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Poster #T267 PREFRONTAL CORTEX THICKNESS IN PTSD AND SCHIZOPHRENIA AND THE ROLE OF CHILDHOOD TRAUMA
S384
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384
Canada; 6 Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Background: The objective of this study was to evaluate the relationship between antipsychotic-induced tardive dyskinesia (TD) and estimated dopamine D2 receptor occupancy levels in patients with schizophrenia, using the dataset from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE). Methods: The dataset from 235 subjects (risperidone, N=88; olanzapine, N=106; ziprasidone, N=41) who presented with a score of zero on the Abnormal Involuntary Movement Scale (AIMS) at baseline in Phase 1 of the CATIE study, and remained for ≥6 months, was used. Peak and trough dopamine D2 receptor occupancy levels on the day of the AIMS assessment at the endpoint were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our D2 prediction model. The estimated dopamine D2 receptor occupancy levels were compared between patients who presented an AIMS score of ≥1 at endpoint and those who did not, using the independent t-test. Results: Estimated dopamine D2 receptor occupancy levels at trough were significantly higher in subjects who developed involuntary movements (N=40) than those who did not (N=195) (71.5±12.4% vs. 64.3±19.3%, p<0.05) while no significant difference was found in the estimated peak D2 receptor occupancy between them (75.1±8.0% vs. 72.1±9.9%, p=0.07). When the analyses were separately conducted for the three drugs, there were no significant differences in estimated peak or trough D2 occupancy although the values were consistently numerically higher among those developing involuntary movements. Discussion: Greater dopamine D2 receptor blockade with antipsychotics at trough may increase the risk of tardive involuntary movements.
Poster #T267 PREFRONTAL CORTEX THICKNESS IN PTSD AND SCHIZOPHRENIA AND THE ROLE OF CHILDHOOD TRAUMA Andre Zugman 1,2 , Elson Asevedo 3 , Rodrigo Mansur 3 , Graccielle Asevedo 3 , Ary Araripe 3 , Lara Faria 3 , Vitor Tardelli 3 , Rodrigo Bressan 3 , Andrea Jackowski 3 , Elisa Brietzke 3 1 Universidade Federal de São Paulo; 2 Laboratório Interdisciplinar de Neurociências Clínicas; 3 UNIFESP Background: Psychosis develops as a result of numerous interacting factors (van Os and McGuffin, 2003). However a number of features link traumatic
events to psychosis. A history of trauma is more common in subjects with psychotic disorders (Bebbington et al., 2004). Traumatic experience during childhood increases the risk of psychosis with cumulative effect (Shevlin et al., 2008) and a history of trauma is associated with psychotic symptoms in the general population (Freeman and Fowler, 2009). Additionally, psychotic symptoms appear to be related to a worse prognosis in post-traumatic stress disorder (PTSD) patients and PTSD co-morbidity is related to a worse prognosis in first episode psychosis (Mueser et al., 2010). Although it has been hypothesized that both PTSD and psychosis are related to a pathological response to traumatic experience (Morrison et al., 2003) there are few studies comparing biological features of both disorders. Methods: 24 subjects with schizophrenia (SCZ) and 29 PTSD subjects were recruited from psychiatric outpatients clinics. Clinical interviews were carried out by trained psychiatrists and diagnoses were confirmed using the Structured Clinical Interview for DSM-IV (SCID-IV). Early Trauma was assessed using the Childhood Trauma Questionnaire (CTQ) (Bernstein, 2003). The CTQ contains five subscales, three assessing abuse (physical, emotional and sexual) and two assessing neglect (physical and emotional). All subjects were receiving treatment as usual at the time of scan. Brain MR images were acquired on a 1.5T Siemens Sonata scanner (TE= 3.4; TR= 2000 ms; FoV= 256; Flip Angle: 15; Slice Thickness 1mm). Images were processed and analysed using freesurfer (http://surfer.nmr.mgh.harvard.edu/). Between group whole cortex vertex-wise thickness analysis was carried out with a threshold of p=0.05 corrected for multiple comparison using a Monte-Carlo simulation. Correlation between early trauma scores and cortical thickness in SCZ and PTSD group was also investigated. Results: SCZ group had a mean age of 35.3 (SD: 10.1 y/o) and mean CTQ score of 42.9 (SD: 13.9). PTSD group had a mean age of 45.7 (SD: 8.6 y/o) and mean CTQ of 50.4 (SD: 21.9). The total CTQ score was not significantly different between both groups (t: 1.4; p: 0.15). A significant thinning of the left anterior cingulate and orbitofrontal cortices were observed in PTSD group when compared to SCZ subjects. The total CTQ score and thickness correlation did not remain significant after correction for multiple comparisons in both groups. There was a significant association between CTQ emotional neglect subscale and the left prefrontal cortex thickness in SCZ group. No other correlation was found between CTQ subscales scores and cortical thickness. Discussion: The prefrontal cortex is a region thought to be involved in reward guided learning and decision making (Rushworth et al., 2011). This region has been previously linked to anhedonia (Frewen et al., 2012) which is a characteristic of both disorders. Our findings may indicate that this region response to trauma in different stage during life may lead to different psychopathology.
