Psychopathology Of Schizophrenia Research Articles

Association between prolactin and thyroid hormones with severity of psychopathology and suicide risk in drug free male schizophrenia

BackgroundHormonal deregulation is associated with suicidal risk in various psychiatric disorders. Thyroid hormones and prolactin play a role in the pathophysiology of schizophrenia. The present study aimed to analyze thyroid hormones and prolactin levels in patients with schizophrenia, and to explore its association with disease severity and suicide risk. MethodsThirty-eight cases and 38 controls were included in the study. Serum thyroid hormones and prolactin were estimated in all the subjects. Disease severity was assessed using the Positive and Negative Syndrome Scale and suicidal ideations were assessed using the Columbia Suicide Severity Rating Scale. ResultsSerum prolactin (p=0.004) and free T4 (p=0.029) were significantly elevated in the schizophrenia group as compared to controls. Serum prolactin was significantly associated with higher negative symptom scores (r=0.418, p=0.008), but not positive symptoms or general psychopathology of schizophrenia. Thyroid hormones were not associated with disease severity scores. Suicidal ideas were more common in schizophrenia patients with higher free T4 (p=0.011). ConclusionProlactin and free T4 were increased in patients with schizophrenia as compared to controls. Suicidal ideation was associated with increased free T4, but not prolactin levels.

Cognitive self-regulation, social functioning and psychopathology in schizophrenia

Aim:To explore relation between cognitive self-regulation, social functioning, and psychopathology in schizophrenia.Materials and Methods:A total of 100 patients diagnosed with schizophrenia according to International Classification of Diseases (ICD)-10 were taken from Department of Psychiatry of two postgraduate hospitals of Kolkata, India. All subjects gave informed consent. After recording sociodemographic and clinical details, the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Schizophrenia Research Foundation India-Social Functioning Index (SCARF-SFI), and specially designed questionnaire on cognitive self-regulation was administered.Results:All the four subtests of SCARF-SFI, that is, self-concern, occupational role, social role and family role, and symptoms scale of PANSS were significantly correlated with cognitive self-regulation. Cognitive self-regulation along with positive and negative symptoms was able to predict social functioning.Conclusion:Cognitive self-regulation is significantly and positively correlated to social functioning. Cognitive self-regulation along with positive and negative symptoms is a significant predictor of social functioning.

Hypothalamic-Pituitary-Adrenal (HPA) Axis Functioning among Patients with Schizophrenia: A Cross Sectional Comparative Study

Objectives: Higher perceived stress and maladaptive coping strategies seems to play an important role in the course and outcome of schizophrenia. The biological effects of stress are mediated by the hypothalamic-pituitary-adrenal (HPA) axis functioning (reflected by cortisol and DHEAS ratio). The aim of this study were, first to compare serum cortisol, DHEA-S concentration and their molar ratio in schizophrenic patients with healthy subjects, and secondly to determine their correlation with psychopathology of schizophrenia. Methods: One hundred clinically established male patients with schizophrenia and fifty ages matched healthy controls participated in this study. Fasting serum cortisol and DHEAS levels were measured by Chemiluminescence Immunoassay (CLIA). Psychopathology was assessed by using the Positive and Negative Syndrome Scale (PANSS). Sociodemographic characteristics, data regarding onset of illness, disease duration and medication history were recorded in self designed semi-structured proforma. The data collected on above tools, were analyzed by z test and Pearson Correlation Coefficient. Results: Serum cortisol levels and cortisol to DHEAS molar ratio were significantly higher in schizophrenic patients [(z=-4.457; p<0.001) (z=-3.787; p<0.001)] than in healthy comparison subjects, while no significant differences were seen in the DHEAS levels. These hormonal indices were not significantly associated with severity of psychopathology, onset of illness and disease duration in schizophrenia patients. Conclusions: Our findings suggest that besides the elevated cortisol level, cortisol to DHEAS ratio might reflect abnormal HPA axis functions in schizophrenic patients. Persistent stress vulnerability in these patients may lead to increased sensitivity to brain insults and in turn dysregulated neurotransmission, resulting in progressive deterioration in cognitive, emotional and psychosocial functions.

