Throughout history, epilepsy has been viewed as being caused by evil possession, a curse, and even as a divine intervention by God. Hippocrates, in The Sacred Disease written in 400 BC, first suggested that epilepsy was a disease with a natural cause, not a divine cause. During the Greco-Roman era, the term “lunatic” was used to describe individuals with epilepsy separate from “maniacs” who were possessed by evil (Hill, 1981). In the Middle Ages, epilepsy was viewed as mystical, magical, or caused by possession of evil spirits, and this view remained as the most prominent cause of epilepsy until the seventeenth and eighteenth centuries (Temkin, 1971).

In the mid- to late nineteenth century with the emergence of neurology from psychiatry (Reynolds & Trimble, 2009), Hughlings Jackson (1931) described epilepsy as “occasional, sudden excessive, rapid and local discharges of gray matter”. In France, Briquet (1859) and Morel (1860) identified psychological disturbances as occurring as part of the seizure itself (ictal) and between seizures (interictal) resulting in cognitive and behavioral dysfunction. Gowers (1881) described the difference between epileptic convulsions and nonepileptic convulsions. In Europe with the development of institutions and hospitals for the insane, individuals with epilepsy were sent to these institutions and were treated by psychiatry until the twentieth century (Reynolds & Trimble, 2009). In the 1940s and 1950s after the EEG began to be used clinically, the temporal lobe focus in epilepsy was identified in 1949, and with the increased understanding of the limbic system, it was often anticipated that people with epilepsy would also have psychological problems. By the 1960s the World Health Organization (WHO) classified epilepsy as a neurological disorder, not a psychiatric disorder due to the identification of preictal, ictal, postictal, and interictal psychiatric symptoms (Reynolds & Trimble, 2009).

Around that time, a study in England reported that 29 % of individuals with epilepsy had psychological issues (Pond & Bidwell, 1960). In Iceland, Gudmundsson (1966) found that 50 % of the sample had psychological or personality changes with more psychological problems associated with brain lesions. Similarly Graham and Rutter (1968) reported a higher rate of psychiatric disorders among individuals with brain lesions and/or mental retardation. Currently, it is understood that there are a complex number of factors including biological, medication, and social factors that influence the expression of psychopathology in epilepsy (LaFrance, Kanner, & Hermann, 2008; Swinkels, Kuyk, van Dyck, & Spinhoven, 2005). Today, it is commonly understood that people with epilepsy are at a higher risk for psychiatric disorders compared to the general population (LaFrance et al., 2008), and this was exemplified by Fisher et al. (2005) proposing that the definition of epilepsy includes the coexistence of psychiatric disorders.

The prevalence of psychiatric disorders ranges from 19 % to 80 % (Swinkels et al., 2005). Swinkels and collaborators (2005) attribute the variability in rates to heterogeneity of samples and lack of control groups. Additionally, very few of these studies are population based, and as a result, many studies are based on tertiary care center samples possibly biasing the sample with more severe forms of epilepsy and higher rates of psychiatric disorders (Lacey, Salzberg, Roberts, Trauer, & D’Souza, 2009). Finally, different methodologies have been utilized to measure the presence or absence of psychiatric comorbidity in epilepsy including medical record reviews, self-report measures, psychiatric interviews, and self-identifying as having a particular psychiatric disorder. Davies, Heyman, and Goodman (2003) and Tellez-Zenteno, Patten, Jette, Williams, and Wiebe (2007) utilized community-based samples and similar interview-based methodologies and reported lower rates of psychiatric comorbidity (37 and 23.5 %, respectively).

The most prevalent psychiatric diagnoses in epilepsy include mood disorders, anxiety disorders, and psychotic disorders. Depression is the most common psychiatric disorder in epilepsy with lifetime prevalence rates reported from 20 to 60 %, which is consistently higher than the general population with lifetime prevalence rates of 16–20 % (Kessler et al., 2005). In community-based samples, Ettinger, Reed, and Cramer (2004) used the Center for Epidemiologic Studies Depression Scale (CES-D) and found that 36 % of the sample endorsed symptoms of depression, while Mensah, Beavis, Thapar, and Kerr (2006) used the Hospital Anxiety and Depression Scale (HADS) and reported that 11.2 % endorsed symptoms of depression. Based on the Clinical Interview Schedule (CIS), Edeh and Toone (1987) reported that 22 % of their sample met criteria for depression. Tellez-Zenteno et al. (2007) utilized the Composite International Diagnostic Interview (CIDI) and reported that 17.4 % of their sample had depression. Adding to the complexity of psychiatric comorbidity in epilepsy, Hesdorffer, Hauser, Annegers, and Cascino (2000) and Hesdorffer, Hauser, Olafsson, Ludvigsson, and Kjartansson (2006) reported that individuals with a history of depressive disorders or suicidal behavior were at increased risk to develop epilepsy overtime, indicating that there may be a bidirectional relationship between psychiatric disorders and epilepsy.

