Brain metabolism changes in women with BPD undergoing olanzapine treatment.
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ABSTRACT:
SUBMITTER: Camchong J
PROVIDER: S-EPMC6368919 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Brain metabolism changes in women with BPD undergoing olanzapine treatment.
Camchong Jazmin J Cullen Kathryn R KR Lim Kelvin O KO Schulz S Charles SC
Psychiatry research. Neuroimaging 20180727
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Project description:The NMDA receptor antagonist phencyclidine (PCP) creates schizophrenia-like symptoms in normal controls. The effect of PCP on non-human primate brain gene expression was examined and compared to changes induced by olanzapine treatment. Experimental studies of PCP and antipsychotic drugs have direct relevance to understanding the patho-physiology and treatment of schizophrenia. Genome-wide changes in prefrontal cortex gene expression revealed alterations of 146 transcripts in the PCP treatment group compared to vehicle controls. Dysregulated genes were enriched in identified classes implicated in neurological and genetic disorders, including schizophrenia genes from the Psychiatric Genomics Consortium 108 loci as well as cell death in PCP-treated primates. Canonical pathway analysis revealed a significant overrepresentation of several groups including synaptic long-term potentiation and calcium signaling. Olanzapine coadministered with PCP normalized 34% of the 146 PCP-induced probe set expression changes, and a network of 17 olanzapine-normalized genes was identified enriched in schizophrenia candidate genes containing RGS4, SYN1 and AKT as nodes. The results of this study support the use of PCP administration in non-human primates as a glutamatergic model of schizophrenia and suggest that a large number of PCP-induced expression differences can be reversed by olanzapine. The results of this study may be informative for identification of potential candidates for pharmacogenetics and biomarker research related to the treatment of schizophrenia.
| S-EPMC4578732 | biostudies-literature
Project description:Treatment-resistant depression (TRD) occurs in many patients and causes high morbidity and mortality. Because TRD subjects are particularly difficult to study especially longitudinally, biological data remain very limited. In a preliminary study to judge feasibility and power, 25 TRD patients were referred from specialty psychiatric practices. All were severely and chronically depressed and mostly had comorbid psychiatric disorders as is typical in TRD. Nine patients were able to complete all required components of the protocol that included diagnostic interview; rating scales; clinical magnetic resonance imaging; medication washout; treatment with maximally tolerated olanzapine-fluoxetine combination for 8 weeks; and pre- and post-treatment fluorodeoxyglucose positron emission tomography. This drug combination is an accepted standard of treatment for TRD. Dropouts arose from worsening depression, insomnia, and anxiety. One patient remitted; three responded. A priori regions of interest included the amygdala and subgenual cingulate cortex (sgACC; Brodmann area BA25). Responders showed decreased metabolism with treatment in the right amygdala that correlated with clinical response; no significant changes in BA25; better response to treatment the higher the baseline BA25 metabolism; and decreased right ventromedial prefrontal metabolism (VMPFC; broader than BA25) with treatment which did not correlate with depression scores. The baseline metabolism of all individuals showed heterogeneous patterns when compared to a normative metabolic database. Although preliminary given the sample size, this study highlights several issues important for future work: marked dropout rate in this study design; need for large sample size for adequate power; baseline metabolic heterogeneity of TRD requiring careful subject characterization for future studies of interventions; relationship of amygdala activity decreases with response; and the relationship between baseline sgACC and VMPFC activity with response. Successful treatment of TRD with olanzapine-fluoxetine combination shows changes in cerebral metabolism like those seen in treatment-responsive major depression.
| S-EPMC6957341 | biostudies-literature
Project description:BackgroundClinically significant weight gain has been reported during treatment with atypical antipsychotics. It has been suggested that weight changes in patients treated with olanzapine may be associated with increased appetite.MethodsData were used from adult patients for whom both appetite and weight data were available from 4 prospective, 12- to 24-week clinical trials. Patients' appetites were assessed with Eating Behavior Assessment (EBA, Study 1), Platypus Appetite Rating Scale (PARS, Study 2), Eating Inventory (EI, Study 3), Food Craving Inventory (FCI, Study 3), and Eating Attitude Scale (EAS, Study 4).ResultsIn Studies 1 (EBA) and 4 (EAS), patients who reported overall score increases on appetite scales, indicating an increase in appetite, experienced the greatest overall weight gains. However, in Studies 2 (PARS) and 3 (EI, FCI), patients who reported overall score increases on appetite scales did not experience greater weight changes than patients not reporting score increases. Early weight changes (2-4 weeks) were more positively correlated with overall weight changes than early or overall score changes on any utilized appetite assessment scale. No additional information was gained by adding early appetite change to early weight change in correlation to overall weight change.ConclusionsEarly weight changes may be a more useful predictor for long-term weight changes than early score changes on appetite assessment scales.Clinical trials registrationThis report represents secondary analyses of 4 clinical studies. Studies 1, 2, and 3 were registered at http://clinicaltrials.gov/ct2/home, under NCT00190749, NCT00303602, and NCT00401973, respectively. Study 4 predates the registration requirements for observational studies that are not classified as category 1 observational studies.
