Hippocampal Availability of the α7 Nicotinic Acetylcholine Receptor in Recent-Onset Psychosis.

Importance: 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. Objective: 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). Main Outcome and Measures: 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. Results: 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). Conclusions and Relevance: 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.

Imaging Brain Injury in Former National Football League Players.

Importance: Pilot studies that involved early imaging of the 18 kDa translocator protein (TSPO) using positron emission tomography (PET) indicated high levels of TSPO in the brains of active or former National Football League (NFL) players. If validated further in larger studies, those findings may have implications for athletes involved in collision sport. Objective: To test for higher TSPO that marks brain injury and repair in a relatively large, unique cohort of former NFL players compared with former elite, noncollision sport athletes. Design, Setting, and Participants: This cross-sectional study used carbon 11-labeled N,N-diethyl-2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide positron emission tomography ([11C]DPA-713 PET) data from former NFL players within 12 years of last participation in the NFL and elite noncollision sport athletes from across the US. Participants were enrolled between April 2018 and February 2023. Main outcomes and measures: Regional [11C]DPA-713 total distribution volume from [11C]DPA-713 PET that is a measure of regional brain TSPO; regional brain volumes on magnetic resonance imaging; neuropsychological performance, including attention, executive function, and memory domains. Results: This study included 27 former NFL players and 27 former elite, noncollision sport athletes. Regional TSPO levels were higher in former NFL players compared with former elite, noncollision sport athletes (unstandardized ß coefficient, 1.08; SE, 0.22; 95% CI, 0.65 to 1.52; P < .001). The magnitude of the group difference depended on region, with largest group differences in TSPO in cingulate and frontal cortices as well as hippocampus. Compared with noncollision sport athletes, former NFL players performed worse in learning (mean difference [MD], -0.70; 95% CI, -1.14 to -0.25; P = .003) and memory (MD, -0.77; 95% CI, -1.24 to -0.30; P = .002), with no correlation between total gray matter TSPO and these cognitive domains. Conclusions and relevance: In this cross-sectional study using [11C]DPA-713 PET, higher brain TSPO was found in former NFL players compared with noncollision sport athletes. This finding is consistent with neuroimmune activation even after cessation of NFL play. Future longitudinal [11C]DPA-713 PET and neuropsychological testing promises to inform whether neuroimmune-modulating therapy may be warranted.