Insular volume abnormalities associated with different transition probabilities to psychosis

Abstract

Background: Although individuals vulnerable to psychosis show brain volumetric abnormalities, structural alterations underlying different probabilities for later transition are unknown. The present study addresses this issue by means of voxel-based morphometry (VBM).

Method: We investigated grey matter volume (GMV) abnormalities by comparing four neuroleptic-free groups: individuals with first episode of psychosis (FEP) and with at-risk mental state (ARMS), with either long-term (ARMS-LT) or short-term ARMS (ARMS-ST), compared to the healthy control (HC) group. Using three-dimensional (3D) magnetic resonance imaging (MRI), we examined 16 FEP, 31 ARMS, clinically followed up for on average 3 months (ARMS-ST, n=18) and 4.5 years (ARMS-LT, n=13), and 19 HC.

Results: The ARMS-ST group showed less GMV in the right and left insula compared to the ARMS-LT (Cohen's d 1.67) and FEP groups (Cohen's d 1.81) respectively. These GMV differences were correlated positively with global functioning in the whole ARMS group. Insular alterations were associated with negative symptomatology in the whole ARMS group, and also with hallucinations in the ARMS-ST and ARMS-LT subgroups. We found a significant effect of previous antipsychotic medication use on GMV abnormalities in the FEP group.

Conclusions: GMV abnormalities in subjects at high clinical risk for psychosis are associated with negative and positive psychotic symptoms, and global functioning. Alterations in the right insula are associated with a higher risk for transition to psychosis, and thus may be related to different transition probabilities.

Fig. 1

Correlation of psychopathology and grey matter volume (GMV) in the right (R) insula. (a) The cluster in the right insula (39, −19, 7) reflects reduced GMV in the short-term at-risk mental state (ARMS-ST) compared to the long-term ARMS (ARMS-LT) group (39, −19, 7) [p<0.05 family-wise error (FEW) corrected]. (b) Correlation of psychopathology and GMV in this cluster across the whole ARMS sample (ARMS-LT+ARMS-ST) [Pearson's correlation coefficient is −0.411 (p=0.05 two-tailed) for Scale for the Assessment of Negative Symptoms (SANS) and 0.473 (p=0.01 two-tailed) for Global Assessment of Functioning (GAF)]. (c) Positive correlation with hallucinations [Pearson's correlation coefficient for Brief Psychiatric Rating Scale (BPRS) item 10 (hallucinations) is 0.564 (p=0.05 two-tailed) for ARMS-ST and 0.632 (p=0.05 two-tailed) for ARMS-LT]. The left side of the brain is shown on the left side of the image.

Fig. 2

Correlation of psychopathology and grey matter volume (GMV) in the left (L) insula. (a) The cluster in the left insula (−31−21 10) reflects more GMV in the first episode of psychosis (FEP) compared to the short-term at-risk mental state (ARMS-ST) group [p<0.05 family-wise error (FEW) corrected]. (b) Correlation of psychopathology and GMV in this cluster across the whole ARMS sample [long-term ARMS (ARMS-LT)+ARMS-ST; Pearson's correlation coefficient is −0.460 (p=0.05 two-tailed) for Scale for the Assessment of Negative Symptoms (SANS) and 0.502 (p=0.01 two-tailed) for Global Assessment of Functioning (GAF)]. (c) Positive correlation of hallucinations with GMV in the ARMS-ST group [Pearson's correlation coefficient for Brief Psychiatric Rating Scale (BPRS) item 10 (hallucinations) is 0.564 (p=0.05 two-tailed) for ARMS-ST and 0.632 (p=0.05 two-tailed) for ARMS-LT]. The left side of the brain is shown on the left side of the image.