抗精神病薬の局所脳血流と脳代謝に及ぼす影響について-臨床的・実験的研究

富山医科薬科大学医学部1 臨床的研究: 分裂病圏の患者11例(男8,女3;平均年令22.9歳)について, 治療開始前と抗精神病薬(ハロペリドール2.25mg/日など)を服用約2週間後の安静閉〓時の局所脳血流の変化を^Xe吸入法で測定した. また, 本検査の再現性をみるために, 建常成人10名について約2週間の間隔をおいて2度目の検査を施行した. その結果建常成人の半球平均血流は49.8〜51.4ml/100g/minで, 再現性も良好であった. 患者群の半球平均血流は, 服薬前はは右55.8, 左54.5服薬後は右51.0左は49.0で減少傾向を示したが有意な変化ではなかった. しかし, 脳部位別にみると, 左前頭領域(服薬前58.7 服薬後52.1)と右側頭頭頂領域(55.5 49.5)で服薬後に有意の減少が認められた. BriefPsychaticRatingScaleで評価した精神症状については, 猜疑の項目が有意に減少していた.2 実験的研究: ウィスター系雄性ラット18匹を用い, ハロペリドール(HPD)0.1mg/kg(5匹)又は1.0mg/kg(6匹)投与による脳血流の変化をオートラジオグラフ法により検討した. ラット股動静脈にカテーテルを留置し, 麻酔覚醒2時間後に薬剤又は対照として生食水200μ/kg(7匹)を静注し, その1時間後にN-isopropy-p-[^I]-Iodoamohetamineを静注した. 動脈採血後に脳を取り出し, 20umの凍結切片を作製(X線フィルムに感光させ, 黒化度を測定した. 局所脳血流はrefrence sample法に従って算出した. その結果, ラット覚醒時の全脳平均血流は, 対照群172,1ml/100g/min, HPD0.1mg/kg投与群180.8, 1.0mg/kg投与群164.5で有意な変化はなかった. 脳各部位の血流分布では, 両側の手網核で有意の上昇(約20%)を認め, 内側前頭前野と側坐核では減少傾向が認められた.1. Clinical studyTo study the effect of antipsychotics on cerebral blood flow, we wxamined regional cerebral blood flow (rCBF) using 133Xe inhalation technique in eleven patients (9 schizophrenics and 2 schizophreniform disorder; mean age, 22.9 years) before and about two weeks after medication. The measurements were also made with a two-week interval for ten normal volunteers without medication (mean age, 31.2 years). RCBF measurements showed good reproducibility in the normal controls. their mean hemispheric blood flow being between 49,8-51.4 ml/100g/min. RCBF in the patients after two-week\u27s medication (haloperidol 2.25-6.0 mg/day or sulpiride 300mg/day) showed a statistically significant decrease in the left frontal and right temporo-parietal region compared with that before treatment, but their mean hemispheric blood flow only showed a tendency to decrease. On the Breif Psychiatric Rating Scale, the score of suspiclousness has significantly dcreased.2. Experimental StudyThe acute effect of antipsychotics on rCBF in 37 discrete regions of the rat brain was studied by the quantitative autoradiographic N-isopropyl-p-[125-I]-Iodoamphetamine technique. There was no significant defference in mean hemispheric blood flow between controls (172.1ml/ 100g/min) and haloperidol 0.1 or 1.0 mg/kg i.v. administated groups (180.8; 164.5). For the regional distribution value of the blood flow, bilateral habenular nucleus showed a significant increase, whereas, medial prefrontal cortex and nucleus accumbens showed a tendency to decrease. The effect of chronic haloperidol administration is not yet completed, but these clinical and experimental studies would contribute to the understanding of the antipsychotic effects of neuroleptics.研究課題/領域番号:60570496, 研究期間(年度):1985 – 1987出典：研究課題「抗精神病薬の局所脳血流と脳代謝に及ぼす影響について-臨床的・実験的研究」課題番号60570496（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-60570496/605704961987kenkyu_seika_hokoku_gaiyo/）を加工して作

<Study 2> Saccadic eye movements and regional cerebral blood flow in schizophrenic patients.

