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PREVALENCE OF DEPRESSIVE SYMPTOMS AND THE EFFECTIVENESS OF ANTIDEPRESSANTS IN ROUTINE CLINICAL PRACTICE OF SCHIZOPHRENIA
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Abstracts
and thickness change was calculated using regression analyses covarying for age and sex. The statistics were corrected for multiple comparisons (alpha=0.05; false discovery rate control). Regression analyses using a locally-weighted running-line smoother with different degrees of freedom were performed to obtain the best descriptions of the age-dependency of the brain measures. Results: Excessive decreases in gray matter volume in patients relative to controls were found. Excessive decreases in gray matter density and cortical thickness in patients relative to controls were found predominantly in the frontal and temporal cortices. Parietal and occipital lobes were relatively spared. Excessive density decreases and cortical thinning seemed more pronounced in the left hemisphere, particularly in the left frontal cortical areas. Moreover, patients show different trajectories of age-related brain volume and cortical thickness change. Discussion: The findings are in line with earlier longitudinal volumetric and voxel-based morphometry studies suggesting progressive changes in schizophrenia patients in particularly frontal and temporal areas in the brain. We found differences in age-related gray and white matter volume and cortical thickness change between patients with schizophrenia and comparison subjects which would be suggestive for abnormal maturation of the brain in adult schizophrenia. References [1] Schnack, 2001. Neuroimage 13, 230–237. [2] Collins, et al., 1995. Hum Brain Mapp 3, 190–208. [3] Kim, et al., 2005. Neuroimage 27, 210–221.
doi:10.1016/j.schres.2010.02.1049
Poster 271 EVIDENCE FOR ALTERED ASYMMETRY OF FRONTAL CORTEX T2 RELAXATION TIME IN PATIENTS AT CLINICAL HIGH-RISK FOR PSYCHOSIS Stephen J. Wood1, Alex Kline1, Alison R. Yung2, Dennis Velakoulis1, Barnaby Nelson2, Patrick D. McGorry2, Christos Pantelis1 1 Melbourne Neuropsychiatry Centre, University of Melbourne Parkville, Victoria, Australia; 2Orygen Youth Health Research Centre, University of Melbourne Parkville, Victoria, Australia Background: There are a number of studies which have identified baseline differences in the volume of various grey matter regions of the frontal lobe between ultra-high risk (UHR) individuals who go on to develop full threshold psychosis and those who do not. However, the exact nature of these differences is unclear, since normal size does not guarantee functionality, nor does absence necessarily indicate dysfunction. T2 relaxometry is a technique that may provide a more sensitive, though non-specific, measure of the neuropathological processes involved in psychosis. Methods: We recruited 66 UHR participants and 29 controls, and scanned them using T2 relaxometry. T2 relaxation times were obtained from grey matter in the right and left anterior cingulate cortex, middle frontal gyrus and inferior frontal gyrus using a region of interest (ROI) approach. T2 relaxation data were compared using repeated-measures analyses-of-variance. Results: No significant differences were found for the anterior cingulate or inferior frontal ROIs (p > 0.5). However, there was a significant group x hemisphere interaction (p = 0.05) for the middle frontal ROI. Post-hoc comparisons revealed this to be due to a reversal of the normal right > left asymmetry in the UHR group (p = 0.01). Sub-analysis by outcome (transition to psychosis) showed that this effect was roughly twice as great in the later psychotic group than the non-transitioned group.
