ORCID Profile
0000-0003-2021-6645
Current Organisation
Princeton University
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Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.PSCYCHRESNS.2016.07.002
Abstract: Episodic memory (EM) impairments in schizophrenia (SZ) are predictive of functional outcome and are a potential endophenotype of the disorder. The current study investigated the neuroanatomical correlates of EM encoding and retrieval in SZ with structural magnetic resonance and diffusion tensor imaging (DTI) measures in 22 patients with SZ and 22 age- and gender-matched healthy controls. Tract-based Spatial Statistics (TBSS) was used to investigate microstructural alterations in white matter (WM), while FreeSurfer surface-based analysis was used to determine abnormalities in grey matter (GM) and WM volumetrics and cortical thickness. Compared to controls, patients demonstrated GM deficits in temporal and parietal regions and lower fractional anisotropy (FA) of WM in diffuse brain regions. Patients also demonstrated reduced functioning in both encoding and retention of auditory-verbal EM. Among patients but not controls, EM encoding correlated with WM volume in the orbitofrontal cortex and increased radial diffusivity in the fornix, whereas EM retrieval correlated with WM volume in posterior parietal cortex. These findings suggest a differential role for frontal and parietal WM in EM encoding and retrieval processes, while myelin integrity of the fornix may play a specific role in mediating EM encoding processes in SZ.
Publisher: Informa UK Limited
Date: 30-08-2017
DOI: 10.1080/15622975.2016.1208839
Abstract: Schizophrenia is characterised by significant episodic memory impairment that is thought to be related to problems with encoding, however the neuro-functional mechanisms underlying these deficits are not well understood. The present study used a subsequent recognition memory paradigm and event-related potentials (ERPs) to investigate temporal aspects of episodic memory encoding deficits in schizophrenia. Electroencephalographic data was recorded in 24 patients and 19 healthy controls whilst participants categorised single words as pleasant/unpleasant. ERPs were generated to subsequently recognised versus unrecognised words on the basis of a forced-choice recognition memory task. Subsequent memory effects were examined with the late positive component (LPP). Group differences in N1, P2, N400 and LPP were examined for words correctly recognised. Patients performed more poorly than controls on the recognition task. During encoding patients had significantly reduced N400 and LPP litudes than controls. LPP litude correlated with task performance however litudes did not differ between patients and controls as a function of subsequent memory. No significant differences in N1 or P2 litude or latency were observed. The present results indicate that early sensory processes are intact and dysfunctional higher order cognitive processes during encoding are contributing to episodic memory impairments in schizophrenia.
Publisher: Elsevier BV
Date: 07-2005
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.SCHRES.2017.05.031
Abstract: Glycine increases N-methyl-d-aspartate receptor (NMDAR) mediated glutamatergic function. Mismatch negativity (MMN) is a proposed biomarker of glutamate-induced improvements in clinical symptoms, however, the effect of glycine-mediated NMDAR activation on MMN in schizophrenia is not well understood. This study aimed to determine the effects of acute and 6-week chronic glycine administration on MMN in schizophrenia patients. MMN litude was compared at baseline between 22 patients (schizophrenia or schizoaffective disorder receiving stable antipsychotic medication multi-centre recruitment) and 21 age- and gender-matched controls. Patients underwent a randomised, double-blind, placebo-controlled clinical trial with glycine added to their regular antipsychotic medication (placebo, n=10 glycine, n=12). MMN was reassessed post-45-minutes of first dose (0.2g/kg) and post-6-weeks treatment (incremented to 0.6g/kg/day). Clinical symptoms were assessed at baseline and post-6-weeks treatment. At baseline, duration MMN was smaller in schizophrenia compared to controls. Acute glycine increased duration MMN (compared to placebo), whilst this difference was absent post-6-weeks treatment. Six weeks of chronic glycine administration improved PANSS-Total, PANSS-Negative and PANSS-General symptoms compared to placebo. Smaller baseline duration MMN was associated with greater PANSS-Negative symptoms and predicted (at trend level) PANSS-Negative symptom improvement post-6-weeks glycine treatment (not placebo). These findings support the benefits of chronic glycine administration and demonstrate, for the first time, that acute glycine improves duration MMN in schizophrenia. This result, together with smaller baseline duration MMN predicting greater clinical treatment response, suggests the potential for duration MMN as a biomarker of glycine-induced improvements in negative symptoms in schizophrenia.
