Elsevier

Epilepsy & Behavior

Volume 64, Part A, November 2016, Pages 180-185
Epilepsy & Behavior

Early childhood trauma and hippocampal volumes in patients with epileptic and psychogenic seizures

https://doi.org/10.1016/j.yebeh.2016.09.015Get rights and content

Highlights

  • Patients with PNES report having experienced significantly more childhood trauma than those with epileptic seizures.

  • An association was found between history of sexual abuse and reduced left hippocampal volume in both patient groups.

  • Patients reporting having experienced childhood trauma scored higher on measures of psychiatric symptomatology.

Abstract

Objective

Exposure to early life childhood trauma has been implicated as resulting in a vulnerability to epileptic and psychogenic nonepileptic seizures (PNES), hippocampal atrophy, and psychiatric disorders. This study aimed to explore the relationships between childhood trauma, epilepsy, PNES, and hippocampal volume in patients admitted to a video-electroencephalogram monitoring (VEM) unit.

Methods

One hundred thirty-one patients were recruited from the Royal Melbourne Hospital VEM unit. The diagnostic breakdown of this group was: temporal lobe epilepsy (TLE) (32), other epilepsy syndromes (35), PNES (47), other nonepileptic syndromes (5), both epilepsy and PNES (6), and uncertain diagnosis (6). All patients completed a questionnaire assessing exposure to childhood trauma, the Childhood Trauma Questionnaire (CTQ), as well as questionnaires assessing psychiatric symptomatology (SCL-90-R), Anxiety and Depression (HADS), quality of life (QOLIE-98) and cognition (NUCOG). Volumetric coronal T1 MRI scans were available for 84 patients. Hippocampal volumes were manually traced by a blinded operator.

Results

The prevalence of childhood trauma in patients with PNES was higher than in patients with other diagnoses (p = 0.005), and the group with PNES overall scored significantly higher on the CTQ (p = 0.002). No association was found between CTQ scores and hippocampal volumes; however, patients with a history of sexual abuse were found to have smaller left hippocampal volumes than patients who had not (p = 0.043). Patients reporting having experienced childhood trauma scored lower on measures of quality of life and higher on measures of psychiatric symptomatology.

Significance

Patients with PNES report having experienced significantly more childhood trauma than those with epileptic seizures, and in both groups there was a relationship between a history of having experienced sexual abuse and reduced left hippocampal volume. Patients with PNES and those with epilepsy who have a history of childhood trauma have overall worse quality of life and more psychiatric symptomatology.

Introduction

Childhood trauma has been identified as a risk factor for a range of psychiatric disorders including depression, schizophrenia, borderline personality disorder, and posttraumatic stress disorder [1]. Hippocampal atrophy has been associated with each of these disorders [2], [3], [4], [5] and may represent an effect of early trauma on hippocampal development. The mechanisms by which early childhood trauma leads to psychiatric conditions and hippocampal atrophy may involve trauma-induced dysregulation of the hypothalamic pituitary axis and increased circulating cortisol levels [6]. These psychiatric conditions are common in people with epilepsy, as is hippocampal atrophy [7]. Exposure to early life stress has been found to be associated with an increased vulnerability to limbic epileptogenesis later in life in rodent models [6], [8], [9]. Exposure to childhood psychological trauma, in particular sexual abuse, has been strongly associated with the development of psychogenic nonepileptic seizures (PNES), which are often comorbid with epilepsy [10]. It is possible that exposure to childhood trauma represents a common predisposing factor to epilepsy, in particular temporal lobe epilepsy (TLE), to the psychiatric comorbidities that affect many patients, and to PNES.

Chronic exposure to stress hormones in early life has been observed to lead to modification of hippocampal ion channel function and neuronal excitability in animal models [11]. A proposed mechanism is that persistent psychological stress results in increased L-type calcium channel amplitude within CA1 [11]. L-type calcium channels are high voltage-activated channels that allow passage of calcium ions through the neuronal cell membrane [11]. Ongoing glucocorticoid receptor-mediated L-type calcium channel enhancement results in increased influx of calcium into CA1 neurons [11]. This results in increased excitability of the cells, impairing normal functioning, and LTP-related plasticity [11]. It has been shown in a range of laboratory animals that increased glucocortisone exposure results in hippocampal structural changes, including atrophy of dendritic processes, death of pyramidal cells in the CA3 and CA1 region, and inhibition of dentate granule cell neurogenesis [12]. In humans, physiological states with prolonged elevation of glucocorticoids, such as Cushing's syndrome, major depression, and posttraumatic syndromes, are associated with reduced hippocampal volume and impaired hippocampal-associated memory [13], [14], [15]. These stress hormone-induced changes represent a possible mechanistic pathway to memory-related issues, psychiatric disorders, and the development of limbic neurological disorders, such as TLE.

Certain forms of early life trauma, in particular, physical and sexual abuse, are commonly reported in patients with PNES [16], [17]. Adults who have experienced severe childhood trauma have a decrease in the volumes of their hippocampus, which has been implicated in their increased risk of developing psychiatric disorders such as depression and anxiety [17]. However, the association between childhood trauma and reduced hippocampal volume has been inconsistently reported, with a number of studies finding no correlation [18], [19]. Studies in animal models of epilepsy have shown that exposure to early life stress is associated with an increased vulnerability to developing epilepsy, particularly TLE [8], [20], [21]. Temporal lobe epilepsy is the most prevalent form of focal-onset epilepsy in adults, and many cases are due to hippocampal mesial temporal sclerosis and atrophy [6].

Despite the growing evidence of neurological damage caused by early life trauma, few studies have specifically investigated the prevalence of childhood trauma in patients with epilepsy, and none have examined the relationship with hippocampal volumes. We report a cross-sectional study that aimed to examine associations between childhood trauma, epileptic syndromes and PNES, and hippocampal volumes. It was hypothesized that patients with PNES would have a higher prevalence of childhood trauma than patients with other diagnoses, and that this would also be higher in patients with TLE than those with other epilepsy syndromes. We also hypothesized that hippocampal volumes would be smaller in patients with a history of childhood trauma as compared with those without.

Section snippets

Recruitment

All eligible patients admitted to the Royal Melbourne Hospital video-EEG monitoring (VEM) unit between May 2011 and August 2013 were invited to participate in this study during their admission. The inclusion criteria included admission to the VEM unit and adequate English language ability. Patients with an intellectual disability severe enough to impair their understanding of the questionnaires were excluded. Two hundred forty-seven eligible patients were admitted to the VEM unit over the

Results

Of the 131 patients recruited to the study, 32 were diagnosed with TLE, 35 with other epilepsy syndromes, 47 with PNES, 5 with other nonepileptic diagnoses, 6 with both epilepsy and NES, and 6 patients were considered nondiagnostic. As the groups with other nonepileptic diagnoses, both epilepsy and NES, and nondiagnostic groups were small in number, they were not included in diagnostic group comparisons. Differences in age, gender, education level and psychiatric comorbidity between diagnostic

Discussion

Previous studies have reported a high prevalence of childhood trauma in patients with PNES [25], [26]; however, relatively few studies have examined the prevalence of childhood trauma in patients with epilepsy. In the current study, a self-report CTQ was used to quantify childhood trauma in patients with epilepsy and PNES. A significantly higher prevalence of early life trauma was found among patients with PNES compared with patients with epilepsy — with 36% of patients with PNES and 15% of

Ethics

We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Disclosure

The study was funded by grants to Terence J. O'Brien from the National Health and Medical Research Council (NHMRC) (grant number 566843) and from the Royal Melbourne Hospital Neuroscience Foundation. The remaining authors have no conflicts of interest.

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