scholarly journals Quantfying the disorganization and the core deficit in classical schizophrenia

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S283-S283
Author(s):  
Mohan Rathnaiah ◽  
Elizabeth B Liddle ◽  
Lauren Gascoyne ◽  
Jyothika Kumar ◽  
Mohammad Zia Ul-Haq Katshu ◽  
...  

AimsTo derive scores for mental disorganization and impoverishment from commonly used rating scales, and test the hypothesis that disorganization and impoverishment, along with impaired cognition and role-function reflect a latent variable that is a plausible candidate for the putative core deficit.BackgroundFor more than 100 years, disorganization and impoverishment of mental activity have been recognised as fundamental symptoms of schizophrenia. These symptoms may reflect a core brain process underlying persisting disability. Delusions and hallucinations have been regarded as accessory features. The psychopathological processes predisposing to persisting disability in schizophrenia are poorly understood. The delineation of a core deficit underlying persisting disability would be potentially of great value in predicting outcome and developing improved treatment.MethodPatients aged 18–55 years were included if: they satisfied DSM IV criteria for schizophrenia or schizoaffective disorder. Healthy controls were recruited by public advertisement and selected to match the patient group in age and sex. Study sample included 39 participants with schizophrenia, 1 with schizoaffective disorder and 44 matched healthy controls. We derived disorganization and impoverishment scores from three symptom scales: PANSS, SSPI and CASH. We computed composite scores for disorganization and for impoverishment and employed Confirmatory Factor Analysis to test the hypothesis that a single factor accounts for the relationships between disorganization, impoverishment, cognitive impairment and impaired role function. We assessed the relationship between this latent “core deficit” and diminished Post Movement Beta Rebound (PMBR), an electrophysiological measure from Magnetoencephalography (MEG), associated with persisting brain disorders.ResultFit indices for the single factor model from CFA indicated a good fit: χ2(2) = 1.817, p = .403; RMSEA <.001 GFI = .979. PMBR was significantly reduced in the schizophrenia group compared to healthy controls, t (68) = 3.55, p < .001. Within the patient group, PMBR was significantly and negatively correlated with the CFA factor scores representing the Core Deficit score, r=−.543, p < .01, indicating that high core deficit scores were associated with reduced PMBR. PMBR was significantly correlated with the composite Disorganization score, r=−.521, p < .001.ConclusionOur findings demonstrate that the shared variance between impoverishment (psychomotor poverty); disorganization; cognitive impairment; and impaired role function can be accounted for by a latent variable that can reasonably be described as the core deficit of classical schizophrenia. The demonstration that the severity of the putative core deficit is correlated with the reduction in PMBR provides evidence that the core deficit is associated with an identifiable abnormality of brain dysfunction.

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S265-S266 ◽  
Author(s):  
Mohanbabu Rathnaiah ◽  
Elizabeth Liddle ◽  
Lauren Gascoyne ◽  
Jyothika Kumar ◽  
Mohammad Katshu ◽  
...  

Abstract Background For more than 100 years, disorganization and impoverishment of mental activity have been recognised as fundamental symptoms of schizophrenia. These symptoms may reflect a core brain process underlying persisting disability. Predisposition to persisting disability is a clinically important aspect of schizophrenia, yet the psychopathological processes predisposing to persisting disability are poorly understood. The delineation of a putative core deficit associated with persisting disability would be of potentially great value in delineating the underlying pathological processes and eventually in enhancing treatment. Aims To derive scores for mental disorganization and impoverishment from commonly used rating scales, and test the hypothesis that disorganization and impoverishment, along with impaired cognition and role-function reflect a latent variable that is a plausible candidate for the putative core deficit. Methods In a group of 40 patients with schizophrenia, we tested the hypothesis that mental disorganization and impoverishment, along with impaired cognition and role-function reflect a latent variable that is a plausible candidate for the core deficit. We derived disorganization and impoverishment factors from three symptom scales: PANSS, SSPI and CASH. For each of the three scales, we demonstrated significant correlation between these factors and impaired role function assessed using the Social and Occupational Functioning Scale (SOFAS) and cognitive impairment measured using the Digit Symbol Substitution Test (DSST). We then assessed the relationship between this latent “core deficit” variable and Post Movement Beta Rebound (PMBR), measured using magnetoencephalography and associated with persisting brain disorders. Results A single factor model provided excellent fit for the four features of core deficit, requiring no further modifications. Results were consistently similar for measures from all three scales. χ2 value was non-significant (range: 0.30 to 2.13, df = 2, p &gt; 0.35), GFI met the threshold of greater than 0.9 (range = .976 to .996) and RMSEA was lesser than 0.06 (range = 0.000 to 0.040). PMBR was found to be significantly reduced in the schizophrenia group compared to healthy controls (t (28) =44.2 ± 12.1, p = 0.001). PMBR was strongly correlated with disorganization (r (40) = .600, p=0.001). In the hierarchical regression, neither age nor medication dose were significant predictors, but PMBR did predict the severity of the core deficit (F (1, 23) = 12.6, P=0.002, R² = -.592). Discussion Scores for the two latent variables representing impoverishment and disorganization of mental activity in schizophrenia can be derived from each of three symptom rating scales. A composite measure of impoverishment, disorganization, impaired cognition and impaired role function reflects an underlying psychopathological process that might be described as the core deficit of classical schizophrenia.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Mohanbabu Rathnaiah ◽  
Elizabeth B Liddle ◽  
Lauren Gascoyne ◽  
Jyothika Kumar ◽  
Mohammad Zia Ul Haq Katshu ◽  
...  

