Psychiatric Comorbidity in Epilepsy

Abstract

Epilepsy is a disease of the brain defined by recurrent epileptic seizures with various clinical presentations. The disorder has neurobiological, cognitive, psychological, and social consequences. Many of the epilepsies are associated with comorbidities with a potential to affect the course and treatment of the disorder. Over the last couple of decades there has been increasing awareness of an association between psychiatric disorders and epilepsy. Psychiatric symptoms in epilepsy were long regarded as mere consequences of the epilepsy and its treatment. However, research has revealed a bidirectional relationship between seizures and psychiatric disorders, meaning that the presence of one increases the risk of developing the other. This thesis comprises four studies on the relationship between epilepsy and psychiatric symptoms. Paper I and III are population-based retrospective observational studies investigating prevalence and directionality. Paper II is a case report illustrating the complexity of ictal psychiatric symptoms and Paper IV is a retrospective case-control study where clinical epilepsy predictors of psychiatric comorbidity are in focus. In Paper I, we used diagnostic codes from the specialist health care services to compare the proportion and age and sex distribution of substance use disorders and psychotic disorders among adults with epilepsy to the population without epilepsy. Overall, 0.9% of Norwegian adults had been registered with epilepsy in somatic hospitals during 2008-2012. We found an elevated adjusted relative risk for substance use disorders, bipolar disorders, and psychoses in people with epilepsy. The prevalence of these disorders was higher in all agegroups and both sexes of people with epilepsy compared to the population without epilepsy, it was also higher when compared to patients with diabetes, another chronic disorder. Paper II is a case report where we explored ictal psychiatric symptoms in the form of complex visual pseudo-hallucinations. The ictal symptoms ranged from simple, unilateral visual phenomena of flickering light to bilateral scenic visions of places feeling familiar. Ictal electroencephalography (EEG) findings and seizure semiology corresponded to a lesion in the posterior section of the right parahippocampal gyrus which is part of the neuronal network responsible for linking visual information with memory and spatial mapping and navigation. The findings suggest that this particular network is crucial for the semiology of experiential seizures with visual hallucinations and elements of recall. In Paper III, we investigated the directionality of epilepsy and psychosis by using prescription data. The prevalence of epilepsy in the adult population of Norway was 0.8%, the same as for psychosis. Moreover, the prevalence of psychosis in epilepsy was 2.8% and that of epilepsy in psychosis was 3.1%. Our study confirmed a bidirectional relationship, but surprisingly, we found that a larger portion of subjects (56%) had started antipsychotic treatment prior to onset of epilepsy treatment than the other way around. In Paper IV we aimed to study the prevalence of psychiatric comorbidity according to clinical epilepsy characteristics in a sample of 448 HUNT-participants with validated and classified epilepsy. We found that 35% had at least one psychiatric disorder. The prevalence was equal in focal and generalized epilepsy but was significantly lower in those with an unknown epilepsy type. In focal epilepsy, unknown etiology, presence of focal to bilateral tonic clonic (FTC) seizures, a younger age at epilepsy onset, and being female were characteristics associated with an increased prevalence of psychiatric comorbidity. Structural etiology and age at epilepsy onset ≥ 60 years were features accompanied by a reduced risk. Interestingly, those with epilepsy resolved at final follow-up had a slightly higher prevalence of psychiatric comorbidity compared to those with active epilepsy. The findings show that prevalence varies according to clinical characteristics of epilepsy and support a potential shared susceptibility for epilepsy and psychiatric disease. The present studies provide clinically relevant knowledge about prevalence and risk factors of psychiatric comorbidity in people with epilepsy in Norway. Future research should further explore the multifactorial mechanisms behind this association.