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Stefan J Borgwardt

sborgwardt@uhbs.ch

Journal articles

2009
Riecher-Rössler, Pflueger, Aston, Borgwardt, Brewer, Gschwandtner, Stieglitz (2009)  Efficacy of Using Cognitive Status in Predicting Psychosis: A 7-Year Follow-Up.   Biol Psychiatry Sep  
Abstract: BACKGROUND: Despite extensive early detection research in schizophrenic psychoses, methods for identifying at-risk individuals and predicting their transition to psychosis are still unreliable. Moreover, there are sparse data on long-term prediction. We therefore investigated long-term psychosis transition in individuals with an At Risk Mental State (ARMS) and examined the relative efficacy of clinical and neuropsychological status in optimizing the prediction of transition. METHODS: Sixty-four individuals with ARMS for psychosis were identified from all referrals to our early detection clinic between March 1, 2000 and February 29, 2004. Fifty-three (83%) were followed up for up to 7 (mean 5.4) years. RESULTS: Twenty-one of the 53 staying in follow-up developed psychosis, corresponding to a transition rate of .34 (Kaplan-Meier estimates). Median time to transition was 10 months (range <1-55). Six of all transitions (29%) occurred only after 12 months from referral. Best transition predictors within this population were selected attenuated psychotic symptoms (suspiciousness), negative symptoms (anhedonia/asociality), and cognitive deficits (reduced speed of information processing). With these predictors in an integrated model for predicting transition to psychosis, the overall predictive accuracy was 80.9% with a sensitivity of 83.3% and a specificity of 79.3%. CONCLUSIONS: Follow-up of ARMS subjects should exceed the usual 12 months. Prediction of transitions could be improved by a stronger weighting of certain early symptoms and by introducing neurocognitive tests into a stepwise risk assessment. Confirmatory research will hopefully further improve risk algorithm, including psychopathology and neuropsychological performance, for clinical application in early detection clinics.
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Kanaan, Borgwardt, McGuire, Craig, Murphy, Picchioni, Shergill, Jones, Catani (2009)  Microstructural Organization of Cerebellar Tracts in Schizophrenia.   Biol Psychiatry Sep  
Abstract: BACKGROUND: Dysconnectivity theories of schizophrenia would suggest that the connectivity of the cerebellum is impaired and that the impairment may be restricted to certain tracts. Attempts to examine the structural connectivity of the cerebellum using diffusion tensor imaging have yielded conflicting results. However, previous studies have employed region-of-interest approaches or have used small or unmatched samples, with a consequent risk of type II error. METHODS: We conducted an appropriately powered case-control study of 33 patients with schizophrenia and 33 matched healthy control subjects. We used tractography to dissect the four white matter tracts of the cerebellum and measured fractional anisotropy (FA) and mean diffusivity (MD) over each tract for each subject. RESULTS: Repeated-measures analysis of variance found that FA was lower in the schizophrenia group compared with the control group, but there were no tract-specific differences between the groups. Mean diffusivity did not differ between the groups. CONCLUSIONS: Though structural connectivity is impaired in the cerebellum, it is not local to any particular tract but appears to have a wider, possibly global, distribution. Reduced fractional anisotropy with normal MD would point to the differences being due to disordered neuronal architecture rather than disordered myelination.
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Fusar-Poli, Allen, Bhattacharyya, Crippa, Mechelli, Borgwardt, Martin-Santos, Seal, O'Carrol, Atakan, Zuardi, McGuire (2009)  Modulation of effective connectivity during emotional processing by Delta9-tetrahydrocannabinol and cannabidiol.   Int J Neuropsychopharmacol 1-12 Sep  
Abstract: Cannabis sativa, the most widely used illicit drug, has profound effects on levels of anxiety in animals and humans. Although recent studies have helped provide a better understanding of the neurofunctional correlates of these effects, indicating the involvement of the amygdala and cingulate cortex, their reciprocal influence is still mostly unknown. In this study dynamic causal modelling (DCM) and Bayesian model selection (BMS) were used to explore the effects of pure compounds of C. sativa [600 mg of cannabidiol (CBD) and 10 mg Delta9-tetrahydrocannabinol (Delta9-THC)] on prefrontal-subcortical effective connectivity in 15 healthy subjects who underwent a double-blind randomized, placebo-controlled fMRI paradigm while viewing faces which elicited different levels of anxiety. In the placebo condition, BMS identified a model with driving inputs entering via the anterior cingulate and forward intrinsic connectivity between the amygdala and the anterior cingulate as the best fit. CBD but not Delta9-THC disrupted forward connectivity between these regions during the neural response to fearful faces. This is the first study to show that the disruption of prefrontal-subocrtical connectivity by CBD may represent neurophysiological correlates of its anxiolytic properties.