Abstract In the classical descriptions of schizophrenia, Kraepelin and Bleuler recognized disorganization and impoverishment of mental activity as fundamental symptoms. Their classical descriptions also included a tendency to persisting disability. The psychopathological processes underlying persisting disability in schizophrenia remain poorly understood. The delineation of a core deficit underlying persisting disability would be of value in predicting outcome and enhancing treatment. We tested the hypothesis that mental disorganization and impoverishment are associated with persisting impairments of cognition and role function, and together reflect a latent core deficit that is discernible in cases diagnosed by modern criteria. We used Confirmatory Factor Analysis to determine whether measures of disorganization, mental impoverishment, impaired cognition, and role functioning in 40 patients with schizophrenia represent a single latent variable. Disorganization scores were computed from the variance shared between disorganization measures from 3 commonly used symptom scales. Mental impoverishment scores were computed similarly. A single factor model exhibited a good fit, supporting the hypothesis that these measures reflect a core deficit. Persisting brain disorders are associated with a reduction in post-movement beta rebound (PMBR), the characteristic increase in electrophysiological beta amplitude that follows a motor response. Patients had significantly reduced PMBR compared with healthy controls. PMBR was negatively correlated with core deficit score. While the symptoms constituting impoverished and disorganized mental activity are dissociable in schizophrenia, nonetheless, the variance that these 2 symptom domains share with impaired cognition and role function, appears to reflect a pathophysiological process that might be described as the core deficit of classical schizophrenia.


2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.


Author(s):  
Ertan Kucuksayan ◽  
Serkan Ozben ◽  
Selma Topaloglu Tuac ◽  
Mesrure Koseoglu ◽  
Ozcan Erel ◽  
...  

Abstract Objectives Restless legs syndrome (RLS) is a common neurological condition. Oxidative stress plays an important role in its pathogenesis. Thiol-disulphide homeostasis (TDH) is a new biomarker of oxidative stress. We studied plasma TDH to determine whether TDH could be used as a new biomarker for RLS and evaluated correlations between TDH and various disease severity rating scales. Methods A total of 25 RLS patients and 25 healthy controls were included into the study. TDH status was determined using an automated spectrophotometric analysis method and correlations were analyzed between the TDH status and various disease rating scales in the RLS patients. Results Plasma total (401 ± 27 μmol/L) and native thiol (354 ± 30 μmol/L) levels were significantly lower, but disulphide level (24 ± 6 μmol/L) was significantly (<0.0001) higher in the RLS patients compared to the controls (455 ± 36, 424 ± 37, 15 ± 5 μmol/L, respectively). The disulphide/native thiol and disulphide/total thiol ratios increased, in contrast, native thiol/total thiol ratio decreased significantly in the RLS patients compared to the healthy controls (<0.0001). The disulphide levels correlated positively with age and various rating scores of the RLS patients. International Restless Legs Syndrome Study Group (IRLSSG) rating score and age correlated negatively with the total and native thiol levels. Conclusions Our findings indicate increased oxidative stress in the RLS patients reflected by decreased native and total thiol, and increased disulphide levels and positive correlations between the disulphide levels and various rating scores. We suggest dynamic TDH status to be used as a novel biomarker for the diagnosis and follow-up of the RLS patients.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junchao Huang ◽  
Jinghui Tong ◽  
Ping Zhang ◽  
Yanfang Zhou ◽  
Yimin Cui ◽  
...  

