Working memory (WM) deficits predict clinical and functional outcomes in schizophrenia but are poorly understood and unaddressed by existing treatments. WM encoding and WM retrieval have not been investigated in schizophrenia without the confounds of illness chronicity or the use of antipsychotics and illicit substances. Moreover, it is unclear if WM deficits may be linked to cannabinoid 1 receptor dysfunction in schizophrenia. Sixty-six volunteers (35 controls, 31 drug-free patients with diagnoses of schizophrenia or schizoaffective disorder) completed the Sternberg Item-Recognition paradigm during an fMRI scan. Neural activation during WM encoding and WM retrieval was indexed using the blood-oxygen-level-dependent hemodynamic response. A subset of volunteers (20 controls, 20 drug-free patients) underwent a dynamic PET scan to measure [¹¹C] MePPEP distribution volume (ml/cm³) to index CB1R availability. In a whole-brain analysis, there was a significant main effect of group on task-related BOLD responses in the superior parietal lobule during WM encoding, and the bilateral hippocampus during WM retrieval. Region of interest analyses in volunteers who had PET/fMRI indicated that there was a significant main effect of group on task-related BOLD responses in the right hippocampus, left DLPFC, left ACC during encoding; and in the bilateral hippocampus, striatum, ACC and right DLPFC during retrieval. Striatal CB1R availability was positively associated with mean striatal activation during WM retrieval in male patients (R = 0.5, p = 0.02) but not male controls (R = −0.20, p = 0.53), and this was significantly different between groups, Z = −2.20, p = 0.02. Striatal CB1R may contribute to the pathophysiology of WM deficits in male patients and have implications for drug development in schizophrenia.

工作记忆（WM）缺陷可以预测精神分裂症的临床和功能结果，但人们对此知之甚少，现有治疗也未能解决这一问题。尚未在精神分裂症中研究 WM 编码和 WM 检索，而不考虑慢性疾病或使用抗精神病药物和非法药物的情况。此外，尚不清楚 WM 缺陷是否与精神分裂症中的大麻素 1 受体功能障碍有关。66 名志愿者（35 名对照者、31 名诊断为精神分裂症或分裂情感障碍的未用药患者）在功能磁共振成像扫描期间完成了 Sternberg 项目识别范例。WM 编码和 WM 检索期间的神经激活使用血氧水平依赖性血流动力学反应进行索引。一部分志愿者（20 名对照者，20 名未用药患者）接受了动态 PET 扫描，以测量 [ ¹¹ C] MePPEP 分布体积 (ml/cm ³ ) 以指数 CB1R 可用性。在全脑分析中，在 WM 编码过程中，组别对顶上小叶的任务相关 BOLD 反应有显着的主效应，在 WM 检索过程中，组对双侧海马体的任务相关 BOLD 反应有显着的主效应。对进行 PET/fMRI 的志愿者进行的兴趣区分析表明，在编码过程中，群体对右侧海马、左侧 DLPFC、左侧 ACC 中与任务相关的 BOLD 反应有显着的主效应；以及检索期间的双侧海马、纹状体、ACC 和右侧 DLPFC。纹状体 CB1R 可用性与男性患者 WM 检索期间的平均纹状体激活呈正相关（R  = 0.5，p  = 0.02），但与男性对照者无关（R  = -0.20，p  = 0.53），并且这在各组之间存在显着差异，Z  = −2.20，p  = 0.02。纹状体 CB1R 可能与男性患者 WM 缺陷的病理生理学有关，并对精神分裂症的药物开发具有影响。