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Kerstin Bendfeldt, Pascal Kuster, Stefan Traud, Hanspeter Egger, Sebastian Winklhofer, Nicole Mueller-Lenke, Yvonne Naegelin, Achim Gass, Ludwig Kappos, Paul M Matthews, Thomas E Nichols, Ernst-Wilhelm Radue, Stefan J Borgwardt (2009)  Association of regional gray matter volume loss and progression of white matter lesions in multiple sclerosis - A longitudinal voxel-based morphometry study.   Neuroimage 45: 1. 60-67 Mar  
Abstract: Previous studies have established regional gray matter (GM) volume loss in multiple sclerosis (MS) but the relationship between development of white matter (WM) lesions and changes of regional GM volumes is unclear. The present study addresses this issue by means of voxel-based morphometry (VBM). T1-weighted three-dimensional magnetic resonance imaging (MRI) data from MS patients followed up for 12 months were analyzed using VBM. An analysis of covariance model assessed with cluster size inference (all corrected for multiple comparisons, p<0.01) was used to compare GM volumes between baseline and follow-up while controlling for age, gender, and disease duration. Lesion burden, i.e. volumes of T1 hypointense and T2 hyperintense lesions and the number of new T2 lesions at year one, was also determined. Comparing all MS patients (n=211) longitudinally, GM volume remained unchanged during one year-follow-up. Focusing on patients with relapsing remitting MS (RRMS) (n=151), significant cortical GM volume reductions between baseline and follow-up scans were found in the anterior and posterior cingulate, the temporal cortex, and cerebellum. Within the RRMS group, those patients with increasing T2 and T1 lesion burden (n=45) showed additional GM volume loss during follow-up in the frontal and parietal cortex, and precuneus. In contrast, patients lacking an increase in WM lesion burden (n=44) did not show any significant GM changes. The present study suggests that the progression of regional GM volume reductions is associated with WM lesion progression and occurs predominantly in fronto-temporal cortical areas.
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Sven Haller, Stefan J Borgwardt, Christian Schindler, Jacqueline Aston, Ernst W Radue, Anita Riecher-Rössler (2009)  Can cortical thickness asymmetry analysis contribute to detection of at-risk mental state and first-episode psychosis? A pilot study.   Radiology 250: 1. 212-221 Jan  
Abstract: PURPOSE: To investigate whether cortical thickness analysis in individuals with an at-risk mental state (ARMS) might contribute to early detection of psychosis. MATERIALS AND METHODS: Ethics committee approval and written informed consent were obtained. Cortical thickness was analyzed because early disease-related morphometric changes were expected to be most pronounced in the cerebral cortex. With the assumption of progressive change in cortical thickness from control subjects, to those with an ARMS, and then to those who have had a first episode (FE) of psychosis, the brain regions that substantially differ between those with FE psychosis and control subjects were identified. Whether these regions help discriminate between the ARMS group and control subjects was tested. Because normal interindividual variation of cortical thickness, even for control subjects, may exceed that expected with early disease-related changes, intraindividual cortical thickness asymmetry was analyzed. Twenty age- and sex-matched individuals for each group (ARMS group, FE group, and control subjects) were recruited within a prospective early-detection study. High-spatial-resolution magnetization-prepared rapid gradient-echo magnetic resonance (MR) brain images were acquired with a 1.5-T MR imager. Cortical thickness asymmetry was analyzed in 41 anatomic regions corresponding to the Talairach standard brain atlas. RESULTS: Direct cortical thickness analysis did not help distinguish between groups. Cortical thickness asymmetry analysis helped distinguish between groups (P = .007); variability increased from control subjects, to the ARMS group, and then to the FE group in seven anatomic regions (P < .0001). Cortical thickness asymmetry in these regions helped distinguish the FE group from control subjects (P = .0006; sensitivity, 70.0%; specificity, 85.0%) and showed a trend toward helping to distinguish the ARMS group from control subjects (P = .06; sensitivity, 75.0%; specificity, 65.0%). CONCLUSION: Cortical thickness asymmetry analysis is more accurate than direct cortical thickness measurement in distinguishing the control from the FE group and might contribute to early detection of an ARMS.
