Stefan Brugger

Bio: Stefan Brugger is an academic researcher from Imperial College London. The author has contributed to research in topics: Psychosis & Schizophrenia. The author has an hindex of 12, co-authored 19 publications receiving 745 citations. Previous affiliations of Stefan Brugger include Hammersmith Hospital & Cardiff University.

Heterogeneity and Homogeneity of Regional Brain Structure in Schizophrenia: A Meta-analysis.

Abstract: Importance Schizophrenia is associated with alterations in mean regional brain volumes However, it is not known whether the clinical heterogeneity seen in the disorder is reflected at the neurobiological level, for example, in differences in the interindividual variability of these brain volumes relative to control individuals Objective To investigate whether patients with first-episode schizophrenia exhibit greater variability of regional brain volumes in addition to mean volume differences Data Sources Studies that reported regional brain volumetric measures in patients and controls by using magnetic resonance imaging in the MEDLINE, EMBASE, and PsycINFO databases from inception to October 1, 2016, were examined Study Selection Case-control studies that reported regional brain volumes in patients with first-episode schizophrenia and healthy controls by using magnetic resonance imaging were selected Data Extraction and Synthesis Means and variances (SDs) were extracted for each measure to calculate effect sizes, which were combined using multivariate meta-analysis Main Outcomes and Measures Relative variability of regional brain volumetric measurements in patients compared with control groups as indexed by the variability ratio (VR) and coefficient of variation ratio (CVR) Hedges g was used to quantify mean differences Results A total of 108 studies that reported measurements from 3901 patients (1272 [326%] female) with first-episode schizophrenia and 4040 controls (1613 [399%] female) were included in the analyses Variability of putamen (VR, 113; 95% CI, 103-124; P = 01), temporal lobe (VR, 112; 95% CI, 104-121; P = 004), thalamus (VR, 116; 95% CI, 107-126; P P −5 ) volume was significantly greater in patients, whereas variability of anterior cingulate cortex volume was lower (VR, 089; 95% CI, 081-098; P = 02) These findings were robust to choice of outcome measure There was no evidence of altered variability of caudate nucleus or frontal lobe volumes Mean volumes of the lateral ( g = 040; 95% CI, 029-051; P g = 043; 95% CI, 026-059; P g = −046; −065 to −026; P g = −026; 95% CI, −043 to −010; P = 005), frontal lobe ( g = −031; 95% CI, −044 to −019; P = 001), hippocampus ( g = −066; 95% CI, −084 to −047; P g = −022; 95% CI, −036 to −009; P = 001), and thalamus ( g = −036; 95% CI, −057 to −015; P = 001) were lower in patients There was no evidence of altered mean volume of caudate nucleus or putamen Conclusions and Relevance In addition to altered mean volume of many brain structures, schizophrenia is associated with significantly greater variability of temporal cortex, thalamus, putamen, and third ventricle volumes, consistent with biological heterogeneity in these regions, but lower variability of anterior cingulate cortex volume This finding indicates greater homogeneity of anterior cingulate volume and, considered with the significantly lower mean volume of this region, suggests that this is a core region affected by the disorder

A Meta-analysis of Immune Parameters, Variability, and Assessment of Modal Distribution in Psychosis and Test of the Immune Subgroup Hypothesis

Abstract: Immune parameters are elevated in psychosis, but it is unclear whether alterations are homogenous across patients or heterogeneity exists, consistent with the hypothesis that immune alterations are specific to a subgroup of patients. To address this, we examine whether antipsychotic-naive first-episode psychosis patients exhibit greater variability in blood cytokines, C-reactive protein, and white cell counts compared with controls, and if group mean differences persist after adjusting for skewed data and potential confounds. Databases were searched for studies reporting levels of peripheral immune parameters. Means and variances were extracted and analyzed using multivariate meta-analysis of mean and variability of differences. Outcomes were (1) variability in patients relative to controls, indexed by variability ratio (VR) and coefficient of variation ratio (CVR); (2) mean differences indexed by Hedges g; (3) Modal distribution of raw immune parameter data using Hartigan's unimodality dip test. Thirty-five studies reporting on 1263 patients and 1470 controls were included. Variability of interleukin-6 (IL6) (VR = 0.19), tumor necrosis factor-α (TNFα) (VR = 0.36), interleukin-1β (VR = 0.35), interleukin-4 (VR = 0.55), and interleukin-8 (VR = 0.28) was reduced in patients. Results persisted for IL6 and IL8 after mean-scaling. Ninety-four percent and one hundred percent of raw data were unimodally distributed in psychosis and controls, respectively. Mean levels of IL6 (g = 0.62), TNFα (g = 0.56), interferon-γ (IFNγ) (g = 0.32), transforming growth factor-β (g = 0.53), and interleukin-17 (IL17) (g = 0.48) were elevated in psychosis. Sensitivity analyses indicated this is unlikely explained by confounders for IL6, IFNγ, and IL17. These findings show elevated cytokines in psychosis after accounting for confounds, and that the hypothesis of an immune subgroup is not supported by the variability or modal distribution.

