Schizophrenia phenomenology revisited: positive and negative symptoms are strongly related reflective manifestations of an underlying single trait indicating overall severity of schizophrenia

CNS Spectrums ◽  
2020 ◽  
pp. 1-10 ◽  
Author(s):  
Abbas F. Almulla ◽  
Hussein K. Al-Hakeim ◽  
Michael Maes
Keyword(s):  
Convergent Validity ◽  
Negative Symptoms ◽  
Discriminant Validity ◽  
Psychomotor Retardation ◽  
Future Research ◽  
Stable Phase ◽  
Deficit Schizophrenia ◽  
Latent Vector ◽  
Thought Disorders ◽  
Positive And Negative Symptoms

Abstract Background. To examine whether negative symptoms, psychosis, hostility, excitation, and mannerism (PHEM symptoms), formal thought disorders (FTD) and psychomotor retardation (PMR) are interrelated phenomena in major neurocognitive psychosis (MNP) or deficit schizophrenia and whether those domains belong to an underlying latent vector reflecting general psychopathology. Methods. In this study, we recruited 120 patients with MNP or deficit schizophrenia and 54 healthy subjects and measured the above-mentioned symptom domains. Results. In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that positive (and PHEM or psychotic) and negative symptoms greatly overlap and probably measure the same latent construct. Soft independent modeling of class analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms. Conclusions. In stable phase MNP, which is a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of “positive” and “negative” symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its reflective manifestations are the key factors of schizophrenia phenomenology.

scholarly journals Schizophrenia Phenomenology Revisited: Positive and Negative Symptoms are Strongly Related Reflective Manifestations of an Underlying Single Trait Indicating Overall Severity of Schizophrenia

2019 ◽  
Author(s):  
Abbas Almulla ◽  
Hussein Al-Hakeim ◽  
Michael Maes
Keyword(s):  
Convergent Validity ◽  
Negative Symptoms ◽  
Discriminant Validity ◽  
Psychomotor Retardation ◽  
Future Research ◽  
Stable Phase ◽  
Latent Vector ◽  
Thought Disorders ◽  
Symptom Domains ◽  
Positive And Negative Symptoms

Schizophrenia comprises various symptom domains, including positive and negative symptoms. Machine learning showed that a) negative symptoms are significantly interrelated with PHEM (psychosis, hostility, excitation, and mannerism) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR); and b) stable phase schizophrenia comprises two distinct classes, namely Major Neuro-Cognitive Psychosis (MNP, largely overlapping with deficit schizophrenia) and Simple NP (SNP). In this study, we recruited 120 MNP patients and 54 healthy subjects and measured the above-mentioned symptom domains. In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that PHEM and negative symptoms greatly overlap and probably measure the same construct. Soft Independent Modeling of Class Analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms. In conclusion, in stable phase MNP, a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of “positive” and “negative” symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its 8 reflective manifestations are the key factors of schizophrenia phenomenology.

Schizophrenia phenomenology revisited: positive and negative symptoms are strongly related reflective manifestations of an underlying single trait indicating overall severity of schizophrenia

2019 ◽  
Author(s):  
Abbas F. Almulla ◽  
Hussein Kadhem Al-Hakeim ◽  
Michael Maes
Keyword(s):  
Convergent Validity ◽  
Negative Symptoms ◽  
Supervised Machine Learning ◽  
Machine Learning Techniques ◽  
Stable Phase ◽  
Type I ◽  
Latent Vector ◽  
Thought Disorders ◽  
Symptom Domains ◽  
Positive And Negative Symptoms

Schizophrenia comprises various symptom domains the two most important being positive <br>and negative symptoms. Nevertheless, using (un)supervised machine learning techniques it was <br>shown that a) negative symptoms are significantly interrelated with PHEM (psychosis, hostility, <br>excitation, and mannerism) symptoms, formal thought disorders (FTD) and psychomotor <br>retardation (PMR); and b) stable phase schizophrenia comprises two distinct classes, namely Major <br>Neuro-Cognitive Psychosis (MNP, largely overlapping with deficit schizophrenia) and Simple <br>NP (SNP). In this study, we recruited 120 MNP patients and 54 healthy subjects and measured the <br>above-mentioned symptom domains. In MNP, there were significant associations between <br>negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially <br>unidimensional, underlies these key domains of schizophrenia and additionally shows excellent <br>internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad <br>Analysis indicates that this latent vector fits a reflective model. Soft Independent Modeling of <br>Class Analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better <br>modeled with PHEM symptoms, FTD and PMR than with negative symptoms. In conclusion, in <br>MNP, a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD <br>and PMR belong to one underlying latent vector reflecting general psychopathology and, therefore, <br>may be used as an overall severity of schizophrenia (OSOS) index. The bi-dimensional concept of <br>positive and negative symptoms and type I and II schizophrenia is revised.

