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S.22.03 Neural correlates of positive symptoms
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S.22 Neuroimaging of the course of psychotic disorders
S.22.02 Brain abnormalities after first psychosis W. Cahn ° , M. Rais, F.P. Stigter, N.E.M. van Haren, E. Caspers, H.E. Hulshoff Pol, Z. Xu, H.G. Schnack, R.S. Kahn. University Medical Centre Utrecht, Department of Psychiatry HP A00.241, Utrecht, The Netherlands Background: Brain volume changes in schizophrenia have been found to be progressive [1,2]. The cause of these progressive brain volume changes is not yet understood, but it is thought that psychosis could be neurotoxic [3]. This MRI study examined firstepisode patients with schizophrenia and related the total duration of psychosis to the progressive brain volume changes over five year period. Method: Patients with first-episode schizophrenia (n = 48) were included in this study. For all subjects magnetic resonance imaging scans were obtained at inclusion (T0) and after five years (T5). Total brain, gray and white matter, lateral ventricle and third ventricle volumes were measured. Percentage of brain volume change was calculated. Diagnosis was assessed at T0 and T5 with the Comprehensive Assessment of Symptoms and History. Duration of psychosis was estimated in months using data from IRAOS (T0 and T5) as well as the PANSS ratings acquired throughout the five year follow-up period and through close investigation of the medical records. The results were finally evaluated with the treating psychiatrist. Linear regression analyses were performed to examine the relation between duration of psychosis and progressive brain volume changes. Results: Duration of psychosis was significantly related to the progressive volume decreases in gray matter (b = −0.05, p = 0.03) and progressive volume increases in lateral (b = −0.38, p < 0.01) and third ventricles (b = −0.39 p = 0.01). Conclusion: These findings suggest that progressive brain volume changes in schizophrenia are related to the duration of psychosis and underpin the hypothesis that psychosis could be neurotoxic. References [1] Cahn W, Hulshoff Pol HE, Lems EBTE, van Haren NEM, Schnack HG, van der Linden JA, Schothorst PF, van Engeland H, Kahn RS, 2002, Brain volume changes in first-episode schizophrenia: a one-year followup study. Arch Gen Psychiatry 59, 1002–1010. [2] Van Haren NEM, Hulshoff Pol HE, Cahn W, Schnack HG, Mandl RC, Collins DL, Evans AC, Kahn RS, 2007 Feb 28, Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacology. [3] Liebermann JA, 1999, Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Biol Psychiatry 46, 729– 739.
S.22.03 Neural correlates of positive symptoms P. McGuire ° . Institute of Psychiatry, Box 67, London, United Kingdom Neuroimaging provides a way of investigating the mechanisms that underlie positive psychotic symptoms in vivo. Most imaging studies of psychotic phenomena have involved patients with schizophrenia, but there has also been work in patients with other disorders, people at high risk of psychosis and in non-clinical groups. Functional imaging studies can reveal the pattern of regional brain activity that is present when subjects are experiencing specific psychotic symptoms and the neural correlates of the cognitive processes that are putatively defective in patients prone
to these symptoms. The neuroanatomical correlates of psychotic symptoms have been investigated using volumetric imaging, while diffusion tensor imaging studies suggest that certain symptoms may be linked to changes in the integrity of cortico-cortical pathways. PET and SPET have been used to examine the relationship between dopamine function and positive symptoms. Among psychotic symptoms, although there has been work on the correlates of formal thought disorder and delusions, auditory verbal hallucinations have been studied in the most detail. These studies indicate that auditory hallucinations are associated with functional changes in the inferior frontal, anterior cingulate and temporal cortex and abnormalities in the functional and anatomical connectivity between these regions. These findings may underlie impairments in the monitoring and appraisal of inner speech. Understanding the pathophysiology of psychotic symptoms can inform the development of novel clinical treatments and may reveal mechanisms that are fundamental to psychosis more generally. References [1] McGuire P, Shah G, Murray R, 1993, Increased blood flow in Broca’s area during auditory hallucinations in schizophrenia. Lancet 342, 703−6. [2] Seal M, Aleman A, McGuire P, 2004, Compelling Imagery, unanticipated speech and deceptive memory: Neurocognitive models of auditory verbal hallucinations in schizophrenia. Cognitive Neuropsychiatry 9, 43−72.