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R Smieskova, P Fusar-Poli, P Allen, K Bendfeldt, R D Stieglitz, J Drewe, E W Radue, P K McGuire, A Riecher-Rössler, S J Borgwardt (2009)  The effects of antipsychotics on the brain: what have we learnt from structural imaging of schizophrenia?--a systematic review.   Curr Pharm Des 15: 22. 2535-2549  
Abstract: Despite a large number of neuroimaging studies in schizophrenia reporting subtle brain abnormalities, we do not know to what extent such abnormalities reflect the effects of antipsychotic treatment on brain structure. We therefore systematically reviewed cross-sectional and follow-up structural brain imaging studies of patients with schizophrenia treated with antipsychotics. 30 magnetic resonance imaging (MRI) studies were identified, 24 of them being longitudinal and six cross-sectional structural imaging studies. In patients with schizophrenia treated with antipsychotics, reduced gray matter volume was described, particularly in the frontal and temporal lobes. Structural neuroimaging studies indicate that treatment with typical as well as atypical antipsychotics may affect regional gray matter (GM) volume. In particular, typical antipsychotics led to increased gray matter volume of the basal ganglia, while atypical antipsychotics reversed this effect after switching. Atypical antipsychotics, however, seem to have no effect on basal ganglia structure.
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Martín-Santos, Fagundo, Crippa, Atakan, Bhattacharyya, Allen, Fusar-Poli, Borgwardt, Seal, Busatto, McGuire (2009)  Neuroimaging in cannabis use: a systematic review of the literature.   Psychol Med 1-17 Jul  
Abstract: BACKGROUND: We conducted a systematic review to assess the evidence for specific effects of cannabis on brain structure and function. The review focuses on the cognitive changes associated with acute and chronic use of the drug.MethodWe reviewed literature reporting neuroimaging studies of chronic or acute cannabis use published up until January 2009. The search was conducted using Medline, EMBASE, LILACS and PsycLIT indexing services using the following key words: cannabis, marijuana, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, neuroimaging, brain imaging, computerized tomography, CT, magnetic resonance, MRI, single photon emission tomography, SPECT, functional magnetic resonance, fMRI, positron emission tomography, PET, diffusion tensor MRI, DTI-MRI, MRS and spectroscopy. RESULTS: Sixty-six studies were identified, of which 41 met the inclusion criteria. Thirty-three were functional (SPECT/PET/fMRI) and eight structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across studies precluded a meta-analysis. The functional studies suggest that resting global and prefrontal blood flow are lower in cannabis users than in controls. The results from the activation studies using a cognitive task are inconsistent because of the heterogeneity of the methods used. Studies of acute administration of THC or marijuana report increased resting activity and activation of the frontal and anterior cingulate cortex during cognitive tasks. Only three of the structural imaging studies found differences between users and controls. CONCLUSIONS: Functional neuroimaging studies suggest a modulation of global and prefrontal metabolism both during the resting state and after the administration of THC/marijuana cigarettes. Minimal evidence of major effects of cannabis on brain structure has been reported.
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Sagnik Bhattacharyya, Paolo Fusar-Poli, Stefan Borgwardt, Rocio Martin-Santos, Chiara Nosarti, Colin O'Carroll, Paul Allen, Marc L Seal, Paul C Fletcher, José A Crippa, Vincent Giampietro, Andrea Mechelli, Zerrin Atakan, Philip McGuire (2009)  Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis.   Arch Gen Psychiatry 66: 4. 442-451 Apr  
Abstract: CONTEXT: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. OBJECTIVES: To investigate the effects of 2 main psychoactive constituents of C. sativa, Delta9-tetrahydrocannabinol (Delta9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. DESIGN: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. SETTING: University research center. PARTICIPANTS: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. MAIN OUTCOME MEASURES: Regional brain activation (blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. RESULTS: Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. CONCLUSION: The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms, respectively.
