Carnitine metabolites and cognitive improvement in patients with schizophrenia treated with olanzapine: a prospective longitudinal study

Objective: Cognitive impairment is one of the core symptoms of schizophrenia, which is stable and lifelong. L-carnitine has been shown to improve cognitive function and decrease the rate of cognitive deterioration in patients with Alzheimer’s disease. However, it remains unclear regarding the role of L-carnitine and its metabolites in cognitive functions in schizophrenia after treatment with olanzapine. The purpose of this study was to evaluate the relationship between changes in plasma levels of L-carnitine metabolites and cognitive improvement after olanzapine treatment.Methods: This was a prospective longitudinal study. In this study, we recruited 25 female patients with first episode schizophrenia (FES) who were drug naïve at baseline and received 4 weeks of olanzapine monotherapy. Cognitive function was assessed at baseline and 4-week follow-up using the RBANS. Plasma L-carnitine metabolite levels were determined by a metabolomics technology based on untargeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).Results: We found that the immediate memory index, delayed memory index and RBANS composite score were significantly increased at the 4-week follow-up after treatment. A total of 7 differential L-carnitine metabolites were identified in FES patients after olanzapine monotherapy. In addition, we found that changes in butyrylcarnitine were positively correlated with improvements in language index and RBANS composite score. Further regression analyses confirmed the association between reduced butyrylcarnitine levels and cognitive improvement after olanzapine monotherapy in FES patients.Conclusion: Our study shows that cognitive improvement after olanzapine treatment was associated with changes in L-carnitine metabolite levels in patients with FES, suggesting a key role of L-carnitine in cognition in schizophrenia

Dance/movement therapy for improving metabolic parameters in long-term veterans with schizophrenia

Abstract Accumulating evidence has supported the implementation of dance/movement therapy (DMT) as a promising intervention for patients with schizophrenia (SCZ). However, its effect on body weight and metabolic profile in SCZ remains unclear. This study aimed to evaluate the outcome of a 12-week DMT session on weight and lipid profile in patients with SCZ using a randomized, single-blinded, controlled trial design. This study encompassed two groups of long-term hospitalized patients with SCZ, who were randomly assigned to the DMT intervention (n = 30) or the treatment as usual (TAU) group (n = 30). Metabolic markers, including weight, body mass index (BMI), fasting glucose, triglycerides, and total cholesterol were measured in both groups at two measurement points (at baseline and the end of the 12-week treatment). We found that DMT intervention significantly decreased body weight (F = 5.5, p = 0.02) and BMI (F = 5.7, p = 0.02) as compared to the TAU group. However, no significance was observed in other metabolic markers, including fasting glucose, triglycerides, and total cholesterol after treatment (all p > 0.05). Our study indicates that a 12-week, 24-session DMT program may be effective in decreasing body weight and BMI in long-term hospitalized patients with SCZ. DMT intervention may be a promising treatment strategy for long-term inpatients in the psychiatric department

Diabetes and cognitive deficits in chronic schizophrenia: a case-control study

Cognitive impairment occurs in both schizophrenia and diabetes. There is currently limited understanding whether schizophrenia with diabetes has more serious cognitive deficits than schizophrenia without diabetes or diabetes only. This study assessed cognitive performance in 190 healthy controls, 106 diabetes only, 127 schizophrenia without diabetes and 55 schizophrenia with diabetes. This study was conducted from January 2008 to December 2010. Compared to healthy controls, all patient groups had significantly decreased total and five index RBANS scores (all p\u3c0.01-

Association between cognitive function and IL-18 levels in schizophrenia: Dependent on<i> IL18</i>-607 A/C polymorphism

Accumulating evidence suggests that immune system dysregulation is associated with debilitating neuro-development in schizophrenia (SZ). Cognitive impairment is a persistent feature that occurs during the onset of SZ and persists throughout the course of the disease. Early studies have found that elevated interleukin (IL)-18 interacts with IL18 polymorphism and is correlated with psychotic symptoms in SZ. This study aimed to investigate whether elevated IL-18 levels interacted with the-607 A/C polymorphism to determine cognitive decline in patients with chronic SZ. We recruited 693 inpatients and 422 healthy controls to measure IL-18 levels and genotype the -607 A/C polymorphism. Further, cognitive function was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We found that IL-18 serum levels were higher in patients than those in healthy controls, and were not associated with IL18 -607 A/C in combined subjects or either patients or healthy controls, respectively. Moreover, -607 A/C was correlated with the visuospatial/ constructional index only in the patients. In addition, our research found that IL-18 levels were positively correlated to immediate memory only in patients with the C/C genotype, but not in patients with C/A or A/A genotype. This study suggests that the relationship of IL-18 with cognitive function depends on the IL18 -607 A/ C polymorphism of SZ patients.</p

