Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
JAMA Netw Open. 2024 Aug 1;7(8):e2427163. doi: 10.1001/jamanetworkopen.2024.27163.
Studies using human postmortem tissue and imaging with positron emission tomography (PET) support a low hippocampal availability of the α7 nicotinic acetylcholine receptor (α7-nAChR) in psychotic conditions, particularly in schizophrenia or schizoaffective disorder (nonaffective psychosis). If validated further, the finding may have implications for clinical diagnosis and treatment.
To test for lower availability of the α7-nAChR in the hippocampus of individuals with recent-onset psychosis compared with healthy control individuals and its association with lower cognitive performance or higher psychotic symptom burden within recent-onset psychosis.
DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, healthy individuals without history of psychosis and patients within 10 years of a first onset of psychotic disorder were recruited from the greater Baltimore, Maryland, and Washington, DC, area. Fluorine 18-labeled ASEM ([18F] ASEM) PET data were acquired from participants enrolled between March 1, 2014, and July 31, 2023, from an academic research institution. Data acquired between March 1, 2014, and January 31, 2018 (n = 26), were published as a pilot study and were combined with new data acquired between January 1, 2019, and July 31, 2023 (n = 33).
Regional [18F]ASEM total distribution volume (VT) that measures α7-nAChR availability, global cognition composite score, and total scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms.
A total of 59 participants (30 women [51%]; mean [SD] age, 25.5 [5.2] years), including 35 with recent-onset psychosis and 24 healthy controls, completed the study. In age-adjusted analyses, lower hippocampal [18F]ASEM VT was found in individuals with recent-onset psychosis (mean [SE], 17.87 [0.60]) compared with healthy controls (mean [SE], 19.82 [0.73]) (P = .04). In addition, [18F]ASEM VT was lower in individuals with nonaffective psychosis (mean [SE], 16.30 [0.83]) compared with healthy controls (P = .006) or those with affective psychosis (mean [SE], 19.34 [0.80]) (P = .03). Across recent-onset psychosis and after controlling for age, lower hippocampal [18F]ASEM VT was associated with more positive (r = -0.44; P = .009) but not negative symptoms, and higher hippocampal VT was associated with better global cognition composite score (r = 0.38; P = .03).
In this cross-sectional study of individuals with recent-onset psychosis compared with healthy controls, a lower hippocampal α7-nAChR availability was found in recent-onset psychosis, and its availability was lower in those with nonaffective vs affective psychosis. Further study of the association between low availability of the α7-nAChR and recent-onset psychosis is warranted toward informing diagnostic or therapeutic strategies related to these findings.
使用人体死后组织和正电子发射断层扫描（PET）进行的研究支持在精神病状态下，特别是在精神分裂症或分裂情感障碍（非情感性精神病）中，α7 烟碱型乙酰胆碱受体（α7-nAChR）在海马体中的可用性较低。如果进一步得到验证，这一发现可能对临床诊断和治疗具有重要意义。
检测与健康对照组相比，近期发病的精神病患者海马体中α7-nAChR 的可用性较低，并研究其与近期发病的精神病患者认知表现较低或精神病症状负担较高之间的关系。
设计、地点和参与者：在这项横断面研究中，来自马里兰州巴尔的摩和华盛顿特区地区的无精神病病史的健康个体和发病 10 年内的首发精神病患者被招募入组。氟 18 标记的 ASEM([18F]ASEM) PET 数据是从 2014 年 3 月 1 日至 2023 年 7 月 31 日期间在一个学术研究机构入组的参与者中获得的。2014 年 3 月 1 日至 2018 年 1 月 31 日（n=26）期间获得的数据已发表为一项试点研究，并与 2019 年 1 月 1 日至 2023 年 7 月 31 日期间获得的新数据（n=33）合并。
衡量 α7-nAChR 可用性的[18F]ASEM 总分布容积（VT）、整体认知复合评分、阳性症状评定量表和阴性症状评定量表的总分。
共有 59 名参与者（30 名女性[51%]；平均[SD]年龄 25.5[5.2]岁）完成了研究，包括 35 名近期发病的精神病患者和 24 名健康对照组。在年龄调整分析中，与健康对照组相比，近期发病的精神病患者海马体[18F]ASEM VT 较低（平均[SE]，17.87[0.60]）（P=0.04）。此外，与健康对照组（P=0.006）或情感性精神病患者（P=0.03）相比，非情感性精神病患者的[18F]ASEM VT 更低。在近期发病的精神病患者中，海马体[18F]ASEM VT 较低与更多的阳性症状相关（r=-0.44；P=0.009），但与阴性症状无关，而较高的海马体 VT 与更好的整体认知复合评分相关（r=0.38；P=0.03）。
在这项与健康对照组比较的近期发病精神病患者的横断面研究中，发现近期发病的精神病患者的海马体中 α7-nAChR 可用性较低，且在非情感性精神病患者中较低。进一步研究 α7-nAChR 可用性低与近期发病精神病之间的关系，有助于为这些发现提供诊断或治疗策略。
