Altered Dopamine-Linked Striatal Hemodynamic Latency in Early Psychosis
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Importance
Psychosis is strongly associated with striatal dopamine dysfunction, but noninvasive measures that capture variation in dopamine remain limited. Hemodynamic latency, which quantifies the timing of low-frequency blood oxygen level-dependent (BOLD) fluctuations, may provide a way to indirectly probe dopamine dysfunction in psychosis.
Objective
To determine whether striatal hemodynamic latency differs between individuals with early psychosis (EP) and healthy control (HC) participants and whether latency is associated with positive or negative symptom severity.
Design
Cross-sectional analysis of resting-state functional magnetic resonance imaging (fMRI) data from the Human Connectome Project (HCP)-EP dataset.
Setting
Multisite study at 4 sites using 3T Siemens Prisma MRI scanners.
Participants
105 individuals with EP and 55 HC participants with usable resting-state fMRI and hemodynamic latency data.
Exposure
EP status.
Main Outcomes and Measures
Voxel-wise hemodynamic latency was estimated using RapidTide and summarized within 6 striatal regions: nucleus accumbens core and shell, anterior and posterior caudate and putamen. Group differences were evaluated using linear mixed-effects models accounting for region and subject-level random effects and controlling for age, sex, and mean framewise displacement. Positive symptoms were measured using the Positive and Negative Syndrome Scale positive subscale; negative symptoms using the Clinical Assessment Interview for Negative Symptoms. Associations with symptoms were assessed using nested linear regressions within the EP group.
Results
Latency was significantly lower in the dorsal than ventral striatum in HC and EP, with a greater difference in EP ( b= -119.46 ms, SE=52.16, p= .022). Follow-up six-subregion models found significant main effects of group F (1,156.55)=7.79, p =.006, and region F (5,2760)=187.99; p < .001, but no group-by-region interaction F (5,2760)=1.74; p =.121. Region-specific contrasts showed lower latency in EP in the anterior caudate ( p =.014), posterior caudate ( p< .001), anterior putamen ( p =.007), and posterior putamen ( p =.029), but not NAc core or shell. Striatal latency was not significantly associated with positive or negative symptom severity among participants with EP.
Conclusions and Relevance
EP was associated with broadly reduced striatal hemodynamic latency, with the strongest differences in the caudate and putamen. Altered striatal latency in psychosis warrants further evaluation as a noninvasive indirect marker of striatal pathophysiology linked to dopamine.
Key Points
Question
Is striatal hemodynamic latency, a novel indirect correlate of dopamine physiology, altered in individuals with early psychosis?
Findings
In this cross-sectional study of 105 individuals with early psychosis and 55 healthy comparison participants, early psychosis was associated with significantly lower striatal hemodynamic latency. Differences were observed in the dorsal striatum (caudate and putamen), whereas ventral striatal (nucleus accumbens) latency did not significantly differ between groups.
Meaning
These findings support further evaluation of striatal hemodynamic latency as a noninvasive, indirect marker of dopamine-linked physiology in early psychosis
