Depression after epilepsy surgery

Depression has become one of the most commonly reported and studied psychiatric co-morbidities of epilepsy. While different forms of depression have been specifi cally related to epilepsy, this paper focuses on neurobiological and psychosocial factors that predict major depression in patients with intractable focal epilepsy. It then examines how these factors may affect patient trajectories and outcome following epilepsy surgery. This provides a model of relevant clinical markers for epilepsy clinicians to identify patients at risk of depression so that preventative treatment strategies can be implemented. Neurology Asia 2013; 18 (Supplement 1) : 47 – 50 Address correspondence to: Sarah Wilson, Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, Victoria, 3010, Australia. Tel: +61-3-8344-6377; Fax: +61-3-9347-6618; e-mail: [email protected] INTRODUCTION A bidirectional relationship between depression and epilepsy has been proposed to account for their heightened comorbidity in terms of a shared pathogenic mechanism. Prevalence rates as high as 50% have been reported for depression in epilepsy, although this varies according to the community or hospital-based sample studied, and the focal or generalised nature of the syndrome. Nevertheless, up to one in two people with epilepsy may have a lifetime history of depression, while the risk of suicide is up to 10 times that of the normal population. This impact is considered more influential than all other co-morbid conditions, with health care costs estimated at 80% higher for depressed compared with nondepressed epilepsy patients. The prevalence of depression after epilepsy surgery is particularly high, and poses a challenge for clinicians to predict as it can arise de novo in patients who appear euthymic before surgery.4 Moreover post-operative suicide attempts highlight the paradoxical nature of outcome in ‘successful’ seizure free patients who no longer wish to live. Thus, a key goal of our Surgical Follow-up and Rehabilitation Program has been to identify those patients at risk of depression after surgery so that preventative strategies can be implemented to proactively manage this risk. The current paper focuses on the research our group has undertaken centering around two questions: (i) What are the factors that predict depression in intractable focal epilepsy? and (ii) How might these factors affect patient trajectories and outcome following epilepsy surgery? In particular, we performed a series of prospective longitudinal studies of patients undergoing mesial temporal resections (MTR) or nonmesial temporal resections (NMTR) for treatment of intractable focal epilepsy4-10, and assessed their mood at regular intervals before and after surgery (1, 3, 6, and 12 months). MARKERS OF DEPRESSION PRESURGERY Medically intractable seizures are well known to cause a range of psychosocial sequelae, some of which have also been linked to pre-operative depression. As shown by our research and that of others (Figure 1), these include a lack of employment and fi nancial dependence, as well as a family history of psychiatric illness, consistent with factors associated with depression in the general population. A family psychiatric history is thought to confer a genetic or “innate” risk, as may certain personality traits such as high neuroticism and low extraversion, with high neuroticism also associated with poor family adjustment. Thus, these fi ndings point to important interactions between innate risk and psychosocial factors in the presentation of depression before epilepsy surgery, rather than simply attributing depression to the psychosocial effects of having a chronic illness. Neurobiological markers of depression in epilepsy have also been identifi ed (Figure 1). In keeping with the general depression literature, our work has targeted limbic system structures and their connections known to play a role in mood disturbance. In particular, using voxel-based Neurology Asia 2013; 18 (Supplement 1) 48 morphometry we found a 27% increase in the volume of the subgenual prefrontal cortex in the contralateral hemisphere of patients with a history of depression. Moreover, a subset of this sample with mesial temporal lobe seizure foci also showed a 20% increase in ipsilateral amygdala volume.10 Consistent with previous research13, these fi ndings indicate that epilepsy patients with depression can have structural changes in their mood network that may be identified from neuroimaging investigations before surgery, providing the opportunity to implement preventative treatment strategies. PROFILING TRAJECTORIES AND PREDICTING OUTCOMES POSTSURGERY Previous research has shown that patients may follow a range of trajectories after surgery that relate not only to their seizure outcome, but also their cognitive, psychological and social functioning. While many patients experience an improvement in mood after surgery, others may show exacerbation of a preexisting mood disturbance or develop de novo depression, despite achieving seizure freedom. Our research profi ling depression after surgery suggests that around a third of patients experience major depressive disorder in the year following surgery, with similar rates for MTR and NMTR patients. The majority of these patients (70%) are diagnosed within the fi rst three months and experience persistent symptoms (65%) for at least 6 months within the follow-up period. Having a history of depression is a strong risk factor, with our data indicating that 75% of patients experiencing depression within 12 months of surgery have a lifetime history of depression, while the remaining 25% arise de novo. Strikingly, we found that only MTR patients developed de novo depression (13%) compared with no NMTR patients.9 Given that de novo patients often appear resilient before surgery and thus, can be challenging to predict, we performed a case series to identify psychosocial factors that were common across patients. These included high levels of perceived stigma before surgery, and signifi cant family confl ict after surgery. Both preceded the onset of de novo depression following MTR, and point to two possible mechanisms for depression after surgery. First, a neurobiological mechanism associated with disruption to limbic structures targeted by the surgical procedure, and second, psychosocial factors associated with adjusting to life after surgery. The latter can arise particularly in seizure free patients, who undergo a change in self-identity to “well” and desire increased autonomy and decreased carer support after surgery, as has been described as part of the burden of normality.14 Figure 1. Key neurobiological and psychosocial markers of patients at risk of major depression before and after surgery for intractable focal epilepsy (percentages represent average values). MTLE = mesial temporal lobe epilepsy; N = neuroticism; E = extraversion.