Investigation of structural brain correlates of neurological soft signs in individuals at ultra-high risk for psychosis

Eur Arch Psychiatry Clin Neurosci. 2021 Dec;271(8):1475-1485. doi: 10.1007/s00406-021-01300-9. Epub 2021 Aug 31.


Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in cerebello-thalamo-cortical structures, but it is unclear whether similar structures underlie NSS prior to the onset of psychosis. The present study investigated the relationship between severity of NSS and grey matter volume (GMV) in individuals at ultra-high risk for psychosis (UHR) stratified for later conversion to psychosis. Structural T1-weighted MRI scans were obtained from 56 antipsychotic-naïve UHR individuals and 35 healthy controls (HC). The UHR individuals had follow-up data (mean follow-up: 5.2 years) to ascertain clinical outcome. Using whole-brain voxel-based morphometry, the relationship between NSS and GMV at baseline was assessed in UHR, HC, as well as individuals who later transitioned (UHR-P, n = 25) and did not transition (UHR-NP, n = 31) to psychosis. NSS total and subscale scores except motor coordination were significantly higher in UHR compared to HC. Higher signs were also found in UHR-P, but not UHR-NP. Total NSS was not associated with GMV in the whole sample or in each group. However, in UHR-P individuals, greater deficits in sensory integration was associated with lower GMV in the left cerebellum, right insula, and right middle frontal gyrus. In conclusion, NSS are present in UHR individuals, particularly those who later transitioned to a psychotic disorder. While these signs show little overall variation with GMV, the association of sensory integration deficits with lower GMV in UHR-P suggests that certain brain areas may be implicated in the development of specific neurological abnormalities in the psychosis prodrome.

Keywords: Grey matter volume; Neurological soft signs; Transition; Ultra-high risk; Voxel-based morphometry.

MeSH terms

  • Brain* / diagnostic imaging
  • Brain* / pathology
  • Gray Matter / diagnostic imaging
  • Gray Matter / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Organ Size
  • Psychotic Disorders* / epidemiology
  • Risk Assessment