Assessment of cigarette smoking status with respect to symptomatic manifestation in first-episode schizophrenia patients

ObjectiveIt has been repeatedly found that cigarette smoking may influence schizophrenia psychopathology. However, little is known about the relationship between nicotine consumption and symptomatic manifestation of first-episode schizophrenia (FES). MethodWe recruited 109 minimally medicated FES patients. Cigarette smoking was assessed using the Fagerström test for nicotine dependence (FTND) and pack-year index. Psychopathology on the day of recruitment was examined using the Positive and Negative Syndrome Scale (PANSS). ResultsSmokers had significantly lower severity of negative and depressive symptoms in comparison with non-smokers. Patients with severe nicotine dependence had significantly later age of psychosis onset in comparison with those with mild nicotine dependence and non-smokers. Significantly lower severity of negative and depressive symptoms was also observed in patients with severe nicotine dependence in comparison with non-smokers. The associations between the severity of nicotine dependence and scores of negative and depressive symptoms as well as age of psychosis onset remained significant after co-varying for gender, education, duration of untreated psychosis (DUP) and measures of antipsychotic treatment. ConclusionOur results indicate that cigarette smoking might be associated with less severe negative and depressive symptoms as well as delayed age of psychosis onset. However, longitudinal studies are required to indicate the direction of causality.

Cytokine Serum Levels as Potential Biological Markers for the Psychopathology in Schizophrenia

We discuss the role of immune system disturbance in schizophrenia and especially changes of serum levels of cytokines in patients with schizophrenia. The cytokines are essential to wide range of functions related to the defense of the organisms from infectious and environmental dangers. However it is not known whether cytokines influence the presentation of psychotic symptoms. Identification of changes in the serum level of certain cytokines and their correlation with distinct psychopathological symptoms may facilitate the identification of subgroups of patients who are likely to benefit from immunotherapy or anti-inflammatory therapy. Such patients may benefit from tailored immunotherapy designed for modulation of abnormal cytokine levels related to specific positive or negative symptoms of schizophrenia.

Possible association between DBH 19 bp insertion/deletion polymorphism and clinical symptoms in schizophrenia with tardive dyskinesia

Overactivity of dopaminergic neurotransmission is a putative mechanism of tardive dyskinesia (TD). Previous studies have found dysfunction in plasma dopamine beta-hydoxylase (DBH) in schizophrenia with TD. Moreover, DBH, whose activity and levels are strongly controlled by the DBH gene, is a key enzyme in the conversion of dopamine (DA) to norepinephrine (NE) associated with excited behavior. This study examined whether the DBH5'-insertion/deletion (Ins/Del) polymorphism was associated with excited behavior in schizophrenia with TD. The presence of the DBH5'-Ins/Del polymorphism was determined in 741 schizophrenia with TD (n = 345) and without TD (n = 396). The Abnormal Involuntary Movement Scale and Positive and Negative Syndrome Scale were used to assess the severity of TD and psychopathology of schizophrenia. There was no significant difference in the allelic and genotypic frequencies of the DBH5'-Ins/Del polymorphism between schizophrenia with and without TD (both p > 0.05). However, the excited symptoms score was significantly different to the DBH5'-Ins/Del genotypic groups in schizophrenia with TD (p < 0.05) but not in the two groups of non-TD and total patients (both p > 0.05). The excited symptoms score was higher in TD patients with the Del/Del genotype than those with Ins alleles (p = 0.015). Our findings suggest that the DBH5'-Ins/Del polymorphism may not contribute directly to the development of TD in schizophrenia, but it may be involved in the excited behavior of TD patients.

P.6.a.011 Role of C1473G polymorphism in mouse tryptophan hydroxylase 2 gene in ethanol treatment effect on behaviour and brain serotonin system

Dysfunction in brain serotonin (5-HT) system has been implicated in the psychopathology of anxiety, depression, drug addiction, and schizophrenia. The 5-HT1A receptors play a central role in the control of 5-HTergic neurotransmission. There are some scarce data showing cross-regulation between 5-HT receptors. Here, we investigated whether interaction exists between 5-HT1A receptor and genes encoding key members in brain 5-HT system. Chronic treatment with selective agonist of 5-HT1A receptor 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.0 mg/kg i.p., 14 days) produced considerable decrease in hypothermic response to acute administration of 8-OH-DPAT in CBA/Lac mice indicating desensitization of 5-HT1A receptors. The decrease in 5-HT1A gene expression as well as decrease in the expression of gene encoding key enzyme in 5-HT synthesis, tryptophan hydroxylase-2 (TPH-2) in the midbrain, and the expression of the gene encoding 5-HT2A receptor in the frontal cortex was shown. There were no significant changes in 5-HT transporter mRNA level in the midbrain. Despite considerable decrease in the expression of the genes encoding tryptophan hydroxylase-2, 5-HT1A and 5-HT2A receptors, chronic 8-OH-DPAT treatment failed to produce significant changes in 5-HT1A-linked behavior (intermale aggression, open-field behavior, light-dark box, and pinch-induced catalepsy), suggesting compensatory and adaptive effect of genes suppression. The obtained data on the effect of 8-OH-DPAT-induced desensitization of 5-HT1A receptors on 5-HT1A, 5-HT2A and TPH-2 gene expression demonstrated the role of 5-HT1A receptor as indirect regulator of gene expression. The results provide the first evidence of receptor-key genes interaction in brain 5-HT system and may have profound implications in understanding the functioning of the brain neurotransmitter systems.

