Visitors Talk: Fei Du, Mclean hospital – Harvard Medical School

Abstract

Impaired functional connectivity is a hallmark of various neuropsychiatric disorders, yet the molecular mechanisms driving these disruptions remain elusive and few in vivo biomarkers are available to guide clinical interventions. Emerging evidence suggests that a central “immuno-oxidative” pathway, involving NMDA receptor hypofunction, redox dysregulation, neuroinflammation and mitochondrial dysfunction, plays a pivotal role and contributes to disrupted brain circuits in neuropsychiatric disorders. In this presentation, I will introduce novel approaches for quantifying in vivo levels of glutamate/GABA, glutathione (GSH), and redox ratio of NAD+ and NADH, alongside measuring creatine kinase/ATPase activities (mitochondrial function) in the same experimental session. Through the integration of the multimodal neuroimaging with assessments of brain structural and functional connectivity, we have identified associations among these measures, but they are compromised in neuropsychiatric patients. Our findings indicate that reduced energy metabolic rates with diminished neurotransmissions might disrupt the long distance and large-scale neuronal communications—thereby leading to brain disorders and suggest that the metabolism-neural synchrony pathway could be a new potential treatment target for various neuropsychiatric diseases including neuropsychiatric disorders. The interventions of NAD+ supplementation and ketogenic therapy as well as diseases progression also will be discussed. These advances might provide the biomarkers for documenting and quantifying the neurobiological abnormalities’ trajectories and effects of interventions using brain imaging approaches.