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Stefan J Borgwardt, Chandlee Dickey, Hilleke Hulshoff Pol, Thomas J Whitford, Lynn E DeLisi (2009)  Workshop on defining the significance of progressive brain change in schizophrenia: December 12, 2008 American College of Neuropsychopharmacology (ACNP) all-day satellite, Scottsdale, Arizona. The rapporteurs' report.   Schizophr Res 112: 1-3. 32-45 Jul  
Abstract: In 1990 a satellite session of the American College of Neuropsychopharmacology (ACNP) Annual Meeting was held that focused on the question of whether progressive changes in brain structure occur in schizophrenia and this session raised considerable controversy. Eighteen years later, on December 12, 2008, after much data have since accumulated on this topic, a group of approximately 45 researchers gathered after the annual ACNP meeting to participate in a similar workshop on several unresolved questions still remaining: (1) How strong and consistent is the evidence? (2) Is there anatomic specificity to changes and is it disease specific or subject specific? (3) What is the time course? (4) What is the underlying pathophysiology (i.e. is it central to the disease process or is it due to neuroleptic treatment or other epiphenomena? (5) What is its clinical significance? and (6) Are there treatment implications? The day was chaired by Lynn E. DeLisi and co-chaired by Stephen J. Wood. Christos Pantelis and Jeffrey A. Lieberman extensively helped with its planning. The ACNP assisted in its organization as an official satellite of its annual meeting and several pharmaceutical companies provided support with unrestricted educational grants. The following is a summary of the sessions as recounted by rapporteurs whose job was to record as closely as possible the outcome of discussions on the above outlined questions.
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Paolo Fusar-Poli, José A Crippa, Sagnik Bhattacharyya, Stefan J Borgwardt, Paul Allen, Rocio Martin-Santos, Marc Seal, Simon A Surguladze, Colin O'Carrol, Zerrin Atakan, Antonio W Zuardi, Philip K McGuire (2009)  Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing.   Arch Gen Psychiatry 66: 1. 95-105 Jan  
Abstract: CONTEXT: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. OBJECTIVE: To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. DESIGN: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. PARTICIPANTS: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. MAIN OUTCOME MEASURES: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. RESULTS: Delta9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. CONCLUSIONS: Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions.
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Su Lui, Wei Deng, Xiaoqi Huang, Lijun Jiang, Luo Ouyang, Stefan J Borgwardt, Xiaohong Ma, Dongming Li, Ling Zou, Hehan Tang, Huafu Chen, Tao Li, Philip McGuire, Qiyong Gong (2009)  Neuroanatomical differences between familial and sporadic schizophrenia and their parents: an optimized voxel-based morphometry study.   Psychiatry Res 171: 2. 71-81 Feb  
Abstract: Symptomatic differences have been reported between patients with familial and sporadic schizophrenia. The present study examined neuroanatomical differences between the two subgroups and their parents using voxel-based morphometry. High-resolution T1-weighted images were obtained using 3 Tesla magnetic resonance imaging from 20 patients with schizophrenia (familial subgroup, n=10; sporadic subgroup, n=10), 20 of their parents (familial subgroup, n=10; sporadic subgroup, n=10) and 20 healthy volunteers. Gray matter density (GMD) was compared between groups on a voxel-by-voxel basis. Compared with the sporadic patients, the familial patients had significantly reduced GMD in the thalamus bilaterally. Reduction of GMD in bilateral thalami was also found in familial parents in comparison with sporadic parents. Compared with controls, both familial and sporadic patients had lower GMD involving bilateral insula, right temporal lobe, right occipital lobe, left lenticular nucleus and right cerebellum. However, only familial patients showed lower GMD than controls in the right thalamus. Compared with controls, only familial parents showed lower GMD in the right insula extending to the right temporal lobe and the right parietal lobule. The present data suggest that familial schizophrenia is associated with more severe structural abnormalities than sporadic schizophrenia, especially in the thalamus.