scholarly journals Schizophrenia phenomenology revisited: positive and negative symptoms are strongly related reflective manifestations of an underlying single trait indicating overall severity of schizophrenia

2019 ◽  
Author(s):  
Abbas F. Almulla ◽  
Hussein Kadhem Al-Hakeim ◽  
Michael Maes
Keyword(s):  
Convergent Validity ◽  
Negative Symptoms ◽  
Supervised Machine Learning ◽  
Machine Learning Techniques ◽  
Stable Phase ◽  
Type I ◽  
Latent Vector ◽  
Thought Disorders ◽  
Symptom Domains ◽  
Positive And Negative Symptoms

Schizophrenia comprises various symptom domains the two most important being positive <br>and negative symptoms. Nevertheless, using (un)supervised machine learning techniques it was <br>shown that a) negative symptoms are significantly interrelated with PHEM (psychosis, hostility, <br>excitation, and mannerism) symptoms, formal thought disorders (FTD) and psychomotor <br>retardation (PMR); and b) stable phase schizophrenia comprises two distinct classes, namely Major <br>Neuro-Cognitive Psychosis (MNP, largely overlapping with deficit schizophrenia) and Simple <br>NP (SNP). In this study, we recruited 120 MNP patients and 54 healthy subjects and measured the <br>above-mentioned symptom domains. In MNP, there were significant associations between <br>negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially <br>unidimensional, underlies these key domains of schizophrenia and additionally shows excellent <br>internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad <br>Analysis indicates that this latent vector fits a reflective model. Soft Independent Modeling of <br>Class Analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better <br>modeled with PHEM symptoms, FTD and PMR than with negative symptoms. In conclusion, in <br>MNP, a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD <br>and PMR belong to one underlying latent vector reflecting general psychopathology and, therefore, <br>may be used as an overall severity of schizophrenia (OSOS) index. The bi-dimensional concept of <br>positive and negative symptoms and type I and II schizophrenia is revised.

Deficit schizophrenia and its features are associated with PON1 Q192R genotypes and lowered paraoxonase 1 (PON1) enzymatic activity: effects on bacterial translocation

CNS Spectrums ◽  
2020 ◽  
pp. 1-10 ◽  
Author(s):  
Andressa K. Matsumoto ◽  
Michael Maes ◽  
Thitiporn Supasitthumrong ◽  
Annabel Maes ◽  
Ana P. Michelin ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Immunoglobulin A ◽  
Quorum Quenching ◽  
Psychomotor Retardation ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Gram Negative ◽  
Deficit Schizophrenia ◽  
Thought Disorders

Abstract Background. Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. Methods. In this case-control study, Thai women and men, aged 18 to 65 years, were divided in DS (n = 40) and NDS (n = 40) and were compared to controls (n = 40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and immunoglobulin A (IgA) levels responses directed to Gram-negative bacteria were measured. Results. DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. Conclusions. The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing toward greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

scholarly journals Chronic Fatigue and Fibromyalgia Symptoms are Key Components of Deficit Schizophrenia and are Strongly Associated with Activated Immune-Inflammatory Pathways

2019 ◽  
Author(s):  
Abbas Almulla ◽  
Hussein Al-Hakeim ◽  
Mokhlad Abed ◽  
André Carvalho ◽  
Michael Maes
Keyword(s):  
Convergent Validity ◽  
Rating Scale ◽  
Somatic Symptoms ◽  
Internal Consistency Reliability ◽  
Chronic Fatigue ◽  
Psychomotor Retardation ◽  
Deficit Schizophrenia ◽  
Thought Disorders ◽  
Symptom Domains

A subset of patients with schizophrenia experience physio-somatic symptoms reminiscent of chronic fatigue and fibromyalgia. In schizophrenia, these symptoms contribute to impaired quality of life, and are strongly related to neuro-cognitive deficits, and increased IgA responses to tryptophan catabolites. Negative and PHEM (psychosis, hostility, excitation, mannerism) symptoms, psychomotor retardation (PMR) and formal thought disorders, appear to be manifestations of a single trait reflecting overall severity of schizophrenia (OSOS). In this study, 120 patients with deficit schizophrenia (DEFSCZ) and 54 healthy subjects were assessed with the FibroFatigue (FF) rating scale, and the above-mentioned symptom domains as well as neuro-cognitive tests and biomarkers were measured. In DEFSCZ, there were robust associations between the FF score and all above-mentioned symptom domains, and impairments in semantic and episodic memory and executive functions. Furthermore, the FF score loaded highly on an OSOS latent vector (LV), which showed adequate convergent validity, internal consistency reliability and predictive relevance and fitted a reflective model. Soft Independent Modelling of Class Analogy (SIMCA) showed that the FF items discriminated DEFSCZ from controls with an overall accuracy of 100%. Interleukin IL-1&beta;, IL-1 receptor antagonist (sIL-1RA), tumour necrosis factor (TNF)-&alpha; and CCL-11 (eotaxin) explained 66.8% of the variance in the FF score and 59.4% of the variance in OSOS. In conclusion, these data show that physio-somatic symptoms are a core component of the phenomenology of DEFSCZ and are largely mediated by neurotoxic effects of activated immune pathways, including aberrations in CCL-11, IL-1&beta; and TNF-&alpha; signalling.

