Preliminary evidence for an association between aggressive and hostile behaviour and 3 alpha,5 alpha-tetrahydroprogesterone plasma levels in schizophrenia

Objective: Because it has been suggested that agents acting on the gamma-aminobutyric acid-A (GABA(A)) receptor complex, such as the neuroactive steroid 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), may be biologic modulators of aggression, we aimed to measure 3alpha,5alpha-THP plasma concentrations in subjects with schizophrenia in order to investigate a possible relation with aggressive and hostile behaviour. Methods: Eight outpatients with schizophrenia diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), were included. Aggression and hostility were assessed using the Modified Overt Aggression Scale and the paranoid/belligerence symptom cluster of the Positive and Negative Syndrome Scale. Plasma samples were obtained 1 hour before psychometric assessment and were quantified for 3alpha,5alpha-THP using a highly sensitive and specific combined analysis by gas chromatography-mass spectrometry. Results: Increased aggressiveness and hostility were associated with increased 3alpha,5alpha-THP plasma levels (Pearson r = 0.72, p = 0.043 and Pearson r = 0.72, p = 0.041, respectively). Conclusions: These preliminary results suggest that the neuroactive steroid 3alpha,5alpha-THP may affect aggression and hostility in humans.