Pathways to psychopathology in epilepsy

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M. Noeker, Ph. D., F. Haverkamp, M.D.



Prevalence of behavioral dysfunction is markedly increased in epilepsy compared to population and even compared to other chronic conditions. A conceptual framework is delineated that outlines and reviews four major causes enhancing the emergence of psychopathology in epilepsy: (a) effects of underlying CNS damage and dysfunction, (b) the impact of epileptic activity, (c) effects and side-effects of antiepileptic drugs (AED) and (d) psychological coping reactions in the patient and in the family. These four groups of variables operate within the biological context of the developing brain structure and functions and the psychosocial context of personality development. From a methodological point of view, the determination of the relative impact of each factor can be very difficult in clinical practice and empirical research because the four factors regularly are highly confounded with each other.

Key words:

epilepsy, psychopathology, adjustment

Epilepsy is more a symptom rather than the cause of central nervous dysfunction resulting from inborn and acquired disorders including genetic conditions, head injury, cerebral infection and metabolic diseases. In childhood, it is the most common neurological disorder. The most prominent feature of epilepsy is seizure but epilepsy may also comprise neurocognitive impairment as well as behavioral problems ranging from subtle maladjustment to manifest psychopathology. Epilepsy shares the general psychosocial and psychopathological risks of chronic disorders. In chronic childhood conditions the risk of psychopathology is about 2.5 times higher than in the general population (1). This rate is markedly enlarged in chronic disorders affecting the central nervous system (2). Comparing behavioral adjustment in children with epilepsy versus asthma Austin (3) found higher rates of internalising behavioral problems in children with epilepsy measured by the Child Behavior Checklist. Hoare (4) found 45% of children with new onset of epilepsy to have psychiatric disturbances compared to 17 % with new onset of diabetes and 10 % of controls. McDermott et al. (5) found a 4.7 times higher prevalence of behavior disorders in children with epilepsy than in healthy children. Here, we review major pathways contributing to this specific risk of psychological maladjustment, resp. comorbid psychopathology in epilepsy with a special focus on childhood epilepsy.

Ictal behavioral alterations

Behavioral alterations in epilepsy may occur during the onset and course of a seizure episode (ictal phase) or during the seizure free interval (inter-ictal phase). Box 1 (cf. 6) informs on ictal behavior responses that are part of the seizure process. Depending on the individual seizure type, the patient´s consciousness and control concerning these behavioral reactions, vary considerably. In a subgroup of patients, cognitive-behavioral approaches can modify ictal behaviors and hence seizure onset and course (7).

Interictial behavioral disturbances: A framework

The general literature and this specific contribution, however, focus on interictal changes in behavioral development that can be observed apart from the acute seizure situation. To date, most studies on development of psychopathology in epilepsy have recruited samples with heterogeneous types of epilepsy. Samples of particular epilepsy disorders have been too small and too limited in statistical power to provide valid evidence on replicable associations between specific types of epilepsy and specific risks for psychopathological comorbidity. Basically, this holds true also for the case of complex-partial epilepsies. Therefore, with the aim to broaden the empirical basis, we review common sources of psychopathology in epilepsy which are relevant across the range of particular epilepsies. Specific risks of psychopathology specifically related to particular epilepsies are outlined (cf. table 1), our major focus, however, refers to the delineation of common factors contributing to the emergence of psychopathology in general, irrespective of a particular epilepsy in question. To that objective, we propose a conceptual framework on the general development of behavior problems and psychopathology in epilepsy. It is depicted in figure 1.

This framework highlights four major causes that have to be differentiated when considering the origin of behavioral dysfunction in an individual patient with epilepsy: (a) effects of underlying CNS damage and dysfunction, (b) the impact of epileptic activity, (c) effects and side-effects of antiepileptic drugs (AED) and (d) psychological coping reactions in the patient and in the family. These four groups of variables develop within the biological context of the developing brain structure and functions (8) and the psychosocial context of normal, i.e. epilepsy-independent development and differentiation of personality and competencies in the individual. In empirical research and in clinical practice, a differentiation of the relative contribution of each of these major pathways to psychopathology may be difficult to achieve because the factors present as highly confounded across a basic dimension of severity: Higher CNS damage and dysfunction is frequently associated to higher severity of seizure activity, to higher doses and / or number of AED´s, to higher disease related burden and to poorer coping and adjustment.