Discussion: Although we did not find an overall increase in T2 in the UHR group, we did show altered asymmetry in the middle frontal gyrus, largely driven by increased T2 in the left hemisphere. This was more pronounced in those who later developed psychosis, and may indicate a neuropathological process involving increased edema, or a reversal of the normal pattern of naturally occurring cell apoptosis. doi:10.1016/j.schres.2010.02.1050
Poster 272 CAN LOW-FREQUENCY RTMS REALLY RELIEVE MEDICATION-RESISTANT AUDITORY VERBAL HALLUCINATIONS? NEGATIVE RESULTS FROM A LARGE RCT Christina W Slotema1, Jan Dirk Blom1, Hans W Hoek1, René S. Kahn2, Iris E Sommer2 1 Parnassia Bavo Psychiatric Institute The Hague Netherlands; 2University Medical Centre Utrecht Utrecht Netherlands Background: Auditory Verbal Hallucinations (AVH) are resistant to antipsychotic medication in 25% of patients with schizophrenia. Several studies have applied low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) directed at the left temporo-parietal area (TP) for the treatment of AVH, but findings on efficacy are inconsistent. Furthermore, a large recent fMRI study indicated that the left TP is not a general focus of activation during the experience of AVH. The aims of this study were twofold: to investigate the effect of rTMS on AVH in a relatively large, double blind, randomized controlled sample, and to investigate if the efficacy of rTMS could be improved with fMRI-guided rTMS. Methods: Sixty-two patients with medication-resistant AVH were randomized over 3 conditions: rTMS targeted at the area of maximal halucinatory activity as demonstrated with individual fMRI scans, rTMS directed at the left TP and sham treatment. Repetitive TMS was applied during 15 sessions of 20 minutes each, at 1 Hertz and 90% of the individual motor threshold. The severity of AVH and other psychotic symptoms were monitored during treatment and 3 months follow-up, using the Auditory Hallucination Rating Scale (AHRS) and the positive items of the Positive and Negative Syndrome Scale (PANSS). Results: Mean decrease in AVH severity was not significantly different between the groups (F = 0.619, p = 0.54), neither was decrease in severity of psychosis (F = 1.640, p = 0.21). Even when guided and non-guided rTMS were combined and compared to sham treatment, no significant differences in efficacy were observed (sum of the AHRS, F = 1.172, p = 0.29). Discussion: Low-frequency rTMS directed at the area of maximal hallucinatory activity and rTMS directed at the left TP are no more effective in the treatment of medication-resistant AVH than sham treatment. It may be time for a change of paradigm, and for a search for other treatment regimens, such as high-frequency rTMS, to expand the psychiatric toolbox of treatment options for medicationresistant AVH. doi:10.1016/j.schres.2010.02.1051
Poster 273 PREVALENCE OF DEPRESSIVE SYMPTOMS AND THE EFFECTIVENESS OF ANTIDEPRESSANTS IN ROUTINE CLINICAL PRACTICE OF SCHIZOPHRENIA Irene Lako1,2, Katja Taxis2, Richard Bruggeman1, Rikus Knegtering1, Durk Wiersma1, Cees Slooff3
Abstracts 1 University Medical Center Groningen, Department of Psychiatry Groningen, Groningen, Netherlands; 2University of Groningen, Division of Pharmacotherapy and Pharmaceutical Care Groningen, Groningen, Netherlands; 3Mental Healt Organization Drenthe, Department of Psychotic Disorders Assen, Drenthe, Netherlands
Background: The prevalence of clinical depression in patients with schizophrenia and related psychotic disorders is about 25%, while that of sub-syndromal depressive symptoms is even higher. Depressive symptoms in schizophrenia are associated with a higher risk for relapse and suicide. About one third of patients with psychotic disorders uses antidepressants, but little is known about the prescribing of antidepressants and course of depressive symptoms in routine clinical practice. The aim of the current study is to determine the prevalence of depressive symptoms in schizophrenia, to compare the characteristics of patients with and without depressive symptoms and to explore the effectiveness of antidepressant therapy in one year follow-up. Methods: The study concerned patients with schizophrenia or related psychotic disorders in a circumscribed area in the Netherlands between January 2003 and April 2007. As part of routine clinical practice patients had yearly assessments of their physical and mental health, including a clinician-rated screening for depressive symptoms. Patients were included if they had a first (T0) and second assessment (T1) within an interval of about 12 months (±3 months). Results: 230 patients were included, with a mean age of 38.3 years (SD 1.7) and a mean duration of illness of 11.7 years (SD 9.4); 132 (57%) were male and 175 (76%) suffered from schizophrenia. At T0 depressive symptoms were prevalent among 44% (n = 102) of the patients. Patients with depressive symptoms had significantly more positive (p < 0.01) and negative (p < 0.05) symptoms than patients without depressive symptoms, but there was no difference in cognitive symptoms or extrapyramidal symptoms as well as in
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somatic health (e.g. BMI and blood pressure). Patients with depressive symptoms scored on average 10% lower on the Global Assessment of Functioning scale (p < 0.001) than patients without depressive symptoms, reported a 12% lower quality of life (p < 0.001) and had fewer daytime activities (p < 0.001), without a significant difference in the frequency of contacts with family or friends. Furthermore, they were prescribed more medications (3.2 compared to 2.4 medicines) than patients without depressive symptoms (p < 0.05). In total 40% (n = 92) used antidepressants (60% selective serotonin reuptake inhibitors, 24% tricyclic antidepressants and the remaining used other classes of antidepressants) while about half of them had depressive symptoms. Of the patients using antidepressants and having depressive symptoms at T0, 68% (32/47) had persistent symptoms, the remaining patients had no symptoms at T1. Of the 45 patients using antidepressants without having depressive symptoms at T0, 22% (10/45) got depressive symptoms at T1. Discussion: In routine clinical practice the prevalence of depressive symptoms was high among patients with psychotic disorders. Patients with depressive symptoms suffered more frequently from positive and negative symptoms and had a lower quality of life. Antidepressants were frequently prescribed, but analysis of the course of depressive symptoms raised doubts about the effectiveness of the antidepressants as depressive symptoms often persisted and reoccurred. The monitoring and treatment of depressive symptoms in psychotic disorders require more attention in clinical practice. doi:10.1016/j.schres.2010.02.1052
Abstracts
and thickness change was calculated using regression analyses covarying for age and sex. The statistics were corrected for multiple comparisons (alpha=0.05; false discovery rate control). Regression analyses using a locally-weighted running-line smoother with different degrees of freedom were performed to obtain the best descriptions of the age-dependency of the brain measures. Results: Excessive decreases in gray matter volume in patients relative to controls were found. Excessive decreases in gray matter density and cortical thickness in patients relative to controls were found predominantly in the frontal and temporal cortices. Parietal and occipital lobes were relatively spared. Excessive density decreases and cortical thinning seemed more pronounced in the left hemisphere, particularly in the left frontal cortical areas. Moreover, patients show different trajectories of age-related brain volume and cortical thickness change. Discussion: The findings are in line with earlier longitudinal volumetric and voxel-based morphometry studies suggesting progressive changes in schizophrenia patients in particularly frontal and temporal areas in the brain. We found differences in age-related gray and white matter volume and cortical thickness change between patients with schizophrenia and comparison subjects which would be suggestive for abnormal maturation of the brain in adult schizophrenia. References [1] Schnack, 2001. Neuroimage 13, 230–237. [2] Collins, et al., 1995. Hum Brain Mapp 3, 190–208. [3] Kim, et al., 2005. Neuroimage 27, 210–221.