When compared to depression, anxiety disorders are less common in the general population with lifetime prevalence rates ranging from 1.9 to 5.1 % (Wittchen et al., 2002; Wittchen, Zhao, Kessler, & Eaton, 1994). However, anxiety disorders are thought to be the second most common psychiatric disorder in epilepsy with prevalence rates ranging from 11 to 40 %. In a multicenter study, 174 consecutive adults were interviewed using the Mini International Neuropsychiatric Interview (MINI), and 30 % of the sample met criteria for an anxiety disorder (Jones et al., 2003). Based on the CIDI, Swinkels, Kuyk, de Graaf, van Dyck, and Spinhoven (2001) reported that in a sample of 209 individuals with epilepsy, 24.9 % had anxiety disorders. Kobau, Gilliam, and Thurman (2006) reported that 39 % of the population-based sample had an anxiety disorder based on self-report.

Psychotic disorders are also more frequent in people with epilepsy compared to the general population (~3 %) (Perala et al., 2007) with some studies reporting rates as high as 10 % (LaFrance et al., 2008). As part of a chart review in a population-based health survey in Sweden, Forsgren (1992) reported that schizophrenia and psychosis were prevalent in 0.8 and 0.7 %, respectively. Utilizing International Classification of Diseases 9 (ICD-9) criteria, Stefansson, Olafsson, and Hauser (1998) found that 1.2 % of the sample had schizophrenia and 6.2 % had psychosis. Using similar criteria, Gaitatzis, Trimble, and Sander (2004) in the United Kingdom reported the prevalence of schizophrenia as 0.7 % and prevalence of psychosis as 9 %.

In summary, in spite of the fact that different methodologies and samples have been used, there is significant evidence to support the overall conclusion that there are higher rates of Axis I disorders among individuals with epilepsy when compared to the general population.

In epilepsy, little research has been conducted on the prevalence and types of Axis II disorders or personality disorders common in people with epilepsy. There are a number of studies using the Minnesota Multiphasic Personality Inventory (MMPI) to identify personality dysfunction in epilepsy, but the use of this instrument in epilepsy has been criticized (Provinciali, Franciolini, del Pesce, & Signorino, 1989), and for purposes of this chapter, the MMPI-based literature in epilepsy will not be reviewed. Additionally, very few studies have been conducted utilizing the Diagnostic and Statistical Manual of Mental Disorders (DSM) or ICD diagnostic criteria to identify and classify personality disorders in epilepsy. In a small sample of individuals with epilepsy (n = 21) and controls with other neurological conditions (n = 24), Schwartz and Cummings (1988) reported that 38 % of the individuals with epilepsy met DSM-III criteria for a personality disorder and only 4 % of controls. Fiordelli, Beghi, Bogliun, and Crespi (1993) evaluated 100 individuals with epilepsy seen in an outpatient clinic compared to 100 controls using the Clinical Interview Schedule (CIS) and DSM-IIIR diagnostic criteria. Only 4 % of individuals with epilepsy and no controls meet criteria for personality disorders. Victoroff, Benson, Grafton, Engel, and Mazziotta (1994) utilized the Structured Clinical Interview for DSM (SCID) to assess 60 surgery candidates and identified 18.33 % as meeting criteria for a personality disorder. Similarly Manchanda et al. (1996) assessed 300 epilepsy surgery candidates using DSM-IIIR criteria and found that 18.3 % had personality disorders with the primary disorders in Cluster C. In a much smaller sample using the SCID, Arnold and Privitera (1996) reported that among 27 people with epilepsy, 18 % were identified with personality disorders, of which avoidant personality disorder was the most common type. Based on the SCID-II, Lopez-Rodriguez et al. (1999) found that 21 % of 52 individuals evaluated for surgery had personality disorders particularly those in Cluster C. In a sample of individuals with epilepsy (n = 35) and individuals with nonepileptic seizures (n = 10), Krishnamoorthy, Brown, and Trimble (2001) found that among individuals with epilepsy, 17 % had personality disorders from Cluster A and 17 % from Cluster C.

