Differential hemodynamic brain activity in schizophrenia patients with blunted affect during quetiapine treatment.
ABSTRACT 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.
European Neuropsychopharmacology 10/2007; 17. DOI:10.1016/S0924-977X(07)70264-X · 5.40 Impact Factor
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ABSTRACT: The aim of this study was to determine brain activation during facial emotion discrimination in first-episode of psychosis. Eighteen patients underwent an fMRI while performing a facial emotion discrimination task during the acute episode, before starting antipsychotic drugs. A second fMRI and clinical evaluation were performed after evident clinical improvement. An equivalent control group underwent the same two fMRIs with a similar period of time between exams. The voxel-wise approach showed pre-treatment hypoactivation in ventro-limbic regions (cluster including right hippocampus and left amygdala; cluster size 528; p cluster <0.004) and facial perception involved in ventral-posterior regions (bilateral lingual gyrus, calcarine fissure and occipital superior gyrus, (k = 1,508, p < 0.001) and fronto-temporal regions. The region of interest approach also confirmed hypoactivation in right and left amygdala (cluster corrected p = 0.035 and 0.043, respectively). After treatment and clinical improvement, the voxel-wise approach showed a significant increase in activity in lingual gyrus and calcarine fissure in the group of patients. The regions of interest analysis showed an increase in amygdala activity during anger discrimination also in the group of patients. The results suggest a state-dependent model depicting a flattened and aberrant response of amygdala to emotion discrimination that could explain the seemingly contradictory previous findings of hypo- and hyper-amygdala activation.European Archives of Psychiatry and Clinical Neuroscience 11/2013; 264(4). DOI:10.1007/s00406-013-0465-5 · 3.36 Impact Factor
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ABSTRACT: Emotional deficits are among the core features of schizophrenia and both associative emotional learning and the related ability to verbalize emotions can be reduced. We investigated whether schizophrenia patients demonstrated impaired function of limbic and prefrontal areas during associative emotional learning. Patients and controls filled out an alexithymia questionnaire and performed an associative emotional learning task with positive, negative and neutral picture-word pairs during fMRI scanning. After scanning, they indicated for each pair whether they remembered it. We conducted standard GLM analysis and Independent Component Analysis (ICA). Both the GLM results and task-related ICA components were compared between groups. The alexithymia questionnaire indicated more cognitive-emotional processing difficulties in patients than controls, but equal experienced intensity of affective states. Patients remembered less picture-word pairs, irrespective of valence. GLM analysis showed significant visual, temporal, amygdalar/hippocampal, and prefrontal activation in all subjects. ICA identified a network of brain areas similar to GLM, mainly in response to negative stimuli. Neither analysis showed differences between patients and controls during learning. Although in previous studies schizophrenia patients showed abnormalities in both memory and emotion processing, neural circuits involved in cross-modal associative emotional learning may remain intact to a certain degree, which may have potential consequences for treatment.10/2013; 214(3). DOI:10.1016/j.pscychresns.2013.08.008