Serum leptin and its relationship with psychopathology in schizophrenia.

Leptin plays an important role in the modulation of the dopaminergic system and has recently been implicated in schizophrenia. There have been conflicting reports on leptin levels in schizophrenia; as well as on the association between leptin levels and clinical symptoms. Therefore, this study aims to examine (i) leptin levels in schizophrenia relative to control, and (ii) the relationship between leptin and symptoms in schizophrenia. One hundred participants with schizophrenia and 89 healthy controls were recruited from the Institute of Mental Health in Singapore. Demographic information and medical histories were collected. Schizophrenia symptoms were assessed using the positive and negative syndrome scale (PANSS) and serum leptin was measured using a commercially available bioplex leptin assay. Linear regressions were performed to examine the relationship between serum leptin and the positive, negative, general psychopathology subscales and total PANSS scores. Contrary to previously published literature, we did not find any significant difference in leptin level between participants with schizophrenia compared to controls, which might be the result of recruited controls being of comparable body mass index. Serum leptin was found to be positively associated with positive symptoms, general psychopathology and total PANSS score. This study provides evidence to suggest a positive association between serum leptin level and symptomatology in schizophrenia. However, since conflicting results in this area of research exist, it is important to understand better the mechanism behind this relationship and to examine temporal fluctuations in leptin levels in relation with changes in clinical symptomatology.

Serum TNF-α, IL-10 and IL-2 in schizophrenic patients before and after treatment with risperidone and clozapine.

Schizophrenia is a disorder of the executive function of both sensory and central nervous system. Recent studies suggest that immune mechanisms play a role in the pathophysiology of this disease. The variations in cytokine concentrations have been associated with psychopathology and treatment of schizophrenia. To investigate the changes in serum concentrations of TNF-α, IL-10, and IL-2 in schizophrenic patients before and 40 days after treatment. In a case-control study, 26 schizophrenic patients and 26 healthy individuals as a control group were enrolled. PANSS scale questionnaire was used for diagnosis and assessing the severity of the disease. All patients were then treated with risperidone or clozapine for 40 days. Serum concentrations of TNF-α, IL-10 and IL-2 were measured by ELISA before and after treatment in both groups. Paired t-test and Independent t-test were used for comparison of data. Comparison of TNF-α and IL-10 concentrations in patients before and after treatment revealed a significance decrease of TNF-α and increase of IL-10 concentrations (p=0.002, and p=0.008, respectively). Serum concentrations of IL-2 were lower than the detection limit of assay and were not detectable. In comparison with healthy controls, serum concentrations of TNF-α in schizophrenic patients were higher, while IL-10 concentrations were lower before treatment although the differences were not significant (p=0.291 and p=0.375, respectively). There was no correlation between cytokine concentrations and the positive and negative scale (PANSS). Also no significant difference in the admission, relapses, and duration of illness before and after treatment was observed. Increase of TNF-α and decrease of IL-10 may have an important role in psychopathology of schizophrenia.

Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to perform a comprehensive meta-analysis of minocycline augmentation therapy in patients with schizophrenia receiving antipsychotic agents. Data published up to 2 June 2014 were obtained from the PubMed, PsycINFO, Google Scholar, and Cochrane Library databases.We conducted a systematic review and meta-analysis of patient data from randomized controlled trials (RCTs) comparing minocycline with placebo. Relative risk (RR), standardized mean difference (SMD), and 95% confidence intervals were calculated. We included four RCTs. The total sample included 330 patients. Minocycline was superior to placebo for decreasing Positive and Negative Syndrome Scale (PANSS) total scores (SMD=0.70), PANSS negative subscale scores (SMD=0.86), and PANSS general subscale scores (SMD=-0.50) but was not different from placebo for PANSS positive subscale scores (SMD=0.26) and depressive symptoms (SMD=0.28). Minocycline was equivalent to placebo for all-cause discontinuation (RR=1.10), discontinuation due to inefficacy (RR=0.42), discontinuation due to adverse events (RR = 1.56), and discontinuation due to death (RR = 3.18). Minocycline was superior to placebo for extrapyramidal side-effect scores (SMD=0.32). Minocycline may improve the psychopathology of schizophrenia, especially the negative symptoms, and seems to be well tolerated.