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2008
Stefan J Borgwardt, Philip K McGuire, Jacqueline Aston, Ute Gschwandtner, Marlon O Pflüger, Rolf-Dieter Stieglitz, Ernst-Wilhelm Radue, Anita Riecher-Rössler (2008)  Reductions in frontal, temporal and parietal volume associated with the onset of psychosis.   Schizophr Res 106: 2-3. 108-114 Dec  
Abstract: BACKGROUND: Volumetric MRI abnormalities similar to those evident in schizophrenia are also evident in people at very high risk of psychosis. Which volumetric abnormalities are related to psychotic illness, as opposed to vulnerability to psychosis is unclear. The aim of the study was to compare regional gray matter volume in people before and after the onset of psychosis using a within-subject prospective design. METHODS: MRI data were acquired from individuals when they presented with an at-risk mental state (ARMS, n=20). Over the following 3 years, 10 subjects developed psychosis and 10 did not. Subjects were re-scanned after the onset of psychosis or at the end of follow-up if they did not become psychotic. Images were processed and analyzed using voxel-based morphometry (SPM5). RESULTS: In subjects who developed psychosis there were longitudinal volume reductions in the orbitofrontal, superior frontal, inferior temporal, medial and superior parietal cortex, and in the cerebellum. There were no longitudinal changes in subjects who did not develop psychosis. CONCLUSIONS: The onset of psychosis was associated with a reduction in gray matter volume in frontal, temporal and parietal cortex. These abnormalities may be particularly associated with psychotic illness, as opposed to a vulnerability to psychosis.
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A Riecher-Rössler, J Aston, J Ventura, M Merlo, S Borgwardt, U Gschwandtner, R - D Stieglitz (2008)  The Basel Screening Instrument for Psychosis (BSIP): development, structure, reliability and validity   Fortschr Neurol Psychiatr 76: 4. 207-216 Apr  
Abstract: BACKGROUND: Early detection of psychosis is of growing clinical importance. So far there is, however, no screening instrument for detecting individuals with beginning psychosis in the atypical early stages of the disease with sufficient validity. We have therefore developed the Basel Screening Instrument for Psychosis (BSIP) and tested its feasibility, interrater-reliability and validity. AIM: Aim of this paper is to describe the development and structure of the instrument, as well as to report the results of the studies on reliability and validity. METHOD: The instrument was developed based on a comprehensive search of literature on the most important risk factors and early signs of schizophrenic psychoses. The interraterreliability study was conducted on 24 psychiatric cases. Validity was tested based on 206 individuals referred to our early detection clinic from 3/1/2000 until 2/28/2003. RESULTS: We identified seven categories of relevance for early detection of psychosis and used them to construct a semistructured interview. Interrater-reliability for high risk individuals was high (Kappa .87). Predictive validity was comparable to other, more comprehensive instruments: 16 (32 %) of 50 individuals classified as being at risk for psychosis by the BSIP have in fact developed frank psychosis within an follow-up period of two to five years. CONCLUSIONS: The BSIP is the first screening instrument for the early detection of psychosis which has been validated based on transition to psychosis. The BSIP is easy to use by experienced psychiatrists and has a very good interrater-reliability and predictive validity.
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Stefan J Borgwardt, Paul Allen, Sagnik Bhattacharyya, Paolo Fusar-Poli, Jose A Crippa, Marc L Seal, Valter Fraccaro, Zerrin Atakan, Rocio Martin-Santos, Colin O'Carroll, Katya Rubia, Philip K McGuire (2008)  Neural basis of Delta-9-tetrahydrocannabinol and cannabidiol: effects during response inhibition.   Biol Psychiatry 64: 11. 966-973 Dec  
Abstract: BACKGROUND: This study examined the effect of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on brain activation during a motor inhibition task. METHODS: Functional magnetic resonance imaging and behavioural measures were recorded while 15 healthy volunteers performed a Go/No-Go task following administration of either THC or CBD or placebo in a double-blind, pseudo-randomized, placebo-controlled repeated measures within-subject design. RESULTS: Relative to placebo, THC attenuated activation in the right inferior frontal and the anterior cingulate gyrus. In contrast, CBD deactivated the left temporal cortex and insula. These effects were not related to changes in anxiety, intoxication, sedation, and psychotic symptoms. CONCLUSIONS: These data suggest that THC attenuates the engagement of brain regions that mediate response inhibition. CBD modulated function in regions not usually implicated in response inhibition.
