Abstract
BackgroundRecent research suggests that individuals at ultra-high risk for psychosis (UHR) show altered resting cerebral blood flow (rCBF) in key regions linked to psychosis pathophysiology: the hippocampus, midbrain, and basal ganglia. Greater perturbations in basal ganglia rCBF were correlated with positive psychotic symptoms, while remission from the UHR state was associated with a longitudinal normalization of hippocampal rCBF. Oxytocin -a neuropeptide with potential anxiolytic and prosocial properties- is currently under investigation as a novel therapeutic for a number of neuropsychiatric disorders. Previous work conducted in healthy males demonstrated that a single acute dose of intranasal oxytocin had marked effects on rCBF across all of the aforementioned regions (hippocampus, basal ganglia, midbrain), as well as the amygdala, anterior cingulate cortex and cerebellum - regions where neurofunctional alterations have been previously reported in UHR groups. Despite these findings, no studies have yet examined the effects of intranasal oxytocin on resting perfusion in UHR individuals.MethodsIn a double-blind, placebo-controlled, crossover design, 30 UHR males underwent two MRI scans at 3 Tesla, once after 40IU intranasal oxytocin and once after matched placebo (one-week wash-out). Arterial spin labeling (ASL) was used to measure rCBF starting approximately 22 minutes post-intranasal administration. The severity of attenuated psychotic symptoms was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS). Measures of social cognition, emotional processing and level of functioning were also acquired. We hypothesized that relative to placebo, a single acute dose of intranasal oxytocin would modulate rCBF in the hippocampus, basal ganglia and midbrain, and that this effect would be greater in those with more severe baseline deficits in social and emotional functioning.ResultsData analysis is currently ongoing and the results will be presented at the conference.DiscussionThese results will provide physiological evidence for a potential first-in-class intervention for UHR patients. Given the current lack of evidence for effective treatments in this patient group, better understanding of the neural correlates of the high-risk state and the physiological basis for the effects of novel therapeutics is desperately warranted.
Highlights
The significant proportion of schizophrenia patients refractory to treatment targeting the dopamine system suggests that more than one mechanism may cause psychotic symptoms
We found that the clustering coefficient of brain functional network in schizophrenia increased (p = 0.032, beta = 0.000194 at the minimum network sparsity 35% in which all the nodes were fully connected), whereas the global efficiency decreased (p = 0.005, beta = -0.000022), as the progression of schizophrenia
Recent research suggests that individuals at ultra-high risk for psychosis (UHR) show altered resting cerebral blood flow in key regions linked to psychosis pathophysiology: the hippocampus, midbrain, and basal ganglia
Summary
We found that the clustering coefficient of brain functional network in schizophrenia increased (p = 0.032, beta = 0.000194 at the minimum network sparsity 35% in which all the nodes were fully connected), whereas the global efficiency decreased (p = 0.005, beta = -0.000022), as the progression of schizophrenia. The main effect of social anhedonia in predicting both the clustering efficient and the global efficiency were not significant, its interaction with the duration of illness was significant (p = 0.021, beta = 0.000038 for the clustering coefficient; p = 0.023, beta = -0.000003 for the global efficiency). Discussion: With the development of schizophrenia, the increase of clustering coefficient and decrease of global efficiency of functional brain network may reflect the pathophysiology of schizophrenia since the onset of illness.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
