Carbonyl stress in schizophrenia

2014 ◽  
Vol 42 (2) ◽  
pp. 468-472 ◽  
Author(s):  
Masanari Itokawa ◽  
Mitsuhiro Miyashita ◽  
Makoto Arai ◽  
Toshio Miyata

We have identified idiopathic carbonyl stress in a subpopulation of schizophrenic patients. We first identified a patient with a mutation in GLO1 (glyoxalase I) who showed increased AGE (advanced glycation end-product) levels and decreased vitamin B6 levels. By applying the observations from this rare case to the general schizophrenic population, we were able to identify a subset of patients (20%) for whom carbonyl stress may represent a causative pathophysiological process. Genetic defects in GLO1 increase the risk of carbonyl stress 5-fold, and the resulting increased AGE levels correlate significantly with PANSS (Positive and Negative Syndrome Scale) scored negative symptoms. Pyridoxamine, an active form of vitamin B6 and scavenger for carbonyl stress, could represent a novel and efficacious therapeutic agent for these treatment-resistant symptoms. In the present article, we describe a unique research approach to identify the causative process in the pathophysiology of a subset of schizophrenia. Our findings could form the basis of a schizophrenia subtype classification within this very heterogeneous disease and ultimately lead to better targeted therapy.

1997 ◽  
Vol 171 (4) ◽  
pp. 360-363 ◽  
Author(s):  
R. G. McCreadie ◽  
S. Latha ◽  
R. Thara ◽  
R. Padmavathi ◽  
J. R. Ayankaran

BackgroundCognitive impairment, frequently found in patients with schizophrenia, may be associated with negative symptoms and dyskinesia. However, antipsychotic medication may be a confounding variable. These putative associations may be clarified by examining never-treated patients.MethodNever-treated elderly schizophrenic patients (n=19) living in south-east India were compared with treated patients (n=25) and normal subjects (n=55). Memory was assessed by the Wechsler Memory Scale, negative symptoms by the Positive and Negative Syndrome Scale, and dyskinesia by the Abnormal Involuntary Movements Scale.ResultsNormal subjects had a higher mean memory quotient than patients. There were no significant differences between never-treated and treated patients. Negative symptoms were associated with a poorer memory in the never-treated group. There was no association between memory and dyskinesia.ConclusionsThere is an association in never-treated patients between a poorer memory and negative symptoms, but not between a poorer memory and dyskinesia.


Author(s):  
Ritha M Sembiring ◽  
Mustafa M Amin ◽  
Elmeida Effendy

 Objective: Negative symptoms are relatively common with a recent study finding that nearly 58% of outpatients had at least one negative symptom, negative symptoms are better predictors of functioning than positive symptom. Antidepressants have been a natural and common choice for the treatment of negative symptoms considering the conceptual proximity of their mode of action and the etiological hypotheses involving related neurotransmitters. This study examined differences negative symptoms scale score between patient that received only risperidone and risperidone with fluoxetine.Method: The sample consist of 44 patients with a diagnosis of schizophrenia according to ICD-10 (International Statistical Classification of Diseases), male, age ranged was between 30 and 50 years, signed informed consent before entering into study which had been conducted at the Prof. Dr. M Ildrem Mental Health Hospital Medan Sumatera Utara Indonesia. The study was designed for 4 weeks, open-label, divided into two groups of 22 each, (1) receiving 4 mg/day risperidone with 20 mg/day fluoxetine and (2) receiving only 4 mg/day risperidone. Negative symptoms were assessed using positive and negative syndrome scale (PANSS).Results: The primary finding of the trial was a significant reduction in score ofnegativescale in patients receiving risperidone with fluoxetinecompared to patients receiving only risperidone at the end of 4 weeks. All the subscales of PANSS negative symptoms scale demonstrated significant improvement.Conclusions: In patients with schizophrenia, treating negative symptoms with adjunctive to fluoxetine appears to carry the benefit of improving negative symptoms.


1994 ◽  
Vol 164 (2) ◽  
pp. 184-189 ◽  
Author(s):  
Robin G. McCreadie ◽  
Jude U. Ohaeri

Two hundred and forty-two Nigerian schizophrenic patients (63% male, 37% female), whose mean age was 42 years and length of illness 12 years, were examined for movement disorders using the Abnormal Involuntary Movements Scale, the Simpson and Angus Parkinsonism Scale and the Barnes Akathisia Scale. Twelve patients had never received antipsychotic medication; and none of these had dyskinesia. Dyskinesia was found in 5 of 49 patients (10%) who had taken medication throughout the course of their illness for a total of up to 3 months, 13 of 74 (18%) who had taken medication for 4–12 months, 14 of 41 (34%) for 1–5 years, and 29 of 66 (45%) who had taken medication for more than 5 years. Of 77 patients who were receiving antipsychotic medication at the time of examination, 9 (12%) had Parkinsonism and 12 (15%) akathisia. Examination of the patients' mental state by the Positive and Negative Syndrome Scale showed an association between dyskinesia and positive, but not negative, schizophrenic symptoms. Nigerian patients showed a low level of negative symptoms.