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384
Canada; 6 Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Background: The objective of this study was to evaluate the relationship between antipsychotic-induced tardive dyskinesia (TD) and estimated dopamine D2 receptor occupancy levels in patients with schizophrenia, using the dataset from the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE). Methods: The dataset from 235 subjects (risperidone, N=88; olanzapine, N=106; ziprasidone, N=41) who presented with a score of zero on the Abnormal Involuntary Movement Scale (AIMS) at baseline in Phase 1 of the CATIE study, and remained for ≥6 months, was used. Peak and trough dopamine D2 receptor occupancy levels on the day of the AIMS assessment at the endpoint were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our D2 prediction model. The estimated dopamine D2 receptor occupancy levels were compared between patients who presented an AIMS score of ≥1 at endpoint and those who did not, using the independent t-test. Results: Estimated dopamine D2 receptor occupancy levels at trough were significantly higher in subjects who developed involuntary movements (N=40) than those who did not (N=195) (71.5±12.4% vs. 64.3±19.3%, p<0.05) while no significant difference was found in the estimated peak D2 receptor occupancy between them (75.1±8.0% vs. 72.1±9.9%, p=0.07). When the analyses were separately conducted for the three drugs, there were no significant differences in estimated peak or trough D2 occupancy although the values were consistently numerically higher among those developing involuntary movements. Discussion: Greater dopamine D2 receptor blockade with antipsychotics at trough may increase the risk of tardive involuntary movements.
Poster #T267 PREFRONTAL CORTEX THICKNESS IN PTSD AND SCHIZOPHRENIA AND THE ROLE OF CHILDHOOD TRAUMA Andre Zugman 1,2 , Elson Asevedo 3 , Rodrigo Mansur 3 , Graccielle Asevedo 3 , Ary Araripe 3 , Lara Faria 3 , Vitor Tardelli 3 , Rodrigo Bressan 3 , Andrea Jackowski 3 , Elisa Brietzke 3 1 Universidade Federal de São Paulo; 2 Laboratório Interdisciplinar de Neurociências Clínicas; 3 UNIFESP Background: Psychosis develops as a result of numerous interacting factors (van Os and McGuffin, 2003). However a number of features link traumatic
events to psychosis. A history of trauma is more common in subjects with psychotic disorders (Bebbington et al., 2004). Traumatic experience during childhood increases the risk of psychosis with cumulative effect (Shevlin et al., 2008) and a history of trauma is associated with psychotic symptoms in the general population (Freeman and Fowler, 2009). Additionally, psychotic symptoms appear to be related to a worse prognosis in post-traumatic stress disorder (PTSD) patients and PTSD co-morbidity is related to a worse prognosis in first episode psychosis (Mueser et al., 2010). Although it has been hypothesized that both PTSD and psychosis are related to a pathological response to traumatic experience (Morrison et al., 2003) there are few studies comparing biological features of both disorders. Methods: 24 subjects with schizophrenia (SCZ) and 29 PTSD subjects were recruited from psychiatric outpatients clinics. Clinical interviews were carried out by trained psychiatrists and diagnoses were confirmed using the Structured Clinical Interview for DSM-IV (SCID-IV). Early Trauma was assessed using the Childhood Trauma Questionnaire (CTQ) (Bernstein, 2003). The CTQ contains five subscales, three assessing abuse (physical, emotional and sexual) and two assessing neglect (physical and emotional). All subjects were receiving treatment as usual at the time of scan. Brain MR images were acquired on a 1.5T Siemens Sonata scanner (TE= 3.4; TR= 2000 ms; FoV= 256; Flip Angle: 15; Slice Thickness 1mm). Images were processed and analysed using freesurfer (http://surfer.nmr.mgh.harvard.edu/). Between group whole cortex vertex-wise thickness analysis was carried out with a threshold of p=0.05 corrected for multiple comparison using a Monte-Carlo simulation. Correlation between early trauma scores and cortical thickness in SCZ and PTSD group was also investigated. Results: SCZ group had a mean age of 35.3 (SD: 10.1 y/o) and mean CTQ score of 42.9 (SD: 13.9). PTSD group had a mean age of 45.7 (SD: 8.6 y/o) and mean CTQ of 50.4 (SD: 21.9). The total CTQ score was not significantly different between both groups (t: 1.4; p: 0.15). A significant thinning of the left anterior cingulate and orbitofrontal cortices were observed in PTSD group when compared to SCZ subjects. The total CTQ score and thickness correlation did not remain significant after correction for multiple comparisons in both groups. There was a significant association between CTQ emotional neglect subscale and the left prefrontal cortex thickness in SCZ group. No other correlation was found between CTQ subscales scores and cortical thickness. Discussion: The prefrontal cortex is a region thought to be involved in reward guided learning and decision making (Rushworth et al., 2011). This region has been previously linked to anhedonia (Frewen et al., 2012) which is a characteristic of both disorders. Our findings may indicate that this region response to trauma in different stage during life may lead to different psychopathology.