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Superoxide Dismutase, BDNF, and Cognitive Improvement in Drug-Naive First-Episode Patients With Schizophrenia: A 12-Week Longitudinal Study.
Wu, Z, Liu, Q, Zhang, Y, Guan, X, Xiu, M, Zhang, X
The international journal of neuropsychopharmacology. 2022;(2):128-135
Abstract
OBJECTIVE Cognitive improvement after antipsychotic agents in patients with schizophrenia (SCZ) appears to involve redox regulation through neurotrophins such as brain derived neurotropic factor (BDNF). This study examined whether cognitive improvement was associated with the increase in superoxide dismutase (SOD) and whether higher levels of BDNF could have a permissive role in allowing SOD to improve cognition. METHODS We examined this hypothesis in 183 drug-naïve first-episode SCZ patients taking risperidone monotherapy for 12 weeks. We measured total copper-zinc SOD (CuZn-SOD), manganese SOD (Mn-SOD), and SOD activities and BDNF levels in these patients and compared their levels with 152 healthy controls. We assessed cognitive functioning and clinical symptoms at baseline and 12-week follow-up. RESULTS After treatment with risperidone, CuZn-SOD activity was significantly increased, and BDNF levels were slightly increased. Increased CuZn-SOD activity was associated with the cognitive effectiveness of risperidone monotherapy. The BDNF levels and SOD activities were correlated at baseline but not after 12-week treatment. Furthermore, baseline CuZn-SOD activity positively correlated with improvement on the delayed memory subscale of the Repeatable Battery for the Assessment of Neuropsychological Status only in the high BDNF subgroup. CONCLUSIONS Our longitudinal study suggests that risperidone can enhance SOD activity and that, in combination with higher baseline BDNF levels acting in a permissive role, can improve cognitive impairments in SCZ. Greater baseline CuZn-SOD activity also may have predictive value for cognitive improvement of delayed memory in SCZ patients receiving risperidone treatment.
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The trajectory of putative astroglial dysfunction in first episode schizophrenia: a longitudinal 7-Tesla MRS study.
Jeon, P, Mackinley, M, Théberge, J, Palaniyappan, L
Scientific reports. 2021;(1):22333
Abstract
Myo-inositol is mainly found in astroglia and its levels has been shown to be reduced in the anterior cingulate cortex (ACC) of patients with schizophrenia. We investigate the status of astroglial integrity indexed by ACC myo-inositol at the onset and over the first 6 months of treatment of first episode schizophrenia. We employed 7 T magnetic resonance spectroscopy (1H-MRS) and quantified myo-inositol spectra at the dorsal ACC in 31 participants; 21 patients with schizophrenia with median lifetime antipsychotic exposure of less than 3 days, followed up after 6 months of treatment, and 10 healthy subjects scanned twice over the same period. We studied the time by group interaction for myo-inositol after adjusting for gender and age. We report significant reduction in myo-inositol concentration in the ACC in schizophrenia at an early, untreated state of acute illness that becomes insignificant over time, after instituting early intervention. This trajectory indicates that dynamic astroglial changes are likely to operate in the early stages of schizophrenia. MRS myo-inositol may be a critical marker of amelioration of active psychosis in early stages of schizophrenia.
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Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer's Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial.
Wilcock, GK, Gauthier, S, Frisoni, GB, Jia, J, Hardlund, JH, Moebius, HJ, Bentham, P, Kook, KA, Schelter, BO, Wischik, DJ, et al
Journal of Alzheimer's disease : JAD. 2018;(1):435-457
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BACKGROUND LMTM is being developed as a treatment for AD based on inhibition of tau aggregation. OBJECTIVES To examine the efficacy of LMTM as monotherapy in non-randomized cohort analyses as modified primary outcomes in an 18-month Phase III trial in mild AD. METHODS Mild AD patients (n = 800) were randomly assigned to 100 mg twice a day or 4 mg twice a day. Prior to unblinding, the Statistical Analysis Plan was revised to compare the 100 mg twice a day as monotherapy subgroup (n = 79) versus 4 mg twice a day as randomized (n = 396), and 4 mg twice a day as monotherapy (n = 76) versus 4 mg twice a day as add-on therapy (n = 297), with strong control of family-wise type I error. RESULTS The revised analyses were statistically significant at the required threshold of p < 0.025 in both comparisons for change in ADAS-cog, ADCS-ADL, MRI atrophy, and glucose uptake. The brain atrophy rate was initially typical of mild AD in both add-on and monotherapy groups, but after 9 months of treatment, the rate in monotherapy patients declined significantly to that reported for normal elderly controls. Differences in severity or diagnosis at baseline between monotherapy and add-on patients did not account for significant differences in favor of monotherapy. CONCLUSIONS The results are consistent with earlier studies in supporting the hypothesis that LMTM might be effective as monotherapy and that 4 mg twice a day may serve as well as higher doses. A further suitably randomized trial is required to test this hypothesis.
