Psychiatric comorbidity in multiple sclerosis : biological and epidemiological aspects

Multiple sclerosis (MS) is a chronic, neuroinflammatory disease and one of the leading reasons for neurological disability among young people in the Western World. MS patients commonly experience neuropsychiatric symptoms including depression and cognitive dysfunction. The aims of this thesis were to (study I-III) epidemiologically study the occurrence of common psychiatric diagnoses and their consequences, such as disability pension (DP) and suicide, among MS patients, and (study IV) examine the association between inflammatory biomarkers, depression and stressful events in a clinical cohort of MS patients. For studies I-III, Swedish national and clinical registers were used to identify patients with MS from the 1960s to 2012 (n=10,75029,617) and non-MS comparison subjects, as well as several covariates including sociodemographic data, disability pension, psychiatric diagnoses, prescriptions of psychiatric drugs, and attempted and completed suicide. Statistical analyses estimated the adjusted risks for a) having psychiatric diagnoses, b) the risk for being granted DP if having a psychiatric diagnosis, c) the prescription patterns of selective serotonin reuptake inhibitors (SSRIs), benzodiazepines and sleeping medications in the years around DP, and d) the risk for attempted and completed suicide. For study IV, 47 patients with MS in a clinical setting were assessed using self-rating scales and clinical interviews regarding symptoms and diagnosis of depression, and exposure to violence in childhood or adult life. Cerebrospinal fluid (CSF) interleukin (IL)-6 and -8 levels were analyzed and compared with results from the psychiatric ratings. In study I-III, MS patients were at higher risk for having most psychiatric diagnoses and medications compared to non-MS subjects. MS patients with psychiatric diagnoses or medications had a higher risk for DP compared to those without. MS patients with DP had a higher risk for prescription of SSRIs and benzodiazepines than non-MS subjects with DP. MS patients had a nearly doubled risk for both attempted and completed suicide. In study IV, higher IL-6 levels were associated with depressive symptoms and exposure to violence in adult life, while IL-8 levels were not associated with any investigated parameters. We conclude that MS patients are at risk for psychiatric comorbidity, with increased rates of serious consequences such as DP and attempted and completed suicide. Furthermore, DP is not associated with a decrease in psychiatric drug prescription, as in non-MS patients. Also, both depressive symptoms and exposure to violence were associated with an inflammatory biomarker in CSF in MS patients, further establishing the association between neuroinflammation, psychiatric symptoms and exposure to stress. LIST OF SCIENTIFIC PAPERS I. Brenner P, Alexanderson K, Bjorkenstam C, Hillert J, Mittendorfer-Rutz E, Tinghög P. Psychiatric diagnoses, medication and risk for disability pension in multiple sclerosis patients; a population-based register study. PLoS One. 2014 Aug 5;9(8):e104165. doi: 10.1371/journal.pone. 0104165 II. Brenner P, Mittendorfer-Rutz E, Jokinen J, Alexanderson K, Hillert J, Tinghög P. Prescribed psychiatric medication among multiple sclerosis patients before and after disability pension: a register study with matched controls. Social Psychiatry and Psychiatric Epidemiology. 2016 Jul;51(7):1047-54. III. Brenner P, Burkill S, Jokinen J, Hillert J, Bahmanyar S, Montgomery S. Multiple sclerosis and risk of attempted and completed suicide a cohort study. European Journal of Neurology. 2016 Aug;23(8):1329-36. IV. Brenner P, Granqvist M, Königsson J, Al Nimer F, Piehl F, Jokinen J. Cerebrospinal fluid immunomarkers in multiple sclerosis; relationship with stress exposure and severity of depression. Manuscript. CONTENTS 1 Background . 7 1.1 Multiple sclerosis . 7 1.1.