A novel radiotracer, [¹¹C]SL25.1188, targets monoamine oxidase-B (MAO-B) enzyme, found primarily in astrocytes, which metabolizes monoamines (including dopamine), particularly in subcortical regions. Altered astrocyte function in schizophrenia is supported by convergent evidence from post-mortem, genetic, transcriptomic, peripheral and preclinical findings. We aimed to test whether levels of MAO-B, an index of astrocyte function are low in the living brains of early psychosis and their high-risk states. Thirty-eight participants including antipsychotic-free/minimally exposed clinical participants with first-episode psychosis (FEP), clinical high-risk (CHR) individuals and healthy volunteers (HVs) underwent a 90-min positron emission tomography (PET) scan with [¹¹C]SL25.1188, to measure MAO-B V_T, an index of MAO-B concentration. Participants were excluded if tested positive on urine drug screen (except for cannabis). This study of 14 FEP (mean[SD] age, 25.7[5.7] years; 6 F), 7 CHR (mean[SD] age, 20.9[3.7] years; 4 F) and 17 HV (mean[SD] age, 31.2[13.9] years; 9 F) demonstrated significant group differences in regional MAO-B V_T (F_(2,37.42) = 4.56, p = 0.02, Cohen’s f = 0.49), controlling for tobacco (F _(1,37.42) = 5.37, p = 0.03) and cannabis use (F_(1,37.42) = 5.11, p = 0.03) with significantly lower MAO-B V_T in CHR compared to HV (Cohen’s d = 0.99). We report a significant cannabis effect on MAO-B V_T (F_(1,39.19) = 12.57, p = 0.001, Cohen’s f = 0.57), with a significant group-by-cannabis interaction (F_(2,37.30) = 3.82, p = 0.03, Cohen’s f = 0.45), indicating lower MAO-B V_T in cannabis-using clinical groups. Lower MAO-B V_T levels were more robust in striatal than cortical regions, in both clinical groups (F_(12,46.84) = 2.08, p = 0.04, Cohen’s f = 0.73) and in cannabis users (F_(6,46.84) = 6.42, p < 0.001, Cohen’s f = 0.91). Lower MAO-B concentration supports astrocyte dysfunction in cannabis-using CHR and FEP clinical populations. Lower MAO-B is consistent with replicated striatal dopamine elevation in psychosis, as well as astrocyte dysfunction in schizophrenia.

一种新型放射性示踪剂 [¹¹C]SL25.1188 靶向单胺氧化酶-B （毛-B） 酶，主要存在于星形胶质细胞中，星形胶质细胞代谢单胺（包括多巴胺），特别是在皮质下区域。来自死后、遗传学、转录组学、外周和临床前发现的收敛证据支持精神分裂症中星形胶质细胞功能的改变。我们旨在测试早期精神病的活脑及其高危状态中 毛-B（星形胶质细胞功能指标）的水平是否较低。38 名参与者，包括无抗精神病药/最低暴露的首发精神病 （FEP） 临床参与者、临床高危 （CHR） 个体和健康志愿者 （HVs），接受了 [¹¹C]SL25.1188 的 90 分钟正电子发射断层扫描 （PET） 扫描，以测量 毛-B V_T，即 毛-B 浓度的指标。如果尿液药物筛查呈阳性（大麻除外），则参与者被排除在外。这项对 14 名 FEP（平均 [SD] 年龄，25.7[5.7] 岁;6 F）、7 名 CHR（平均 [SD] 年龄，20.9[3.7] 岁;4 F）和 17 名 HV（平均 [SD] 年龄，31.2[13.9] 岁;9 F）的研究显示，区域 毛-B V_T（F_{（2,37.42）} = 4.56，p = 0.02，Cohen's f = 0.49），控制烟草（F _{（1,37.42）} = 5.37， p = 0.03）和大麻使用（F_{（1,37.42）} = 5.11，p = 0.03），与 HV 相比，CHR 中的 毛-B V_T 显着降低 （Cohen 的 d = 0.99）。 我们报道了大麻对 毛-B V_T 的显着影响 （F_{（1,39.19）} = 12.57，p = 0.001，科恩的 f = 0.57），具有显着的大麻组相互作用 （F_{（2,37.30）} = 3。 82，p = 0.03，Cohen 的 f = 0.45），表明使用大麻的临床组中 毛-B V_T 较低。在临床组 （F_{（12,46.84）} = 2.08，p = 0.04，Cohen 的 f = 0.73） 和大麻使用者 （F_{（6,46.84）} = 6.42，p < 0.001，Cohen 的 f = 0.91）中，纹状体区域的较低 毛-B V_T 水平比皮质区域更强大。较低的 毛-B 浓度支持使用大麻的 CHR 和 FEP 临床人群中的星形胶质细胞功能障碍。较低的 毛-B 与精神病中重复的纹状体多巴胺升高以及精神分裂症中的星形胶质细胞功能障碍一致。