Validation of the German version of the Clinical Assessment Interview for Negative Symptoms (CAINS)

Validated assessment instruments could contribute to a better understanding and assessment of negative symptoms and advance treatment research. The aim of this study was to examine the psychometric properties of a German version of the Clinical Assessment Interview for Negative Symptoms (CAINS). In- and outpatients (N=53) with schizophrenia or schizoaffective disorder were assessed with standardized interviews and questionnaires on negative and positive symptoms and general psychopathology in schizophrenia, depression, the ability to experience anticipatory and consummatory pleasure, and global functioning. The results indicated good psychometric properties, high internal consistency and promising inter-rater agreement for the German version of the CAINS. The two-factor solution of the original version of the CAINS was confirmed, indicating good construct validity. Convergent validity was supported by significant correlations between the CAINS subscales with the negative symptom scale of the Positive and Negative Syndrome Scale, and with consummatory pleasure. The CAINS also exhibited discriminant validity indicated by its non-significant correlations with positive symptoms, general psychopathology and depression that are in line with the findings for the original version of the CAINS. In addition, the CAINS correlated moderately with global functioning. The German version of the CAINS appears to be a valid and suitable diagnostic tool for measuring negative symptoms in schizophrenia.

Decreased serum TNF-alpha levels in chronic schizophrenia patients on long-term antipsychotics: correlation with psychopathology and cognition.

A substantial body of evidence implicates TNF-alpha (TNFα) and TNFα-related signaling pathways in the pathophysiology of schizophrenia. The current study examined the relationship between TNFα serum levels and both psychopathological as well as cognitive symptoms in schizophrenia. Serum TNFα levels were assessed in 89 patients diagnosed with schizophrenia and compared to 43 healthy control subjects matched for age and gender. Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS), and serum TNFα levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). TNFα levels were significantly lower in patients with chronic schizophrenia relative to healthy control subjects (p<0.01). Correlation analysis revealed a significant negative correlation between the TNFα levels and the PANSS total score (p<0.01). Additionally, TNFα levels were significantly negatively correlated with scores on general psychopathology (p<0.01), positive (p<0.05) and cognitive subscales (p<0.05). Stepwise multiple regression analysis identified TNFα levels as a significant predictor of scores on the general psychopathology subscale of the PANSS. The significant relations observed in the current study between TNFα and the PANSS and its subscales suggest that immune disturbance may be involved in the psychopathology and cognitive deficits of schizophrenia.

Long range frontal/posterior phase synchronization during remembered pursuit task is impaired in schizophrenia

Although smooth pursuit eye movement (SPEM) is a reliable endophenotype of schizophrenia, exact underlying cognitive and neural substrates remain unknown. A simple mechanistic model of SPEM assumes an efficient interaction in integrating sensory input from the medial temporal (MT)/medial superior temporal (MST) brain regions and subsequent motor response through the frontal eye field (FEF). Poor functional connectivity between these two regions could explain impaired motion perception and SPEM maintenance in schizophrenia. In the present study, we combined an eye tracking paradigm with electroencephalography (EEG) recordings to investigate the putative functional connectivity among frontal/posterior brain regions in mediating the modulation of SPEM. Twenty four schizophrenic (SZ) and 22 healthy control (HC) participants performed remembered pursuit tasks with EEG recordings. Behaviorally, HC subjects showed significant improvement in SPEM response on repeated presentations of target compared to SZ subjects. Neurophysiologically HC subjects showed higher frontal/posterior phase synchronization in the beta to low gamma range frequency bands during all target presentations. In addition there was a significant increase in phase synchronization in the beta-2 frequency band in HC subjects during late compared to early target presentation. In contrast, higher frontal/posterior phase synchronization in the beta-2 frequency predicted better performance during late target presentation and lower enduring psychosis in SZ subjects. These data suggest a pathologically perturbed connectivity between frontal and posterior cortical regions during SPEM in SZ. The integrative eye tracking-EEG approach used in this study to dissect the endophenotype may reveal novel targets for studying schizophrenia psychopathology.

