturally, all the nuances of these problems (many of which require separate consideration) cannot be presented in the format of an article.

            Methods used in compiling the review. The authors held the view that the identification of important variables in the study of any problem is considered one of the goals of the literature review.234 Therefore, the diachronic method of literature analysis was chosen.

When citing literary sources, the Harvard system was followed (surname, initials of the author and the year of publication of the work). In the selection of literary sources, a time-based approach was used - selective relevant open sources (elibrary.ru and RSCI systems), reflecting views on the problems analyzed for the last 100 years (scientific and practical guidelines, original articles).                     

Conceptual framework for a literature review

  1. The main directions and facts in the study of the etiology, dynamics, criteria for the diagnosis of schizophrenia
  2. The main controversial aspects of the etiology, views on the diagnosis and dynamics of schizophrenia
  3. The main perspectives in the study of schizophrenia

Views on the etiology of schizophrenia

         According to data of various years of research, schizophrenia is one of the most common mental disorders, but its recognition often comes 5-10 years later that the onset of disease.5-14. At the same time, considering the socio-economic significance, the issue of the promptness of recognition and the correct early therapeutic and rehabilitation tactics for schizophrenia can be seen as one of the priorities in psychiatric practice. This position is noted in various forms by many authors.12, 15-19                                 

        Scientists around the world were long occupied with the cause of schizophrenia. In different historical periods, the disease, according to the symptoms corresponding to the modern diagnostic criteria of schizophrenia, was associated with various factors, and scientists returned to some of them after decades, which seems significant. Gradually, many researchers came to the concept of a multidisciplinary study of the cause of schizophrenia. In 1972, a monograph was published in Russia, edited by A.V. Snezhnevsky:  “Schizophrenia. Multidisciplinary Research”.20 Later, for more than a quarter of a century, the consideration of the indicated problem - the causes of schism and mental defect - was studied in various directions, but without any sort of "consolidation" or determination of correlations by 2-3 parameters.21 For a long time, it was not clear whether multidisciplinary approaches are needed in psychiatry. The literature reflects the debate whether the cause of the disease, in particular, schizophrenia, can be identified in discrete works at a new level of scientific capabilities. 22-24

         Chronologically, the study of the causes of schizophrenia over the past 100 years can be presented in the following sequence.

  1. Kraepelin 25 having created the theory of the so-called early dementia at the end of the 19th and beginning of the 20th century, believed that it was a hereditary disease that inevitably leads to a pronounced defect. This point of view, with minor variations, remained in psychiatry until the 1960-1980s. However, V.P. Serbsky (1902)26, in a debate with him, argued that it was impossible to find out what "traits are characteristic of diseases leading to such a defect." He also noted that the disease can develop not only in adolescence, but also at 40, 55 years, which shows the abuse of the term in the writings of E. Kraepelin.25. The positive consequences of the works of the German psychiatrist was the desire to study the hereditary-genetic and other biological mechanisms of the disease, as well as the possibilities of influencing them. At the same time, his views led to underestimation of the role of socio-psychological causes of the disease, often unjustified social restrictions, neglect of psychotherapy, negative social position in relation to patients – stigmatization. 27 The medico-social relevance of destigmatization in psychiatry is emphasized by V.S. Yastrebov 28, Y.V. Makushkin et al.22, many other Russian and foreign psychiatrists. However, the role of the hereditary factor in the emergence of schizophrenia has never been abandoned, and it began to be understood as dual - genetic and constitutional. As noted by A.M. Reznik et al.29, citing the works of other authors in recent years,30-32 schizophrenia is "one of the most hereditary common human diseases."  In the late XX th - early XXI st century, heredity began to be studied at a different level - the chromosomal one. The genetics of neurocognitive deficits in schizophrenia are also being discussed,   but so far it is difficult to talk about the results. At the same time, the interpretation of genetic data in psychopathology is hampered by the complexity of their reproduction under identical methodological conditions and non-Mendelian mechanisms of inheritance. 33-35 Recently, it was concluded that "there is no definitive genetic cause of schizophrenia". 29,36

       In a number of Western countries, the causes of schizophrenia have long been seen in wrong behavior of mother. To a certain extent, this was the beginning of psychoanalytic theory, which has become quite popular in the 1930s – 1950s and is not losing ground. It was even assumed that the patient's condition may improve as a result of psychoanalysis - although there were many cases of deterioration. Despite this history, at the end of the 20th century scientists returned to this theory in the etiology of schizophrenia with the clarification of psychotraumas in childhood and adolescence. 37-39

         Almost 20 years ago it was concluded at the Academic Council of the Ministry of Health of the Russian Federation that 30% of all research methods for schizophrenia are biological. 40 In the next 20 years, according to the analysis of the literary sources of the RSCI system and elibrary.ru, this figure has increased significantly.  