AbstractA number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia. Among these metabolites, kynurenic acid (KYNA), 5-hydroxyindole (5-HI), and quinolinic acid (QUIN) are documented in their diverse effects on α-7 nicotinic acetylcholine receptor (α7nAChR) and/or N-methyl-D-aspartate receptor (NMDAR), two of the receptor types thought to contribute to cognitive impairment in schizophrenia. In this study, serum levels of KYNA, 5-HI, and QUIN were measured in 195 patients with schizophrenia and in 70 healthy controls using liquid chromatography-tandem mass spectrometry; cognitive performance in MATRICS Consensus Cognitive Battery and cortical thickness measured by magnetic resonance imaging were obtained. Patients with schizophrenia had significantly lower serum KYNA (p < 0.001) and QUIN (p = 0.02) levels, and increased 5-HI/KYNA (p < 0.001) and QUIN/KYNA ratios (p < 0.001) compared with healthy controls. Multiple linear regression showed that working memory was positively correlated with serum 5-HI levels (t = 2.10, p = 0.04), but inversely correlated with KYNA concentrations (t = −2.01, p = 0.05) in patients. Patients with high 5-HI and low KYNA had better working memory than other subgroups (p = 0.01). Higher 5-HI levels were associated with thicker left lateral orbitofrontal cortex (t = 3.71, p = 2.94 × 10−4) in patients. The different effects of 5-HI and KYNA on working memory may appear consistent with their opposite receptor level mechanisms. Our findings appear to provide a new insight into the dynamic roles of tryptophan pathway metabolites on cognition, which may benefit novel therapeutic development that targets cognitive impairment in schizophrenia.


2021 ◽  
Vol 13 (3) ◽  
pp. 343-358
Author(s):  
Hormazd D. Minwalla ◽  
Peter Wrzesinski ◽  
Allison Desforges ◽  
Joshua Caskey ◽  
Brittany Wagner ◽  
...  

Purpose of Review: This is a comprehensive review of the literature regarding the use of paliperidone in the treatment of schizophrenia and schizoaffective disorder. It covers the background and presentation of schizophrenia and schizoaffective disorder, as well as the mechanism of action and drug information for paliperidone. It covers the existing evidence of the use of paliperidone for the treatment of schizophrenia and schizoaffective disorder. Recent Findings: Schizophrenia and schizoaffective disorder lead to significant cognitive impairment. It is thought that dopamine dysregulation is the culprit for the positive symptoms of schizophrenia and schizoaffective disorder. Similar to other second-generation antipsychotics, paliperidone has affinity for dopamine D2 and serotonin 5-HT2A receptors. Paliperidone was granted approval in the United States in 2006 to be used in the treatment of schizophrenia and in 2009 for schizoaffective disorder. Summary: Schizophrenia and schizoaffective disorder have a large impact on cognitive impairment, positive symptoms and negative symptoms. Patients with either of these mental illnesses suffer from impairments in everyday life. Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder.


2021 ◽  
Author(s):  
Noel Valencia ◽  
Johann Lehrner

Summary Background Visuo-Constructive functions have considerable potential for the early diagnosis and monitoring of disease progression in Alzheimer’s disease. Objectives Using the Vienna Visuo-Constructional Test 3.0 (VVT 3.0), we measured visuo-constructive functions in subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and healthy controls to determine whether VVT performance can be used to distinguish these groups. Materials and methods Data of 671 participants was analyzed comparing scores across diagnostic groups and exploring associations with relevant clinical variables. Predictive validity was assessed using Receiver Operator Characteristic curves and multinomial logistic regression analysis. Results We found significant differences between AD and the other groups. Identification of cases suffering from visuo-constructive impairment was possible using VVT scores, but these did not permit classification into diagnostic subgroups. Conclusions In summary, VVT scores are useful indicators for visuo-constructive impairment but face challenges when attempting to discriminate between several diagnostic groups.


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