Schizophrenomorphical psychosis in the late period of craniocerebral trauma: clinical picture and management

A comparative clinical and psychopathological examination of psychotic manifestations in the patients of three groups - with schizophrenomorphical disorders in the late period of craniocerebral trauma (35 patients) with schizophrenia (33 patients), and with a combination of schizophrenia and TBI (32 patients). Marked clinical and diagnostic evaluation criteria allow to differentiate the hallucinatory-delusional disorders within shizophreniamorphical disorders in traumatic disease of the brain from an equal psychopathology in schizophrenia. Particular issues of treatment and prognosis are highlighted.

Continuous kynurenine administration during the prenatal period, but not during adolescence, causes learning and memory deficits in adult rats

Cognitive dysfunctions, including deficits in hippocampus-mediated learning and memory, are core features of the psychopathology of schizophrenia (SZ). Increased levels of kynurenic acid (KYNA), an astrocyte-derived tryptophan metabolite and antagonist of α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors, have been implicated in these cognitive impairments. Following recent suggestive evidence, the present study was designed to narrow the critical time period for KYNA elevation to induce subsequent cognitive deficits. KYNA levels were experimentally increased in rats (1) prenatally (embryonic day (ED) 15 to ED 22) or (2) during adolescence (postnatal day (PD) 42 to PD 49). The KYNA precursor kynurenine was added daily to wet mash fed to (1) dams (100 mg/day; control: ECon; kynurenine-treated: EKyn) or (2) adolescent rats (300 mg/kg/day; control: AdCon; kynurenine-treated: AdKyn). Upon termination of the treatment, all animals were fed normal chow until biochemical analysis and behavioral testing in adulthood. On the last day of continuous kynurenine treatment, forebrain KYNA levels were significantly elevated (EKyn +472 %; AdKyn +470 %). KYNA levels remained increased in the hippocampus of adult EKyn animals (+54 %), but were unchanged in adult AdKyn rats. Prenatal, but not adolescent, kynurenine treatment caused significant impairments in two hippocampus-mediated behavioral tasks, passive avoidance and Morris water maze. Collectively, these studies provide evidence that a continuous increase in brain KYNA levels during the late prenatal period, but not during adolescence, induces hippocampus-related cognitive dysfunctions later in life. Such increases may play a significant role in illnesses with known hippocampal pathophysiology, including SZ.

Prolactin and psychopathology in schizophrenia: a literature review and reappraisal.

Secretion of the anterior pituitary hormone prolactin can be significantly increased by antipsychotic drugs, leading to a range of adverse effects in patients with schizophrenia. However, there is evidence from a variety of studies that prolactin may also be related to symptom profile and treatment response in these patients, and recent work has identified variations in prolactin secretion even in drug-free patients. In this paper, a selective review of all relevant studies pertaining to prolactin and schizophrenia, including challenge and provocation studies, is presented. The implications of this work are discussed critically. A tentative model, which synthesizes these findings and argues for a significant role for prolactin in the development of schizophrenia, is outlined.

EPA-0281 – Life time diagnosis of cannabis abuse affects psychopathology of first-episode schizophrenia

There is no doubt that cannabis abuse contributes to the development of schizophrenia. However, the influence of cannabis on schizophrenia psychopathology remains unclear. This study aimed at investigating the association between life time diagnosis of cannabis abuse (LTCA) and psychopathological manifestation of first-episode schizophrenia (FES). We recruited 45 FES patients. Schizophrenia was diagnosed based on DSM-IV and ICD-10 criteria, and confirmed using Operational Criteria for Psychotic Illness (OPCRIT). Additionally, all patients were assessed using Positive and Negative Syndrome Scale (PANSS). Patients with drug and/or alcohol abuse within one year of onset of psychotic symptoms were excluded. Assessment with OPCRIT revealed that LTCA is associated with longer duration of excessive (p = 0.044) and reckless activity (p = 0.023), reduced need for sleep (p = 0.023), other primary delusions (p = 0.046), as well as thought withdrawal (p = 0.01) and thought broadcast (0.01). There was no significant difference in the total score of PANSS subscales (i.e. positive, negative and general). However, FES patients with LTCA experienced significantly more severe excitement (p = 0.031) and grandiosity (p = 0.018), as well as poorer impulse control (p = 0.008). Our results indicate that LTCA has a differential influence on psychopathology of FES exacerbating delusions of thought broadcast and withdrawal, affective symptoms and behavioural manifestation of experienced psychotic symptoms.