| S-EPMC2945973 | biostudies-literature
Project description:ObjectiveThis randomized, 24-week, flexible-dose study compared changes in glucose metabolism in patients with DSM-IV schizophrenia receiving initial exposure to olanzapine, quetiapine, or risperidone.MethodThe hypothesized primary endpoint was change (baseline to week 24) in area under the curve (AUC) 0- to 2-hour plasma glucose values during an oral glucose tolerance test (OGTT); primary analysis: olanzapine versus quetiapine. Secondary endpoints included mean change in AUC 0- to 2-hour plasma insulin values, insulin sensitivity index, and fasting lipids. The first patient enrolled on April 29, 2004, and the last patient completed the study on October 24, 2005.ResultsMean weight change (kg) over 24 weeks was +3.7 (quetiapine), +4.6 (olanzapine), and +3.6 (risperidone). Based on data from 395 patients (quetiapine, N = 115 [mean dose = 607.0 mg/day], olanzapine, N = 146 [mean dose = 15.2 mg/day], and risperidone, N = 134 [mean dose = 5.2 mg/day]), mean change in AUC 0- to 2-hour glucose value (mg/dL x h) at week 24 was significantly lower for quetiapine versus olanzapine (t = 1.98, df = 377, p = .048). Increases in AUC 0- to 2-hour glucose values were statistically significant with olanzapine (+21.9 mg/dL x h, 95% CI = 11.5 to 32.4 mg/dL x h) and risperidone (+18.8 mg/dL x h, 95% CI = 8.1 to 29.4 mg/dL x h), but not quetiapine (+9.1 mg/dL x h, 95% CI = -2.3 to 20.5 mg/dL x h). AUC 0- to 2-hour insulin values increased statistically significantly with olanzapine (+24.5%, 95% CI = 11.5% to 39.0%), but not with quetiapine or risperidone. Reductions in insulin sensitivity index were statistically significant with olanzapine (-19.1%, 95% CI = -27.9% to -9.3%) and risperidone (-15.8%, 95% CI = -25.1% to -5.4%), but not quetiapine. Total cholesterol and low-density lipoprotein levels increased statistically significantly with olanzapine (+21.1 mg/dL, 95% CI = 13.0 to 29.2 mg/dL, and +20.5 mg/dL, 95% CI = 13.8 to 27.1 mg/dL, respectively) and quetiapine (+13.1 mg/dL, 95% CI = 4.3 to 21.9 mg/dL, and +13.3 mg/dL, 95% CI = 6.1 to 20.5 mg/dL, respectively), but not risperidone. Statistically significant increases in triglycerides (+30.9 mg/dL, 95% CI = 10.9 to 51.0 mg/dL), total cholesterol/high-density lipoprotein (HDL) ratio (0.5, 95% CI = 0.2 to 0.8), and triglyceride/HDL ratio (0.3, 95% CI = 0.0 to 0.6) were observed with olanzapine only.ConclusionThe results indicate a significant difference in the change in glucose tolerance during 6 months' treatment with olanzapine versus quetiapine, with significant reductions on olanzapine and risperidone, but not quetiapine; these differential changes were largely explained by changes in insulin sensitivity.Trial registrationclinicaltrials.gov Identifier: NCT00214578.