The american journal of psychiatry

Abstract: Articles 1278 An Inflammatory Biomarker as a Differential Predictor of Outcome of Depression Treatment With Escitalopram and Nortriptyline Rudolf Uher et. al 1287 Identification and Replication of a Combined Epigenetic and Genetic Biomarker Predicting Suicide and Suicidal Behaviors Jerry Guintivano et. al 1297 Clinical Outcomes and Genome-Wide Association for a Brain Methylation Site in an Antidepressant Pharmacogenetics Study in Mexican Americans Ma-Li Wong et. al

Glutamate and dopamine in schizophrenia: an update for the 21st century

Abstract: The glutamate and dopamine hypotheses are leading theories of the pathoaetiology of schizophrenia. Both were initially based on indirect evidence from pharmacological studies supported by post-mortem findings, but have since been substantially advanced by new lines of evidence from in vivo imaging studies. This review provides an update on the latest findings on dopamine and glutamate abnormalities in schizophrenia, focusing on in vivo neuroimaging studies in patients and clinical high-risk groups, and considers their implications for understanding the biology and treatment of schizophrenia. These findings have refined both the dopamine and glutamate hypotheses, enabling greater anatomical and functional specificity, and have been complemented by preclinical evidence showing how the risk factors for schizophrenia impact on the dopamine and glutamate systems. The implications of this new evidence for understanding the development and treatment of schizophrenia are considered, and the gaps in current knowledge highlighted. Finally, the evidence for an integrated model of the interactions between the glutamate and dopamine systems is reviewed, and future directions discussed.

Neural correlates of the LSD experience revealed by multimodal neuroimaging

Abstract: Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD’s marked effects on the visual cortex did not significantly correlate with the drug’s other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of “ego-dissolution” and “altered meaning,” implying the importance of this particular circuit for the maintenance of “self” or “ego” and its processing of “meaning.” Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

Schizophrenia-An Overview

Abstract: Importance Schizophrenia is a common, severe mental illness that most clinicians will encounter regularly during their practice. This report provides an overview of the clinical characteristics, epidemiology, genetics, neuroscience, and psychopharmacology of schizophrenia to provide a basis to understand the disorder and its treatment. This educational review is integrated with a clinical case to highlight how recent research findings can inform clinical understanding. Observations The first theme considered is the role of early-life environmental and genetic risk factors in altering neurodevelopmental trajectories to predispose an individual to the disorder and leading to the development of prodromal symptoms. The second theme is the role of cortical excitatory-inhibitory imbalance in the development of the cognitive and negative symptoms of the disorder. The third theme considers the role of psychosocial stressors, psychological factors, and subcortical dopamine dysfunction in the onset of the positive symptoms of the disorder. The final theme considers the mechanisms underlying treatment for schizophrenia and common adverse effects of treatment. Conclusions and Relevance Schizophrenia has a complex presentation with a multifactorial cause. Nevertheless, advances in neuroscience have identified roles for key circuits, particularly involving frontal, temporal, and mesostriatal brain regions, in the development of positive, negative, and cognitive symptoms. Current pharmacological treatments operate using the same mechanism, blockade of dopamine D2receptor, which contribute to their adverse effects. However, the circuit mechanisms discussed herein identify novel potential treatment targets that may be of particular benefit in symptom domains not well served by existing medications.

Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment

Abstract: Community-based studies suggest that cannabis products that are high in Δ⁹-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600 mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥ 3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ²=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6 ± 18.9%) compared with the CBD group (-0.4% ± 9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.