EPA-1103 - Personality across the aggressive spectrum - a cross-sectional study of 358 males with paranoid schizophrenia

Aggressiveness is one of the most stigmatization symptoms of paranoid schizophrenia with its possible roots in personality and/or acute psychopathology of schizophrenia. To explore general and personality differences among suicidal, homicidal and non-aggressive male subjects with paranoid schizophrenia. We recruited all consecutive inpatients fulfilling the ICD-10 criteria of paranoid schizophrenia during 2009-2011. Personality traits were determined by the NEO Five-Factor Inventory (NEO-FFI) scale which measures the five major personality traits: emotional stability, extraversion, openness to experience, agreeableness and conscientiousness). The study included 359 male subjects diagnosed with paranoid schizophrenia. Their mean age was 37,8 yrs (SD 11,9) and duration of illness 13,77 yrs (SD 12,1). Majority were single (N=271, 75,5%), with 8-12 yrs of education (N=266, 75%) and unemployed (N=193, 53,8%). In an attempt to assess their auto and heteroagressivness, subjects were divided into three groups: subjects with suicide ideation (N=66, 18.4%), subjects with suicide attempt (N=67, 18,7%) and subjects with homicidal behavior (N= 86, 24%). These groups were compared against the comparative group of subjects without suicidal ideation, suicide or homicide behavior (N=140, 39%). Subjects with homicide behavior were significantly older, with longer duration of illness, majority were diagnosed with comorbid alcohol addiction and these participants scored higher on the emotional stability subscale (ANOVA F=7.8, df= 3, P=0.001). These findings might contribute to discussion of the role of personality characteristics in paranoid schizophrenia.

Multimodal Sensory Distortions in Postpartum Exacerbation of Schizophrenia

Sensory distortions of body image commonly occur during migraine, seizures, nondominant cortical infarcts and hallucinogen abuse. We report the case of a 30-year-old woman with paranoid schizophrenia presenting with postpartum onset multimodal sensory distortions in the absence of any neurological disorders or substance use. Her symptoms involved persistent facial/body metamorphopsia (distorted images) and vocal paracousis (distorted voices), in the absence of visual hallucinations, illusions or agnosia. Neuropsychological assessments revealed deficits on visual processing tasks. Neuroimaging, electroencephalography and ophthalmological evaluation revealed no abnormalities. The multimodal sensory distortions responded to antipsychotic treatment, paralleling improvement in other schizophrenia psychopathology, over a period of one month. Prominent and persistent multimodal sensory distortions like metamorphopsia and paracousis in the presence of psychotic symptoms warrant a detailed neurological and general medical work-up. These symptoms presenting in the absence of neurological or substance use disorders may be a component of schizophrenia.

Perspectivity in Psychiatric Research: The Psychopathology of Schizophrenia in Postwar Germany (1955–1961)

The reorganization of psychiatric knowledge at the turn of the twentieth century derived from Emil Kraepelin’s clinical classification of psychoses. Surprisingly, within just few years, Kraepelin’s simple dichotomy between dementia praecox (schizophrenias) and manic-depressive psychosis (bipolar disorders) succeeded in giving psychiatry a new framework that is still used until the present day. Unexpectedly, Kraepelin’s simple clinical scheme based on the dichotomy replaced the significantly more differentiated nosography that dominated psychiatric research in the last three decades of the nineteenth century (Janzarik in Themen und Tendenzen der deutschsprachigen Psychiatrie. Springer, Berlin, 1974). Moreover, although all the components of the future development were already available shortly after 1868, the real course, which led to Kraepelin’s dichotomy, was unpredictable then. This paper explores the ways in which the unpredictability of psychiatric knowledge and the postulate of a rationality underlying psychopathological phenomena interacted in the debates regarding the classification of psychoses. It examines the “natural antagonism” between the practical aspirations of an increasingly specialized medical nosology and unitary conceptions, which, in a psychopathological countermovement, emphasized that no somatic criteria can be specified for the majority of psychic abnormalities and that all nosological distinctions are not binding (Janzarik 1974, 20). In this context, this paper investigates the revival of unitary theories of psychosis in postwar German psychiatry and seeks to understand why the forms of thinking that dominated nineteenth-century psychiatry have proved to be very lasting. Furthermore, this paper emphasizes the perspectivity underlying psychiatric research on psychoses and explores the ways in which writing the history of the schizophrenia concept involves inevitably writing the history of the entire psychiatry.