Differential Hemodynamic Brain Activity in Schizophrenia Patients With Blunted Affect During Quetiapine Treatment

Department of Neurological Sciences, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 09/2005; 25(4):367-71. DOI: 10.1097/
Source: PubMed


Blood-oxygenation-level-dependent (BOLD) brain changes underlying response to quetiapine were examined using passive viewing of emotionally negative stimuli. Twelve DSM-IV schizophrenia patients with blunted affect (BA+) were scanned before and after 22 weeks of quetiapine treatment. Whole-brain, voxel-based methods were used to assess the differential hemodynamic response to quetiapine. In addition, a post hoc comparison to an independent group of 11 schizophrenia patients without blunted affect (BA-) was performed to compare them with BA+ (postquetiapine) in response to emotion processing. A 22-week treatment with quetiapine resulted in significant clinical improvement in the 12 study completers (mean +/- SD posttreatment PANSS blunted affect score of 5.50 +/- 0.76 at baseline to 2.08 +/- 1.00 at end point; t = 7.78, df = 11, P < 0.0001). Treatment response was associated with significant BOLD changes: increases in prefrontal cortex activation particularly in the right dorsolateral prefrontal cortex (DLPFC, BA 46) and the right anterior cingulate cortex (ACC, BA 32); and in the left putamen, right anterior temporal pole (ATP), and right amygdala. Conversely, before treatment with quetiapine, the same subjects activated the midbrain bilaterally and the right pons. The post hoc conjunctional analyses demonstrated that BA- subjects activated the left ACC, left insula, left ATP (BA 21), left ATP (BA 38), left amygdala, and right medial prefrontal cortex. Quetiapine seems to affect clinical recovery by modulating the functioning of specific brain regions. Unique BOLD changes in the putamen and DLPFC with quetiapine, in the BA+ postquetiapine, may reflect modality-specific effects. Controlled studies are needed to further assess these preliminary findings.

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    • "On the other hand, only two studies in patients with schizophrenia with blunted affect (Fahim et al., 2005; Stip et al., 2005) have assessed the effect of longitudinal treatment with quetiapine on brain activity during emotion processing. These studies, which did not include a control group and did not control for potential repetition effects, reported that longitudinal treatment with quetiapine increases activity in prefrontal cortex during passive viewing of sad films (Stip et al., 2005) and in amygdala during passive viewing of pictures with negative affective valence (Fahim et al., 2005). Inconsistencies between our data and these earlier studies may arise from different factors. "
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    ABSTRACT: Earlier imaging studies in schizophrenia have reported abnormal amygdala and prefrontal cortex activity during emotion processing. We investigated with functional magnetic resonance imaging (fMRI) during emotion processing changes in activity of the amygdala and of prefrontal cortex in patients with schizophrenia during 8 weeks of olanzapine treatment. Twelve previously drug-free/naive patients with schizophrenia were treated with olanzapine for 8 weeks and underwent two fMRI scans after 4 and 8 weeks of treatment during implicit and explicit emotional processing. Twelve healthy subjects were also scanned twice to control for potential repetition effects. Results showed a diagnosis by time interaction in left amygdala and a diagnosis by time by task interaction in right ventrolateral prefrontal cortex. In particular, activity in left amygdala was greater in patients than in controls at the first scan during both explicit and implicit processing, while it was lower in patients at the second relative to the first scan. Furthermore, during implicit processing, right ventrolateral prefrontal cortex activity was lower in patients than controls at the first scan, while it was greater in patients at the second relative to the first scan. These results suggest that longitudinal treatment with olanzapine may be associated with specific changes in activity of the amygdala and prefrontal cortex during emotional processing in schizophrenia.
    Full-text · Article · Jun 2009 · Psychiatry Research
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    • "Medication related enhancements of frontal activation were e.g. described by Fahim et al. (2005) and Stip et al. (2005). Following cognitive or motor trainings, patients showed an increased cerebral activation in task-related brain areas, while healthy subjects were characterized by diminished activations (Wexler et al., 2000; Wykes et al., 2002; Kodama et al., 2001). "
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    ABSTRACT: Aberrant brain activation during facial emotion discrimination has been described in chronic schizophrenia, while little is known about early stages of the illness. The aim of the current study was to investigate valence-specific brain activation of emotion discrimination in first-episode schizophrenia. These patients provide the advantage of lacking the effects of long-term medication and chronic illness course and can hence further enhance the understanding of underlying psychopathological mechanisms. Using event-related fMRI, we investigated 18 first-episode schizophrenia patients and 18 matched healthy subjects during an explicit emotion discrimination task presenting happy, sad and neutral monochromatic facial expressions. A repeated measure analysis of variance (ANOVA) with the factors Group (patients, healthy subjects), Gender and Emotion (happy, sad, neutral) was performed on behavioural and functional data. Behavioural performance did not differ between groups. Valence-independent hypoactivations in patients were observed for the anterior cingulate and orbitofrontal cortex while hyperactivations emerged in the posterior cingulate and the precuneus. Emotion-specific group differences were revealed in inferior parietal and orbitofrontal brain areas and the hippocampus. First-episode schizophrenia already affects areas involved in processing of both, emotions and primary facial information. Our study underlines the role of dysfunctional neural networks as the basis of disturbed social interactions in early schizophrenia.
    Full-text · Article · Mar 2009 · Journal of Psychiatric Research
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    • "It is important to note that the proposed IVA method may be effective in analyses of fMRI data that are susceptible to atypical BOLD signals among the subjects and brain areas (in terms of magnitude, duration, and timing of onsets). This applies to the analysis of, for example, data obtained from individuals with neuroleptic medications (Eyler et al., 2004; Fahim et al., 2005; Ford et al., 2005) or substance abuse (Gollub et al., 1998; Lee et al., 2003; Chang et al., 2006; Van Horn et al., 2006). "
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    ABSTRACT: During functional MRI (fMRI) studies, blood oxygenation-level dependent (BOLD) signal associated with neuronal activity acquired from multiple individuals are subject to the derivation of group-averaged brain activation patterns. Unlike other cortical areas, subcortical areas such as the thalamus and basal ganglia often manifest smaller, biphasic BOLD signal that are aberrant from signals originating from cortices. Independent component analysis (ICA) can offer session/individual specific brain activation maps without a priori assumptions regarding the timing or pattern of the signal responses. The small activation loci within the subcortical areas are sparsely distributed among the subjects, and a conventional group processing method based on the general linear model (GLM) or ICA may fail to characterize the activation loci. In this paper, we present an independent vector analysis (IVA) to overcome these limitations by offering an analysis of additional dependent components (compared to the ICA-based method) that are assigned for use in the automated grouping of dependent (i.e. similar) activation patterns across subjects. The proposed IVA algorithm was applied to simulated data, and its utility was confirmed from real fMRI data employing a trial-based hand motor task. A GLM and the group ICA of the fMRI toolbox (GIFT) were also applied for comparison. From the analysis of activation patterns within subcortical areas, in which the hemodynamic responses (HRs) often deviate from a canonical, model-driven HR, IVA detected task-related activation loci that were not detected through GLM and GIFT. IVA may offer a unique advantage for inferring group activation originating from subcortical areas.
    Full-text · Article · Jan 2008 · International Journal of Imaging Systems and Technology
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