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"Schizophrenia"
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Double-blind, randomized, placebo-controlled pilot clinical trial with gamma-band transcranial alternating current stimulation for the treatment of schizophrenia refractory auditory hallucinations
Gamma oscillations are essential for brain communication. The 40 Hz neural oscillation deficits in schizophrenia impair left frontotemporal connectivity and information communication, causing auditory hallucinations. Transcranial alternating current stimulation is thought to enhance connectivity between different brain regions by modulating brain oscillations. In this work, we applied a frontal-temporal-parietal 40 Hz-tACS stimulation strategy for treating auditory hallucinations and further explored the effect of tACS on functional connectivity of brain networks. 32 schizophrenia patients with refractory auditory hallucinations received 20daily 20-min, 40 Hz, 1 mA sessions of active or sham tACS on weekdays for 4 consecutive weeks, followed by a 2-week follow-up period without stimulation. Auditory hallucination symptom scores and 64-channel electroencephalograms were measured at baseline, week2, week4 and follow-up. For clinical symptom score, we observed a significant interaction between group and time for auditory hallucinations symptoms (F(3,90) = 26.964, p < 0.001), and subsequent analysis showed that the 40Hz-tACS group had a higher symptom reduction rate than the sham group at week4 (p = 0.036) and follow-up (p = 0.047). Multiple comparisons of corrected EEG results showed that the 40Hz-tACS group had higher functional connectivity in the right frontal to parietal (F (1,30) = 7.24, p = 0.012) and right frontal to occipital (F (1,30) = 7.98, p = 0.008) than the sham group at week4. Further, functional brain network controllability outcomes showed that the 40Hz-tACS group had increased average controllability (F (1,30) = 6.26, p = 0.018) and decreased modality controllability (F (1,30) = 6.50, p = 0.016) in the right frontal lobe compared to the sham group. Our polit study indicates that 40Hz-tACS combined with medicine may be an effective treatment for targeting symptoms specific to auditory hallucinations and altering functional connectivity and controllability at the network level.
Journal Article
S203. EFFECT OF LONG-ACTING INJECTIONS OF PALIPERIDONE PALMITATE ON CLINICAL AND FUNCTIONAL OUTCOMES IN PATIENTS WITH SCHIZOPHRENIA BASED ON ILLNESS DURATION
BackgroundWhile early intervention shows a better outcome in patients with schizophrenia, the benefit of early administration of long-acting injectable antipsychotics (LAI) in schizophrenia is not well-studied. Paliperidone Palmitate is one of the most frequently used LAI, and it is usually administered in the later stage of the illness than oral medication. In this study, the difference in clinical and functional improvement by illness duration after the administration of Paliperidone LAI was evaluated.MethodsPatients with schizophrenia who planned to switch their antipsychotic treatment from oral ones to once-monthly Paliperidone LAI were recruited from hospitals in South Korea from 26 July 2010 to 25 July 2017. The clinical and functional change was measured every 4 weeks with Clinical Global Impression Severity (CGI-S) scale and Personal and Social Performance (PSP) scale for 6 months after initiation of Paliperidone LAI. Compared to baseline, improvements after switching to Paliperidone LAI were analyzed based on the duration of illness (DI) (less than 3 years, 3 to 10 years, over 10 years).Results1166 participants (DI≤3 years, N=240; 310 years, N=484) were enrolled. The change in CGI-S score was significantly different according to the DI and those with DI less than 3 years showed the most improvement in the aspect of clinical symptoms (DI, p<0.001; week, p<0.001; DI*week, p=0.013). All three groups showed significant improvements in PSP scores after the treatment with Paliperidone LAI and patients with DI less than 3 years demonstrated the highest PSP scores (DI, p<0.001; DI*week, p=0.436; week, p<0.001).DiscussionSwitching to Paliperidone LAI showed significantly better outcomes in schizophrenia patients especially with those with shorter DI. This result suggests that earlier administration of LAI in schizophrenia might lead to better clinical and functional outcomes.
Journal Article
Models of madness : psychological, social, and biological approaches to psychosis
\"This second edition of Models of Madness challenges those who hold to simplistic, pessimistic and often damaging theories and treatments of madness. In particular it challenges beliefs that madness can be explained without reference to social causes and challenges the excessive preoccupation with chemical imbalances and genetic predispositions as causes of human misery, including the conditions that are given the name 'schizophrenia'. This edition updates the now extensive body of research showing that hallucinations, delusions etc. are best understood as reactions to adverse life events and that psychological and social approaches to helping are more effective and far safer than psychiatric drugs and electroshock treatment. A new final chapter discusses why such a damaging ideology has come to dominate mental health and, most importantly, how to change that.\" -- Publisher's description.
Book
N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis
Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC's impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSHmPFC by 23% (P = .005) and GSHBC by 19% (P = .05). In patients with high-baseline GPxBC compared to low-baseline GPxBC, subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarker-guided treatment.
Journal Article
Inflammation in Schizophrenia: Pathogenetic Aspects and Therapeutic Considerations
Abstract
This paper discusses the current evidence from animal and human studies for a central role of inflammation in schizophrenia. In animal models, pre- or perinatal elicitation of the immune response may increase immune reactivity throughout life, and similar findings have been described in humans. Levels of pro-inflammatory markers, such as cytokines, have been found to be increased in the blood and cerebrospinal fluid of patients with schizophrenia. Numerous epidemiological and clinical studies have provided evidence that various infectious agents are risk factors for schizophrenia and other psychoses. For example, a large-scale epidemiological study performed in Denmark clearly showed that severe infections and autoimmune disorders are such risk factors. The vulnerability-stress-inflammation model may help to explain the role of inflammation in schizophrenia because stress can increase pro-inflammatory cytokines and may even contribute to a chronic pro-inflammatory state. Schizophrenia is characterized by risk genes that promote inflammation and by environmental stress factors and alterations of the immune system. Typical alterations of dopaminergic, serotonergic, noradrenergic, and glutamatergic neurotransmission described in schizophrenia have also been found in low-level neuroinflammation and consequently may be key factors in the generation of schizophrenia symptoms. Further support for the relevance of a low-level neuroinflammatory process in schizophrenia is provided by the loss of central nervous system volume and microglial activation demonstrated in neuroimaging studies. Last but not least, the benefit of anti-inflammatory medications found in some studies and the intrinsic anti-inflammatory and immunomodulatory effects of antipsychotics provide further support for the role of inflammation in this debilitating disease.
Journal Article
Genetic Association Between NRXN3 Variants (rs12879016 & rs2270964) and Risk of Schizophrenia (SCZ)
There hasn't been much study on the link between schizophrenia (SCZ) and neurexin 3 (NRXN3) genetic variations. The first association study of the NRXN3 rs12879016 G>C,T and rs2270964 C>A,T single-nucleotide polymorphisms (SNP)in a Saudi population is shown here.We used real-time PCR to assess the genotypes for the polymorphisms in one hundred seventeen patients with SCZ and Seventy-eight healthy controls. We used endonuclease digestion of amplified genomic DNA to establish the genotypes for the polymorphisms in 117 patients with DSM-IV and PANSS (Positive and Negative Syndrome Scale) evaluations of schizophrenia and 78 healthy controls.We aim to find out if there is a relation between NRXN3 variations (rs12879016 and rs2270964) and susceptibility of developing SCZ in a Saudi population.We hypothesis that SCZ can be related to patients with NRXN3 variations (rs12879016 / rs2270964) among Saudi population.According to our result both rs12879016 and rs2270964 polymorphisms were shown to be unrelated to the risk of schizophrenia.
Journal Article