S.22.04 Neural correlates of negative and affective symptoms E. Stip1 ° , C. Fahim1 , A. Mancini-Marie1 , L. Ait Bentaleb1 , B. Mensour2 . 1 Centre de Recherche Fernand Seguin, Psychiatry, Montreal, Canada; 2 University Hospital Centre of Montreal (CHUM), Radiology, Montreal, Canada Our studies investigated the neurobiologically based heterogeneity comparing schizophrenia patients with (BA+group, N = 14) to without (BA-group, N = 11) blunted affect and quetiapine as a treatment. Study I: Patients were scanned using functional magnetic resonance imaging (fMRI) while passively viewing film excerpts depicting sad and neutral social situations. BA-group showed activation in the caudate nucleus, ventrolateral prefrontal cortex (VLPFC), middle and medial prefrontal, and anterior cingulate cortex (ACC) while BA+group activated the hippocampus, cerebellum, anterior temporal pole (ATP), and midbrain. The temporal and midbrain activation seen in the BA+group may indicate that these brain regions were working harder to compensate for inactivation in other regions. The hypofrontality and distributed dysfunctional circuits observed in the BA+group may form the neural basis of abnormal processing of affective input and disturbed affective output, thereby leading to symptoms such as blunted affect. Study II: Cerebral activations during aversive and neutral stimuli were examined in 12 BA+ patients using fMRI following 5.5 months treatment with quetiapine. After treatment a significant clinical improvement in the 12 BA+ patients (PANSS flat affect score: Baseline: Mean = 5.50, SD=±0.76; Endpoint: Mean = 2.08, SD=±1.00 (t = 7.78, df = 11, p < 0.0001). Treatment response was associated with blood oxygenation level-dependent (BOLD) signal changes in: prefrontal-cortex, ACC, ATP and amygdala. Conversely, before quetiapine treatment, only subcortical structures: midbrain bilaterally and right pons were activated. Quetiapine seems to affect clinical recovery by modulating
S.22 Neuroimaging of the course of psychotic disorders
S.22.02 Brain abnormalities after first psychosis W. Cahn ° , M. Rais, F.P. Stigter, N.E.M. van Haren, E. Caspers, H.E. Hulshoff Pol, Z. Xu, H.G. Schnack, R.S. Kahn. University Medical Centre Utrecht, Department of Psychiatry HP A00.241, Utrecht, The Netherlands Background: Brain volume changes in schizophrenia have been found to be progressive [1,2]. The cause of these progressive brain volume changes is not yet understood, but it is thought that psychosis could be neurotoxic [3]. This MRI study examined firstepisode patients with schizophrenia and related the total duration of psychosis to the progressive brain volume changes over five year period. Method: Patients with first-episode schizophrenia (n = 48) were included in this study. For all subjects magnetic resonance imaging scans were obtained at inclusion (T0) and after five years (T5). Total brain, gray and white matter, lateral ventricle and third ventricle volumes were measured. Percentage of brain volume change was calculated. Diagnosis was assessed at T0 and T5 with the Comprehensive Assessment of Symptoms and History. Duration of psychosis was estimated in months using data from IRAOS (T0 and T5) as well as the PANSS ratings acquired throughout the five year follow-up period and through close investigation of the medical records. The results were finally evaluated with the treating psychiatrist. Linear regression analyses were performed to examine the relation between duration of psychosis and progressive brain volume changes. Results: Duration of psychosis was significantly related to the progressive volume decreases in gray matter (b = −0.05, p = 0.03) and progressive volume increases in lateral (b = −0.38, p < 0.01) and third ventricles (b = −0.39 p = 0.01). Conclusion: These findings suggest that progressive brain volume changes in schizophrenia are related to the duration of psychosis and underpin the hypothesis that psychosis could be neurotoxic. References [1] Cahn W, Hulshoff Pol HE, Lems EBTE, van Haren NEM, Schnack HG, van der Linden JA, Schothorst PF, van Engeland H, Kahn RS, 2002, Brain volume changes in first-episode schizophrenia: a one-year followup study. Arch Gen Psychiatry 59, 1002–1010. [2] Van Haren NEM, Hulshoff Pol HE, Cahn W, Schnack HG, Mandl RC, Collins DL, Evans AC, Kahn RS, 2007 Feb 28, Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacology. [3] Liebermann JA, 1999, Is schizophrenia a neurodegenerative disorder? A clinical and neurobiological perspective. Biol Psychiatry 46, 729– 739.
