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

Abstract

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.

Figure 1.. Group Comparisons Between Fluorine 18–Labeled ASEM ([¹⁸F]ASEM) Total Distribution Volume (V_T) Values

Estimated mean (SE) of [¹⁸F]ASEM V_T values in hippocampus (primary end point) and additional regions (secondary end points) from healthy controls (n = 24), patients with affective psychosis (AP) (n = 18), and patients with nonaffective psychosis (NP) (n = 17). V_T was estimated from images corrected for partial volume. ^aP < .001. ^bP < .01. ^cP < .05.

Figure 2.. Partial Regression Plot of the Association Between Hippocampal Fluorine 18–Labeled ASEM ([¹⁸F]ASEM) Total Distribution Volume (V_T) and Global Cognition Composite Score of Patients With Recent-Onset Psychosis After Adjusting for Age

Data from individuals with history of nicotine use are marked (dark blue dots). Within the total study population with recent-onset psychosis (n = 35), 1 individual who also had history of nicotine use did not complete neuropsychological testing.