LAUSR

Abstract Background There is growing evidence suggesting that the abnormal pituitary volume (PV) may be an essential deficit in schizophrenia spectrum disorders, and PV may change depending on the stage of the illness. However, previous studies assessing PV in schizophrenia spectrum disorders, especially in ultra-high risk individuals, were confounding. The present study aimed to assess whether there would be alteration of the PV in patients with first-episode schizophrenia and their non-affected first-degree relatives. Methods This study recruited 147 subjects, including subjects with 62 first-episode schizophrenia (31 man, 31 female), 25 non-psychotic first-degree relatives (11 male, 14 female), and 60 healthy controls (30 male, 30 female). All of them underwent a T1 weighted image magnetic resonance imaging using 3T MRI Scanner (Siemens, Germany). All volumes were examined with the 3D-Slicer 4.10.1 (Surgical Planning Laboratory, Brigham and Women’s Hospital, USA; http://www. slicer.org/). The PV was traced in all coronal slices with well-defied boundaries (such as diaphragma sellae (superiorly), the sphenoid sinus (inferiorly), the cavernous sinuses(bilaterally)). The infundibular stalk was excluded while the bright posterior pituitary was included. All images were tranced manually by a trained rater who was blind to the participants’ group assignment. In a random subset of 24 cases, both the inter-rater reliability (intraclass correlation coefficient r=0.916, p<0.001) and the intra-rater reliability (intraclass correlation coefficient r=0.924 p<0.001) were high. We conducted MANCOVA with gender, and whole brain volumes (WBV) as covariates to compare the PV among the groups. Results We found no significant differences in gender ratio, age, and WBV (p>0.05) among the three groups, but patients with first-episode schizophrenia showed shorter length of education than healthy controls (p<0.001). As expected, we found that male participants in general (Mean ± SD: 486.85 ± 100.24) exhibited a prominently smaller PV than female participants (Mean ± SD: 562.13 ± 102.90) after controlling for WBV (t=25.087, p<0.001). Findings from MANCOVA analysis showed that although first-episode schizophrenia patients (Mean ± SD: 523.81 ± 116.41) and healthy controls (Mean ± SD: 513.17 ± 103.57) showed no significant difference in PV (F=0.581, p=0.447), there was a trend of statistical significance in their non-psychotic first-degree relatives (Mean ± SD: 557.85 ± 93.58) compared with healthy controls (F=3.334, p=0.072). We also found a negative correlation between the duration of treatment and PV in female schizophrenia patients (r=-0.398, p=0.029), whose mean duration of treatment was 4.71 months (SD=2.18 months). No significant correlation was observed in in male patients. Discussion Our findings found no alteration of PV in first-episode schizophrenia patients but a trend of enlargement was observed in their non-psychotic first-degree relatives. Moreover, female schizophrenia patients with longer duration of treatment exhibited smaller PV. These findings suggested that the enlarged PV might be an early detection signal for individuals with potentially high risk of developing into schizophrenia, and such an enlargement of PV might be responsive to antipsychotic medications.