For a long time, the correlation between epilepsy, seizures, and emotions has been a matter of debate, fascinating generations of clinicians and neuroscientists. In his famous quotation, Hippocrates reported that “melancholics ordinarily become epileptics, and epileptics, melancholics: what determines the preference is the direction the malady takes; if it bears upon the body, epilepsy, if upon the intelligence, melancholy.”1 This ancient observation has been recently revitalized by modern epidemiological data that suggest a bidirectional relationship between epilepsy and mood disorders and between epilepsy and suicide.2,3 However, psychiatric comorbidity in epilepsy represents not only a matter of intellectual interest but also an important variable that affects prognosis in terms of morbidity and mortality.
Mood and anxiety disorders are the most frequently reported psychiatric comorbidities with epilepsy, with a prevalence of 20% to 22%; however, in select populations, the prevalence can reach 50%.4 Reasons for the association are both biological and psychosocial. Epilepsy is a chronic disorder that brings about a number of social limitations and discriminations that lead to demoralization and poor self-esteem. Moreover, epilepsy and mood disorders seem to share a common neurobiology, with involvement of the limbic structures and the modulation of major neurotransmitter pathways by anticonvulsant medications.
Compared with mood disorders, psychoses seem to be relatively rare in patients with epilepsy but represent serious complications that affect morbidity and mortality. Epidemiological data indicate that the incidence of non-organic, non-affective psychoses, including schizophrenia and related disorders, is generally overrepresented in patients with epilepsy compared with the general population or those with other chronic medical conditions. Higher prevalence has been seen in hospitalized patients.5,6 The relationship between epilepsy and psychoses has strong neurobiological underpinnings related to the involvement of specific brain areas.
The issue of phenomenology and diagnosis of mood disorders
Mood disorders in epilepsy frequently go unrecognized and untreated because of lack of time, lack of training, and clinicians’ reluctance to refer patients because of psychiatric symptoms. In addition, up to 50% of patients with epilepsy and depression present psychiatric symptoms that are not captured by standardized classificatory systems, such as DSM and ICD-5.7,8 This is particularly evident in the case of interictal dysphoric disorder (IDD).
The concept of IDD is derived from Kraepelin and Diefendorf9 and Bleuler,10 who observed that in patients with untreated epilepsy, a pleomorphic pattern of depressive symptoms intermixed with euphoric moods, irritability, fear, and anxiety as well as with anergia, pain, and insomnia could develop. This concept has been subsequently rejuvenated by Blumer,11 who coined the term “IDD” and described 8 key symptoms, grouped into 3 categories: labile depressive symptoms (depressive mood, anergia, pain, insomnia); labile affective symptoms (fear, anxiety); and “specific” symptoms (paroxysmal irritability, euphoric moods).
The specific symptoms are a peculiar symptom cluster characterized by periodic mood changes and outbursts of irritability and aggressive behavior. These episodes occur without external triggers and without clouding of consciousness; they begin and end quickly and recur fairly regularly (every few days to every few months and last from a few hours to 2 days). The symptom cluster described in patients with IDD and epilepsy is quite peculiar and is rarely reported in psychiatric practice, even in patients with rapid cycling bipolar disorder or cyclothymia. It is interesting to note that in about 50% of patients, dysphoric symptoms present a clear-cut relationship with epileptic seizures occurring either preictally or postictally.12
Epileptic seizures are characterized not only by the ictal phase but also by a number of behavioral manifestations that may precede or follow the seizure. Such peri-ictal symptoms may fail to meet temporal DSM criteria when too short-lasting. However, it appears that they are highly responsible for the atypical presentations of psychiatric disorders in epilepsy.13
Alternatively, peri-ictal symptoms may be misleadingly interpreted as psychiatric manifestations when they are long-lasting. In fact, a cross-sectional study of patients shows that a diagnosis of bipolar disorder can be overestimated in epilepsy if peri-ictal mood changes are not correctly identified.14 In fact, of the 11.8% of DSM-based diagnoses of bipolar disorder, only 1.4% can be considered as a “pure” psychiatric diagnosis because in all other cases, manic/hypomanic symptoms are temporally related to seizures that occur either postictally or preictally. Thus a careful assessment of seizure-based behavioral manifestations should always be part of a routine assessment, with treatment strategies based on peri-ictal symptoms.
The Interictal Dysphoric Disorder Inventory (IDDI) is used for the evaluation of IDD and the identification of seizure-associated symptoms.8 This 38-item, self-report questionnaire looks at a time interval of 12 months and provides a total score in addition to 3 subscale scores that mirror the major symptom categories of IDD. The questionnaire is also used to measure the degree of interference or distress caused by mood symptoms. The IDDI has demonstrated good internal consistency, acceptable sensitivity, and excellent specificity. The Appendix to the questionnaire includes 6 questions that pinpoint the time course and duration of mood symptoms and their associations with seizures or antiepileptic drug therapy.
Dr Mula is Consultant in Neurology and Epileptology with the Epilepsy Group in the department of neurology at St George’s Hospital in London. At the time of the writing of this article, Dr Mula was in the division of neurology at Trinity Hospital in Borgomanero, Italy. He reports no conflicts of interest concerning the subject matter of this article.
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