        Such studies began to gain more and more importance from the second half of the 20th century. For almost 40 years, one of the most popular was the so-called "dopamine" hypothesis of schizophrenia. It was largely confirmed by the discovery of antipsychotics that suppress dopamine, as mentioned in research papers of various years.41-44, 14 According to abovementioned hypothesis, productive symptoms are associated with long-term elevated levels of dopamine in the brain striatum, and negative symptoms are associated with long-term decreased levels of dopamine in this region of brain (compared to healthy people).45 However, even among the supporters of the dopamine theory of schizophrenia and other psychoses in the last 10 years, two main trends can be distinguished: some consider this phenomenon to be congenital, others – acquired. 41,46  It has been proven that antipsychotics block dopamine D2 receptors, which suppresses positive symptoms, but since their action is selective and affects such receptors not only in the mesolimbic system, their use may be accompanied by extrapyramidal side effects. 14 The second part of the classical dopamine hypothesis links the hypoactivity of dopamine receptors in the cortex with negative symptoms, including the formation of severe cognitive deficit. Neurochemical correlates of glucose metabolism in central neurons with changes in thinking, attention, speech were established.47 Investigations of biogenic amines are closely related to intravital visualization of brain structures (using computed tomography, neurochemical studies). According to A.S. Atyakova, G.S. Kovtyukh48, this method allows you to better understand the pathological processes of the brain in schizophrenia.

       In 1976, British scientists T.J. Crou and E.Johnston49  published data from positron emission tomography of the brain, proving the expansion of the lateral ventricles in progressive mental pathology with predominantly negative symptoms. Based on these data, in 1980 T.J. Crou 50 formulated a hypothesis about two types of schizophrenia, differing in etiology and pathogenesis - with a predominance of negative or productive symptoms. In case of the second type of disorder, there is an increase in the activity of D2 dopamine receptors (during posthumous autopsy an increase in their density was found). Research by T.J. Crou was supplemented by the American psychiatrist N.C. Andreasen.51 She correlated the data on positive and negative symptoms with defects in cognitive and emotional spheres during therapy with antipsychotics, revealing that their long-term use leads to atrophy of the prefrontal cortex. Autopsy, including posthumous autopsy, during the last 20 years has given new  impetus to the cytochemical direction in the search for the causes of schizophrenia. For 20 years scientists have been turning to the analysis of the characteristics of neuroglia in schizophrenia, and stable deviations from the norm have been found - using the examples of the groups of middle age and advanced age patients. 47, 52-53

      Some foreign researchers argue (from a biological standpoint) that schizophrenia is an organic mental illness. However, MRI, scanning of the brain of patients, did not produce significant results. The concept of a “functional” nature of schizophrenia became vulnerable after CT scans found out that the brain of schizophrenic patients (especially the hippocampus and amygdala) was reduced in volume due to the expansion of the cerebral ventricles. There is also a connection between changes in cognitive functions in schizophrenia and progressive loss of the gray matter of the brain. 54-56 This confirms the long-standing statement of K. Kahlbaum (1874) that anatomical justification may also be important in the understanding of mental illnesses.

          The role of stress in schizophrenia has not been denied by psychiatrists since the isolation of this disorder, however at the beginning of the XX th  century it was clearly overestimated by doctors, and at the end of the same century - by relatives of patients and patients themselves. Of course, even with a hereditary predisposition to schizophrenia, it cannot be denied as a "triggering factor". 58-62, 11  The majority of Russian psychiatrists during the 20th century and nowadays adhere to the concept of the interaction of endogenous and exogenous factors in the genesis of schizophrenia. 63-70,58

        At the beginning of the ХХ th century the onset of schizophrenia was associated with an unknown virus or infection, along with a mystical mechanism - "diabolizing".71-73 We see it fit to note that these factors again began to be seen as real at the end of the 20th century and even at the beginning of the 21st century, that is, at a completely different level of development of science. 74,75 However, almost a century later, the viral-infection theory acquired an "addition" - a connection with seasonal patterns - in winter, mother suffers from infectious and viral diseases more often, which affects the fetus, especially boys born in February. It is believed that this is due to the peculiarities of the genome, as well as to sexual dimorphism.76-80 However, the interpretation of these data, as well as changes in the frequency of disorders of gene locus, in particular, 16p11.2 and 22q11.2. in schizophrenia, requires the development of a general cqncept of the risk of the disorder with a clarification of the role of  genetic factors. 81,82 In a number of studies in schizophrenia, viral RNAs have been identified that are somewhat similar to HIV and herpes viruses. It is believed that elucidating the effect of HIV infection on the psychopathology of endogenous disorders is important in understanding the etiology and pathogenesis of both diseases. 83,84

        Since the late 1990s attention is paid in schizophrenia to dysontogenesis as a consequence of intrauterine hazards. In such cases, cytochemical data showed a relatively frequent immaturity of the cellular systems of the brain, synaptic connections and receptors.53, 85  At the same time, dysontogenesis is seen as a risk factor for the development of schizophrenia, and the cause of manifestation is stress.     In our opinion, this brings this theory closer to other works regarding the place of endogenous and exogenous factors in the genesis of schizophrenia.