doi:10.1016/j.schres.2010.02.1049
Poster 271 EVIDENCE FOR ALTERED ASYMMETRY OF FRONTAL CORTEX T2 RELAXATION TIME IN PATIENTS AT CLINICAL HIGH-RISK FOR PSYCHOSIS Stephen J. Wood1, Alex Kline1, Alison R. Yung2, Dennis Velakoulis1, Barnaby Nelson2, Patrick D. McGorry2, Christos Pantelis1 1 Melbourne Neuropsychiatry Centre, University of Melbourne Parkville, Victoria, Australia; 2Orygen Youth Health Research Centre, University of Melbourne Parkville, Victoria, Australia Background: There are a number of studies which have identified baseline differences in the volume of various grey matter regions of the frontal lobe between ultra-high risk (UHR) individuals who go on to develop full threshold psychosis and those who do not. However, the exact nature of these differences is unclear, since normal size does not guarantee functionality, nor does absence necessarily indicate dysfunction. T2 relaxometry is a technique that may provide a more sensitive, though non-specific, measure of the neuropathological processes involved in psychosis. Methods: We recruited 66 UHR participants and 29 controls, and scanned them using T2 relaxometry. T2 relaxation times were obtained from grey matter in the right and left anterior cingulate cortex, middle frontal gyrus and inferior frontal gyrus using a region of interest (ROI) approach. T2 relaxation data were compared using repeated-measures analyses-of-variance. Results: No significant differences were found for the anterior cingulate or inferior frontal ROIs (p > 0.5). However, there was a significant group x hemisphere interaction (p = 0.05) for the middle frontal ROI. Post-hoc comparisons revealed this to be due to a reversal of the normal right > left asymmetry in the UHR group (p = 0.01). Sub-analysis by outcome (transition to psychosis) showed that this effect was roughly twice as great in the later psychotic group than the non-transitioned group.
Discussion: Although we did not find an overall increase in T2 in the UHR group, we did show altered asymmetry in the middle frontal gyrus, largely driven by increased T2 in the left hemisphere. This was more pronounced in those who later developed psychosis, and may indicate a neuropathological process involving increased edema, or a reversal of the normal pattern of naturally occurring cell apoptosis. doi:10.1016/j.schres.2010.02.1050
Poster 272 CAN LOW-FREQUENCY RTMS REALLY RELIEVE MEDICATION-RESISTANT AUDITORY VERBAL HALLUCINATIONS? NEGATIVE RESULTS FROM A LARGE RCT Christina W Slotema1, Jan Dirk Blom1, Hans W Hoek1, René S. Kahn2, Iris E Sommer2 1 Parnassia Bavo Psychiatric Institute The Hague Netherlands; 2University Medical Centre Utrecht Utrecht Netherlands Background: Auditory Verbal Hallucinations (AVH) are resistant to antipsychotic medication in 25% of patients with schizophrenia. Several studies have applied low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) directed at the left temporo-parietal area (TP) for the treatment of AVH, but findings on efficacy are inconsistent. Furthermore, a large recent fMRI study indicated that the left TP is not a general focus of activation during the experience of AVH. The aims of this study were twofold: to investigate the effect of rTMS on AVH in a relatively large, double blind, randomized controlled sample, and to investigate if the efficacy of rTMS could be improved with fMRI-guided rTMS. Methods: Sixty-two patients with medication-resistant AVH were randomized over 3 conditions: rTMS targeted at the area of maximal halucinatory activity as demonstrated with individual fMRI scans, rTMS directed at the left TP and sham treatment. Repetitive TMS was applied during 15 sessions of 20 minutes each, at 1 Hertz and 90% of the individual motor threshold. The severity of AVH and other psychotic symptoms were monitored during treatment and 3 months follow-up, using the Auditory Hallucination Rating Scale (AHRS) and the positive items of the Positive and Negative Syndrome Scale (PANSS). Results: Mean decrease in AVH severity was not significantly different between the groups (F = 0.619, p = 0.54), neither was decrease in severity of psychosis (F = 1.640, p = 0.21). Even when guided and non-guided rTMS were combined and compared to sham treatment, no significant differences in efficacy were observed (sum of the AHRS, F = 1.172, p = 0.29). Discussion: Low-frequency rTMS directed at the area of maximal hallucinatory activity and rTMS directed at the left TP are no more effective in the treatment of medication-resistant AVH than sham treatment. It may be time for a change of paradigm, and for a search for other treatment regimens, such as high-frequency rTMS, to expand the psychiatric toolbox of treatment options for medicationresistant AVH. doi:10.1016/j.schres.2010.02.1051
