32 research outputs found
Ultra-high-frequency left prefrontal transcranial magnetic stimulation as augmentation in severely ill patients with depression: a naturalistic sham-controlled, double-blind, randomized trial
Background and Aim: Repetitive transcranial magnetic stimulation (rTMS) is supposed to be not as effective in severe depression as it is in medium depression. We evaluated the treatment response to an ultra-high-frequency (UHF; 30 Hz) approach, which was used to maximize the rTMS efficacy in severely ill patients. Methods: 43 severely depressed patients were included in the randomized, double-blind study and received either rTMS with 30 Hz over the left dorsolateral prefrontal cortex or sham condition for 3 weeks as an add-on therapy to stable antidepressant medication. Hamilton Depression Rating Scale (HDRS) and cognitive performance were evaluated before and after the intervention. Results: In the active UHF group, the HRDS score was reduced by about 7.2, whereas the sham condition showed a smaller reduction of the HDRS score with 3.9. However, lithium as a covariant was responsible for the outcome difference, not the group of stimulation. No adverse events were reported. Comparing the differences of both groups in the pre- and post-study performance in a trail-making test, a group effect for the UHF group that was not influenced by the lithium intake was observed. Conclusion: A 30-Hz left prefrontal rTMS in severely depressed patients was safe and no adverse events occurred. Due to a strong effect of lithium as a covariate, we could not demonstrate favorable antidepressant effects of the UHF stimulation compared to sham. However, we found an improvement of processing speed performance in the UHF group, which covaried with improvement of psychomotor retardation. Copyright (C) 2012 S. Karger AG, Base
Long-term course of brain-derived neurotrophic factor serum levels in a patient treated with deep brain stimulation of the lateral habenula
Introduction: According to the neurotrophin hypothesis, a brain-derived neurotrophic factor (BDNF) decrease has been postulated as a pivotal pathomechanism in affective disorder, and the treatment-associated increase in peripheral BDNF has been linked to therapeutic efficacy of antidepressant drugs and electroconvulsive therapy. However, in deep brain stimulation (DBS), a still experimental antidepressant treatment approach, this issue has not yet been investigated. Methods: We examine the long-term course of serum BDNF levels in a 64-year-old woman who is being treated with DBS of the lateral habenula for severe major depressive disorder. Results: Our main findings are a significant increase in BDNF serum levels following DBS of the lateral habenula and an inverse U-shaped correlation of depression scores and BDNF levels. Discussion: The data indicate that DBS, like other effective antidepressant treatments, may contribute to an increase in peripheral BDNF levels, which are thought to reflect central nervous DBS-induced neuroplastic changes. Moreover, our observations underscore the complex nature of disease-associated BDNF alterations. Their identification as either state or trait marker remains controversial and requires larger-scale longitudinal studies. Copyright (C) 2012 S. Karger AG, Base
CSF Metabolic and Proteomic Profiles in Patients Prodromal for Psychosis
BACKGROUND: The initial prodromal state of psychosis (IPS) is defined as an early disease stage prior to the onset of overt psychosis characterized by sub-threshold or more unspecific psychiatric symptoms. Little is known regarding the biochemical changes during this period. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the metabolic/proteomic profiles of cerebrospinal fluid (CSF) of first-onset drug naĂŻve paranoid schizophrenia patients (n = 54) and individuals presenting with initial prodromal symptoms (n = 24), alongside healthy volunteers (n = 70) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy and surface enhanced laser desorption ionization (SELDI) mass spectrometry, respectively. Partial least square discriminant analysis (PLS-DA) showed that 36%/29% of IPS patients displayed proteomic/metabolic profiles characteristic of first-onset, drug naĂŻve schizophrenia, i.e., changes in levels of glucose and lactate as well as changes in a VGF-derived peptide (VGF23-62) and transthyretin protein concentrations. However, only 29% (n = 7) of the investigated IPS patients (who to date have been followed up for up to three years) have so far received a diagnosis of schizophrenia. The presence of biochemical alterations in the IPS group did not correlate with the risk to develop schizophrenia. CONCLUSIONS/SIGNIFICANCE: Our results imply that schizophrenia-related biochemical disease processes can be traced in CSF of prodromal patients. However, the biochemical disturbances identified in IPS patients, at least when measured at a single time point, may not be sufficient to predict clinical outcome
Validation of a Blood-Based Laboratory Test to Aid in the Confirmation of a Diagnosis of Schizophrenia
We describe the validation of a serum-based test developed by Rules-Based Medicine which can be used to help confirm the diagnosis of schizophrenia. In preliminary studies using multiplex immunoassay profiling technology, we identified a disease signature comprised of 51 analytes which could distinguish schizophrenia (n = 250) from control (n = 230) subjects. In the next stage, these analytes were developed as a refined 51-plex immunoassay panel for validation using a large independent cohort of schizophrenia (n = 577) and control (n = 229) subjects. The resulting test yielded an overall sensitivity of 83% and specificity of 83% with a receiver operating characteristic area under the curve (ROC-AUC) of 89%. These 51 immunoassays and the associated decision rule delivered a sensitive and specific prediction for the presence of schizophrenia in patients compared to matched healthy controls
Evidence for Increased Genetic Risk Load for Major Depression in Patients Assigned to Electroconvulsive Therapy
Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant
depression; disorder severity and unfavorable treatment outcomes are shown to be influenced
by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment
and response/nonresponse are associated with an increased genetic burden for major
depression (MD) using polygenic risk score (PRS), which summarize the contribution of diseaserelated
common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive
episode underwent ECT. MD-PRS were calculated for these inpatients and a separate
population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary
statistics from the Psychiatric Genomics Consortium MDD-working group (Cases:
n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status
between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher
MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between
ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response
(50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate
that ECT cohorts show an increased genetic burden for MD and are consistent with the
hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic
risk for MD. Larger samples are needed to better substantiate these findings