        Since the 20th century, the interest of psychiatrists in immunological factors as the cause of schizophrenia has hardly waned. Almost until the end of the 20th century the priority was the study of cellular immunity86-88 and autoimmune factors - antibodies to one's own brain, including brain ones. 89-97 Since the first decade of the 21st century, priority has been given to those immunological factors that are not products of one's own brain - interleukins, in particular Ig-2; Ig-10. 98-102 The authors of these and foreign scientific studies consider their development to be caused by stress. The place of these factors in the onset of the disease is also not entirely clear: it is possible that they are either its consequence or a correlating factor.98,99,103

      In addition, the most pronounced immunological disorders have recently been identified with negative manifestations of schizophrenia. This contradicts some other works, according to which bright psychotic symptoms are "consistent" with a significant distortion of immune indicators. 97, 89, 104. Perhaps the observed tendency towards a particularly unfavorable course in carriers of the AB (IV); Rh (-) phenotypes is important; but no satisfactory interpretation was determined. In the last 20 years, considerable attention has been paid to the permeability of the BBB in mental disorders, including schizophrenia. It is considered promising to study its permeability for a number of cytoplasmic proteins - such a violation of the BBB is currently referred to as additional diagnostic and prognostic parameters, but its etiological significance, including in schizophrenia, cannot be ruled out.98, 105-107

     During the same period, a hypothesis was put forward about cortical disintegration as the basis of mental disorders, including schizophrenia. The argument is the decrease in gamma activity in the EEG in patients with schizophrenia, and the fact that the analysis of interhemispheric coherent connections in the gamma range of waves in the EEG showed their absence or weakening. 108-111 In attempts to understand psychopathology, quantitative electroencephalography began to develop. Thus, the evoked potentials showed differences in the parameters of the P 300 wave in patients with schizophrenia, and a connection was found between the indicator and impaired interhemispheric interactions. However, the International and American Societies of Electroencephalography and the American Academy of Neurology consider even quantitative EEG as a functional diagnostics method only, without linking its results directly with the possible causes of the disorder. A.S. Tiganov112  stated that objective (paraclinical) research methods in psychiatry do not have an independent meaning yet and should be considered in the diagnostic process as a part of the system which includes other data as well. The same opinion is shared by A.A. Aleksandrovsky and other scientists.113-115

         Perhaps the search for the causes of schizophrenia will turn out to be productive in a direction that now seems unimaginable. For example, frequent combinations of psychopathology, including  schizophrenia, and exceptional talents have long been noticed (Сербский, 1900).116 When arguing the prospects of systematic studies of such persons, it is stated that in both cases there exists frequent factual closeness of manifestations of symbolism, originality (which can be interpreted as absurdity) and psychopathology. A number of discoveries in technology are due to a non-standard logic.117,118 Thus, we can conclude that although the etiology of schizophrenia remains largely a mystery, there is no single unified concept of its disclosure. Scientists are trying to find the "starting point of the disease" based on their own scientific ideas and methodological interests. Perhaps a systematic interdisciplinary approach will be more productive at the present stage of the development of science than in the 1970s. Other scientists suggest the same idea in various forms as well. 112, 29, 120


         The first descriptions of the manifestations of a mental disorder which was named "ideophrenia" in 19th century, and “schizophrenia” in 1908, refer to the XVII th century BC: the Book of Hearts, Egyptian papyrus of Ebers, mentioned "phrenitis". 20,121 Avicenna called this disease "a heavy madness".122 It seems to us that to some extent, in these terms one can see the prototype of some views on the etiology, diagnostic criteria and searches for synonyms for the diagnosis of schizophrenia.

      In the 1930s K. Schneider developed the nosological concept of schizophrenia and formulated "symptoms of the 1st rank." They have become the basis for diagnostic criteria for schizophrenia in several ICD and DSM. Back in the 1930s G.E. Sukharevа and D.E. Melekhov proposed to distinguish two types of schizophrenia - remitting and continuous. However, until the 1950s the type of course and form of the disorder were not indicated in the diagnosis (sometimes the leading syndrome was noted). The term "remission" was not used, but cases of practical recovery with personality traits different from premorbid ones were sometimes described. Perhaps many aspects were not yet fully known to practicing psychiatrists. Despite the different methods of therapy, the dynamics of schizophrenia mainly depended on the biological characteristics of the body and changes in the situation upon admission to the hospital.

 In most studies and in forensic psychiatric reports, written before the introduction of antipsychotics into practice, schizophrenia was considered a disorder with an almost obligate progression and an unfavorable outcome. Psychiatrists of the period 123  considered the diagnosis of schizophrenia synonymous with incurability. They did not attach much importance to temporary improvements in patients’ condition, considering them undurable. N.P. Tatarenko124  agreed with the opinion of psychiatrists of the 1920s 125 about the progression of the course of the disease and worsening of the condition after each attack, pointing out that "the patient's fate is determined by the limit of his compensatory mechanisms." Despite such practical views, the concepts of remission and intermission were known in science since the 19th century. For instance, J.-E. Esquirol 126 insisted on the need to distinguish, along with recovery, also "incomplete recovery" (la guerison relative), "recovery only to a certain degree." This term he used to define not only the tendency to relapse, but also "damage to the brain and reason, expressed in the fact that patients, living in society, cannot play the role that they played before the disease." Improvements in the condition of patients with schizophrenia that meet the criteria for remission were described in the XIX  th century by Russian authors.127

As you know, E. Kraepelin.25  and E. Bleuler 129 admitted the possibility of long and complete remissions, a picture of practical recovery though with symptoms of mental weakness, some alienation from the outside world. They divided the defect conditions according to their severity. Both scientists believed that remission does not exclude new attacks of the disease and doubted that with schizophrenia recovery is possible (especially E. Kraepelin).