Poster 273 PREVALENCE OF DEPRESSIVE SYMPTOMS AND THE EFFECTIVENESS OF ANTIDEPRESSANTS IN ROUTINE CLINICAL PRACTICE OF SCHIZOPHRENIA Irene Lako1,2, Katja Taxis2, Richard Bruggeman1, Rikus Knegtering1, Durk Wiersma1, Cees Slooff3
Abstracts 1 University Medical Center Groningen, Department of Psychiatry Groningen, Groningen, Netherlands; 2University of Groningen, Division of Pharmacotherapy and Pharmaceutical Care Groningen, Groningen, Netherlands; 3Mental Healt Organization Drenthe, Department of Psychotic Disorders Assen, Drenthe, Netherlands
Background: The prevalence of clinical depression in patients with schizophrenia and related psychotic disorders is about 25%, while that of sub-syndromal depressive symptoms is even higher. Depressive symptoms in schizophrenia are associated with a higher risk for relapse and suicide. About one third of patients with psychotic disorders uses antidepressants, but little is known about the prescribing of antidepressants and course of depressive symptoms in routine clinical practice. The aim of the current study is to determine the prevalence of depressive symptoms in schizophrenia, to compare the characteristics of patients with and without depressive symptoms and to explore the effectiveness of antidepressant therapy in one year follow-up. Methods: The study concerned patients with schizophrenia or related psychotic disorders in a circumscribed area in the Netherlands between January 2003 and April 2007. As part of routine clinical practice patients had yearly assessments of their physical and mental health, including a clinician-rated screening for depressive symptoms. Patients were included if they had a first (T0) and second assessment (T1) within an interval of about 12 months (±3 months). Results: 230 patients were included, with a mean age of 38.3 years (SD 1.7) and a mean duration of illness of 11.7 years (SD 9.4); 132 (57%) were male and 175 (76%) suffered from schizophrenia. At T0 depressive symptoms were prevalent among 44% (n = 102) of the patients. Patients with depressive symptoms had significantly more positive (p < 0.01) and negative (p < 0.05) symptoms than patients without depressive symptoms, but there was no difference in cognitive symptoms or extrapyramidal symptoms as well as in
535
somatic health (e.g. BMI and blood pressure). Patients with depressive symptoms scored on average 10% lower on the Global Assessment of Functioning scale (p < 0.001) than patients without depressive symptoms, reported a 12% lower quality of life (p < 0.001) and had fewer daytime activities (p < 0.001), without a significant difference in the frequency of contacts with family or friends. Furthermore, they were prescribed more medications (3.2 compared to 2.4 medicines) than patients without depressive symptoms (p < 0.05). In total 40% (n = 92) used antidepressants (60% selective serotonin reuptake inhibitors, 24% tricyclic antidepressants and the remaining used other classes of antidepressants) while about half of them had depressive symptoms. Of the patients using antidepressants and having depressive symptoms at T0, 68% (32/47) had persistent symptoms, the remaining patients had no symptoms at T1. Of the 45 patients using antidepressants without having depressive symptoms at T0, 22% (10/45) got depressive symptoms at T1. Discussion: In routine clinical practice the prevalence of depressive symptoms was high among patients with psychotic disorders. Patients with depressive symptoms suffered more frequently from positive and negative symptoms and had a lower quality of life. Antidepressants were frequently prescribed, but analysis of the course of depressive symptoms raised doubts about the effectiveness of the antidepressants as depressive symptoms often persisted and reoccurred. The monitoring and treatment of depressive symptoms in psychotic disorders require more attention in clinical practice. doi:10.1016/j.schres.2010.02.1052