Volumetric differences in hippocampal subfields and associations with clinical measures in myalgic encephalomyelitis/chronic fatigue syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients suffer from a cognitive and memory dysfunction. Because the hippocampus plays a key role in both cognition and memory, we tested for volumetric differences in the subfields of the hippocampus in ME/CFS. We estimated hippocampal subfield volumes for 25 ME/CFS patients who met Fukuda criteria only (ME/CFS_Fukuda ), 18 ME/CFS patients who met the stricter ICC criteria (ME/CFS_ICC ), and 25 healthy controls (HC). Group comparisons with HC detected extensive differences in subfield volumes in ME/CFS_ICC but not in ME/CFS_Fukuda . ME/CFS_ICC patients had significantly larger volume in the left subiculum head (p < 0.001), left presubiculum head (p = 0.0020), and left fimbria (p = 0.004). Correlations of hippocampus subfield volumes with clinical measures were stronger in ME/CFS_ICC than in ME/CFS_Fukuda patients. In ME/CFS_Fukuda patients, we detected positive correlations between fatigue and hippocampus subfield volumes and a negative correlation between sleep disturbance score and the right CA1 body volume. In ME/CFS_ICC patients, we detected a strong negative relationship between fatigue and left hippocampus tail volume. Strong negative relationships were also detected between pain and SF36 physical scores and two hippocampal subfield volumes (left: GC-ML-DG head and CA4 head). Our study demonstrated that volumetric differences in hippocampal subfields have strong statistical inference for patients meeting the ME/CFS_ICC case definition and confirms hippocampal involvement in the cognitive and memory problems of ME/CFS_ICC patients.