        According to A.I. Molochek130, schizophrenic post-process stage, remission, is a stage of functional restructuring. Patients may demonstrate vulnerability, autism, even impaired thinking, but they are subject to reactive mechanisms. M. Ya. Sereisky included cases of nosocomial improvement in the concept of remission as well.

Having in mind such concepts of the dynamics of schizophrenia, K.Kolle 131 in the same years argued that the most frequent outcome of the disorder is recovery with a defect and described three types of defect states. 5. D.E. Melekhov136 emphasized that researchers of the manifestations of the defect and remissions analyze the same conditions. He considered it natural, since in the 1960s, according to his data and the materials of N.M. Zharikov132, patients with “A” type of remission (according to the classification of M. Ya. Sereisky) amounted to about 4.5% of all patients. Such figures could be explained by the narrow use of antipsychotics in the therapy of patients.

 Zenevich G.V.133,  Morozov V.M., Tarasov Yu.K.134 emphasized that in case of remission, there is a desire to overcome the defect, and in case of a defective state – some sort of adaptation to it. In general, remission was viewed as a dynamic concept.

Complications of antipsychotic therapy, including the one used as support during remission, can manifest themselves as cerebrasthenic, depressive syndromes. 135 Moreover, some patients, critically assessing their current state of mental health, do not show sufficient criticism of the past, while in case of others it is vice versa. Already in 1981, D.E. Melekhov 136 emphasized that 90% of remissions involve a defect-state that is milder than dementia. The concept of "practical recovery" remains ambiguous - it is only the disappearance of symptoms of the disease without a complete restoration of mental functions or "new health" as described by F.V. Kondratyev. 7. From our point of view, it is important to note that despite more than half a century of study of remission in schizophrenia (filled with controversy), despite the use of various methods and schemes of therapy (according to the data of the last 5 years), this concept has not been reflected in practical psychiatry. It is stated both in Russian and foreign studies that the so-called psychosocial remissions are formed in no more than 15% of patients29, 140  A.V. Potapov et al 141note that in case of modern therapy compliance with international criteria for symptomatic remission is found in about 20% of patients. In our view, this fact demonstrates a very incomplete understanding of the etiology and pathogenesis of schizophrenic spectrum disorders. It can be considered that the existing theoretical developments of the problem of the positive dynamics of such disorders, especially schizophrenia, are only the basis for new concepts.

         Over the last 20 years, in Russian and foreign psychiatry many specialists have begun to pin their hopes on comprehending the essence, dynamics and diagnosis of schizophrenia using psychometric methods. 141 At the same time, other Russian researchers in general refuse measuring, instrumental approaches in psychiatry, trying to find an adequate replacement for them in the form of a functional characteristic of the patient's condition.142, 143, 113, 170 It seems, that rapid development of "technogenic" medicine, along with the attitude to the brain as a "great mystery” may allow not only to find a consensus, but also to come to a deeper understanding of mental processes. 145,146

        At the same time, the abovementioned authors note that at the beginning of the 21st century, the majority of categorical classifications are based on the concept of remission in schizophrenia by G.V. Zenevich 133 - "the weakening and mitigation of all symptoms, providing some sort of social adaptation." This very concept should allow the development of a promising model for the diagnosis of this condition.

        A.V. Snezhnevsky and R.A. Nadzharov147 identified three types of schizophrenia: continuous, paroxysmal-progressive (shift-like) and periodic. In the 1930s febrile schizophrenia was described. 148,40   After the 1960s, that is, already in the "era of antipsychotics", it was found out that febrile seizures are possible in recurrent and paroxysmal-progressive schizophrenia, more often in young people. Such attacks are rare and should be differentiated from neuroleptic malignant syndrome.148-151

          In the 1960s, in agreement with E. Bleuler's 152 idea of ​​the secondary importance of acute productive symptoms in the long-term course of schizophrenia, A.V. Snezhnevsky introduced to psychiatry concept of "sluggish schizophrenia", similar to the latent form described by E. Bleuler (1911). The polymorphism of clinical manifestations led to the ongoing controversy regarding this disorder, and it was not included in the ICD-10 and in the ICD-11. DSM-5 describes the diagnostic criteria for schizotypal disorder, which is closest in symptomatology to sluggish schizophrenia, but it belongs to the category of "personality disorders".153,154, 22

 From the history of medicine of 1000 years ago - Avicenna's "Canon of Medicine"122 - one can learn that the diagnosis of a disorder corresponding to modern descriptions of schizophrenia was only possible through exclusion of affective, personality disorders, without ignoring the laws of logic. Due to the aging of population, including the mentally ill patients, it is important that recently it was decided to abandon the requirement for the development of the first symptoms of the disease before the age of 45.154  The late onset of schizophrenia (51-60 years) is described in many  works in different yers.154-161 During the last 10 years, all authors have paid attention to the differential diagnosis of schizophrenia and schizophreniform psychoses of various origins.

