On Friday 23 April 2021, Professor Dost Öngür from Havard Medical school and McLean Hospital will give a presentation entitled "Magnetic resonance spectroscopy studies in psychotic disorders".

Abstract:

Background: Multiple lines of evidence from genetic, cellular, imaging, and clinical studies implicate abnormalities in mitochondrial function and brain energy availability in psychotic disorders. Our group has been conducting a series of 31P Magnetic Resonance Spectroscopy (31P MRS) studies to probe relevant processes in the brain in individuals with schizophrenia and bipolar disorder.

Methods: In a series of studies, we have recruited patients with chronic and stable schizophrenia and bipolar disorder with matched healthy controls, as well as with patients experiencing a first episode of schizophrenia and bipolar disorder (maximum 1 year of symptoms and 1 hospitalization) with matched healthy controls. We conduct clinical evaluations including full SCID as well as PANSS, YMRS, and MADRS at the time of visit.  We collect 31P MRS data on a 4 Tesla Varian scanner using a dual-tuned surface coil. The region of interest is a 6x6x4cm voxel including the medial and anterior prefrontal cortex. 31P MRS data are frequency/phase corrected and analyzed using homegrown software to quantify: ATP & PCr concentrations, creatine kinase forward reaction rate (CK Kf) and flux, pH, NAD+ and NADH concentrations. We conduct statistical evaluations using Chi-squares and ANOVAs as appropriate.

Results: We have reported significant reductions in CK Kf and acidic pH, consistent with a slowing down of ATP synthesis and compensatory shift to glycolysis and lactate build-up in chronic schizophrenia patients. This is accompanied by redox imbalance as reflected in the NAD+/NADH ratio, indicating downstream effects of metabolic distress.  In first episode schizophrenia we find evidence for reduced CK Kf but with normal pH values. There is also a reduction in NAD+/NADH that corresponds to a Cohen’s d effect size of 0.78 and is greater than that seen in our previous work with chronic schizophrenia patients. 

Conclusions: In young people experiencing a first episode of schizophrenia, we see evidence for impaired ATP synthesis through the CK enzyme as well as redox dysregulation; the latter is even greater here than in chronic patients. By contrast, pH is not acidic in first episode as it is in chronic patients, suggesting that the slowing of ATP synthesis and accompanying redox imbalance has not yet led to a compensatory shift towards glycolysis in the first episode. Our results provide new insights into the unfolding cascade of mitochondrial function and bioenergetic abnormalities in psychotic disorders.  We will also discuss implications of these findings for treatment interventions.

The meeting takes place Friday April 23 at 9:15. You can join the meeting via Teams by clicking here.