| S-EPMC3703648 | biostudies-literature
Project description:This study compared weight and cardiometabolic changes after short-term treatment of olanzapine/samidorphan and olanzapine. Eligible criteria for an included trial were ≤ 24 weeks, randomized controlled trials (RCTs) that compared olanzapine/samidorphan and olanzapine treatments in patients/healthy volunteers and reported weight or cardiometabolic outcomes. Three databases were searched on October 31, 2020. Primary outcomes included weight changes and all-cause dropout rates. Standardized mean differences (SMDs) and risk ratios (RRs) were computed and pooled using a random-effect model. This meta-analysis included four RCTs (n = 1195). The heterogeneous data revealed that weight changes were not significantly different between olanzapine/samidorphan and olanzapine groups (4 RCTs, SDM = - 0.19, 95% CI - 0.45 to 0.07, I2 = 75%). The whole-sample, pooled RR of all-cause dropout rates (4 RCTs, RR = 1.02, 95% CI 0.84 to 1.23, I2 = 0%) was not significant different between olanzapine/samidorphan and olanzapine groups. A lower percentage of males and a lower initial body mass index were associated with the greater effect of samidorphan in preventing olanzapine-induced weight gain. Current evidence is insufficient to support the use of samidorphan to prevent olanzapine-induced weight gain and olanzapine-induced cardiometabolic abnormalities. Samidorphan is well accepted by olanzapine-treated patients.
| S-EPMC8027382 | biostudies-literature
Project description:BackgroundPrior study of patients with urgency urinary incontinence by functional magnetic resonance imaging showed altered function in areas of the brain associated with interoception and salience and with attention. Our randomized controlled trial of hypnotherapy for urgency urinary incontinence demonstrated marked improvement in urgency urinary incontinence symptoms at 2 months. A subsample of these women with urgency urinary incontinence underwent functional magnetic resonance imaging before and after treatment.ObjectiveThis study aimed to determine if hypnotherapy treatment of urgency urinary incontinence compared with pharmacotherapy was associated with altered brain activation or resting connectivity on functional magnetic resonance imaging.Study designA subsample of women participating in a randomized controlled trial comparing hypnotherapy vs pharmacotherapy for treatment of urgency urinary incontinence was evaluated with functional magnetic resonance imaging. Scans were obtained pretreatment and 8 to 12 weeks after treatment initiation. Brain activation during bladder filling and resting functional connectivity with an empty and partially filled bladder were assessed. Brain regions of interest were derived from those previously showing differences between healthy controls and participants with untreated urgency urinary incontinence in our prior work and included regions in the interoceptive and salience, ventral attentional, and dorsal attentional networks.ResultsAfter treatment, participants in both groups demonstrated marked improvement in incontinence episodes (P<.001). Bladder-filling task functional magnetic resonance imaging data from the combined groups (n=64, 30 hypnotherapy, 34 pharmacotherapy) demonstrated decreased activation of the left temporoparietal junction, a component of the ventral attentional network (P<.01) compared with baseline. Resting functional connectivity differed only with the bladder partially filled (n=54). Compared with pharmacotherapy, hypnotherapy participants manifested increased functional connectivity between the anterior cingulate cortex and the left dorsolateral prefrontal cortex, a component of the dorsal attentional network (P<.001).ConclusionSuccessful treatment of urgency urinary incontinence with both pharmacotherapy and hypnotherapy was associated with decreased activation of the ventral (bottom-up) attentional network during bladder filling. This may be attributable to decreased afferent stimuli arising from the bladder in the pharmacotherapy group. In contrast, decreased ventral attentional network activation associated with hypnotherapy may be mediated by the counterbalancing effects of the dorsal (top-down) attentional network.
| S-EPMC10739935 | biostudies-literature
Project description:BackgroundSecond generation antipsychotics (SGAs) induce glucometabolic side-effects, such as hyperglycemia and insulin resistance, which pose a therapeutic challenge for mental illness. Sphingolipids play a role in glycaemic balance and insulin resistance. Endoplasmic reticulum (ER) stress contributes to impaired insulin signalling and whole-body glucose intolerance. Diabetogenic SGA effects on ER stress and sphingolipids, such as ceramide and sphingomyelin, in peripheral metabolic tissues are unknown. This study aimed to investigate the acute effects of clozapine and olanzapine on ceramide and sphingomyelin levels, and protein expression of key enzymes involved in lipid and glucose metabolism, in the liver and skeletal muscle.MethodsFemale rats were administered olanzapine (1 mg/kg), clozapine (12 mg/kg), or vehicle (control) and euthanized 1-h later. Ceramide and sphingomyelin levels were examined using electrospray ionization (ESI) mass spectrometry. Expression of lipid enzymes (ceramide synthase 2 (CerS2), elongation of very long-chain fatty acid 1 (ELOVL1), fatty acid synthase (FAS) and acetyl CoA carboxylase 1 (ACC1)), ER stress markers (inositol-requiring enzyme 1 (IRE1) and eukaryotic initiation factor (eIF2α) were also examined.ResultsClozapine caused robust reductions in hepatic ceramide and sphingolipid levels (p < 0.0001), upregulated CerS2 (p < 0.05) and ELOVL1 (+ 37%) and induced significant hyperglycemia (vs controls). In contrast, olanzapine increased hepatic sphingomyelin levels (p < 0.05 vs controls). SGAs did not alter sphingolipid levels in the muscle. Clozapine increased (+ 52.5%) hepatic eIF2α phosphorylation, demonstrating evidence of activation of the PERK/eIF2α ER stress axis. Hepatic IRE1, FAS and ACC1 were unaltered.ConclusionsThis study provides the first evidence that diabetogenic SGAs disrupt hepatic sphingolipid homeostasis within 1-h of administration. Sphingolipids may be key candidates in the mechanisms underlying the diabetes side-effects of SGAs; however, further research is required.