The main changes in the diagnosis of schizophrenia in comparison with ICD -10 in ICD-11 are: a) decrease in the significance of 1st rank symptoms; b) the introduction of “6 dimensions”; c) exclusion of clinical forms; d) inclusion of such sign as "the course of the disease"162, 163, schizophrenia is characterized by multiple mental dysfunctions. Chronic delusional symptoms, hallucinations, thought disorders, and impaired self-awareness are considered nuclear symptoms, and at least 2 of these must be present for 1 month or more. 164

       The six main diagnostic criteria for schizophrenia, adopted in previous versions of the DSM, with minor changes, were retained in DSM-5: delusions, hallucinations, disorganized speech, severely disorganized or catatonic behavior, negative symptoms. Along with this, the clinical space of schizophrenia is limited only by its most severe forms. DSM-5 also excludes all relatively mild forms of the disorder. 165-167.

        Considering the development of medical science, an increase in dimensions can be assumed in the diagnosis of schizophrenia as well. In our opinion, perhaps, knowledge of neuroanatomical dimensions, reflecting the specific localization of structural and functional disorders, will make it possible to clarify the clinical symptoms, course, and outcomes of schizophrenic spectrum disorders.  Back in 1940 A.S. Kronfeld 168 believed that "the syndrome can only be understood as a result of the activity of the whole brain." Later it became obvious that in addition to knowing the localization of the pathological process of the brain, it is necessary to take into account the reaction of the body as a whole, in particular, neurohumoral and neurochemical changes.169  Therefore, ICD-11 and DSM-5 are not "ultimate truths"; in their daily work, clinicians will continue to use many of the undefined constructs of the first classification, and researchers – of the second one,  along with the further development of diagnostic criteria. 170-172, 23, 166

        Appealing to the undesired stigmatization of patients  many scientists admit that the term "schizophrenia" has already outlived its usefulness as a clinical concept denoting an independent disease.173-175 There are proposals to replace it with neurophysiological terms at the level of syndromes: "dopaminergic system dysregulation syndrome" 176; "saliens dysregulation syndrome"1  177, and in 2002 by the decision of the Japanese society of psychiatrists and neurologists and the community of relatives of patients, the diagnosis of schizophrenia was changed to "disorder of loss of coordination"178 In some countries  schizophrenia has become a "psychosis  susceptibility syndrome"180  However, in our opinion, it is obvious that destigmatization of patients needs not only  replacing the terms established in psychiatry. Such a substitution may come from socio-psychological desires without correlation with medical realities.

      In the middle of the 20th century, a non-academic approach to psychopathology called the "antipsychiatry movement" developed, which opposes the orthodox view of schizophrenia as a disease. According to the participants of this movement scientists 180 -183  mentally ill patients, including patients with schizophrenia, are not really sick, they are individuals with non-standard thoughts and behavior, inconvenient for society. It was noted that society is unfair, classifying their behavior as a disease and “subjecting it to treatment.” T. Sass182 even argued that schizophrenia does not exist, it is a society’s construct based on the notion of norm and not norm. However, ambiguous criteria for the need or not need for therapy may contribute to the use of psychiatry and especially the diagnosis of schizophrenia for manipulative purposes.184

In our view «antipsychiatry" is a topic for a separate analysis that is not included in this article.


       Diagnostic discrepancies and errors in psychiatry remain not only possible, but also a relatively frequent phenomenon, and at the turn of the century this was noted by S.S. Korsakov185, V.P. Serbsky 116. According to the data of the State Research Center of Social and Forensic Psychiatry n.a. V.P. Serbsky, for 50 years (1960-2010), about one third of the repeated forensic psychiatric examinations (FPS) differed from the conclusions of the primary FPS.8,9,186-189,7 In most cases, schizophrenia was one of the diagnoses. The indicator of discrepancies in different years and among other Russian authors on general psychiatry190-,192 ,  as well as among foreign psychiatrists is similar.193-195  In the monograph by N.G. Shumsky196  225 cases of under- or overdiagnosis of schizophrenia are recorded for the period of 1962-1983 during repeated FPS in the State Research Center n.a. V.P. Serbsky. In the study of M.V. Yakovleva 190, such changes were revealed in 268 patients with schizophrenia of Indo-European origin in Khabarovsk Region, hospitalized in the period of 1965-1970  and 2006-2009 to Regional Psychiatric Hospital n.a. professor I.B Galant.

     According to the author, the diagnostic errors demonstrated traditional and still unadressed in practice ideas stating that psychologically understandable behavior is uncharacteristic for patients with schizophrenia, insufficient attention to special changes in nonverbal behavior, emotional deficiency.