2018 ◽  
Vol 32 (5) ◽  
pp. 524-532 ◽  
Author(s):  
Yanling Zhou ◽  
Guannan Li ◽  
Dan Li ◽  
Hongmei Cui ◽  
Yuping Ning

Background: The long-term effects of dose reduction of atypical antipsychotics on cognitive function and symptomatology in stable patients with schizophrenia remain unclear. We sought to determine the change in cognitive function and symptomatology after reducing risperidone or olanzapine dosage in stable schizophrenic patients. Methods: Seventy-five stabilized schizophrenic patients prescribed risperidone (≥4 mg/day) or olanzapine (≥10 mg/day) were randomly divided into a dose-reduction group ( n=37) and a maintenance group ( n=38). For the dose-reduction group, the dose of antipsychotics was reduced by 50%; for the maintenance group, the dose remained unchanged throughout the whole study. The Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery were measured at baseline, 12, 28, and 52 weeks. Linear mixed models were performed to compare the Positive and Negative Syndrome Scale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects and MATRICS Consensus Cognitive Battery scores between groups. Results: The linear mixed model showed significant time by group interactions on the Positive and Negative Syndrome Scale negative symptoms, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, attention/vigilance, working memory and total score of MATRICS Consensus Cognitive Battery (all p<0.05). Post hoc analyses showed significant improvement in Positive and Negative Syndrome Scale negative subscale, Negative Symptom Assessment-16, Rating Scale for Extrapyramidal Side Effects, speed of processing, working memory and total score of MATRICS Consensus Cognitive Battery for the dose reduction group compared with those for the maintenance group (all p<0.05). Conclusions: This study indicated that a risperidone or olanzapine dose reduction of 50% may not lead to more severe symptomatology but can improve speed of processing, working memory and negative symptoms in patients with stabilized schizophrenia.


2017 ◽  
Vol Ano 7 ◽  
pp. 8-12
Author(s):  
Ana Beatriz de Oliveira Assis ◽  
Jayse Gimenez Pereira Brandão ◽  
Pedro Otávio Piva Espósito ◽  
Osmar Tessari Junior ◽  
Bruno Berlucci Ortiz

Objetivo: Ainda não está claro quais são os fatores de risco para a esquizofrenia resistente ao tratamento (ERT) em primeiro episódio psicótico (PEP). O objetivo deste trabalho é investigar indicadores de risco para ERT em PEP. Métodos: Foram selecionados 53 pacientes em primeiro episódio psicótico, com diagnóstico de esquizofrenia, que deram entrada à enfermaria de psiquiatria do Hospital das Clínicas Luzia de Pinho Melo entre 2011 e 2015. Ao ser admitido na enfermaria, o paciente era avaliado com a Escala de Sintomas para as Síndromes Positiva e Negativa (Positive and Negative Syndrome Scale – PANSS) e recebia tratamento inicial por 4 semanas. Caso sua resposta fosse inferior a 40% de redução na PANSS, o antipsicótico era trocado, e as escalas eram aplicadas novamente após mais 4 semanas. Após a falha com dois antipsicóticos, em doses plenas, por 4 semanas cada, a clozapina era introduzida, e o paciente era considerado ERT. Uma regressão logística foi aplicada onde sexo, idade de início, tempo de doença não tratada, uso de substâncias, avaliação global do funcionamento inicial e PANSS inicial total foram inseridos como variáveis independentes, e ERT foi inserida como variável dependente. Resultados: Tempo de doença não tratada apresentou significância de p = 0,038 e Exp (B) = 4,29, enquanto que PANSS total apresentou p = 0,012 e Exp (B) = 1,06. Conclusão: Identificar os fatores associados à resistência precoce ao tratamento poderia permitir aos clínicos evitar o atraso na introdução da clozapina e prevenir um pior prognóstico para esses pacientes.


2002 ◽  
Vol 17 (5) ◽  
pp. 272-277 ◽  
Author(s):  
Sonia Dollfus ◽  
Jacqueline A. Buijsrogge ◽  
Karim Benali ◽  
Pascal Delamillieure ◽  
Perrine Brazo

SummarySinistrality, characterized by an excess of non-right-handedness, has been reported in schizophrenic patients, but the findings are controversial.Aim.As sinistrality could be linked to a failure of hemisphere specialization in schizophrenia that would translate into language disorders, sinistrality was found out in disorganized and positive schizophrenic patients characterized by language disorders.Methods.Seventy-three schizophrenic patients (DSM IV) and 81 controls were evaluated with the Edinburgh Handedness Inventory (EHI). Patients were evaluated and classified into five subtypes (deficit, positive, disorganized, mixed and residual) with the Positive and Negative Syndrome Scale and the Schedule for the Deficit Syndrome.Results.Disorganized patients had a significantly more severe sinistrality in comparison to the deficit, residual and mixed subtypes and controls. A negative correlation was found between the disorganization and the EHI scores (r = – 0.34; P < 0.01). A significantly more severe sinistrality was also observed in the positive subtype in comparison to controls, but there was no correlation between hallucinatory and EHI scores (r = 0.06).Conclusion.The findings provided further evidence that the defects in the normal process of lateralization observed in schizophrenia affects primarily disorganized patients.