scholarly journals In Schizophrenia, PON1 Q192R Genotypes and/or Lowered Paraoxonase 1 (PON1) Enzymatic Activity are Significantly Associated with the Deficit Syndrome, Negative Symptoms, Formal Thought Disorders, Psychomotor Retardation, Excitation and Increased IgA Levels to Gram-Negative Microbiota

2019 ◽  
Author(s):  
Andressa Keiko Matsumoto ◽  
Michael Maes ◽  
Annabel Maes ◽  
Ana Paula Michelin ◽  
Laura de Oliveira Semeão ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Quorum Quenching ◽  
Psychomotor Retardation ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Phenyl Acetate ◽  
Gram Negative ◽  
Deficit Syndrome ◽  
Deficit Schizophrenia ◽  
Thought Disorders

Background: Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. Methods: In this case-control study, Thai women and men, aged 18-65 years, were divided in DS (n=40) and NDS (n=40) and were compared to controls (n=40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and IgA levels responses directed to Gram-negative bacteria were measured. Results: DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. Conclusions: The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing towards greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

scholarly journals Lowered Antioxidant Defenses and Increased Oxidative Toxicity Are Hallmarks of Deficit Schizophrenia: Neurocognitive and Symptom Correlates

2020 ◽  
Author(s):  
Michael Maes ◽  
Sunee Sirivichayakul ◽  
Andressa Keiko Matsumoto ◽  
Anna Paula Michelin ◽  
Laura de Oliveira Semeão ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Psychomotor Retardation ◽  
Antioxidant Defenses ◽  
Paraoxonase 1 ◽  
Pon1 Activity ◽  
Lipid Hydroperoxides ◽  
Sh Groups ◽  
Deficit Schizophrenia ◽  
Immune Biomarkers ◽  
Thought Disorders

Background: There is now evidence that schizophrenia and deficit schizophrenia are neuro-immune conditions and that oxidative stress toxicity (OSTOX) may play a pathophysiological role. Aims of the study: To compare OSTOX biomarkers and antioxidant (ANTIOX) defenses in deficit versus non-deficit schizophrenia. Methods: We examined lipid hydroperoxides (LOOH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), sulfhydryl (-SH) groups, paraoxonase 1 (PON1) activity and PON1 Q192R genotypes, total radical-trapping antioxidant parameter (TRAP) as well as immune biomarkers in patients with deficit (n=40) and non-deficit (n=40) schizophrenia and healthy controls (n=40). Results: Deficit schizophrenia is characterized by significantly increased levels of AOPP and lowered -SH, and PON1 activity, while no changes in the OSTOX/ANTIOX biomarkers were found in non-deficit schizophrenia. An increased OSTOX/ANTIOX ratio was significantly associated with deficit versus non-deficit schizophrenia (Odds ratio=3.15, p&lt;0.001). Partial least squares analysis showed that 47.6% of the variance in a latent vector extracted from psychosis, excitation, hostility, mannerism, negative symptoms, psychomotor retardation, formal thought disorders, and neurocognitive test scores was explained by LOOH+AOPP, PON1 genotype + activity, CCL11, tumor necrosis factor (TNF)-&alpha;, IgA responses to neurotoxic tryptophan catabolites (TRYCATs), whereas -SH groups and IgM responses to MDA showed indirect effects mediated by OSTOX and neuro-immune biomarkers. Discussion: Our findings indicate that with increasing overall severity of schizophrenia, neuro-immune and neuro-oxidative (especially protein oxidation indicating chlorinative stress) toxicities become more prominent and together with lowered antioxidant defenses and impairments in innate immunity-associated resilience against neurotoxic processes shape a distinct nosological entity, namely deficit schizophrenia.