Primary brain damage and dysfunction

A major approach to disentangle effects of underlying brain damage from effects of epilepsy or medication is the assessment of behavioral adjustment in children concerning the period prior to the manifestation of epilepsy. Scores of increased psychopathology before (observed !) seizure onset compared to norms can only be attributed to already existing CNS dysfunction but not to effects of epilepsy, medication and coping reactions. A series of studies has applied this strategy and study design: Stores (9) identified behavioral problems already before initiation of antiepileptic medication concluding that psychiatric disturbances are not primarily related to medication side effects but to underlying CNS dysfunction. Williams et al. (10) found high internalising behavioral disorders compared to norms already at the day of making the diagnosis of epilepsy. To exclude negative effects of initial coping with diagnosis Dunn et al. (11) asked the parents of 42 children with new onset of epilepsy to rate their child´s behavior referring to the six month period prior to diagnosis. Seizure activity was rated according to three degrees of severity (high, moderate, low). Behavior problems before seizure onset were most intense in the subgroup of children with the severe type of epilepsy indicating that a more severe CNS dysfunction has caused both a more severe epilepsy and more severe behavioral disorders. Behavioral adjustment improved among all three groups at a follow up after four month after seizure onset. In the high severity group, however, maladjustment was still half a standard deviation above the mean. Despite the close correlation between severity of epilepsy and intensity of behavioral maladjustment the study has not ruled out a confounding effect of antiepileptic medication which is systematically related to severity of epilepsy. A recent study by Austin et al. (12) has provided the most differentiated approach to disentangle distinct effects resulting from CNC dysfunction, severity of epilepsy and medication. The sample consisted of 224 children (4-14 years old) with a first recognized seizure and their 135 siblings. In the total seizure sample 32,1 % of the children were found to be among the clinical or at-risk range of clinical behavior problems. Rates of behavioral problems increased to 39.5 % in children whose parents reported prior episodes of strange behavior that may be interpreted as early manifestation of CNS dysfunction retrospectively. Children with epilepsy had already higher scores in total, internalizing, attention, thought, and somatic problem areas than their siblings concerning their adjustment during the period before first recognized seizure. Interestingly, also the siblings revealed elevated scores compared to test norms probably indicating difficulties in the family coping process. In the epilepsy sample, underlying CNS dysfunction already active before first clinically apparent seizure may have caused subclinical epileptiform discharges and/or transient cognitive impairments (TCI). These TCI´s may suppress normal brain functioning thus affecting also psychosocial functioning and interpersonal interactions via impaired interpretation and response to social cues and situations. Summarized, the data provided by the studies investigating behavioral adjustment before first recognized seizure provide evidence that emerging psychopathology already starts with the onset of CNS dysfunction and associated subclinical discharges and not with manifestation of clinical epilepsy or subsequent initiation of medication or dysfunctional coping reactions. A recent study by Dunn et al (13) has replicated the findings based on teacher assessment of the child´s behavioral adjustment. This data source further excludes the possible bias of altered parental perception as a consequence of coping responses to diagnosis (14, 15). Also some intervention studies that have administered AED´s in children with TCI´s but without manifest seizures support indirectly the major contribution of direct CNS effects to psychopathology (16).

Epilepsy associated risk factors

Research has identified particular characteristics of epilepsy associated to psychopathological outcome. Parameters investigated comprise age at onset, seizure frequency, type of epilepsy and associated neuropsychological impairment. Children with early onset of epilepsy before four years of age have been reported to be more likely to show behavior disturbance than those with later age at onset (17). There is a consistent link between seizure frequency and mental health dysfunction (4). Again it remains difficult to disentangle the impact of an underlying increased severity of the disorder from detrimental effects of recurring seizures. The relation between primary CNS disorder and secondary epilepsy may be recursive. Recurrent, intractable severe seizures or status epilepticus may enhance extent of CNS damage and dysfunction maintaining a vicious circle between impaired CNS structure and function. As a result, cumulative impairment of CNS induced by seizure activity may additionally reduce mental resources for adequate psychosocial functioning.

