7. Annotated Bibliography

Abstract

This annotated bibliography contains 6 peer reviewed scientific articles that show a linkage between schizophrenia and the usage of cannabis. I wish summarize each article and input on how it ties with my scientific controversy paper. The articles that will be used in this annotated bibliography are: “Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not” by Aas, Melle, Bettella et al. “White matter fractional anisotropy over two time points in early onset schizophrenia and adolescent cannabis use disorder: A naturalistic diffusion tensor imaging study” by Epstein and Kumra. “Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence” by French, Gray, Leonard, et al. “Cannabis, psychosis and schizophrenia: unravelling a complex interaction” by Hamilton. “The link between schizophrenia and substance use disorder: A unifying hypothesis” by Khokhar, Dwiel, Henricks, et el. “Schizophrenia risk from complex variation of complement component 4” by Sekar, Bialas, Rivera et al.

Annotated Bibliography

Aas, M., Melle, I., Bettella, F., Djurovic, S., Hellard, S. L., Bjella, T., … Tesli, M. (2017). “Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not”. Psychological Medicine48(1), 43–49. doi: 10.1017/s0033291717001209

In the paper “Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not,” Monica Aas and her researchers sought to demonstrate the link between psychosis (specifically schizophrenia and bipolar disorder) with use of cannabis before the first symptoms of the disease. They divided their study between frequency of use (daily/weekly/sporadic/no) and age of first use (before or after 18). They cited a Swedish study that showed those who used cannabis before the age of 18 were 2.4 times more likely to develop schizophrenia than those who did not use at all. Other studies referenced also showed that the more frequent the use, the earlier the symptoms of psychosis presented themselves. Through their study of 601 patients with psychosis and a control group of 415 healthy Norwegians, they were able to show that frequent use (daily or weekly) before the first symptoms was associated with a higher risk. Furthermore, the biggest difference in risk was between those who used frequently before 18, and those who never used. They also showed that a genetic risk of psychosis also implies a higher risk of using cannabis, suggesting that patients could be self-medicating the premorbid symptoms, but also stating that a separate study would need to be conducted to determine the reasons. They also suggested that a more detailed study could be conducted on their subject if the researchers had data on cannabis use in the control group, which Aas and her team did not. This paper helps me show the how cannabis can be associated with schizophrenia.

Epstein, K. A., & Kumra, S. (2015). “White matter fractional anisotropy over two time points in early onset schizophrenia and adolescent cannabis use disorder: A naturalistic diffusion tensor imaging study”. Psychiatry Research: Neuroimaging232(1), 34–41. doi: 10.1016/j.pscychresns.2014.10.010

In Katherine A. Epstein and Sanjiv Kumra’s paper “White matter fractional anisotropy over two time points in early onset schizophrenia and adolescent cannabis use disorder: A naturalistic diffusion tensor imaging study,” the researchers attempted to better understand the neurobiological mechanism underlying the increased risk of psychosis in adolescent cannabis users, specifically the effects use has on neurodevelopmental changes in white matter. They observed a group of adolescents with early onset schizophrenia disorders, and cannabis use disorder, and compared them to a healthy control group of adolescents, all between the ages of 10-23. They used diffusion tensor imaging to monitor fractional anisotropy in the brain at a baseline and once again after 18 months. Their study concluded that those with cannabis use disorder may demonstrate an adverse effect on white matter development in the parts of the brain that are associated with early onset schizophrenia disorders.  Use as an example of how there is a correlation between schizophrenia and cannabis.

French, L., Gray, C., Leonard, G., Perron, M., Pike, G. B., Richer, L., … Paus, T. (2015). “Early Cannabis Use, Polygenic Risk Score for Schizophrenia and Brain Maturation in Adolescence”. JAMA Psychiatry72(10), 1002. doi: 10.1001/jamapsychiatry.2015.1131

            In Leon French’s paper “Early Cannabis Use, Polygenic Risk Score for Schizophrenia, and Brain Maturation in Adolescence,” French and his researchers sought to determine whether cannabis use and brain maturation (specifically in males) is moderated by a polygenic risk score for schizophrenia. They gathered data on 1,574 participants across three different groups in Canada, Europe, and England, with the European group receiving a follow up MRI, four years later. Data included: information on cannabis use, magnetic resonance imaging studies of the brain, and a polygenic risk score for schizophrenia. The brain development they observed was specifically the mean cortical thickness. They found that, among those male adolescents with higher genetic risk for schizophrenia, that cannabis use had a adverse association with cortical thickness, but those males with low-risk genetics, and all females sampled, showed no similar associations. Use it as an example of opposing view and study for what I am trying to show.

Hamilton, I. (2017). “Cannabis, psychosis and schizophrenia: unravelling a complex interaction”. Addiction112(9), 1653–1657. doi: 10.1111/add.13826

In Ian Hamilton’s paper “Cannabis, psychosis and schizophrenia: unraveling a complex interaction,” Hamilton highlights the shortcomings of the many studies done on the subject, and the attempts of researchers to correct them — focusing specifically on two papers by Sven Andreasson and Wayne Hall. He goes on to detail the many reasons why studies on the subject before Andreasson and Hall’s were flawed, citing an initial failure to consider the dose-response relationship between cannabis use and psychosis, and a failure to adhere to the stress vulnerability model. Furthermore, he points out Hall’s reiteration of the fact that there was a lack in proper controlled studies of cannabis use, as they neglected to consider the use of tobacco and alcohol concurrently with cannabis. Hamilton then discusses how Andreasson was the first to acknowledge the importance of both dose-response considerations, and the application of the stress-vulnerability model. As a result, his findings we able to show that there was indeed a dose-response relationship between schizophrenia and cannabis use, along with the significant discovery that illnesses like schizophrenia can lie dormant until triggered by exposure to a psychoactive drug like cannabis. However, neither researcher was able to confidently prove a direct causal relationship between cannabis use and psychosis and schizophrenia. Hamilton concludes by commending these researchers on applying more considerate models to the study of this subject, while also pointing out there is still much left to consider in regard to conducting more detailed and controlled studies. I can use this as a counterargument for my thesis

Khokhar, J. Y., Dwiel, L. L., Henricks, A. M., Doucette, W. T., & Green, A. I. (2018). The link between schizophrenia and substance use disorder: A unifying hypothesis. Schizophrenia research194, 78-85.

                  In Khokhar’s paper, they looked at other studies looking at the epidemiological and genetic association with substance use and schizophrenia. Using these studies, they were able to make a hypothesis that genetic determinants of schizophrenia are increased when there is a risk of addiction. An increase of substances like cannabis in adolescence can increase the risk of development. Khokhar believes further studies should be done to strengthen this claim and help underpin the co-occurring disorders and also identifying potential intervention to treat this disorder. This article can be used as evidence of how the diathesis-stress model/ vulnerability-stress model can be applied to the link between schizophrenia and cannabis usage.

Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., … & Genovese, G. (2016). Schizophrenia risk from complex variation of complement component 4. Nature530(7589), 177.

                   In Aswin Sekar’s paper “Schizophrenia risk from complex variation of complement component 4”, Sekar discusses the genetic components that are associated with schizophrenia through gene expression and. C4 which is found in alleles is mostly associated with schizophrenia when there is a greater genes expression of C4A. They believe that synaptic pruning is also associated with schizophrenia, when viable synapses are damaged or eliminated. This can happen when there is a significant presence of C4 in the synapsis. This information can help explain the biological aspect of how the receptor CB1 is associated with C4 and the increase of synaptic pruning.