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2007
Stefan J Borgwardt, Anita Riecher-Rössler, Paola Dazzan, Xavier Chitnis, Jacqueline Aston, Margret Drewe, Ute Gschwandtner, Sven Haller, Marlon Pflüger, Evelyne Rechsteiner, Marcus D'Souza, Rolf-Dieter Stieglitz, Ernst-Wilhelm Radü, Philip K McGuire (2007)  Regional gray matter volume abnormalities in the at risk mental state.   Biol Psychiatry 61: 10. 1148-1156 May  
Abstract: BACKGROUND: Individuals with an At Risk Mental State (ARMS) have a very high risk of developing a psychotic disorder but the basis of this risk is unclear. We addressed this issue by studying gray matter volume in this group with magnetic resonance imaging (MRI). METHODS: Thirty-five individuals with an ARMS, 25 patients with first episode schizophrenia, and 22 healthy volunteers were studied using a 1.5T MRI scanner. Twelve (34%) of the ARMS group developed schizophrenia in the 2 years subsequent to scanning. RESULTS: There were significant volumetric differences between the three groups in the left insula, superior temporal gyrus, cingulate gyrus and precuneus. In these regions, the volume in the ARMS group was smaller than in volunteers but not significantly different from that in the first episode (FE) group. Direct comparison of the ARMS and control groups revealed additional areas of reduced volume in the left medial temporal cortex. Within the ARMS group, those subjects who later developed psychosis had less gray matter than subjects who did not in the right insula, inferior frontal and superior temporal gyrus. CONCLUSIONS: The ARMS was associated with reductions in gray matter volume in areas that are also reduced in schizophrenia, suggesting that these are a correlate of an increased vulnerability to psychosis. Volumetric differences within the ARMS group may be related to the subsequent onset of schizophrenia in a subset of those at high risk.
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A Riecher-Rössler, U Gschwandtner, J Aston, S Borgwardt, M Drewe, P Fuhr, M Pflüger, W Radü, Ch Schindler, R - D Stieglitz (2007)  The Basel early-detection-of-psychosis (FEPSY)-study--design and preliminary results.   Acta Psychiatr Scand 115: 2. 114-125 Feb  
Abstract: Early detection and therapy of schizophrenic psychoses have become broadly accepted aims in psychiatry, recently even in very early stages of the disorder when clear diagnostic criteria are not yet fulfilled. However, reliable and widely applicable methods do not yet exist. This study aims at contributing to the improvement of the early assessment of psychosis. Method: Individuals potentially at risk are identified by a newly developed stepwise screening procedure. Identified subjects are then examined extensively and followed-up for at least 5 years to detect actual transition to psychosis. RESULTS: Of 50 subjects who have been followed up for 1-5 years by now, 16 have progressed to frank psychosis, 12 of them during the first 12 months of follow-up. CONCLUSION: At this stage, our approach seems to be promising for the early detection of psychosis. Further results from this ongoing study will hopefully permit us to optimize the assessment procedure.