This study examined tracking eye movements on predetermined stationary targets inpatients with schizophrenia spectrum dis order.The targets were 8 black points or 8 arabics\u27 numbered points placed on the circumference of a circle.Self-paced eye movements during clockwise tracking of these points by 23 patients and 23 normal controls were recorded using an infrared eye-mark recorder.Eye movements were an alyzed at two settings : first, when "fixation point" was defined as a point at which a gaze was held for at least 200 msec, and second, when held for at least 100 msec.The results indicated that at the 200 msec setting schizophrenic patients track with significantly fewer correct scores and more deviant scores than controls under black-point conditions.At the 100-msec setting, however, the correct scores of the patients were not significantly different from those of the controls, although the patients displayed more aberrant paths than the controls.The superfluous fixations in the patients improved significantly under numbered-point conditions, but patients still achieved lower correct scores than the controls. Four of the 23 patients exhibited centering (aberrant path directed toward the center point), suggesting immature control of eye movements under black-point conditions but not numbered-point conditions.These results suggest that some schizophrenic patients viewed the targets too quickly and that they have impaired directed attention, which can be improved by cues, and may have impaired preprogramming of eye movements, which is not improved by external cues.This study examined saccadic eye movements using simple stationary targets, in schizophrenic patients.The targets were 8 black points or 8 arabic-numbered points placed in randomized order on the circumference of a circle.Self-paced eye movements during clockwise tracking of these points, by 23 patients and 23 controls, were recorded using an infrared eye-mark recorder.Then the relationship between the saccades and clinical syndromes was investigated. Finally, the relationship between the performance of the saccades and resting regional cerebral blood flow (rCBF) was examined using single photon emission computed tomography with 99mTc-hexamethyl propyleneamine oxime (HMPAO).The results indicate that patients track with significantly fewer correct scores and more deviant scores than controls, in agreement with our previous study.There were two groups of patients : an ordinary group who obtained a full target hitting score at a 200 ms setting and a fast group who obtained the full score at 100 ms but not at 200 ms.Some patients displayed significantly more hypermetria than controls.Significant correlations were found between alienation syndrome (auditory hallucination and disturbance of the self) and correct scores, or delusion syndrome and deviant score.With respect to relative rCBF, fast group patients showed significantly decreased rCBF in the left limbic and inferior parietal areas as compared with ordinary group patients.These findings suggest that some schizophrenic patients view the stationary targets too fast and this may be related to dysfunction in the limbic-parietal association area in the left hemisphere.富山医科薬科大学・博士(医学)・乙第283号・松井三枝・1995/6/28富山医科薬科大

Classification of First-Episode Schizophrenia Patients and Healthy Subjects by Automated MRI Measures of Regional Brain Volume and Cortical Thickness

BACKGROUND: Although structural magnetic resonance imaging (MRI) studies have repeatedly demonstrated regional brain structural abnormalities in patients with schizophrenia, relatively few MRI-based studies have attempted to distinguish between patients with first-episode schizophrenia and healthy controls. METHOD: Three-dimensional MR images were acquired from 52 (29 males, 23 females) first-episode schizophrenia patients and 40 (22 males, 18 females) healthy subjects. Multiple brain measures (regional brain volume and cortical thickness) were calculated by a fully automated procedure and were used for group comparison and classification by linear discriminant function analysis. RESULTS: Schizophrenia patients showed gray matter volume reductions and cortical thinning in various brain regions predominantly in prefrontal and temporal cortices compared with controls. The classifiers obtained from 66 subjects of the first group successfully assigned 26 subjects of the second group with accuracy above 80%. CONCLUSION: Our results showed that combinations of automated brain measures successfully differentiated first-episode schizophrenia patients from healthy controls. Such neuroimaging approaches may provide objective biological information adjunct to clinical diagnosis of early schizophrenia