Association between Changes in Total Antioxidant Levels and Clinical Symptom Improvement in Patients with Antipsychotic-Naive First-Episode Schizophrenia after 3 Months of Risperidone Monotherapy

Schizophrenia (SCZ) is associated with aberrant redox regulation in the early stages of brain development. There is growing evidence that the antioxidant defense system is closely associated with the therapeutic response to antipsychotics in SCZ patients. The aim of this study was to examine the effect of risperidone monotherapy on total antioxidant status (TAS) and the relationship between symptom improvement and changes in TAS in patients with antipsychotic-naive first-episode (ANFE) SCZ. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Two hundred and forty-six ANFE patients were treated with risperidone for 3 months. PANSS and TAS levels were assessed at baseline and at a 3-month follow-up. Relative to healthy controls, ANFE patients had higher TAS levels, which increased even further during the treatment. Moreover, baseline TAS levels were a predictor of symptom reduction after risperidone treatment. In addition, there was a significant association between increased TAS levels and the decreased cognitive factor. Our findings suggest that antioxidant protection is possibly associated with clinical improvement in ANFE patients after risperidone treatment

A pilot study to examine the association between COX-2 rs5275 polymorphism and the response to repetitive transcranial stimulation in schizophrenia

Abstract High frequency (HF)-rTMS has been shown to improve cognitive functions in patients with schizophrenia (SCZ). This study aimed to investigate whether COX-2 rs5275 variants were associated with cognitive improvements following rTMS treatment in patients with SCZ. Forty-eight hospitalized patients with SCZ were assigned to the neuronavigation HF-rTMS group and 28 patients to the sham group over left DLPFC for 1 month. Cognitive function was evaluated using the repeatable battery for the assessment of neuropsychological status (RBANS) at weeks 0 and 4. COX-2 rs5275 polymorphism was genotyped by a technician. At baseline, C allele carriers showed better cognitive performance relative to patients with TT homozygote. Additionally, C allele carriers had greater improvement in memory from the follow-up to baseline following rTMS stimulation, while patients with the TT genotype showed no significant improvement in memory index. More importantly, we found that COX-2 rs5275 was correlated with the response to rTMS after controlling for the covariates. This study data indicate that COX-2 rs5275 was associated with improvements in immediate memory after HF-rTMS treatment in patients with SCZ. rTMS shows an effect on memory only in C allele carriers, but not in those with the TT genotype

Diabetes mellitus, cognitive deficits and serum BDNF levels in chronic patients with schizophrenia: A case-control study

The relationship between serum BDNF levels and cognitive dysfunction in schizophrenia (SCZ) patients comorbid with type 2 diabetes mellitus (T2DM) has not been reported. Hence, this study aimed to explore whether and how the changes of serum BDNF levels were correlated with cognitive impairment in SCZ patients comorbid with T2DM. We recruited 472 inpatients with chronic SCZ (54 T2DM and 418 non-T2DM), and 225 healthy controls. Serum BDNF levels and routine biochemical parameters were measured. Psychopathological symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS) and cognitive function was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). SCZ patients with T2DM had significantly higher serum BDNF levels than SCZ patients without T2DM (F = 11.31, p = 0.001). SCZ patients with T2DM scored higher in delayed memory than SCZ patients without T2DM (77.17 +/- 18.44 vs.66.24 +/- 19.51, p = 0.000), and still showed significance after controlling for confounders. Further stepwise multiple regression analysis identified serum BDNF as an independent contributor to the RBANS attention of SCZ patients with T2DM (beta = 0.30, t = 2.09, p = 0.042). The increase of BDNF levels and better cognitive performance, especially delayed memory, may be related to the pathophysiological process of T2DM in chronic SCZ patients.</p

Serum BDNF levels, glycolipid metabolism in deficit schizophrenia: A case-control study