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Stefan J Borgwardt, Philip K McGuire, Jacqueline Aston, Gregor Berger, Paola Dazzan, Ute Gschwandtner, Marlon Pflüger, Marcus D'Souza, Ernst-Wilhelm Radue, Anita Riecher-Rössler (2007)  Structural brain abnormalities in individuals with an at-risk mental state who later develop psychosis.   Br J Psychiatry Suppl 51: s69-s75 Dec  
Abstract: BACKGROUND: Neuroanatomical abnormalities are a well-established feature of schizophrenia. However, the timing of their emergence and the extent to which they are related to vulnerability to the disorder as opposed to psychotic illness itself is unclear. AIMS: To assess regional grey matter volume in the at-risk individuals who subsequently developed psychosis. METHOD: Magnetic resonance imaging data from at-risk individuals who developed psychosis (n=12) within the following 25 months were compared with data from healthy volunteers (n=22) and people with first-episode psychosis (n=25). RESULTS: Compared with healthy volunteers, individuals who subsequently developed psychosis had smaller grey matter volume in the posterior cingulate gyrus, precuneus, and paracentral lobule bilaterally and in the left superior parietal lobule, and greater grey matter volume in a left parietal/posterior temporal region. Compared with first-episode patients, they had relatively greater grey matter volume in the temporal gyrus bilaterally and smaller grey matter volume in the right lentiform nucleus. CONCLUSIONS: Some of the structural brain abnormalities in individuals with an at-risk mental state may be related to an increased vulnerability to psychosis, while others are associated with the development of a psychotic illness.
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Paolo Fusar-Poli, Jorge Perez, Matthew Broome, Stefan Borgwardt, Anna Placentino, Eduardo Caverzasi, Mariachiara Cortesi, Pierangelo Veggiotti, Peirluigi Politi, Francesco Barale, Philip McGuire (2007)  Neurofunctional correlates of vulnerability to psychosis: a systematic review and meta-analysis.   Neurosci Biobehav Rev 31: 4. 465-484 01  
Abstract: An understanding of the neurobiological correlates of vulnerability to psychosis is fundamental to research on schizophrenia. We systematically reviewed data from studies published from 1992 to 2006 on the neurocognitive correlates (as measured by fMRI) of increased vulnerability to psychosis. We also conducted a meta-analysis of abnormalities of activation in the prefrontal cortex (PFC) in high-risk and first episode subjects, and reviewed neuroimaging studies of high-risk subjects that used PET, SPECT and MRS. Twenty-four original fMRI papers were identified, most of which involved tasks that engaged the PFC. In fMRI studies, vulnerability to psychosis was associated with medium to large effect sizes when prefrontal activation was contrasted with that in controls. Relatives of patients affected with psychosis, the co-twins of patients and subjects with an At Risk Mental State (ARMS) appear to share similar neurocognitive abnormalities. Furthermore, these are qualitatively similar but less severe than those observed in the first episode of illness. These abnormalities have mainly been described in the prefrontal and anterior cingulated cortex, the basal ganglia, hippocampus and cerebellum.
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2006
A Riecher-Rössler, U Gschwandtner, S Borgwardt, J Aston, M Pflüger, W Rössler (2006)  Early detection and treatment of schizophrenia: how early?   Acta Psychiatr Scand Suppl 429. 73-80  
Abstract: OBJECTIVE: Whereas early detection and therapy of schizophrenic psychoses until some time ago concentrated on frank schizophrenia, during the last years some centres have also started to treat patients even before a clear diagnosis could be established. This paper attempts to discuss if and when this is justified in the light of recent research. METHOD: Mini review of literature. RESULTS: The rationale for early detection and treatment of schizophrenia is based on several observations: diagnosis and treatment of schizophrenia are often seriously delayed. Consequences of the disease are severe already in the early undiagnosed phase of the disorder and early treatment seems to improve the course of the disease. It can therefore be stated quite safely that patients should be treated as early as possible. However, the question of how early has not been sufficiently answered up to now. CONCLUSION: We are at the moment in an ethical dilemma between either diagnosing and treating this disorder too late or too early. The only way and prerequisite for solving this dilemma is a more reliable identification of individuals at risk and the beginning disease process.
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Ute Gschwandtner, Marlon Pflüger, Jacqueline Aston, Stefan Borgwardt, Margret Drewe, Rolf-Dieter Stieglitz, Anita Riecher-Rössler (2006)  Fine motor function and neuropsychological deficits in individuals at risk for schizophrenia.   Eur Arch Psychiatry Clin Neurosci 256: 4. 201-206 Jun  
Abstract: Deficits in fine motor function and neuropsychological performance have been described as risk factors for schizophrenia. In the Basel FEPSY study (Früherkennung von Psychosen; English: Early Detection of Psychosis) individuals at risk for psychosis were identified in a screening procedure (Riecher-Rössler et al. 2005). As a part of the multilevel assessment, 40 individuals at risk for psychosis and 42 healthy controls matched for age, sex and handedness were investigated with a fine motor function test battery and a neuropsychological test battery. Individuals at risk showed lower performances in all subtests of the fine motor function tests, predominantly in dexterity and velocity (wrist/fingers and arm/hand). In the neuropsychological test battery, individuals at risk performed less well compared to healthy controls regarding sustained attention, working memory and perseveration. The combined evaluation of the two test batteries (neuropsychological and fine motor function) separates the two groups into individuals at risk and healthy controls better than each test battery alone. A multilevel approach might therefore be a valuable contribution to detecting beginning schizophrenia.