Increased Levels of Plasma Tumor Necrosis Factor-α Mediate Schizophrenia Symptom Dimensions and Neurocognitive Impairments and Are Inversely Associated with Natural IgM and Paraoxonase 1 Activity

2019 ◽  
Author(s):  
Michael Maes ◽  
Sunee Sirivichayakul ◽  
Andressa Keiko Matsumoto ◽  
Annabel Maes ◽  
Ana Paula Michelin ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Cognitive Impairments ◽  
Word List ◽  
Psychomotor Retardation ◽  
Paraoxonase 1 ◽  
Necrosis Factor Alpha ◽  
Symptom Dimensions ◽  
Deficit Schizophrenia ◽  
Thought Disorders ◽  
Natural Igm

Accumulating evidence suggests that TNF-&alpha;-mediated immune-neurotoxicity contributes to cognitive impairments and the overall severity of schizophrenia (OSOS). There are no data whether peripheral IL-6 and IL-4 may affect the phenome of schizophrenia above and beyond the effects of TNF-&alpha; and whether those cytokines are regulated by lowered natural IgM to malondialdehyde (MDA) and paraoxonase 1 enzyme activity. We assessed the aforementioned biomarkers in schizophrenia patients with (n=40) and without (n=40) deficit schizophrenia and 40 healthy controls. Deficit schizophrenia was best predicted by a combination of increased IL-6 and PON1 status (QQ genotype and lowered CMPAase activity) and lowered IgM to MDA. Partial Least Squares bootstrapping shows that 41.0% of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, and formal thought disorders was explained by increased TNF-&alpha; and PON1 status (QQ genotype and lowered CMPAase activity), lowered IL-4 and IgM to MDA as well as male sex and lowered education. We found that 47.9% of the variance in verbal fluency, word list memory, true recall, Mini-Mental State Examination, and executive functions was predicted by increased TNF-&alpha; and lowered IL-4, IgM to MDA and education. In addition, both TNF-&alpha; and IL-4 levels were significantly associated with lowered IgM to MDA, while TNF-&alpha; was correlated with PON1 status. These data provide evidence that the symptomatic (both the deficit subtype and OSOS) and cognitive impairments in schizophrenia are to a large extent mediated by the effects of immune-mediated neurotoxicity as well as lowered regulation by the innate immune system.

Development and Construct Validation of the German Workplace Trust Survey (G-WTS)

2010 ◽  
Vol 26 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Nale Lehmann-Willenbrock ◽  
Simone Kauffeld
Keyword(s):  
Convergent Validity ◽  
Affective Commitment ◽  
Discriminant Validity ◽  
Organizational Context ◽  
Organizational Trust ◽  
Three Dimensional ◽  
Future Research ◽  
Work Related ◽  
Reliable Assessment ◽  
Workplace Trust

In research on trust in the organizational context, there is some agreement evolving that trust should be measured with respect to various foci. The Workplace Trust Survey (WTS) by Ferres (2002) provides reliable assessment of coworker, supervisor, and organizational trust. By means of a functionally equivalent translation, we developed a German version of the questionnaire (G-WTS) comprising 21 items. A total of 427 employees were surveyed with the G-WTS and questionnaires concerning several work-related attitudes and behaviors and 92 of these completed the survey twice. The hypothesized three-dimensional conceptualization of organizational trust was confirmed by confirmatory factor analysis. The G-WTS showed good internal consistency and retest reliability values. Concerning convergent validity, all of the three G-WTS dimensions positively predicted job satisfaction. In terms of discriminant validity, Coworker Trust enhanced group cohesion; Supervisor Trust fostered innovative behavior, while Organizational Trust was associated with affective commitment. Theoretical and practical contributions as well as opportunities for future research with the G-WTS are discussed.

Development of the Fear of Intimacy Components Questionnaire (FICQ)

2015 ◽  
Vol 31 (4) ◽  
pp. 302-309 ◽  
Author(s):  
Maria Pedro Sobral ◽  
Maria Emília Costa
Keyword(s):  
Convergent Validity ◽  
Discriminant Validity ◽  
Two Dimensions ◽  
Dimensional Structure ◽  
Future Research ◽  
Fear Of Intimacy ◽  
Confirmatory Factor Analyses ◽  
New Instrument ◽  
Confirmatory Factor ◽  
Test Retest Reliability

Abstract. We developed a new instrument designed to measure fear of intimacy in romantic relationships. We suggest assessing fear of intimacy through two dimensions: self-revelation and dependence. The Fear of Intimacy Components Questionnaire (FICQ) was validated across three studies in which a 10-item solution systematically emerged. Consistently with a two component perspective, a two-factor solution fitted data the best: fear of losing the self (FLS) and fear of losing the other (FLO). Qualitative analyses verified content validity. Exploratory and confirmatory factor analyses tested the factor structure. Multigroup analyses supported the structural invariance across gender, age, and relationship status. Both factors showed adequate discriminant validity and internal consistency, and good 3-week period test-retest reliability. Associations between the FICQ and insecure attachment orientations demonstrated convergent validity. The association between the FICQ and relationship satisfaction above and beyond a preexisting measure offered criterion validity. By going beyond traditional self-revelation-focused conception of fear of intimacy, that is, by proposing a bi-dimensional structure to fear of intimacy, we believe that this new measure will contribute to future research on fear of intimacy.

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