Cortical thickness abnormalities associated with depressive symptoms in temporal lobe epilepsy

Abstract

Depression in patients with temporal lobe epilepsy (TLE) is highly prevalent and carries significant morbidity and mortality. Its neural basis is poorly understood. We used quantitative, surface-based MRI analysis to correlate brain morphometry with severity of depressive symptoms in 38 patients with TLE and 45 controls. Increasing severity of depressive symptoms was associated with orbitofrontal cortex (OFC) thinning in controls, but with OFC thickening in TLE patients. These results demonstrate distinct neuroanatomical substrates for depression with and without TLE, and suggest a unique role for OFC, a limbic region for emotional processing strongly interconnected with medial temporal structures, in TLE-related depressive symptoms.

Introduction

Depression is a significant yet underappreciated problem affecting up to 55% of patients with treatment-resistant epilepsy [1]. Mood more powerfully predicts quality of life than seizure severity [2], and patients with epilepsy have a fivefold increased risk for suicide [3]. Although depressed mood may result partly from an expected psychological reaction to lifestyle limitations and stigma, there is evidence that depression in people with epilepsy differs phenomenologically and perhaps neurobiologically from depression in people without epilepsy.

Phenomenologically, depression in people with versus without epilepsy has been characterized by greater temporal variability in symptoms related to peri-ictal mood changes [1], prominent anhedonia [1], and decreased sadness [4]. These differences mean that depressive symptoms in epilepsy, although significant and requiring treatment, may not qualify for a diagnosis of major depression according to standard DSM-IV [5] criteria [6], [7], [8].

Neurobiologically, potential differences underlying depression in people with versus without epilepsy has not to our knowledge been investigated directly; the small number of prior studies examining the neuroanatomical correlates of depression in epilepsy has not included healthy controls. These studies have shown that in patients with temporal lobe epilepsy (TLE), the most common treatment-resistant adult epilepsy, major depression as well as subsyndromic depressive symptoms are associated with hippocampal atrophy [9], [10] and relative amygdalar enlargement [11], [12], [13]. In patients with depression but without epilepsy, a similar neuroanatomic pattern of hippocampal atrophy and relative amygdalar enlargement has been demonstrated [14], [15]. However, the majority of recent research attention has been focused on depression-related abnormalities in frontal regions involved in emotional regulation such as orbitofrontal cortex (OFC) [16], [17], anterior cingulate cortex [18], and dorsolateral prefrontal cortex [19]. Because studies of epilepsy-related depression have focused primarily on the temporal lobe, it is not known whether these frontal or other extratemporal regions are also involved in epilepsy-related depression.

To address these issues, we used unbiased whole-cortex MRI morphometric assessment to identify brain regions associated with depressive symptoms in patients with TLE and control subjects without TLE. To assess depressive symptoms, we used the Beck Depression Inventory II [20]. The BDI-II is self-report inventory assessing symptoms of depression that has been validated for use in medically healthy people as well as patients with epilepsy [21].