        T.B Dmitrieva et al.191, F.V. Kondratyev7 believed that the main part of diagnostic discrepancies and errors in psychiatry is associated with the difficulty of distinguishing schizophrenia from psychopathy-like, neurosis-like manifestations of personality disorders, including those of organic genesis, mainly in terms of underdiagnosis of endogenic disorder. According to N.G. Shumsky 196, personality disorder was most often misdiagnosed, in 2nd and 3rd places - reactive states and organic lesions, personality disorders and acute reactions to stress according to ICD-10.

        As revealed in a study of a continuous sample of patients in Moscow, in 2/3 of cases the diagnosis of schizophrenia was established during the first visit to the city psychiatric service.12 At the same time, the authors noted that almost a third of the examined patients were not diagnosed with schizophrenia at first. There is evidence in the literature that when a diagnosis of schizophrenia is made according to the DSM-V, according to the Cohen’s coefficient the indicator is 0,46, which means that the likelihood of coincidence of this diagnosis even for two doctors is very small.197 Causes and consequences of errors in differential diagnosis in a psychiatric hospital, including when differentiating schizophrenia, were analyzed in other works as well.188, 189

       Based on the analysis of the literature and our own observations, cases of change of diagnosis (in under- and overdiagnosis of schizophrenia) can be divided into 2 main options: errors of the previous diagnosis with the objective possibility of correct qualification of psychopathological condition (1st option) and the impossibility of this at some stage of the disease (2nd option). In turn, the 1st option is associated with subjective and objective causes of diagnostic errors and discrepancies.

       N.G. Shumsky196 saw the main reasons for the errors and discrepancies in the insufficient use of methods of examination adopted in psychiatry, the principles of deontology, as well as in the imperfection of the diagnostic approach. According to him, the identified causes of underdiagnosis of schizophrenia are characteristic of both general and forensic psychiatry, and are found both in outpatient and inpatient settings.

         At the same time differential diagnosis in case of underdiagnosis of schizophrenia can be complicated by many factors - relative personal and social integrity of patients, dissimulation, pathomorphosis, even though the true debut can well occur before patient addresses psychiatrists 7, 198,191,6, 12, 170  , as well as comorbid pathology – addiction to psychoactive substances, alcohol; organic hazards. A.A. Dvirsky197, OG Eryshev 200, other authors noted the difficulties in diagnosing schizophrenia in combination with chronic intoxications 20 years ago. In recent decades, against the background of the general growth of psychoactive substances use, we can state that the factor of comorbid pathology with pathoplasty of schizophrenia has taken a significant place in the differential diagnostic process. 201-205  

As has long been known, the influence of pathoplastic psychogenic factor on the clinical picture in a patient with schizophrenia cannot be ruled out. According  to AA. Shmilovich 11, stressful provocative situations took place in half of the cases of the onset of paranoid schizophrenia. This is confirmed by other researches as well. 186, 7 According to N.S. Lebedeva, 4-6% of patients with schizophrenia get wrong diagnoses annually. Atypical psychopathological conditions due to exposure to exogenous factors may have significant phenomenological similarity to stress responses. Each exogenous factor contributes its psychopathological elements to the structure of the clinical picture of schizophrenia. At the same time, differences with true exogenous disorders may be minor and unstable. In case of schizophrenia with prevalence of psychopathy-like disorders stereotypeness of clinical representations is possible. N.G. Shumsky 196 also emphasized that psychopathological conditions of patients with schizophrenia with psychopathy-like disorders are most often assessed incorrectly.

           According to his observations , there is a certain subjective significance in the underdiagnosis of schizophrenia for fear of damaging the patient by such diagnosis (but mainly in combination with other factors mentioned above). This can be psychologically explained by the predominance of people with the onset of this disease in childhood and adolescence. Same author noted that at the time of establishing the correct psychiatric diagnosis, the duration of the disease reached 10-20 years. In a number of studies authors revealed a significant pathomorphosis of schizophrenia with blurring of boundaries between schizophrenia and other nosological forms, atypical clinical design of the disorder with a decrease in the brightness of many syndromes and symptoms. 186, 190, 6 At the same time, the importance of catamnesis in clarifying the nosology of a mental disorder increases. F.V. Kondratiev7 noted that despite the external loss of affect, patients with schizophrenia are often capable of emotional experiences at a normal or even elevated level, especially during stressful or negative events. He also stressed that worldwide the number of people in different countries which suffer from schizophrenic psychoses is almost the same, but the symptoms on the basis of which the diagnosis is made vary significantly depending on time and culture. Thus, cultural pathoplasty of schizophrenia is also possible (which coincides with the data of yakut author). 190

       Recently were described the observations of untimely diagnosis of schizophrenia, noting the underestimation of anamnestic data on early autism, indigenous fluctuations and disorders of attraction (dromomania) in adolescence, the emergence of aggressive and autoaggressive tendencies. Author noted that the external lack of motivation for serious violent crimes was not always analyzed. At the same time, the role of the psychogenic-traumatic situation in the inaccessibility of the subject to productive contact, hypochondriac experiences, and senestopathy was overestimated.205

