Understanding and mitigating adverse health outcomes in mental illness

  • Author / Creator
    Lodhi, Rohit J.
  • Patients who have a severe mental illness such as psychosis experience a greater burden in terms of poor physical and mental health outcomes or adverse health outcome/s (AHO). The etiological factors for AHO include the illness itself, medication side effects, poor diet and lifestyle, substance use, and co-morbid medical conditions. AHO have a significant impact on the quality of life of those experiencing psychosis and efforts should be made to mitigate them. Poor bone health and metabolic syndrome are two physical AHO that have a close relationship with antipsychotic and other medications. Almost half of those who have psychosis also have a lifetime history of substance misuse, and substances such as cocaine and cannabis can independently produce a range of physical and psychological AHO. Cannabis has been associated with the AHO of a reduction in the age of onset of psychosis. The goal of my thesis is to understand and examine interventions to mitigate selected AHO in those with a mental illness. The selected AHO examined by me are poor bone health, excessive body weight, substance use and earlier age of onset of psychosis. In Chapter 2, I investigated the effect of adding and/or switching to aripiprazole on markers of bone turnover and gonadal hormones. A number of studies have now reported that antipsychotic medications are associated with an increased risk of reduced bone mass, osteoporosis and, metabolic syndrome. Aripiprazole is a partial agonist at the D2 receptor and hence does not elevate levels of the hormone prolactin. The work presented in Chapter 2 demonstrates that switching to and/or addition of aripiprazole in patients who have been on other antipsychotic medications significantly reduces the AHO of high prolactin. In terms of the effects of the same intervention on the AHO of poor bone health, I also observed that markers of bone turnover changed in a beneficial manner, only in those switching to aripiprazole. Chapter 3 has three subsections on the AHO of metabolic syndrome and excessive weight/ high BMI (body mass index). In 3.1, I compared groups of patients treated at either of two metabolic treatment clinics and a control group. My main outcome measure was weight loss over time. The population treated at a metabolic clinic with a dietician was the only one with significant weight loss. The work in Chapter 3 highlights the importance of access to a dietician in reversing the AHO of excessive weight in those with a severe mental illness. I also present two reviews in Chapters 3.2 and 3.3 highlighting the relationship between cannabis, alcohol, and measures of metabolic dysfunction. In Chapter 4, I examine a genetic variant and lifetime cocaine use in psychiatric patients. In a group of Canadian Caucasian patients who were referred for psychosis, I observed that the likelihood of having a history of cocaine use was significantly related to the G/G genotype of COMT rs4680 [G>A], even after adjustment for relevant covariates. COMT rs4680 [G/G] had a stronger association if the number of other lifetime substances was used in generating a new categorical variable for those with a history lifetime cocaine use. Lastly, in Chapter 5, I examined the potential contributions from interaction of two single nucleotide polymorphisms, BDNF rs6265 [G>A] and AKT1 rs2474732 [T>C], with gender and/or regular cannabis use for an effect on age of onset of psychosis in Canadian Caucasian patients. I observed a trend for BDNF rs6265 [A/A] by gender interaction on the age of onset of psychosis when adjusted for age of regular cannabis use.

  • Subjects / Keywords
  • Graduation date
    Spring 2018
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
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