Similar to the general population, Axis II disorders are less prevalent compared to Axis I disorders. The above studies indicated that approximately 18 % of the samples met criteria for a personality disorder. Additionally, Cluster C personality disorders appear to be a more common personality disorder in epilepsy. In the worldwide population, prevalence estimates indicate that 6.1 % have any personality disorder and of those 3.6 % are Cluster A, 1.5 % are Cluster B, and 2.7 % are Cluster C (Huang et al., 2009). Cluster A personality disorders include odd or eccentric characteristics and correspond to paranoid, schizoid, and schizotypal personality disorders. Cluster B personality disorders are described as dramatic, emotional, and erratic and include antisocial, borderline, narcissistic, and histrionic personality disorders. Cluster C personality disorders are those disorders that are considered anxious or fearful and include avoidant personality disorder, dependent personality disorder, and obsessive-compulsive personality disorder.

In a voxel-based morphometry (VBM) study, using the SCID-II, de Araujo Filho et al. (2009) examined the relationship between personality disorders, specifically Cluster B, juvenile myoclonic epilepsy (JME), and structural brain abnormalities. Significant reductions in the thalamus and increases in the mesioprefrontal and frontobasal region volumes were reported in individuals with JME and personality disorders. Since the orbitofrontal cortex is believed to be involved in mood reactivity, impulsivity, and social behavior and is considered to be dysfunctional in individuals with Cluster B personality disorders, the authors hypothesized that there is some indication there may be neuronal dysfunction impacting the development of seizures and personality disorders.

There have been a few personality disorder studies that have compared individuals with epilepsy to those individuals with nonepileptic psychogenic events (NES). In a study by Harden et al. (2009) using the SCID-II, individuals with NES were compared to individuals with epilepsy in order to identify the complex personality problems associated with NES and epilepsy. Individuals with NES were significantly more likely to have Cluster A and B diagnoses compared to individuals with epilepsy who were more likely to present with Cluster C diagnoses. Additionally, Kuyk, Swinkels, and Spinhoven (2003), using the CIDI, compared individuals with NES to individuals with NES and epilepsy. Among individuals with NES, somatoform disorders were more common, and those with combined NES and epilepsy were more likely to present with personality disorders with significantly higher rates of Cluster C disorders.

Similar to Axis I disorders, Axis II disorders appear to be common in individuals with epilepsy. However, the research in this area is somewhat limited and additional population-based studies in epilepsy need to be conducted.

When evaluating psychopathology in epilepsy, it is important to determine if there is a relationship between the psychiatric symptoms and the seizure itself. The most common symptoms associated with seizures are depression, anxiety, and psychosis. Typically, preictal depressive symptoms are reported as a dysphoric mood and may be present from hours to 1–3 days before a seizure (Blanchet & Frommer, 1986). Kanner, Soto, and Gross-Kanner (2004) systematically studied postictal symptoms of depression in individuals with refractory partial seizures and found that depressive symptoms were present 50 % of the time and lasted for a median duration of 24 h and occurred in 43 % of the sample. The most frequently reported depressive symptoms in the ictal phase include anhedonia, guilt, and suicidal ideation. Mood changes are typically brief, stereotypical, and followed by a change in consciousness as the ictus moves from a simple to complex partial seizure (LaFrance et al., 2008). Additionally, an interictal form of depression, interictal dysphoric disorder, has been described in the literature and is reported to be present in about 30 % of individuals with epilepsy and mood disorders. The symptoms are often described as chronic dysthymic symptoms that are variable and can be mixed with periods of euphoria, irritability, anxiety, paranoid feelings, and somatic symptoms (Blumer & Altshuler, 1998).

Symptoms of anxiety and fear are the most commonly reported ictal psychiatric symptoms. It can be the sole or predominant clinical symptom of a partial seizure or aura. It is usually believed to originate in the temporal lobe. Ictal panic can also be present. Ictal panic is short in duration lasting only 30 s; it is stereotypical in presentation, is out of context with the situation, and is often associated with confusion, altered consciousness, and automatisms. In 25 % of individuals with ictal panic, interictal panic attacks are also reported (Vazquez & Devinsky, 2003).

Ictal psychotic symptoms typically occur in the context of nonconvulsive status and are often accompanied by automatisms and unresponsiveness. An EEG will assist in confirming that the psychotic symptoms are ictal phenomenon. Postictal psychotic disorders in epilepsy typically have a short duration from hours to a few days and occur in 7 % of individuals with partial epilepsy (Kanner, 2004). The first symptom is often insomnia, and this is followed by symptoms that are often affective and delusional. An increase in secondarily generalized seizures, seizure duration of more than 10 years, and bilateral focus are risk factors for postictal psychotic episodes associated with epilepsy (LaFrance et al., 2008). Following a temporal lobectomy, new cases of psychotic disorders have been reported in 3.8–35.7 % of the surgical cases (Trimble, 1992), and some have hypothesized that this is related to the concept of “forced normalization” (Akanuma et al., 2005), which is believed to occur following the normalization of the EEG and subsequent appearance of psychotic symptoms.