         As it was mentioned, in forensic psychiatric and general psychiatric practice often there are patients who do not externally demonstrate any mental disorders that require active care and they are not rejected by social environment. After achieving remission, many of them seek to withdraw from psychiatric supervision. Insufficient study of long-term postpsychotic states (when patients at some stage of life appear before a psychiatrist as primary ones is acknowledged often saw the cause of diagnostic discrepancies in the relationship (confrontation) of a patient with schizophrenia and the doctor, as the patient believes that the diagnosis will estrange him from society. At the same time manifestations of a disease are dissimulated. Objective information about the mental state can be quite contradictory, which may be related to the very essence of schizophrenia. According to the abovementioned author, the complexity of diagnosing schizophrenia is currently exacerbated by the frequency of early organic pathology of the brain, the consequences of head injuries.7, 198,202    

       The reasons for untimely diagnosis of paranoid schizophrenia with sexual disorders are described: activity of presenting persecutory complaints, variability of personal response, including hysterical forms, orderliness of behavior and smoothness of emotional manifestations when describing psychotic experiencesю.206  According to the author, the diagnostic errors demonstrated traditional and still unadressed in practice ideas stating that psychologically understandable behavior is uncharacteristic for patients with schizophrenia, insufficient attention to special changes in nonverbal behavior, emotional deficiency. Also, in another qualification of psychopathology, autoerotic activity with elements of pretentiousness is not analyzed. It is noted that in such  cases as well it is important to take into account the characteristics of comorbid disorders in the differential diagnosis of the schizophrenic process. The transformation of the paraphilic complex in close connection with the manifestation of schizophrenic psychosis in literature also was described, with the modification of initially involuntary urges into violent ones, which makes it difficult to take into account the formation of complex paranoid experiences. 207

           Among the errors of the diagnostic process in the overdiagnosis of schizophrenia, a large place is taken by the objective difficulty of correlating the signs that are "alarming" in relation to schizophrenia with limited catamnesis, with other information links.

        The results of research of S.N. Oskolkova 8 also testify to the relative frequency of cases of impossibility of correct qualification of a psychopathological condition at a certain stage of clinical dynamics. The nosological conclusion at the same time is inappropriate and the preference is given to the syndromic diagnosis. We note the continuing validity of situation up-to-date.  In the analysis of the overdiagnosis of schizophrenia in personality disorder, it is emphasized that only a catamnesis can show the absence of a clear psychopathological shift or a manifest attack during life. In addition, the causes of misdiagnosis of schizophrenia may be a simulation for different purposes, using a certain supply of psychiatric knowledge which patient possesses. 8,208 Difficulties in distinguishing between schizophrenia and dissocial personality disorder were described. 209 On one hand, changes in the emotional-volitional sphere can be demonstrated, including the inability to higher forms of emotional response, which is considered characteristic of both disorders. On the other hand, disorders that are obligatory for the schizophrenic process (delusions of attitude, persecution, influence) can be transient.

        Naturally, diagnostic errors and discrepancies are always possible due to the simulated behavior of the subjects as well. No less relevant in this regard are mental changes that mimic the manifestations of schizophrenia and are caused by somatic diseases, social factors, including macroeconomic (difficulties with job, etc.). At the same time, a decrease in energy potential, apathetic-abulic disorders can be observed not only in the schizophrenic process, but also in chronic infections (tuberculosis, hepatitis, etc.), which has also been observed since ancient times.

Subjective causes of under- and overdiagnosis of schizophrenia may be caused by insufficient qualifications of the psychiatrist, not allowing specialist to properly assess the mental state. It is known that in ICD-10 several diagnoses can be placed in the same axis, which does not facilitate compliance with methodological standards and does not reduce the frequency of diagnostic discrepancies. In ICD-11, this trend persists, the boundaries of psychopathology and behavioral characteristics are more "blurred", which is already a concern for psychiatrists around the world. For instance, polymorphism and atypical manifestations of manic depressive disorder, personality disorders in combination with a low level of social adaptation can lead to diagnostic errors. 210, 211, 170 As we know, no unambiguous criteria for distinguishing manic depressive disorder and schizophrenia have been found during the last one hundred years.212 Well known, that even psychoses in schizophrenia and epilepsy remain a subject of comparison. 213  We may assume objective and subjective reasons of the errors caused by this fact, and the subjective ones are possible due to the incorrect explanation of mechanisms of adaptation level. However, the criteria for the level of adaptation may change parallel with social change. Objective and subjective causes of diagnostic discrepancies may be related to inaccurate understanding or application of dimensional and categorical diagnostic models. This, in turn, can erase the boundaries of normality and pathology and underscores the importance of strictly following a systematic approach at all stages of diagnostic analysis. 214,215 Disagreements in the diagnostic approaches of general psychiatry often have a particularly negative effect on the diagnostic argument in forensic psychiatry and have legally significant consequences. Of certain importance among the causes of misdiagnosis may be the indifference of specialists to their work and, accordingly, the fate of the patient. This, in turn, corresponds with the data that at the end of the 19th century doctors were much more likely to pay attention to their own mistakes than in the 20th - early 21st century when mistakes were ignored. 216, 217   Serbsky V.P.  128  wrote that “ accurate diagnosis is nit limited to only naming the disease, gluing a label to the phenomenon that remains no less incomprehensible” and that “the task of real diagnostics is far from easy”. In general, diagnosis in psychiatry is still largely subjective, so the "doctor factor" plays main role in assessing psychopathology. 172, 183