Table 1 presents associations between specific types of epilepsy and specific behavioral disorders (18). It has to be emphasised that empirical data on specific epilepsy-psychopathology correlations are still limited. The fact that specific epilepsies are related to specific psychopathology does not necessarily mean that the type of epilepsy is the causal factor leading to a specific clinical psychopathological presentation. Patients with specific epilepsy disease categories also share specific CNS-bound etiology or localisations of lesion. Specific psychopathology in a epilepsy syndrome, therefore, may not reflect a disorder-specific seizure symptomatology but result from common CNS pathology. Depression has been shown to be a good predictor of mesial temporal sclerosis in adult patients with temporal lobe epilepsy (19) indicating the predictive value of localisation of epileptogenic lesion for the development of specific psychopathology. Associations between neuropsychological and behavioral dysfunction: A recent study of Hermann et al. (20) has provided evidence that patients with childhood-onset temporal lobe epilepsy who exhibited widespread deficits in neuropsychological performance also were characterized by a substantial reduction in white matter brain tissue volumes compared with healthy controls and adulthood onset temporal lobe epilepsy patients. It can be assumed that such decline in brain structure in early onset patients does not only affect neuropsychological but also behavioral development. Especially subfunctions of attention control may be an important link between neuropsychological and behavioral functioning (21). Attention disorder, reduced impulse control and hyperactivity are especially frequent and relevant behavioral disorders in children with epilepsy (cf. table 1). We assume that their high prevalence may be based on an epilepsy-specific pattern of neuropsychological deficits. We found evidence for a characteristic vulnerability in sequential information processing in childhood epilepsy comprising deficits in attention performance and (short term) working memory (22). The vulnerability for neuropsychological deficits in sequential processing may be a key risk factor also for the development of behaioural disturbances presenting as attention deficit and hyperactivity disorder in childhood epilepsy.

Antiepileptic drugs

Individuals with an epilepsy difficult to control are more likely to receive higher doses or numbers of AED´s and, thus, are more prone to the induction of cognitive and behavioral medication side effects (23). Scientifically sound, systematic variation of type and doses of medication in homogenous samples comprising patients with nearly identical epilepsies is strongly limited due to clinical and ethical reasons (24). From a methodological point of view, the impact of AED´s on behavior is strongly confounded with the impact of type and severity of epilepsy and its response to treatment. In general, AED´s may entail positive psychotropic effects resulting from a suppression of psychopathological concomitants of the CNS dysfunction as well as negative effects ranging from minor changes in behavior to an induction of affective disorder or psychoses. A high potential for provocation of psychopathological reactions refers to drugs with GABAnergic properties (25). After drug withdrawal, parents frequently report improvements in areas of activation (alertness, drowsiness) but not in particular behavioral adjustment (depression, aggression) (cf. 26). Classical as well as new generation AED´s have been linked to specific behavioral side effects. Overall, recent research and reviews reveal that adverse effects of AED´s on behavior have been overrated in the past compared to the influence of other factors (23, 27). Mandelbaum and Burack (28) identified no significant deterioration over a 12-month period in behavioral adjustment associated to the initiation of anticonvulsant therapy. The traditional overemphasis on medication side effects as an explaation for behavioral deviance in epilepsy is especially held by patients or parents that frequently mix up disease and treatment effects. The explanation of behavioral dysfunction in the child as a simple side effects from AED´s may be appealing as it reduces actual complexity and promotes hope for an easy solution by just changing medication. The subgroup of patients who really remain at risk require clinical expertise based on knowledge about risk potential of specific AED´s and based on close monitoring of clinical associations between changes in drugs and doses of anticonvulsant medication, on the one side, and emergence or decline of psychopathological reactions, on the other side, over the disease and treatment course.

