Of the patients with prodromal symptoms, 14 had light-to-middle depressive syndrome and 1 had an obsessive–compulsive disorder. Less than half of the UHR patients (11/29) had taken either risperidone or olanzapine in low dosages and only for a few days (mean 1.9, SD 1.2 d); the others were free of medication. Six of the 23 patients with first-episode schizophrenia had taken typical or atypical neuroleptics at clinical dosages but only for a few days (mean 2.6, SD 1.9 d). The others had never taken a neuroleptic.
Within 9 months after MRI scanning, 2 of the 29 UHR patients made the transition to schizophrenic psychosis, and we lost contact with 6 patients, probably because they transitioned into full-blown psychosis (assume based on the patients’ clinical information). Thus, we were able to include 8 converters (5 male, 3 female; mean age 24.4, SD 5.1 yr) and 21 patients (14 male, 7 female; mean age 25.9, SD 4.0 yr) who remained clinically stable over the observation period of 9 months (conversion rate 28%).
Intrarater and interrater reliability for determining the size and extension of the ROIs, whole brain volumes and grey matter volumes were within acceptable ranges (intraclass correlation coefficients ranged from 0.64 [p < 0.05] to 0.89 [p < 0.001]). For the amygdala, intrarater reliability was 0.92 (p = 0.001) and interrater reliability was 0.85 (p = 0.003). For the hippocampus, intrarater reliability was 0.97 (p = 0.001) for the whole hippocampus, 0.86 (p = 0.001) for the corpus/tail and 0.96 (p = 0.001) for the head. The interrater reliability was 0.85 (p = 0.001) for the whole hippocampus, 0.74 (p = 0.02) for the corpus/tail and 0.78 (p = 0.01) for the head.
There were no differences between the UHR group, first-episode group and control group for age, sex distribution or handedness. Whole-brain volume did not differ significantly between the 3 groups ().
We observed significant differences among the 3 groups in the size of the right hippocampal corpus and tail (F2,78 = 5.40, p = 0.006), and the differences approached significance for the volumes of the left hippocampal corpus and tail (F2,78 = 2.84, p = 0.064). Exploratory analysis revealed differences in the volume of the left amygdala among the groups (F2,78 = 3.17, p = 0.047). We found no differences in the size of the right amygdala and in the volume of the right and left hippocampus. Post-hoc t tests revealed that the UHR patients had significantly smaller volumes of the right (t56 = −2.90, p = 0.005) () and left hippocampal corpus and tail (t56 = −2.09, p = 0.047) () than did the controls.
Mean right hippocampal corpus/tail volumes, with p values from post-hoc t tests. *Significant at p < 0.05 compared with healthy controls. **Significant at p < 0.01 compared with healthy controls.
Mean left hippocampal corpus/tail volumes, with p values from post-hoc t tests. #Significant at p < 0.10 compared with healthy controls. *Significant at p < 0.05 compared with healthy controls.
Ultra high-risk converters had significantly smaller volumes of the right hippocampal corpus and tail than did nonconverting UHR patients (mean 1.42 [SD 0.21] v. 1.58 [SD 0.18] cm3; Z = −2.23, p = 0.037) After we corrected the values for sex, the difference was still significant (Z = −2.47, p = 0.031), whereas the difference for the left side was not significant (mean 1.43 [SD 0.21] v. 1.53 [SD 0.22] cm3; Z = −1.37, p = 0.13). There was no difference in amygdalar volume (mean 1.82 [SD 0.34] v. 1.91 [SD 0.29] cm3; p = 0.83). Converters were slightly more ill compared with nonconverters (PANSS positive: 12.4 [SD 3.4] v. 10.4 [SD 3.0]; Z = −1.74, p < 0.10; PANSS negative: 15.1 [SD 5.0] v. 9.3 [SD 2.8]; Z = −4.01, p < 0.01).
First-episode patients differed from controls not only in their right (t50 = −2.31, p = 0.025) and left hippocampal corpus and tail volumes (t50 = −1.83, p = 0.061) but also in the left amygdalar volume (t50 = −2.27, p = 0.028), which was considerably smaller in first-episode patients than in controls (). The UHR and first-episode patients differed significantly only in left amygdalar volume, with first-episode patients having smaller volumes (t50 = 2.27, p = 0.028). We found no differences in right or left hippocampal volume between UHR and first-episode patients.
Mean left amygdala volumes, with p values from post-hoc t tests. *Significant at p < 0.05 compared with healthy controls.
We found no significant correlation coefficients for whole brain volume and any of the ROI parameters (p > 0.05). Our analyses of variance using whole brain volume as a covariate revealed that group differences for right hippocampal corpus and tail volume remained significant (F2,78 = 5.06, p = 0.009). There was only a marginal influence of whole brain volume on left hippocampal corpus and tail size (F2,78 = 2.48, p = 0.091) as well as on the left amygdala (F2,78 = 3.06, p = 0.053) (). Although medication (2-level factor: medication taken or not) in the 2 patient groups significantly influenced group comparisons of the left hippocampal corpus and tail volume (F2,50 = 1.54, p = 0.22); no such effect was observed for right hippocampal corpus and tail volume (F2,50 = 4.00, p = 0.022) or left amygdalar size (F2,50 = 3.35, p = 0.040).
Values of hippocampal and amygdalar volumes for ultra high-risk, first-episode and healthy participants
The main results did not change when we performed ANCOVA using sex or age as covariates. When we performed a multivariate ANCOVA (general linear model) analysis with “right/left hippocampus corpus/tail” as repeated measurements within the participant factor, “group” and “sex” as between-subject factors and “total brain volume” as a covariate, the effect for “group” was still significant (F2,76 = 4.22, p = 0.018). When we performed the same analysis for “left/right amygdala,” there was no longer a significant effect of group (F2,76 = 1.96, p = 0.14). Finally, we found no significant differences in size between the left and right amygdala (t79 = 0.73, p = 0.47) and hippocampal corpus/tail (t79 = 0.11, p = 0.92). There were no significant correlations between general, positive or negative symptomatology, as measured with PANSS, and any of the volume parameters for the ROIs.