   In recent years, the differential diagnosis of schizophrenia is often difficult due to significant migration of the population, including ethnically diverse groups. Ethnocultural factors in the diagnosis of schizophrenia are important in many countries, objectively complicating the diagnostic process. According to an extensive study of British citizens of African-American descent, they are twice as likely to be diagnosed with psychosis as citizens, which are not a part of racial minority, but  are 3-9 times more likely to be diagnosed with schizophrenia.174 At the same time disease is diagnosed on the basis of less number of symptoms in comparison with white patients. 173 Such a situation can be regarded as a pathoplastic influence of religious worldview and socially conditioned forms of behavior on the design of the picture of psychopathology and as a certain conscious bias of specialists in relation to non-white patients (conclusions of abovementioned study).

       However, according to other data, in different ethnic groups with different content of psychopathological experiences there is a basic similarity of psychoses, which allows to build a correct nosological hypothesis.117 Studies have shown that migration is objectively a factor of the potential provocation of the manifestation or exacerbation of endogenous diseases. 218,219 Certain groups of migrants in The Netherlands and Sweden have an increased risk of non-affective psychotic disorders compared to indigenous peoples and other migrants. At the same time, it is acknowledged that this problem is not sufficiently studied.220. Non-optimal language skills and psychogenic pathoplasty can objectively complicate the diagnostic process, along with subjective factors (mutual distrust of the migrant and non-migrant doctor and patient, ethnosocial barriers). 218, 221

         As noted above, similar diagnostic problems have been observed in many countries in recent decades. As follows from the abovementioned studies, in case of follow-up change of the diagnosis of endogenous disorder (schizophrenia), diagnostic error may have complex genesis - objective and subjective, as well as deliberate aggravation of the diagnosis.

          Diagnostic discrepancies and errors in psychiatry in all countries are analyzed not only in medical, but also in social and legal aspects. A special place is occupied by various abuses of psychiatry for various purposes. As a rule, it is a question of legality or illegality of diagnosis of schizophrenia. It should be noted that abuses in this field of medicine have long been identified, which is reflected in the works on the history of psychiatry.222, 223, 224  The problem appears to require separate consideration beyond the scope of this article.


Thus, the cause of schizophrenia remains virtually unclear by the beginning of the 21st century. But the medical and social significance of the disease is so great that relevant research remains among the priorities in psychiatry. It cannot be ruled out that simply new approaches to interpreting the existing results of certain studies will make it possible to understand the cause -or the causes - of schizophrenia. This will change the lives of patients, as it will be possible to really talk about optimal therapy, and perhaps even prevention of this disease.

        The review of the literature on approaches to the diagnosis of schizophrenia for about 100 years suggests that psychiatrists have always had the basis for various views on this disorder, variants of its dynamics and criteria for dynamic stages, including remission. The latter should also be considered a separate aspect of the analysis. In various years, scientists have found arguments for looking at schizophrenia both as one disorder or as two or even a group of disorders. The polymorphic symptoms and typical dynamics of various forms of schizophrenia have been systematized, but neither in Russia nor in other countries the etiology has been proven and the concept of pathogenesis has not been formed even within certain types of disorder. From the point of view of the authors of the article, the above causes of under-and overdiagnosis of schizophrenia cannot cover all the possible objective and subjective difficulties that arise in the diagnostic process.

     In general, as follows from Russian and foreign literature, it would still take a very long time before the problem of schizophrenia would be solved. It seems that this largely depends on the position of society, the development of the biological sciences and the pathomorphosis of the disorder itself. Many aspects of schizophrenia may become clearer and less controversial with systematic studies based on previous and subsequent data.

       A review of the literature on the abovementioned aspects of schizophrenia can contribute to the attention of scientists to certain research results at a new stage of methodological possibilities, with a different analysis and synthesis of information.

        In addition to the above, a literature review on a specific topic can contribute to the development of innovative technologies aimed at solving strategic problems. In psychiatry, one of them is the identification and comprehensive assessment of schizophrenia and schizophrenic spectrum disorders. Considering that innovative activity contains qualitative advantages in understanding of a particular issue by YuA Aleksandrovskii225, all the ways of approximating such an understanding are important in the science and practice of this discipline


About the authors

Sofia Natanovna Oskolkova

Author for correspondence.
Email: oskolkova.1954@mail.ru
ORCID iD: 0000-0003-1334-7866
SPIN-code: 7284-3874
Scopus Author ID: 6603176840
ResearcherId: G-8650-2013
Russian Federation

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Copyright (c) Осколкова С.

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