Publisher: Elsevier BV
Date: 06-2015
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.CLINPH.2016.03.013
Abstract: P50 suppression refers to the P50 ERP litude-reduction to the second (S2) relative to the first (S1) of identical brief auditory stimuli (SOA=500ms). Its reduction in schizophrenia is argued to represent impaired inhibitory input (II) mechanisms. Enhancing attention enhances II functionality (reducing S2P50 litude and increasing P50 difference) in healthy subjects. We determined whether the effect of attention on P50 suppression differs between schizophrenia patients (SCZ) and controls (CON) and thus is a confound in P50 schizophrenia research. We manipulated the direction of attention (attention, non-attention) in 21 SCZ and 18 CON in the P50 suppression task. Directing attention towards stimulus pairs (versus non-attention) increased P50 suppression (P50 difference). This effect differed between groups, with attention increasing S1P50, reducing S2P50 and increasing P50 suppression (P50 difference and reducing P50 ratio) in CON only. No group differences were found for P50 difference or ratio. Attention is a confound in schizophrenia P50 research and thus should be carefully controlled. When attention was controlled, P50 group differences were not found. The SCZ-CON P50 difference reported in the literature may be related to uncontrolled attention (and not impaired P50 suppression per se).
Publisher: Wiley
Date: 20-08-2021
DOI: 10.1111/EIP.13204
Abstract: Specialist early intervention (SEI) service models are designed to treat symptoms, promote social and vocational recovery, prevent relapse, and resource and up‐skill patients and their families. The benefits of SEI over the first few years have been demonstrated. While early recovery can be expected to translate to better long‐term outcomes by analogy with other illnesses, there is limited evidence to support this from follow‐up studies. The current study involves the long‐term follow‐up of a sub‐set of first episode psychosis (FEP) patients, with a range of diagnoses, who were first treated at Orygen's Early Psychosis Prevention and Intervention Centre (EPPIC) between 1998 and 2000. The aim of this paper is to present the methodology for this follow‐up study. Between January 1998 and December 2000, 786 patients between the ages of 15–29 years were treated at EPPIC, located in Melbourne, Australia. Our cohort consists of 661 people (82 were transferred/discharged and 43 were not diagnosed with a psychotic disorder at time of discharge). The 18‐month treatment characteristics of this cohort have been extensively examined in the First Episode Psychosis Outcome Study (FEPOS). The ≥15 year outcomes of this cohort are being examined in this study, known as FEPOS15. Participant follow‐up is ongoing. In order to extend and assess broader outcomes of the cohort, data linkage with health‐related databases will be conducted. This study will provide a comprehensive evaluation of the long‐term trajectory of psychotic disorders after treatment for FEP in a SEI service.
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.PBB.2005.04.010
Abstract: Working memory impairments in the n-back task in schizophrenia have been linked to sustained deficiency in mesocortical dopamine function. More recently, abnormalities in the cholinergic system have also been documented in schizophrenia, with cortical reductions in both nicotinic and muscarinic receptors. While the cholinergic hypothesis of memory is well established, the role of cholinergic receptors in modulating n-back working memory is not known. We investigated the effects of selective and simultaneous muscarinic and nicotinic antagonism on spatial and object n-back working memory performance. The study was a double-blind, placebo-controlled repeated-measures design in which 12 healthy subjects were tested under four acute treatment conditions placebo (P), mecamylamine (M), scopolamine (S) and mecamylamine+scopolamine (MS). Muscarinic antagonism with scopolamine significantly impaired both object and spatial n-back working memory, whereas nicotinic antagonism with mecamylamine had little effect. Simultaneous antagonism of both muscarinic and nicotinic receptors produced greater impairments in both object and spatial n-back working memory performance than muscarinic or nicotinic antagonism alone. These results suggest that: (1) both muscarinic and nicotinic receptors may functionally interact to synergistically modulate n-back working memory, and (2) that n-back working memory impairments in schizophrenia may in part be due to reductions in both muscarinic and nicotinic receptors.
Publisher: Society of Exploration Geophysicists
Date: 05-2006
DOI: 10.1190/1.2202654
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
No related grants have been discovered for Frederik Simons.