Coping in the patient and the family Living with epilepsy implies several stressors and restrictions of quality of life which can be hard to adapt to (29, 30). Children may experience teasing if seizures have occurred in public. Experiences of stigmatisation may gradually impair self-concept development (17). Automatisms occurring in complex partial seizures may appear very bizarre to observing peers; tonic-clonic seizures may look very dramatic and frightening in the eye of the innocent beholder. Coping strategies to avoid public seizure or just states of absences may gradually lead to fear of social contact and public places. Safety rules concerning for example swimming may reinforce or, at least justify tendencies of social withdrawal and isolation. Feelings of shame due to the disorder and reduced self-esteem may promote both anxiety as well as affective and mood disorders (31). How adaptive or maladaptive coping reactions are, however, is not only a simple function of disease parameters such as seizure type and frequency. Austin et al. (32) identified 5 risk factors to be associated with major behavioral problems in a sample of 127 children with epilepsy, aged 8-12 years. Besides seizure frequency and female gender, psychosocial factors of family stress, lack of family mastery and lack of extended family support determined adjustment outcome. In a study of Suurmeijer, Reuvekamp & Aldenkamp (33) the psychosocial factors of “psychosocial distress”, “loneliness”, “adjustment and coping” and “stigma perception” and not characteristics of epilepsy but were most predictive for quality of life in a sample of 210 patients with epilepsy. Psychological adaptation is far more a function of available cognitive and behavioral competencies in the individual and of social support received from family, peers, school, social network, and - last, not least - from health professionals.

Unfortunately, individual coping capacities can be restricted by concomitant cognitive impairments resulting from the disorder. Learning disability may hamper the prompt, assertive and effective verbal response to stigmatising teasing and provocation which otherwise may be a valuable resource for the patient to protect self-esteem and social integration. The patient´s individual psychological coping reaction to epilepsy mutually interacts with the coping reactions of “significant others”, especially of the family (34, 35). If the family succeeds to develop a fundamental acceptance of the disorder this will strengthen the patient´s self-confidence and self-efficacy. Provided with positive emotional support from the family, the patient may develop self-esteem and personal self-acceptance not primarily dependent on the fact to have epilepsy or not.

Etiologically independent comorbidity

When considering the origin of individual psychopathology in epilepsy the possibility of a psychopathological vulnerability or comorbidity which is etiologically not related to the epilepsy or its underlying cause has always to be taken into account. For example, preexisting “idiopathic” attention deficit disorder and hyperactivity has to be ruled out in childhood epilepsy out before interpretation of such symptoms as consequence of epilepsy or medication side effect. The manifestation of clinical affective disorder or schizophrenia (36) has to take into account the high prevalence of subclinical and clinical psychopathology among the general population. Comprehensive assessment requires examination of prior psychiatric history in the patient (37). Differentiation of secondary, symptomatic psychopathology based on epilepsy and its neurological causes from primary, comorbid psychopathology has major implications for treatment planning.


The heterogeneity of causes of psychopathology in epilepsy requires a corresponding selection of therapeutic approaches. Differential diagnoses of the etiologically relevant factors should guide the development of the treatment strategy. Interventions range from surgery (38, 39, 40, 1) to optimisation of anticonvulsant therapy specifying its administration to psychopathological treatment objectives (maximising positive psychotropic effects as well as minimizing negative psychotropic side effects), psychopharmacology and psychological approaches such as counselling and psychotherapy. The objective to apply causal therapy wherever possible requires to improve epilepsy therapy in cases where psychopathology is mainly a symptom of epilepsy or its underlying neuropathological cause or a side effect of its treatment. The indication for specific AED´s may not be guided alone on their potency to control seizure activity but also on beneficial, respectively less harmful psychotropic effects on neuropsychological and behavioral functioning (23, 27, 28). If the optimum of antiepileptic therapy is achieved with at the same time psychopathology persisting, psychopharmacology (40, 42) and psychotherapy (43) may offer promising symptomatic treatment approaches. In comorbid psychopathology with little or no causal association with the epileptogenic process, psychotherapy and psychopharmacology may be administered taking into account potential drug interaction effects.


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