S.22.03 Neural correlates of positive symptoms P. McGuire ° . Institute of Psychiatry, Box 67, London, United Kingdom Neuroimaging provides a way of investigating the mechanisms that underlie positive psychotic symptoms in vivo. Most imaging studies of psychotic phenomena have involved patients with schizophrenia, but there has also been work in patients with other disorders, people at high risk of psychosis and in non-clinical groups. Functional imaging studies can reveal the pattern of regional brain activity that is present when subjects are experiencing specific psychotic symptoms and the neural correlates of the cognitive processes that are putatively defective in patients prone
to these symptoms. The neuroanatomical correlates of psychotic symptoms have been investigated using volumetric imaging, while diffusion tensor imaging studies suggest that certain symptoms may be linked to changes in the integrity of cortico-cortical pathways. PET and SPET have been used to examine the relationship between dopamine function and positive symptoms. Among psychotic symptoms, although there has been work on the correlates of formal thought disorder and delusions, auditory verbal hallucinations have been studied in the most detail. These studies indicate that auditory hallucinations are associated with functional changes in the inferior frontal, anterior cingulate and temporal cortex and abnormalities in the functional and anatomical connectivity between these regions. These findings may underlie impairments in the monitoring and appraisal of inner speech. Understanding the pathophysiology of psychotic symptoms can inform the development of novel clinical treatments and may reveal mechanisms that are fundamental to psychosis more generally. References [1] McGuire P, Shah G, Murray R, 1993, Increased blood flow in Broca’s area during auditory hallucinations in schizophrenia. Lancet 342, 703−6. [2] Seal M, Aleman A, McGuire P, 2004, Compelling Imagery, unanticipated speech and deceptive memory: Neurocognitive models of auditory verbal hallucinations in schizophrenia. Cognitive Neuropsychiatry 9, 43−72.
S.22.04 Neural correlates of negative and affective symptoms E. Stip1 ° , C. Fahim1 , A. Mancini-Marie1 , L. Ait Bentaleb1 , B. Mensour2 . 1 Centre de Recherche Fernand Seguin, Psychiatry, Montreal, Canada; 2 University Hospital Centre of Montreal (CHUM), Radiology, Montreal, Canada Our studies investigated the neurobiologically based heterogeneity comparing schizophrenia patients with (BA+group, N = 14) to without (BA-group, N = 11) blunted affect and quetiapine as a treatment. Study I: Patients were scanned using functional magnetic resonance imaging (fMRI) while passively viewing film excerpts depicting sad and neutral social situations. BA-group showed activation in the caudate nucleus, ventrolateral prefrontal cortex (VLPFC), middle and medial prefrontal, and anterior cingulate cortex (ACC) while BA+group activated the hippocampus, cerebellum, anterior temporal pole (ATP), and midbrain. The temporal and midbrain activation seen in the BA+group may indicate that these brain regions were working harder to compensate for inactivation in other regions. The hypofrontality and distributed dysfunctional circuits observed in the BA+group may form the neural basis of abnormal processing of affective input and disturbed affective output, thereby leading to symptoms such as blunted affect. Study II: Cerebral activations during aversive and neutral stimuli were examined in 12 BA+ patients using fMRI following 5.5 months treatment with quetiapine. After treatment a significant clinical improvement in the 12 BA+ patients (PANSS flat affect score: Baseline: Mean = 5.50, SD=±0.76; Endpoint: Mean = 2.08, SD=±1.00 (t = 7.78, df = 11, p < 0.0001). Treatment response was associated with blood oxygenation level-dependent (BOLD) signal changes in: prefrontal-cortex, ACC, ATP and amygdala. Conversely, before quetiapine treatment, only subcortical structures: midbrain bilaterally and right pons were activated. Quetiapine seems to affect clinical recovery by modulating