Antiepileptic drugs (AEDs) can cause psychiatric symptoms (McConnell & Duncan, 1998). The GABAergic properties of some AEDs, like phenobarbital, primidone, benzodiazepines, tiagabine, and vigabatrin, can cause depressive symptoms. Additionally some of the newer AEDs also cause depressive symptoms including felbamate, topiramate, levetiracetam, and zonisamide (Kanner, 2003). Finally, depressive symptoms are associated with the discontinuation of some AEDs, and these medications include carbamazepine, valproic acid, and lamotrigine (Ketter et al., 1994).

Mood and anxiety disorders have been associated with the surgical treatment of epilepsy and primarily with anterior temporal lobectomy. Symptoms often present during the first 3–12 months following surgery. Depressive episodes are more likely to occur in individuals with a history of mood disorders. However, it is possible for there to be a complete remission of a mood disorder associated with a remission of seizures from surgery. Devinsky et al. (2005) reported that depression and anxiety improved after surgery in a group of patients with improved seizure control. Altshuler, Rausch, Delrahim, Kay, and Crandall (1999) reported that among individuals with temporal lobe epilepsy, 77 % had a history of depression prior to surgery, and 50 % had a remission in depressive symptoms following surgery. Only 10 % reported de novo depressive disorders after surgery.

It is important to have a clear understanding of the psychiatric symptoms that are present prior to, during, and after the seizure occurs. The relationship between the psychiatric symptoms and the seizure needs to be identified so that an appropriate diagnosis can be made.

Psychiatric disorders can negatively impact overall psychosocial functioning and quality of life among individuals with epilepsy. Several studies have demonstrated the negative effect of depression on quality of life. Using the BDI, Gilliam (2002) reported that the more symptoms of depression independently correlated with lower health-related quality of life when seizure frequency did not. Cramer, Blum, Reed, and Fanning (2003) found that depression, as measured by the CES-D, negatively impacted quality of life regardless of seizure type. Additionally, it was reported that even mild levels of depression had a negative impact on health-related quality of life. Also using the BDI, Boylan et al. (2004) found that in treatment resistant epilepsy, depression was a significant predictor of poorer quality of life compared to seizure variables which had little impact on quality of life. Finally, Johnson, Jones, Seidenberg, and Hermann (2004) reported that depression and anxiety disorders were independently more powerful predictors of lower quality of life than seizure variables like frequency and severity.

When examining psychosocial outcomes, a number of studies have identified a link between symptoms of depression and psychosocial status. Among individuals with epilepsy, Reisinger and DiIorio (2009) reported that unemployment, social support, and stigma were related to higher rates of depressive symptoms, as measured by the CES-D. Lee, Lee, and No (2009) found that social support, unemployment, anxiety, and self-efficacy were predictors of increased depressive symptoms as measured by the BDI. Grabowska-Grzyb, Jedrzejczak, Naganska, and Fiszer (2006) also examined the relationship between depression and psychosocial factors in individuals with epilepsy. They found that unemployment and low educational attainment were significant predictors of depressive symptoms as measured by the BDI and Ham-D. The authors discussed the high prevalence rates of unemployment and depression in people with epilepsy and indicated that it was difficult to understand if this significant relationship with unemployment was secondary to depression or separate from depression. Depression is known to have a negative impact on all facets of life including family, work, school, and friends, making it difficult to determine which came first.

The impact of psychiatric comorbidity in epilepsy on healthcare utilization has been examined in a few studies. Cramer, Blum, Fanning, and Reed (2004) reported that depression in epilepsy contributed to increased healthcare utilization. Based on the CES-D, depression, not seizure type, increased medical and psychiatric visits but did not increase emergency room visits or total hospital days. In a community-based sample of 652 individuals with epilepsy, Lacey et al. (2009) examined levels of psychological distress in a sample as measured by the Kessler 10 (K10) to see if there was a relationship between psychological distress and healthcare utilization. High levels of distress were reported in 24 % of the sample with epilepsy, and this was elevated compared to the general population (13 %). Individuals with epilepsy and high to very high levels of distress had significantly more visits to the general practitioner, hospital outpatient clinic, and emergency department compared to those with low to moderate distress. Additionally, individuals treated only by a specialist or in combination with a general practitioner had higher levels of distress compared to those who were treated solely by a general practitioner.

