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.