Evidence that reduced gray matter volume in psychotic disorder is associated with exposure to environmental risk factors.

The aim of this study was to examine whether cannabis use, childhood trauma and urban upbringing are associated with total gray matter volume (GMV) in individuals with (risk for) psychotic disorder and whether this is sex-specific. T1-weighted MRI scans were acquired from 89 patients with a psychotic disorder, 95 healthy siblings of patients with psychotic disorder and 87 controls. Multilevel random regression analyses were used to examine main effects and interactions between group, sex and environmental factors in models of GMV. The three-way interaction between group, sex and cannabis (χ2 =12.43, p<0.01), as well as developmental urbanicity (χ2 = 6.29, p = 0.01) were significant, indicating that cannabis use and developmental urbanicity were associated with lower GMV in the male patient group (cannabis: B= -32.54, p < 0.01; developmental urbanicity: B= -10.23, p=0.03). For childhood trauma, the two-way interaction with group was significant (χ2 = 5.74, p = 0.02), indicating that childhood trauma was associated with reduced GMV in the patient group (B=-9.79, p=0.01). The findings suggest that reduction of GMV in psychotic disorder may be the outcome of differential sensitivity to environmental risks, particularly in male patients.

Bone Mineral Density as a Marker of Cumulative Estrogen Exposure in Psychotic Disorder: A 3 Year Follow-Up Study.

Altered estrogen-induced neuroprotection has been implicated in the etiology of psychotic disorders. Using bone mineral density as a marker of lifetime estrogen exposure, a longitudinal family study was conducted to discriminate between etiological mechanisms and secondary effects of disease and treatment. Dual X-ray absorptiometry scans were acquired twice, with an interval of 3 years, in 30 patients with psychotic disorder (male (M)/female (F): 24/6, mean age of 32 years at second measurement), 44 non-psychotic siblings of patients with a psychotic disorder (M/F: 26/18, mean age 32) and 27 controls (M/F: 7/20, mean age 35). Total bone mineral density, Z-scores and T-scores were measured in the lumbar spine and proximal femur. Associations between group and bone mineral density changes were investigated with multilevel random regression analyses. The effect of prolactin-raising antipsychotic medication was evaluated. (Increased risk of) psychotic disorder was not associated with disproportionate bone mineral density loss over a three year period. Instead, femoral bone mineral density measures appeared to decrease less in the patient versus control comparison (total BMD: B = 0.026, 95% CI 0.002 to 0.050, p = 0.037; Z-score: B = 0.224, 95% CI 0.035 to 0.412, p = 0.020; and T-score: B = 0.193, 95% CI 0.003 to 0.382, p = 0.046). Current or past use of a prolactin-raising antipsychotic medication was not associated with bone mineral density changes. In this small longitudinal study, there was no evidence of ongoing estrogen deficiency in psychotic disorder as there was no excessive loss of bone mineral density over a 3-year period in patients using antipsychotic medication.