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S J Borgwardt, E - W Radue, K Götz, J Aston, M Drewe, U Gschwandtner, S Haller, M Pflüger, R - D Stieglitz, P K McGuire, A Riecher-Rössler (2006)  Radiological findings in individuals at high risk of psychosis.   J Neurol Neurosurg Psychiatry 77: 2. 229-233 Feb  
Abstract: OBJECTIVE: To assess the prevalence of radiological magnetic resonance imaging (MRI) findings in individuals at high risk of schizophrenia. METHODS: MRI scans from individuals at high risk of schizophrenia (HR; n = 37) were assessed by a radiologist blind to group status and compared with scans from patients with first episode psychosis (FE; n = 30), depressive controls (DC; n = 17), and healthy controls (HC; n = 26). RESULTS: There was a significantly higher proportion of radiological findings in individuals at high risk of schizophrenia (35%) and patients with first-episode psychosis (40%) than in patients with depression (18%) or healthy controls (12%). These differences were specific to findings regarded as potentially clinically significant as opposed to normal variants; however, there was no indication for medical treatment. CONCLUSIONS: The results suggest that a large proportion of those at high risk of psychosis have radiological findings on MRI scanning, and that the prevalence of radiological findings in this group is similar to that in patients with first episode psychosis.
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2004
U Gschwandtner, S Borgwardt, J Aston, M Drewe, E W Radü, A Riecher-Rössler (2004)  Chronic subdural hemorrhage in a patient with suspected schizophrenia prodrome   Nervenarzt 75: 7. 691-693 Jul  
Abstract: A patient showing "prodromal symptoms" of suspected psychosis was referred to our clinic specialized in early recognition of schizophrenia where an MRI brain scan showed a chronic subdural hemorrhage. Based on this case, it will be shown that organic brain disease, in addition to incipient schizophrenia, needs to be considered in patients with marked personality changes, social withdrawal, aggressiveness, and suspiciousness. Diagnosis of the first episode and prodromal stage of schizophrenia should include-apart from the case history as well as the psychopathological and physiological findings-certain obligatory medical examinations (EEG, cCT, or MRI) in order to identify possible organic causes and avoid misdiagnoses.
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2003
U Gschwandtner, J Aston, S Borgwardt, M Drewe, C Feinendegen, D Lacher, A Lanzarone, R - D Stieglitz, A Riecher-Rössler (2003)  Neuropsychological and neurophysiological findings in individuals suspected to be at risk for schizophrenia: preliminary results from the Basel early detection of psychosis study - Früherkennung von Psychosen (FEPSY).   Acta Psychiatr Scand 108: 2. 152-155 Aug  
Abstract: OBJECTIVE: Our study aims to establish a scientific basis for the very early detection of patients at risk for schizophrenia during the nonspecific prodromal phase of the disorder and to predict its outbreak. METHOD: A multidomain approach is used. After screening, approved psychopathological, neurophysiological, neuropsychological and neuroradiological investigations are used to assess a sample of individuals suspected to be at risk for schizophrenia. RESULTS: Neuropsychological and fine motor functioning tests as well as eye movement measurements showed statistically significant differences (P<0.01) between individuals suspected to be at risk for schizophrenia and healthy controls. CONCLUSION: Individuals suspected to be at risk for schizophrenia show specific impairments in various investigations including neuropsychological and fine motor functioning tests as well as eye movement measurements. A set of methods sensitive to even subtle changes in normal functioning may prove useful in predicting the subsequent outbreak of schizophrenia.
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