Bioenergetics and abnormal functional connectivity in psychotic disorders

Area of Science:

• Neuroscience
• Psychiatry
• Neuroimaging
• Metabolic Neuroscience

Background:

• Psychotic disorders, including schizophrenia (SZ) and bipolar disorder (BD), exhibit altered functional connectivity (FC) within neural networks, notably the default mode network (DMN).
• Abnormalities in brain energy metabolism are also observed in psychotic disorders, impacting synaptic function and neural communication.
• The relationship between bioenergetic processes and large-scale brain network organization in SZ and BD remains incompletely understood.

Purpose of the Study:

• To investigate the association between brain energy metabolism, indexed by creatine kinase (CK) reaction flux, and functional connectivity (FC) in the medial prefrontal cortex (MPFC).
• To explore how this association differs between patients with schizophrenia (SZ), bipolar disorder (BD), and healthy controls (HC).

Main Methods:

• ³¹P magnetization transfer spectroscopy was used to measure CK flux in the MPFC, serving as an index of regional energy production rate.
• Whole-brain functional magnetic resonance imaging (fMRI) was employed to generate FC maps with the MPFC as the seed region.
• Data were collected from demographically matched groups of SZ, BD, and HC subjects.

Main Results:

• Schizophrenia (SZ) patients exhibited significantly lower CK flux compared to healthy controls (HC).
• Both SZ and BD patients showed decreased anticorrelation between the MPFC and task-positive networks (TPN).
• In HC, CK flux positively correlated with FC within the DMN and negatively with anticorrelation between MPFC and TPN; these correlations were attenuated in BD and SZ.

Conclusions:

• Medial prefrontal cortex (MPFC) energy metabolism rates are associated with intact functional connectivity (FC) within and between brain networks in healthy individuals.
• This association is diminished in schizophrenia (SZ) and bipolar disorder (BD), where both bioenergetic and FC abnormalities are present.
• Impaired brain energy production may be a contributing factor to the aberrant neural connectivity observed in psychotic disorders.