PM477. Social functioning and prefrontal hemodynamic responses during a verbal fluency task in schizophrenia
چکیده
s | 73 Abstract Background: Increasing evidence show that disruption of connectivity has been implicated as a central abnormality in schizophrenia, and the alterations in white matter (WM) may be the core basis for this disconnection. Diffusion tensor imaging (DTI) has shown WM abnormalities in first episode schizophrenia. However, few studies have examined the correlation between clinical symptoms and WM abnormalities in first-episode and drug-naïve schizophrenia. Method: The WM fractional anisotropy (FA) values of the wholebrain were determined using voxel-based DTI in 39 first-episode and drug-naïve schizophrenia patients (diagnosed according to DSM-IV) and 30 healthy controls matched for age and gender. The psychopathology of schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). Results: The patients showed widespread FA reduction in several brain regions, including corpus callosum, brainstem, internal capsule, cingulate and cerebellum in first-episode patients with schizophrenia when compared to healthy controls (all p<0.01 after adjusting for gender, age and education). The correlation analysis showed a significant negative correlation between the FA value in the left cerebellum and positive symptoms (r=-0.32, df=38, p<0.05), and a significantly positive correlation between the FA values in the corpus callosum and both the PANSS general psychopathology subscore (r=0.39, df=38, p=0.01) and the PANSS total score (r=0.33, df=38, p<0.05). Conclusions: Our results indicate that widespread disruption of white matter integrity occurs in an early stage of schizophrenic onset, suggesting an important role in pathogenesis and symptomatology of schizophrenia.Background: Increasing evidence show that disruption of connectivity has been implicated as a central abnormality in schizophrenia, and the alterations in white matter (WM) may be the core basis for this disconnection. Diffusion tensor imaging (DTI) has shown WM abnormalities in first episode schizophrenia. However, few studies have examined the correlation between clinical symptoms and WM abnormalities in first-episode and drug-naïve schizophrenia. Method: The WM fractional anisotropy (FA) values of the wholebrain were determined using voxel-based DTI in 39 first-episode and drug-naïve schizophrenia patients (diagnosed according to DSM-IV) and 30 healthy controls matched for age and gender. The psychopathology of schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). Results: The patients showed widespread FA reduction in several brain regions, including corpus callosum, brainstem, internal capsule, cingulate and cerebellum in first-episode patients with schizophrenia when compared to healthy controls (all p<0.01 after adjusting for gender, age and education). The correlation analysis showed a significant negative correlation between the FA value in the left cerebellum and positive symptoms (r=-0.32, df=38, p<0.05), and a significantly positive correlation between the FA values in the corpus callosum and both the PANSS general psychopathology subscore (r=0.39, df=38, p=0.01) and the PANSS total score (r=0.33, df=38, p<0.05). Conclusions: Our results indicate that widespread disruption of white matter integrity occurs in an early stage of schizophrenic onset, suggesting an important role in pathogenesis and symptomatology of schizophrenia. PM476 d-Amphetamine-induced sensitization of the dopaminergic system in healthy human subjects: A [11C]-(+)-PHNO-PET study Popovic Ana 1, Bauer Martin 1,2, Bartova Lucie 1, Sauerzopf Ulrich 1, Nicole PraschakRieder, Rami-Mark Christina3, Nics Lukas 3, Cecile Philippe 3, Mitterhauser Markus 3 Wolfgang Wadsak3, Kasper Siegfried 2, Willeit Matthäus 1 1 Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria 2 Department of Clinical Pharmacology, Medical University of Vienna, Austria 3 Department of NuclearMedicine, Medical University of Vienna, Austria Abstract Background: In accordance with the dopamine hypothesis of schizophrenia, studies demonstrate that patients with schizophrenia are super-sensitive towards dopamine-releasing agents such as amphetamine. Therefore, amphetamine-induced sensitization of amphetamine-induced dopamine release in healthy subjects provides a suitable model for studying the dopaminergic alterations in schizophrenia. Objectives: To quantify d-amphetamine-induced dopamine release using changes in non-displacable binding potential (BPND) of the D2,3 agonist radioligand (+)-4-Propyl-9hydroxynaphthoxazine and positron emission tomography ([11C]-(+)-PHNO-PET) and behavioral measures of d-amphetamine effects with drug effects questionnaire (DEQ) and subjective states questionnaire (SSQ). The goal of the study is to investigate d-amphetamine induced sensitization in healthy subjects on a behavioral and neurochemical level with [11C]-(+)-PHNO-PET in order to gain more knowledge on sensitization-induced changes in the dopaminergic system of patients with schizophrenia. Methods: Three 90-min. [11C]-(+)-PHNO-PET-scans and four oral administrations of d-amphetamine were performed in 12 stimulant-naïve healthy male subjects. A naïve baseline scan was followed by a PET scan with previous ingestion of 0,4 mg/ kg body-weight of d-amphetamine 90–120 minutes