Pituitary volume and clinical trajectory in young relatives at risk for schizophrenia

Stress and vulnerability likely interact to play a major role in psychosis. While much has been written about the neural diathesis-stress model in psychosis and its clinical risk states, little is known about HPA axis biomarkers in non-help-seeking individuals at familial high risk (FHR). We sought to prospectively measure pituitary volume (PV) in adolescents and young adults at FHR for schizophrenia and to follow their emerging sub-clinical psychotic symptoms and clinical trajectories. Forty healthy controls and 38 relatives of patients with schizophrenia or schizoaffective disorder were identified in Pittsburgh, USA. PV was derived from baseline 1.5 T magnetic resonance imaging. Chapman's schizotypy scales were acquired at baseline, and structured clinical interviews for DSM-IV-TR Axis I diagnoses were attempted annually for up to 3 years. Seven individuals converted to psychosis. PV did not differ between FHR and control groups overall. Within the FHR group, PV was positively correlated with Chapman's positive schizotypy (Magical Ideation and Perceptual Aberration) scores, and there was a significant group × PV interaction with schizotypy. PV was significantly higher in FHR subjects carrying any baseline Axis I diagnosis (p = 0.004), and higher still in individuals who went on to convert to psychosis (p = 0.0007). Increased PV is a correlate of early positive schizotypy, and may predict trait vulnerability to subsequent psychosis in FHR relatives. These preliminary findings support a model of stress-vulnerability and HPA axis activation in the early phases of psychosis.