Background: Few studies have compared serum BDNF and glycolipid profiles in patients with deficit schizophrenia (DS) and non-deficit schizophrenia (NDS). We aimed to compare BDNF and glycolipid profiles between DS and NDS patients and healthy controls, and to investigate the relationship between BDNF, glycolipid profiles in DS and NDS patients.& nbsp;Methods: A total of 591 patients with chronic schizophrenia (SZ) and 238 healthy controls participated in this study. According to Proxy for the Deficit Syndrome Scale, SZ patients were divided into DS (n = 158) and NDS (n = 273) patients. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Serum BDNF levels were measured using enzyme-linked immunosorbent assay (ELISA).& nbsp;Results: BDNF levels were significantly lower in SZ patients than those in healthy controls (7.81 & PLUSMN; 2.98 ng/ml vs. 11.96 & PLUSMN; 2.29 ng/ml, P < 0.01). Furthermore, BDNF levels were lower in DS group than those in NDS group (P = 0.007, OR = 0.846, 95% CI = 0.750-0.955). Lower triglyceride levels were also an independent predictor for DS patients (P = 0.007, OR = 0.846, 95% CI = 0.750-0.955). Serum BDNF levels were negatively associated with the severity of deficit syndrome in SZ patients (beta =-1.151, t =-2.559, P = 0.011). In DS group, triglycerides were associated with PANSS negative subscore (beta =-0.262, t =-2.994, P = 0.003) and depressive factor subscore (beta = 0.282, t = 2.146, P = 0.035).& nbsp;Conclusion: Serum BDNF and triglycerides may be informative biomarkers of DS in SZ patients. The differences in glycolipid metabolism patterns between DS and NDS patients indicate that deficit syndrome is an independent endophenotype of SZ patients

Prevalence and clinical correlates of impaired glucose tolerance in first-episode versus chronic patients with schizophrenia

Aim Studies using oral glucose tolerance tests (OGTT) have shown that impaired glucose metabolism presents in the early stages of schizophrenia (SCZ). However, there is a lack of studies on changes in glucose metabolism with the stage of the disease. We first explored the features of glucose metabolic pattern at different phases of male SCZ. Methods We recruited 83 male first episode drug-naive patients with SCZ (FEDN-SCZ) and 64 male chronic patients with SCZ (CH-SCZ), as well as 14 male healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology of patients. OGTT, fasting plasma glucose and lipid profiles of all participants were examined. Results While the impaired glucose tolerance (IGT) rate of male SCZ patients was higher than that of HC (P < .05), there was no difference in IGT prevalence between FEDN-SCZ and CH-SCZ. In male FEDN-SCZ, LDL (OR = 2.64, 95% CI = 1.11-6.29, P = .028) and PANSS total score (OR = 1.03, 95% CI = 1.00-1.06, P = .046) were positively correlated with IGT; in male CH-SCZ, BMI (OR = 1.7, 95% CI = 1.08-2.67, P = .023), PANSS total score (OR = 0.82, 95% CI = 0.70-0.96, P = .015) and positive symptoms (OR = 0.45, 95% CI = 0.20-0.99, P = .046) were significantly correlated with IGT. Conclusions Our findings reflect different glucose metabolism patterns in different stages of SCZ

Interaction of oxidative stress and BDNF on executive dysfunction in patients with chronic schizophrenia

Executive dysfunction is increasingly recognized as one of the widely observed dimensions of cognitive impairments in the course of schizophrenia (SCZ). However, the potential molecular pathological mechanisms remain elusive. Previous studies have demonstrated that decreased brain-derived neurotrophic factor (BDNF) and oxidative damage may be associated with the psychopathology and cognitive impairment of SCZ. The present study aims to assess whether the interaction between BDNF and oxidative damage is involved in the disruption of executive function (EF) in patients with chronic SCZ. Serum BDNF and plasma oxidative stress markers were measured in 189 patients and 60 control subjects. EFs were evaluated by Wisconsin card sorting tests (WCST), Stroop word/color test (Stroop), and verbal fluency tests (VFT). The results showed that patients performed worse in the VFT, WCST and Stroop tests than healthy subjects. Moreover, patients had lower activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and lower BDNF levels, but higher malondialdehyde (MDA) levels than healthy controls. In patients, BDNF was negatively correlated with SOD (p &lt; 0.01). For patients, catalase (CAT) activity was negatively associated with WCST error score (p = 0.02) and BDNF was positively correlated to VFT score (p = 0.02). However, all these correlations between biomarkers and EF domains did not pass Bonferroni corrections. Finally, multiple regression analyses identified BDNF x SOD activity and BDNF x MDA as influencing factors for VFT score in patients (both p &lt; 0.05). Our results highlight the complex interplay between OS parameters and BDNF in the pathophysiology of EF impairment in SCZ, consistent with its neurodevelopmental hypothesis.</p