Convergent data from epidemiological studies have found an association between cannabis use in adolescence and schizophrenia. Previously we have shown that schizophrenia is associated with FA abnormalities of frontal lobe. Present study describes the impact of cannabis use on frontal white matter development using DTI. We hypothesized those areas of the brain where there is ongoing development of white matter might be most susceptible to the neurotoxic influence of cannabis.
METHOD AND MATERIALS
Subject consisted of two groups of 28 adolescents with schizophrenia (cannabis-users=10) and 28 healthy volunteers (cannabis-users=6). A 3D SPGR and 25 directions DTI with matching FSE sequences were obtained. DTI images were corrected for spatial distortion and were transferred into Talairach space. Voxelwise statistical analysis was carried out using a t test (p<0.01) and an extent threshold of 200 voxels. Since the supplementary motor area (SMA) is consistently been observed as the area with ongoing development during adolescent we have primary focused on this region. Additionally, we have found a significant relationship between age and FA values in healthy comparison subjects (without substance abuse/dependence) in this region.
A two-way ANCOVA was performed with FA levels in the SMA as the dependent measure, patient grouping and cannabis status (+/-) as main effects and age as a covariate. The overall model was significant (p<0.001) with cannabis status (p<0.002) and age (p<0.003) as significant main effects. In patients, after controlling for gender and premorbid social deficits, cannabis use accounted for 20% of the variance in FA values of SMA. In patients, abnormalities of FA in the SMA region were significantly associated (r=0.55, p=0.008) with worse performance of working memory.
These data suggest that cannabis use is associated with an exacerbation of abnormal developmental trajectories of prefrontal cortex in schizophrenia. The relationship between lower FA values in the SMA and working memory provide further support for a hypothesis that adolescence-related neurodevelopmental events may contribute to the pathophysiology of cognitive dysfunction in schizophrenia.