Psychopathological and peripheral levels of neurobiological correlates of obsessive–compulsive symptoms in patients with epilepsy: A hospital-based study

Abstract

Objectives

Obsessive–compulsive symptoms (OCSs) and disorder (OCD) are often underdiagnosed in the out-patient epilepsy clinic. This work aimed at determining the risks and comorbidities (psychopathological and neurobiological correlates) of OCSs in treated adults with idiopathic epilepsy recruited from a university hospital.

Methods

Psychiatric evaluation was done using DSM-IV (The Diagnostic and Statistical Manual of Mental Health Disorders). Obsessive–compulsive disorder was identified using the Mini International Neuropsychiatric Interview (MINI). The Beck Depression Inventory (BDI-II), Hamilton Anxiety Rating Scale (HAM-A), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) were used to determine the severity of the related psychiatric symptoms.

Results

Out of 474 patients screened, included in this study were 107 with no psychiatric symptoms and 188 with OCSs [classified as those with at least OCSs = 93; mild OCSs = 36; moderate, severe, and extreme OCSs = 59]. A hundred healthy subjects were included as controls. Blood concentrations of serotonin, adrenaline, noradrenaline, and dopamine were measured. Compared with controls, patients with OCSs had higher frequencies of depression and anxiety. Low concentrations of serotonin, adrenaline, noradrenaline, and dopamine were reported regardless of the presence or the absence of psychiatric symptoms, OCS severities, and antiepileptic drug (AED)-related variables (dose and serum drug level). Significant correlations were identified between Y-BOCS, BDI-II, and HAM-A scores, age, age at onset, and concentrations of noradrenaline.

Conclusion

This study indicates that a) OCSs are common in patients with epilepsy. Male sex, age, duration of illness, seizure focus, lateralization, and intractability to AEDs are its main risks; b) depression and anxiety are comorbid psychopathologies; and c) serotonin, catecholamines, and dopamine are linked to epilepsy-related variables and its comorbid psychopathies but not to its medications.

Introduction

Epilepsy is one of the most common neurological and medical disorders, with a prevalence of ~ 8.2–12.9 per 1000 in the general population [1]. Fortunately, the majority (~ 65–80%) of patients with epilepsy of unknown etiology (idiopathic or primary epilepsy) become seizure-free after treatment with antiepileptic drugs (AEDs) for at least 2–5 years, while the seizures of the remaining (~ 20–35%) are difficult to control even with the addition of 2nd or 3rd AED (conventional or new) for a significant period of time (intractable or refractory epilepsies) [2]. Patients with recurrent, intractable, or refractory seizures are at increased risk for a number of medical, endocrinal, and neurobehavioral (such as cognitive, emotional, and psychosocial) abnormalities or comorbidities which are related to epilepsy itself and/or its medications [3], [4], [5], [6]. Sometimes, such comorbidities negatively impact the patient's quality of life. It has been estimated that approximately 70–88% of patients with epilepsy have inter-ictal psychiatric symptoms and disorders (such as depression, anxiety, psychosis, obsession–compulsion, personality disorders, aggression, and even suicide) [5], [6], [7], [8], [9], [10], [11], [12], [13].

Obsession is the 3rd most frequent psychiatric comorbidity with epilepsy after depression and anxiety. Obsessive–compulsive symptoms (OCSs) and disorder (OCD) have a prevalence of 10–25%, particularly with temporal lobe epilepsy (TLE), compared with 2.5–3% in the general population [14]. Obsessive–compulsive disorder is defined as a range of clinical characteristics with two major components: a) the intrusion of thoughts and ideas which are often allied with compulsive actions and b) the resulting trigger of abnormal behaviors or rituals. Obsessive–compulsive symptoms are seen in OCD itself or other psychiatric conditions (depression, anxiety, psychosis, personality disorders, etc.). In epilepsy, intrusive thoughts such as imaginary sins or mistakes, religiosity, symmetry/exactness, indecision, checking behaviors, doubting, ordering, hoarding, excessive writing, and over-representation of contamination themes such as hand washing and emotional dyscontrol are commonly seen OCSs [10], [11], [12], [13].

The exact mechanisms which associate epilepsy with OCD are complex and less understood. Studies implicate structural or pathophysiologic abnormalities of certain brain areas and their related connections (such as the frontal lobe, temporal lobe, cingulate region, limbic system, basal ganglia, and thalamic, orbito-fronto-thalamic, and fronto-thalamic-pallidal-striatal-anterior cingulate-frontal circuits, and amygdala-cingulate network) and their connections and neurobiologic mediators (such as glutamate, serotonin, dopamine, and gammaaminobutyric acid or GABA) as causes of OCSs and OCD in patients with epilepsy [15], [16], [17], [18], [19], [20], [21]. These implications are mainly based on the structural and functional comorbidities between OCD and other neuropsychiatric disorders [5], [15], [18], [19] and the observations of improvement or induction of OCSs and changes in functional neuroimaging in patients with TLE or refractory epilepsy after surgical intervention (temporal lobectomy) [22], [23], [24], [25], [26], [27].

Obsessive–compulsive symptoms and obsessive–compulsive disorder are often underdiagnosed in the out-patient epilepsy clinic. This work was undertaken to determine the risks and comorbidities (psychopathological and peripheral blood neurobiologic correlates) of OCSs in adult patients with idiopathic epilepsy recruited from a university hospital.