| S-EPMC5932814 | biostudies-literature
Project description:Objective: To investigate the mental health of women undergoing assisted reproductive technology (ART) treatment during the novel coronavirus pneumonia (COVID-19) pandemic outbreak in Xi'an, China. Methods: A repeated cross-sectional study was administered to women undergoing ART treatment during the outbreak period (599 women in February 2020) and the control period (892 women in May 2020) at the Northwest Women's and Children's Hospital, Xi'an, China. Results: Both the ART-treated women surveyed during the outbreak period and those surveyed during the control period had high scores on the fear dimension (0.88, 0.51). The total scores for mental health among the participants during the control period were lower than those during the outbreak period (difference = -0.22; 95% CI = -0.25, -0.18). Lower scores were also seen during the control period, compared to those in the outbreak period, for depression (difference = -0.18; 95% CI = -0.23, -0.13), neurasthenia (difference = -0.31; 95% CI = -0.36, -0.25), fear (difference = -0.37; 95% CI = -0.43, -0.31), compulsion anxiety (difference = -0.13; 95% CI = -0.16, -0.09), and hypochondriasis (difference = -0.09; 95% CI = -0.12, -0.06). Conclusions: During the COVID-19 global pandemic, the mental health of women undergoing ART treatment in Xi'an, China, was primarily manifested as fear. As the pandemic was brought under control, the mental health of ART-treated women improved. As evidenced by these results, the COVID-19 pandemic influences the mental health of women undergoing ART treatment, and clinicians should be aware of this for similar future situations.
| S-EPMC8185191 | biostudies-literature
Project description: Not available
| S-EPMC7529832 | biostudies-literature
Project description:BackgroundEvidence-based outpatient psychotherapeutic programs are first-line treatment of borderline personality disorder (BPD). Early and effective treatment of BPD is crucial to the prevention of its individual, psychosocial, and economic consequences. However, in spite of recent advantages in diagnosing adolescent BPD, there is a lack of cost-effective evidence-based treatment programs for adolescents. Mentalization-based treatment is an evidence-based program for BPD, originally developed for adults.Methods/designAims/hypothesesWe will investigate whether a specifically designed mentalization-based treatment in groups is an efficacious treatment for adolescents with BPD or subthreshold BPD compared to treatment as usual. The trial is a four-center, two-armed, parallel-group, assessor-blinded randomized clinical superiority trial. One hundred twelve patients aged 14 to 17 referred to Child and Adolescent Psychiatric Clinics in Region Zealand are randomized to 1 year of either mentalization-based treatment in groups or treatment as usual. Patients will be included if they meet at least four DSM-5 criteria for BPD. The primary outcome is self-reported borderline features at discharge. Secondary outcomes will include self-harm, depression, BPD criteria, externalizing and internalizing symptoms, and social functioning, together with parental reports on borderline features, externalizing and internalizing symptoms. Measures of attachment and mentalization will be included as mediational variables. Follow-up assessment will take place at 3 and 12 months after end of treatment.DiscussionThis is the first randomized controlled trial to test the efficacy of a group-based mentalization-based treatment for adolescents with BPD or subthreshold BPD. If the results confirm our hypothesis, this trial will add to the treatment options of cost-effective treatment of adolescent BPD.Trial registrationClinicaltrials.gov NCT02068326 , February 19, 2014.
| S-EPMC4942923 | biostudies-literature