Neurometabolic dysfunction in psychosis observed with 7 T MRS

Altered brain chemistry is thought to contribute to impairments in cognitive and perceptual functioning in people with psychotic psychopathology (PwPP). As heritable genetic factors shape the development of psychosis, these alterations in brain chemistry may extend to biological relatives of PwPP. Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantifying the concentration of various neurochemicals in the human brain. A number of MRS studies in different brain regions have been performed in PwPP, and to a lesser extent in relatives, but results have been largely mixed. There are a number of methodological issues that may have influenced previous findings. We show here that when such issues are addressed, MRS reveals a pattern of neurometabolic dysfunction in PwPP. We acquired MRS data at 7 tesla with an ultra-short echo time (TE = 8 ms) sequence in both occipital and prefrontal cortices from 43 healthy controls, 42 first-degree biological relatives, and 64 PwPP. We saw reduced levels of N -acetyl-aspartate (NAA) in the occipital lobe in PwPP and their relatives (versus controls), and lower N -acetyl-aspartyl-glutamate (NAAG) in prefrontal cortex in PwPP versus controls. Surprisingly, we also saw markedly increased levels of glucose in both occipital and prefrontal cortices in PwPP. Hierarchical clustering analyses showed that higher glucose levels were linked to higher psychiatric symptom levels and impairments in visual task performance. Together, our findings point to a disruption in neural metabolism across multiple brain areas in PwPP that is associated with impaired cognitive and perceptual functioning. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by funding from the National Institutes of Health (U01 MH108150). Salary support for MPS was provided in part by K01 MH120278. Support for MR scanning at the University of Minnesota Center for Magnetic Resonance Research was provided by P41 EB015894 and P30 NS076408. This work used tools from the University of Minnesota Clinical and Translational Science Institute that were supported by UL1 TR002494. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of The University of Minnesota gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Our data are publicly available through the Human Connectome Project and the National Data Archive.