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Title: The impact of substance use on brain structure in people at elevated genetic risk of schizophrenia
Author: Welch, Killian A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2011
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A variety of structural abnormalities are consistent findings in schizophrenia. These include enlargement of the lateral and third ventricles and reduced volume of the frontal lobes, medial temporal lobes and thalami. These abnormalities are present in first episode subjects and may be detectable before the onset of clinical disorder. There is accruing evidence that substance misuse may contribute to an individual's risk of developing schizophrenia. Substance misuse is associated with similar brain abnormalities to those seen in schizophrenia and is often well established at the time of first presentation. This makes it difficult to ascertain if any of the structural abnormalities seen when individuals first present with psychosis are attributable to substance misuse. An understanding of the relationship between substance misuse and structural imaging abnormalities in people who are well but at high risk of schizophrenia is thus of great importance. It has the potential to yield important insights in to: (1) the role substance misuse may play in the development of structural brain abnormalities; and (2) how substance use may influence risk of developing the condition. A prospective cohort study with nested case-controlled comparison design was employed to examine the relationship between substance misuse, brain imaging abnormalities and the subsequent development of schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls at point of entry to the study. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco and structure volume were identified, this relationship being elucidated through the use of both volumetric and voxel-based morphometric image analysis techniques. Additionally, we established whether substance misuse up to the point of recruitment was associated with later risk of schizophrenia. In addition to the baseline scan, the first 57 high risk subjects recruited to the study also had a follow-up scan after approximately 18 months. As substance use between scanning points was known, this enabled longitudinal comparison of brain structural changes in high risk subjects who did and did not use the aforementioned drugs of abuse. This comparison was made using both volumetric and tensor-based morphometric image analysis techniques. In the baseline analysis, increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. The longitudinal analysis demonstrated that cannabis use between scanning points was associated with both bilateral thalamic and right anterior hippocampal volume loss. Alcohol and cannabis misuse by point of entry in to the study were associated with an increased subsequent risk of schizophrenia. This study provides prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available