Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, The Netherlands.
J Clin Psychopharmacol. 2011 Apr;31(2):146-53. doi: 10.1097/JCP.0b013e31820e3f58.
The influence of antipsychotic medication on brain morphology in schizophrenia may confound interpretation of brain changes over time. We aimed to assess the effect of discontinuation of atypical antipsychotic medication on change in brain volume in patients. Sixteen remitted, stable patients with first-episode schizophrenia, schizoaffective or schizophreniform disorder and 20 healthy controls were included. Two magnetic resonance imaging brain scans were obtained from all subjects with a 1-year interval. The patients either discontinued (n = 8) their atypical antipsychotic medication (olanzapine, risperidone, or quetiapine) or did not (n = 8) discontinue during the follow-up period. Intracranial volume and volumes of total brain, cerebral gray and white matter, cerebellum, third and lateral ventricle, nucleus caudatus, nucleus accumbens, and putamen were obtained. Multiple linear regression analyses were used to assess main effects for group (patient-control) and discontinuation (yes-no) for brain volume (change) while correcting for age, sex, and intracranial volume. Decrease in cerebral gray matter and caudate nucleus volume over time was significantly more pronounced in patients relative to controls. Our data suggest decreases in the nucleus accumbens and putamen volumes during the interval in patients who discontinued antipsychotic medication, whereas increases were found in patients who continued their antipsychotics. We confirmed earlier findings of excessive gray matter volume decrements in patients with schizophrenia compared with normal controls. We found evidence suggestive of decreasing volumes of the putamen and nucleus accumbens over time after discontinuation of medication. This might suggest that discontinuation reverses effects of atypical medication.
抗精神病药物对精神分裂症患者脑形态的影响可能会混淆对随时间变化的脑变化的解释。我们旨在评估停止使用非典型抗精神病药物对患者脑体积变化的影响。纳入了 16 名缓解期、稳定的首发精神分裂症、分裂情感性或分裂样障碍患者和 20 名健康对照者。所有受试者均进行了两次间隔 1 年的磁共振成像脑扫描。患者要么停止（n=8）使用非典型抗精神病药物（奥氮平、利培酮或喹硫平），要么在随访期间不停止（n=8）。获得了颅内体积和全脑、大脑灰质和白质、小脑、第三脑室和侧脑室、尾状核、伏隔核和壳核的体积。采用多元线性回归分析，在校正年龄、性别和颅内体积后，评估脑体积（变化）的主要组间效应（患者-对照组）和停药（是-否）。与对照组相比，患者的大脑灰质和尾状核体积随时间的减少更为明显。我们的数据表明，在停止抗精神病药物治疗的患者中，伏隔核和壳核的体积在间隔期间减少，而继续服用抗精神病药物的患者则增加。我们证实了以前的研究结果，即与正常对照组相比，精神分裂症患者的大脑灰质体积减少过多。我们发现，停药后，壳核和伏隔核的体积随时间推移而减少，这可能表明停药逆转了非典型药物的作用。
