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The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing.~Context~Background~To examine the effects of ¿9-tetrahydrocannabinol (¿9-THC) and cannabidiol (CBD) on regional brain function during salience processing.~Objective~Objective~Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of ¿9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli.~Design~Methods~University center.~Setting~Methods~Fifteen healthy men with minimal previous cannabis use.~Participants~Methods~Symptom ratings, task performance, and regional brain activation.~Main Outcome Measures~Methods~During the processing of oddball stimuli, relative to placebo, ¿9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. ¿9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of ¿9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of ¿9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation.~Results~Results~¿9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.~Conclusions~Conclusions [ABSTRACT FROM AUTHOR]

Background. Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. Method. fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age- matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object-location paired-associate memory task, with experimental manipulation of mnemonic load. Results. In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. Conclusions. Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Impaired cognitive function has been identified as a core feature of schizophrenia. However, a significant proportion of patients do not show any cognitive deficits. The aim of this study was to assess if there were differences in white matter integrity between patients with and without cognitive impairment. METHOD: A diffusion tensor imaging study and neurocognitive assessment were conducted in 49 patients with first-episode psychosis and 41 healthy comparison subjects. Subjects were assessed using the Continuous Performance Test, the Grooved Pegboard Test, the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B. For each test, the patient sample was subdivided according to performance, with those scoring more than one standard deviation below the normative mean categorized as impaired. For each cognitive domain, white matter fractional anisotropy in deficit and nondeficit subgroups was compared using a voxel-based analysis. A nonparametric statistical method, controlling for multiple comparisons, was applied. RESULTS: Impairment on the Trail Making Test Part B was associated with reduced fractional anisotropy in the right/left anterior thalamic radiation and inferior fronto-occipital fasciculus, forceps minor, and left superior and inferior longitudinal fasciculi. Patients exhibiting Grooved Pegboard Test impairment showed reduced fractional anisotropy in the forceps minor, inferior fronto-occipital fasciculus, anterior thalamic radiation, and corticospinal and corticopontine tracts. Impaired performance on the Rey Auditory Verbal Learning Test and Continuous Performance Test was not associated with significant differences in fractional anisotropy. CONCLUSION: Deficits in executive and motor functioning in patients with first-episode psychosis are associated with reductions in white matter integrity in the major fasciculi that connect the frontal and temporal cortices as well as in pathways connecting cortical and subcortical regions. Their presence at the onset of illness, in minimally medicated patients, indicates that these findings are not attributable to effects of chronic illness or its treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Schizophrenic patients tend to attribute internal events to external agents, a bias that may be linked to positive symptoms. We investigated the effect of emotional valence on the cognitive bias.MethodMale schizophrenic subjects (n=30) and an experimenter alternatively produced neutral and negative words. The subject then decided whether he or the experimenter had generated the item. RESULTS: External misattributions were more common than self-misattributions, and the bias was greater for patients with active hallucinations and delusions relative to patients in remission. Actively psychotic patients but not patients in remission were more likely to generate external misattributions with negative relative to neutral words. CONCLUSIONS: Affective modulation of the externalizing cognitive bias in source monitoring is evident in patients with hallucinations and delusions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cognitive models propose that auditory verbal hallucinations arise through defective self-monitoring and external attribution of inner speech. We used a paradigm that engages verbal self-monitoring to examine how deficits in this process are related to symptoms and diagnosis in patients with psychosis. METHOD: We tested 45 patients with schizophrenia. Fifteen had current auditory hallucinations, 15 had a history of (but no current) auditory hallucinations, and 15 had delusions but neither current nor previous hallucinations. We also tested 10 patients with affective psychosis and current auditory hallucinations, and 20 healthy volunteers. Participants read single adjectives aloud while the source and the pitch of the on-line auditory verbal feedback was manipulated, then immediately identified the source of the speech they heard ('self'/'other'/'unsure'). RESULTS: When reading aloud with distorted feedback of their own voice, patients with schizophrenia who had auditory hallucinations were more likely than controls to misidentify its source as 'other'. Patients with delusions but no current hallucinations displayed a similar deficit, although there was a trend for this to be less marked. Patients with a history of hallucinations did not differ from controls. Patients with hallucinations in the context of an affective disorder made more unsure responses rather than misattributions. CONCLUSIONS: Difficulty with source monitoring was related to the acute psychotic state rather than a predisposition to hallucinations, and was evident in patients with affective psychosis as well as schizophrenia. External misattribution of source may reflect an impairment in verbal self-monitoring and/or the appraisal of ambiguous sensory material. [ABSTRACT FROM AUTHOR]

BACKGROUND: The relationship between cognitive function and symptomatology in bipolar disorder is unclear. This study assessed executive function during the manic, depressed and remitted stages of bipolar I disorder. METHOD: Tasks assessing phonological and semantic verbal fluency, the Hayling Sentence Completion Test, the Stroop Neuropsychological Screening Test and the Cognitive Estimates Test were administered to manic (n = 15), depressed (n = 15), and remitted (n = 15) bipolar I patients, and to healthy controls (n = 30). Multiple regression analyses and analyses of covariance were used to identify potential determinants of executive dysfunction in the three bipolar groups. RESULTS: Executive function deficits were particularly associated with the manic state. In general, manic patients performed less accurately than the remitted and depressed groups, and their performance deficit was related to the severity of positive thought disorder. The depressed and remitted bipolar groups showed a less widespread pattern of impairment. Deficits in response initiation, strategic thinking and inhibitory control were evident in all the bipolar groups. CONCLUSIONS: Executive function deficits in bipolar I disorder are most evident during mania, and are particularly associated with formal thought disorder. However, deficits in response initiation, strategic thinking and inhibitory control may be more related to the underlying disorder than a particular symptom profile. [ABSTRACT FROM AUTHOR]

At what levels of brain organization might pathological change in schizophrenia be anatomically expressed: global, regional or supra-regional? We hypothesized that brain structure reflects a set of supra-regional anatomical systems with common developmental influences. We conducted an exploratory analysis to identify supra-regional brain systems and to investigate whether abnormal brain architecture in schizophrenia is manifested within one or more of these systems. Magnetic resonance (MR) images were acquired from 27 patients with schizophrenia and 37 control subjects. After segmentation and registration of each individual MRI dataset in the standard space of Talairach and Tournoux, grey matter and ventricular-cerebrospinal fluid (CSF) maps were automatically parcellated into 104 regions. We used principal components analysis of the multiple regional grey matter and ventricular-CSF measurements, on all 64 subjects, to extract the five main normative supra-regional systems. The first two of these components represented global variation in grey matter and ventricular-CSF regional measures. We interpreted the other three components as representing supra-regional systems comprising: a frontal-parietal system, a frontal-temporal system and a frontal-basal ganglia system. Schizophrenic group mean scores on the first component (global grey matter-ventricular contrast) and fourth component (frontal-temporal system) were significantly reduced compared to controls. These results suggest that pathological changes in schizophrenia may be expressed at two mutually independent levels of anatomical organization: global change in a grey matter/ventricular system and supra-regional change in a frontal-temporal system. [ABSTRACT FROM AUTHOR]