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Superwellness Program: a cognitive-behavioral therapy-based group intervention to reduce weight gain in patients treated with antipsychotic drugs.
Magni, LR, Ferrari, C, Rossi, G, Staffieri, E, Uberti, A, Lamonaca, D, Boggian, I, Merlin, S, Primerano, G, Mombrini, A, et al
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999). 2017;(3):244-251
Abstract
OBJECTIVE To assess the effectiveness of a cognitive-behavioral therapy-based intervention (Superwellness Program) on weight gain compared with a treatment-as-usual (TAU) approach in patients treated with antipsychotics, and to evaluate the relationship between body mass index (BMI) variation and clinical variables. METHOD Eighty-five patients treated with antipsychotics were allocated across two groups, experimental (n=59) and control (n=26). The Superwellness Program (experimental group) consisted of 32 twice-weekly 1-hour sessions, conducted by a psychologist and a nutritionist/nurse, concurrently with moderate food intake and moderate physical activity plans. Sociodemographic, clinical, and biological variables were collected at baseline, at the end of intervention (16 weeks), and after 6 months. RESULTS BMI change from baseline differed significantly between the experimental and control groups, with a larger decrease in the experimental group (F = 5.5, p = 0.021). Duration of illness moderated the effect of treatment on BMI (p = 0.026). No significant (p = 0.499) effect of intervention during the follow-up period was found. Interestingly, the intervention indirectly induced a significant (p = 0.024) reduction in metabolic risk by reducing BMI. CONCLUSION A cognitive-behavioral therapy-based intervention could be useful in reducing weight in a clinical population taking antipsychotics, with consequent benefit to physical and mental health.
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Improvement in Body Image, Perceived Health, and Health-Related Self-Efficacy Among People With Serious Mental Illness: The STRIDE Study.
Yarborough, BJ, Leo, MC, Yarborough, MT, Stumbo, S, Janoff, SL, Perrin, NA, Green, CA
Psychiatric services (Washington, D.C.). 2016;(3):296-301
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Abstract
OBJECTIVE The authors examined secondary outcomes of STRIDE, a randomized controlled trial that tested a weight-loss and lifestyle intervention for individuals taking antipsychotic medications. METHODS Hierarchical linear regression was used to explore the effects of the intervention and weight change at follow-up (six, 12, and 24 months) on body image, perceived health, and health-related self-efficacy. RESULTS Participants were 200 adults who were overweight and taking antipsychotic agents. Weight change × study arm interaction was associated with significant improvement in body image from baseline to six months. From baseline to 12 months, body image scores of intervention participants improved by 1.7 points more compared with scores of control participants; greater weight loss was associated with more improvement. Between baseline and 24 months, greater weight loss was associated with improvements in body image, perceived health, and health-related self-efficacy. CONCLUSIONS Participation in STRIDE improved body image, and losing weight improved perceived health and health-related self-efficacy.
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Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder.
Umehara, H, Numata, S, Tajima, A, Nishi, A, Nakataki, M, Imoto, I, Sumitani, S, Ohmori, T
PloS one. 2016;(6):e0157232
Abstract
BACKGROUND Selective serotonin reuptake inhibitors (SSRI) are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics. METHODS We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD. RESULTS While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses. CONCLUSIONS Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients.
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Selected factors determining a way of coping with stress in type 2 diabetic patients.
Sobol-Pacyniak, AB, Szymczak, W, Kwarta, P, Loba, J, Pietras, T
BioMed research international. 2014;:587823
Abstract
OBJECTIVES The aim of the study was to examine factors which determine stress coping styles in type 2 diabetic (T2D) patients, with regard to selected demographic variables, clinical diabetes-related variables and selected psychical variables (anxiety level and assessment of depressive disorders). METHODS 50 T2D patients, aged 59.9 ± 10.2 years were assessed by Coping Inventory for Stressful Situations (CISS), Spielberger State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). In the statistical analysis simple and multivariable logistic regression models were used. RESULTS Variables significantly increasing the selection risk of stress coping style different from preferred task-oriented strategy in a simple logistic regression model are: hypoglycemia within three months prior to the research: odds ratio (OR) = 6.86 (95% confidence interval (CI) 1.25-37.61), taking antidepressants or neuroleptics: OR =15.42 (95% CI 2.42-98.33), severe depression in Beck's scale: OR = 84.00 (95% CI 6.51-1083.65), high state-anxiety level: OR = 9.60 (95% CI 1.08-85.16), and high trait-anxiety level: OR = 18.40 (95%CI 2.96-114.31), but in a multivariable model, diagnosed depression is the strongest factor: OR = 32.38 (95% CI 4.94-212.13). CONCLUSIONS In T2D patients, the strategy to cope with stress appears to be mostly influenced by psychical predisposition.
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A potential role for adjunctive vitamin D therapy in the management of weight gain and metabolic side effects of second-generation antipsychotics.