before scanning. Then, subjects were sensitized to d-amphetamine with a constant dose on two separate days. Subsequently, another PET scan with previous d-amphetamine ingestion was performed. DEQ and SSQ were administered before, 60 min., 90–120 min., and 210 min. after amphetamine ingestion. Results: We found significant sensitization effects on a behavioral level and neurochemical level after four administrations of d-amphetamine. Items of the SSQ, with significant sensitization effects were “outgoing”, “energetic”, “lively”, “alert” and “focused”. d-Amphetamine induced changes in [11C]-(+)-PHNO BPND values were significantly larger after sensitization. Conclusions: Using [11C]-(+)-PHNO-PET for the first time in this paradigm, we were able to measure significant behavioral and neurochemical sensitization in 12 healthy male subjects. Amphetamine-induced sensitization of the dopaminergic system will be useful for studying the neurobiology of schizophrenia.Background: In accordance with the dopamine hypothesis of schizophrenia, studies demonstrate that patients with schizophrenia are super-sensitive towards dopamine-releasing agents such as amphetamine. Therefore, amphetamine-induced sensitization of amphetamine-induced dopamine release in healthy subjects provides a suitable model for studying the dopaminergic alterations in schizophrenia. Objectives: To quantify d-amphetamine-induced dopamine release using changes in non-displacable binding potential (BPND) of the D2,3 agonist radioligand (+)-4-Propyl-9hydroxynaphthoxazine and positron emission tomography ([11C]-(+)-PHNO-PET) and behavioral measures of d-amphetamine effects with drug effects questionnaire (DEQ) and subjective states questionnaire (SSQ). The goal of the study is to investigate d-amphetamine induced sensitization in healthy subjects on a behavioral and neurochemical level with [11C]-(+)-PHNO-PET in order to gain more knowledge on sensitization-induced changes in the dopaminergic system of patients with schizophrenia. Methods: Three 90-min. [11C]-(+)-PHNO-PET-scans and four oral administrations of d-amphetamine were performed in 12 stimulant-naïve healthy male subjects. A naïve baseline scan was followed by a PET scan with previous ingestion of 0,4 mg/ kg body-weight of d-amphetamine 90–120 minutes before scanning. Then, subjects were sensitized to d-amphetamine with a constant dose on two separate days. Subsequently, another PET scan with previous d-amphetamine ingestion was performed. DEQ and SSQ were administered before, 60 min., 90–120 min., and 210 min. after amphetamine ingestion. Results: We found significant sensitization effects on a behavioral level and neurochemical level after four administrations of d-amphetamine. Items of the SSQ, with significant sensitization effects were “outgoing”, “energetic”, “lively”, “alert” and “focused”. d-Amphetamine induced changes in [11C]-(+)-PHNO BPND values were significantly larger after sensitization. Conclusions: Using [11C]-(+)-PHNO-PET for the first time in this paradigm, we were able to measure significant behavioral and neurochemical sensitization in 12 healthy male subjects. Amphetamine-induced sensitization of the dopaminergic system will be useful for studying the neurobiology of schizophrenia. PM477 Social functioning and prefrontal hemodynamic responses during a verbal fluency task in schizophrenia Shenghong Pua,*, Kazuyuki Nakagomeb, Masashi Itakuraa, Takehiko Yamanashia, Takuya Sugiea, Akehiko Miuraa, Takahiro Satakea, Masaaki Iwataa, Izumi Nagataa, Koichi Kanekoa aDivision of Neuropsychiatry, Department of Brain and Neuroscience, Tottori University Faculty of Medicine: 36-1 Nishi-cho, Yonago, Tottori, 683–8504, Japan bNational Center of Neurology and Psychiatry: 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187–8551, Japan Abstract Objective: Impaired social functioning is a characteristic of schizophrenia that affects patients’ quality of life. The aim of the study was to assess prefrontal hemodynamic responses during a cognitive task and establish its influence on psychiat-Objective: Impaired social functioning is a characteristic of schizophrenia that affects patients’ quality of life. The aim of the study was to assess prefrontal hemodynamic responses during a cognitive task and establish its influence on psychiatric symptoms, cognitive function, global functioning, and selfreported social functioning in patients with schizophrenia. Method: Thirty-three patients with schizophrenia and 30 ageand sex-matched healthy controls participated in the study. We measured hemodynamic responses in the prefrontal and superior temporal cortical surface areas with 52-channel nearinfrared spectroscopy (NIRS) during a verbal fluency task (VFT). Self-reported social functioning was assessed using the Social Functioning Scale (SFS). Results: Regional hemodynamic responses were significantly smaller in the prefrontal and temporal regions in subjects with schizophrenia than in the controls, and prefrontal hemodynamic responses during the VFT showed a strong correlation with SFS total scores. Conclusion: These results suggest an association between selfreported social functioning and prefrontal activation in subjects with schizophrenia. The present study provides evidence that NIRS imaging could be helpful in understanding the neural basis of social functioning.