2001 ◽  
Vol 16 (6) ◽  
pp. 354-361 ◽  
Author(s):  
S. Moritz ◽  
B. Andresen ◽  
D. Jacobsen ◽  
K. Mersmann ◽  
U. Wilke ◽  
...  

SummaryThere is widespread evidence that schizophrenic symptomatology is best represented by three syndromes (positive, negative, disorganized). Both the disorganized and negative syndrome have been found to correlate with several neurocognitive dysfunctions. However, previous studies investigated samples predominantly treated with typical neuroleptics, which frequently induce parkinsonian symptoms that are hard to disentangle from primary negative symptoms and may have inflated correlations with neurocognition. A newly developed psychopathological instrument called the Positive and Negative and Disorganized Symptoms Scale (PANADSS) was evaluated in 60 schizophrenic patients. Forty-seven participants treated with atypical neuroleptics performed several neurocognitive tasks.A three-factor solution of schizophrenic symptomatology emerged. Negative symptomatology was associated with diminished creative verbal fluency and digit span backward, whereas disorganization was significantly correlated with impaired Stroop, WCST and Trail-Making Test B performance.Data suggest that disorganization is associated with tasks that demand executive functioning. Previous findings reporting correlations between negative symptomatology and neurocognition may have been confounded by the adverse consequences of typical neuroleptics.


2016 ◽  
Vol 33 (S1) ◽  
pp. s226-s226
Author(s):  
Y.S. Woo ◽  
J.E. Park ◽  
D.H. Kim ◽  
I.K. Sohn ◽  
T.Y. Hwang ◽  
...  

IntroductionEvidences for antipsychotics augmentation for schizophrenic patients with suboptimal efficacy have been lacking although it has been widespread therapeutic strategy in clinical practice.ObjectivesThe purpose of this study was to investigate the efficacy and tolerability of blonanserin augmentation with an atypical antipsychotics (AAPs) in schizophrenic patients.MethodsA total of 100 patients with schizophrenia partially or completely unresponsive to treatment with an AAP recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to existing AAPs which were maintained during the study period. Efficacy was primarily evaluated using Positive and Negative Syndrome Scale (PANSS) at baseline, week 2, 4, 8, and 12. Predictors for PANSS response (≥ 20% reduction) was investigated.ResultsThe PANSS total score was significantly decreased at 12 weeks after blonanserin augmentation (–21.0 ± 18.1, F = 105.849, P < 0.001). Response rate on PANSS at week 12 was 51.0%. Premature discontinuation was occurred in 17 patients (17.0%) and 4 patients among them discontinued the study due to adverse events. Nine patients experienced significant weight gain during the study. Response to blonanserin augmentation was associated with severe (PANSS > 85) baseline symptom (OR = 10.298, P = 0.007) and higher dose (> 600 mg/day of chlorpromazine equivalent dose) of existing AAPs (OR = 4.594, P = 0.014).ConclusionsBlonanserin augmentation improved psychiatric symptoms of schizophrenic patients in cases of partial or non-responsive to an AAP treatment with favorable tolerability. Patients with severe symptom despite treatment with higher dose of AAP were benefited from this augmentation. These results suggested that blonanserin augmentation could be an effective strategy for specific patients with schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2005 ◽  
Vol 72 (2-3) ◽  
pp. 123-129 ◽  
Author(s):  
A. Fresán ◽  
C. De la Fuente-Sandoval ◽  
C. Loyzaga ◽  
M. Garcı́a-Anaya ◽  
N. Meyenberg ◽  
...  

2018 ◽  
Vol 49 ◽  
pp. 50-55 ◽  
Author(s):  
Aida Farreny ◽  
Judith Usall ◽  
Jorge Cuevas-Esteban ◽  
Susana Ochoa ◽  
Gildas Brébion

AbstractSchizophrenia research based on traditional assessment measures for negative symptoms appears to be, to some extent, unreliable. The limitations of the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS) have been extensively acknowledged and should be taken into account. The aim of this study is to show how the PANSS and the SANS conflate negative symptoms and cognition and to offer alternatives for the limitations found.MethodsA sample of 117 participants with schizophrenia from two independent studies was retrospectively investigated. Linear regression models were computed to explore the effect of negative symptoms and illness duration as predictors of cognitive performance.ResultsFor the PANSS, the item “abstract thinking” accounted for the association between negative symptoms and cognition. For the SANS, the “attention” subscale predicted the performance in verbal memory, but illness duration emerged as a stronger predictor than negative symptoms for outcomes of processing speed, verbal and working memory.ConclusionUtilizing alternative models to the traditional PANSS and SANS formats, and accounting for illness duration, provide more precise evidence on the relationship between negative symptoms and cognition. Since these measures are still extensively utilized, we recommend adopting more rigorous approaches to avoid misleading results.


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