Nwosu, BU, Meltzer, B, Maranda, L, Ciccarelli, C, Reynolds, D, Curtis, L, King, J, Frazier, JA, Lee, MM
Journal of pediatric endocrinology & metabolism : JPEM. 2011;(9-10):619-26
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Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best ways to address them. Studies that examined lifestyle modification and pharmaceutical agents have yielded mixed results. Therefore, clinical studies using agents, such as vitamin D, which are inexpensive, readily available, with low side effects profile, and have mechanisms to counteract the metabolic side effects of SGA agents, are warranted. Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects. Its role as an adjunctive therapy for the management of metabolic side effects of SGA agents has not been adequately studied. Effective strategies to curb these side effects will improve the overall health of youths with psychiatric illnesses who receive SGAs. Herein we present a pilot study on the use of vitamin D in patients on treatment with SGAs.
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Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects.
Graham, KA, Cho, H, Brownley, KA, Harp, JB
Schizophrenia research. 2008;(1-3):287-94
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OBJECTIVE To examine prospective changes in cardiovascular disease (CVD) and type-2 diabetes risk factors in young adult first episode psychotic (FEP) patients treated with second generation antipsychotic medications. METHODS At baseline, fasting serum and anthropometric measures were obtained from 45 FEP patients and 41 healthy adults (controls) of similar age, ethnicity and sex; sixteen of the FEP patients remained on the same antipsychotic medication and were available for a second blood draw at 24 weeks of treatment. Serum was assayed for glucose, insulin, triglycerides, total cholesterol and high and low density lipoproteins (HDL, LDL), adiponectin, leptin, interleukin 6, E-selectin and VCAM-1. Wilcoxon nonparametric tests were used to compare risk markers between the FEP and control group at baseline and to evaluate pre-post treatment changes within the FEP group. RESULTS At baseline, the distributions of risk marker values were similar between the two groups and the percentages of FEP patients and healthy controls who were overweight/obese, dyslipidemic, hyperglycemic, and hyperinsulinemic did not differ. At 24 weeks, compared to baseline, FEP patients showed significant increases in BMI (p=0.0002), glucose (p=0.0449), insulin (p=0.0161), cholesterol (p=0.0129), leptin (p=0.0215), and E-selectin (p=0.0195), and a decrease in adiponectin (p=0.0371). CONCLUSIONS Among patients with first episode psychosis, 6-month treatment with second generation antipsychotics is associated with the exacerbation of pre-existing and emergence of new CVD and diabetes risk factors.
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Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: prospective data from phase 1.
Meyer, JM, Davis, VG, Goff, DC, McEvoy, JP, Nasrallah, HA, Davis, SM, Rosenheck, RA, Daumit, GL, Hsiao, J, Swartz, MS, et al
Schizophrenia research. 2008;(1-3):273-86
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BACKGROUND The metabolic syndrome (MS) is associated with increased risk for diabetes mellitus and coronary heart disease, and is highly prevalent among schizophrenia patients. Given concerns over antipsychotic metabolic effects, this analysis explored MS status and outcomes in phase 1 of the CATIE Schizophrenia Trial. METHODS The change in proportion of subjects with MS and individual criteria was compared between antipsychotic treatment groups, along with mean changes for individual criteria. Primary analyses examined subjects with fasting laboratory assessments at baseline and 3 months. Other analyses examined 3-month changes in MS status, waist circumference (WC), HDL cholesterol and blood pressure in all subjects, metabolic changes at the end of phase 1 participation (EOP), and repeated measures changes in HDL, blood pressure (BP) and WC over phase 1. RESULTS At 3 months, there were no significant between-drug differences for the change in proportion of subjects meeting MS status or individual MS criteria in the smaller fasting cohort (n = 281) or for those meeting criteria for parameters not dependent on fasting status (BP, HDL, WC) among all subjects (n=660). Among all subjects whose MS status could be determined at 3 months (n=660), MS prevalence increased for olanzapine (from 34.8% to 43.9%), but decreased for ziprasidone (from 37.7% to 29.9%) (p=.001). Although effect sizes varied across subgroups, at 3 months olanzapine and quetiapine had the largest mean increase in waist circumference (0.7 in. for both) followed by risperidone (0.4 in.), compared to no change for ziprasidone (0.0 in.) and a decrease in waist circumference for perphenazine (-0.4 in.). Olanzapine also demonstrated significantly different changes in fasting triglycerides at 3 months (+21.5 mg/dl) compared to ziprasidone (-32.1 mg/dl). EOP exposure data was obtained, on average, nine months from baseline for all metabolic variables. Results from EOP and repeated measures analyses were consistent with those at 3 months for mean changes in WC and fasting triglycerides, but between group differences emerged for HDL and SBP. CONCLUSIONS This large non-industry sponsored study confirms the differential metabolic effects between antipsychotics. Clinicians are advised to monitor all metabolic parameters, including WC, HDL and serum triglycerides, during antipsychotic treatment.