In summary, psychiatric comorbidity in epilepsy has adverse consequences on many life outcomes, making it a priority to identify and provide appropriate treatment to individuals with epilepsy who are doubly impacted by seizures and psychiatric disorders. Psychiatric comorbidity has been recognized as a priority and is listed as a Research Benchmark in the National Institute of Neurological Disorders and Stroke (NINDS) (Kelley, Jacobs, & Lowenstein, 2009). Additionally, with the recent alert in 2008 issued by the US Food and Drug Administration (FDA) that indicated that AEDs increased suicidal risk, there is a heightened urgency and awareness to assess and treat individuals with epilepsy and comorbid psychiatric conditions in order to reduce the risk of suicidal ideation and suicide in this population (US Department of Health and Human Services, May 21, 2008). As clinicians working with and providing services to people with epilepsy, it important for us to understand the implications and impact of psychiatric comorbidity in epilepsy. It is increasingly part of our responsibility to assess, identify, and provide recommendations for treatment of psychiatric disorders in this population.

General Health Questionnaire (GHQ) (Goldberg, 1972; Goldberg & Williams, 1991) is a screening instrument used to assess psychiatric distress related to general medical illness. It does not provide a psychiatric diagnosis but rather a screening instrument to determine if further evaluation is required. The GHQ has a threshold score indicating 95 % probability that criteria will be met for a psychiatric disorder. The GHQ was designed to evaluate psychological stress and ill health. It assesses the individual’s ability to carry out daily functions and identifies the development of new psychiatric symptoms not lifelong personality characteristics. The GHQ is a paper and pencil, self-administered questionnaire. There are four officially recognized versions: 60 items, 30 items, 28 items, and 12 items. The GHQ-30 is considered a better measure of psychological distress because it excludes items present in physical illness. It takes 3–15 min to complete depending upon which version is utilized.

Reliability: Good internal consistency was demonstrated on the 60-, 30-, and 12-item versions with Cronbach α coefficients from 0.82 to 0.93 and split-half coefficients from 0.78 to 0.95. The test-retest reliability appears to be the best for the 28-item version (r = 0.90).

Validity: The manual reports adequate content validity with each item having discrimination between those who are psychologically distressed and those who are not. The GHQ scores have been shown to correlate with psychiatric diagnoses based on structured interviews (r = 0.65–0.70). All versions demonstrated acceptable sensitivity and specificity with the 60-item version demonstrating the best specificity (89 %).

Utility: The GHQ has been used in a variety of clinical settings. It has been translated into 36 different languages. It is useful in screening for general emotional distress but should not be used for a diagnosing a specific disorder.

How to find it: The four different versions of the GHQ and manual are available from nferNelson: toll free, +44 845 602 1037; email, information@nfer-nelson.co.uk; or Web, www.​nfer-nelson.​co.​uk.

Kessler 10 (K10) and Kessler 6 (K6) (Kessler et al., 2002, 2003) are 10-item and 6-item self-report measures, respectively, that are used to produce a global measure of nonspecific psychological distress. They are based on questions of nervousness, agitation, psychological fatigue, and depression (e.g., feeling so sad that nothing can cheer you up) during the past 30 days. Responses are based on a 5-category Likert scale: all of the time, most of the time, some of the time, a little of the time, and none of the time. These scales were developed based on modern item response theory methods to improve the precision of the scales. This results in a dimensional measure of nonspecific distress in the range found in clinical samples in order to maximize the ability to discriminate cases of serious mental illness from noncases. The K10 and K6 scales were developed to be used in the US National Health Interview Survey (NHIS). The K10 was used in the National Comorbidity Survey Replication as well as in all the national surveys in the World Health Mental Health (WMH) Initiative. The K10 has been translated into 15 different languages.

Reliability: Internal consistency is high for both measures. The Cronbach α is reported to be 0.93 for the K10 and 0.89 for the K6.

Validity: The sensitivity of both measures ranges from 90th to the 99th percentile. A small validation study indicated that the six-item scale is as sensitive as the ten-item scale for distinguishing serious mental illness from noncases. The K10 and K6 have been shown to outperform the GHQ-12 (Furukawa, Kessler, Slade, & Andrews, 2003). The K6 has been shown to be more consistent in samples with physical disabilities.

Utility: It can be easily completed in 2–3 min. The K10 and K6 have been demonstrated to identify cases of anxiety and depression based on DSM-IV criteria. Additionally, the K10 and K6 can be used to measure secondary outcomes of nonspecific impairments as indicated by the Global Assessment of Functioning (GAF).

How to find it: It is one of the projects in the National Comorbidity Survey Harvard Medical School. Web, http://​www.​hcp.​med.​harvard.​edu/​ncs/​k6_​scales.​php.