Rochelle Caplan

Depression and Anxiety Disorders in Pediatric Epilepsy

Summary:  Purpose: This study examined affective disorders, anxiety disorders, and suicidality in children with epilepsy and their association with seizure‐related, cognitive, linguistic, family history, social competence, and demographic variables.

Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities.

Purpose:  Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absence epilepsy (CAE) suggests long‐term unmet mental health, social, and vocational needs. This cross‐sectional study examined behavioral/emotional, cognitive, and linguistic comorbidities as well as their correlates in children with CAE.

Behavioral Disorders in pediatric epilepsy: Unmet psychiatric need

Summary:  Purpose: This study examined the relation between psychiatric diagnosis and mental health services in children with epilepsy and the associated demographic, cognitive, linguistic, behavioral, and seizure‐related variables.

Psychiatric comorbidity in children with new onset epilepsy

The aim of this study was to characterize the distribution, timing, and risk factors for psychiatric comorbidity in children with recent onset epilepsy. Children aged 8 to 18 years with recent onset epilepsy (<1 year in duration) of idiopathic etiology (n=53) and a healthy comparison group (n=50) underwent a structured psychiatric diagnostic interview to characterize the spectrum of lifetime‐to‐date history of comorbid psychiatric disorder. There was no significant difference between the children with recent onset epilepsy and healthy comparison children in sex (31 males, 22 females vs 23 males, 27 females) or mean age 12.7y [SD 3.3] vs 12.7y [SD 3.2]). Children with recent onset epilepsy exhibited an elevated rate of lifetime‐to‐date Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM‐IV) Axis I disorders compared with the comparison group. They showed significantly higher rates of depressive disorders (22.6 vs. 4%, p=0.01), anxiety disorders (35.8 vs 22%, p<0.05), and attention‐deficit‐hyperactivity disorder (26.4 vs 10%, p=0.01) with elevated but less prevalent rates of oppositional defiant and tic disorders. A subset of children with epilepsy (45%) exhibited DSM‐IV Axis I disorders before the first recognized seizure, suggesting the potential influence of antecedent neurobiological factors that remain to be identified. The increased prevalence of psychiatric comorbidity antedating epilepsy onset may be consistent with the presence of underlying neurobiological influences independent of seizures, epilepsy syndrome, and medication treatment.

Behavioral and Psychiatric Comorbidities in Pediatric Epilepsy: Toward an Integrative Model

Summary:  It is well recognized that children with epilepsy are at heightened risk for developing behavior problems and psychiatric disorders. Studies identifying factors associated with child behavior were reviewed and findings were placed into two broad categories for review and critique: illness‐related variables and psychosocial variables. Illness‐related variables were seizure frequency and seizure control, type of epilepsy, age of onset, duration of illness, and antiepileptic drugs. Psychosocial variables were reviewed using a family stress framework: stressors, perceptions, adaptive resources, coping, and family adjustment. After the literature on each category is reviewed, an integrated heuristic model that includes key illness‐related and psychosocial variables is presented.

Depression and epilepsy: Epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence☆

Depression is the most frequent psychiatric comorbidity in people with epilepsy (PWE) with lifetime prevalence rates ranging between 30 and 35%. Multifactorial variables play a pathogenic role in the high comorbid occurrence of these two disorders. These variables were critically examined during an international symposium held in Chicago in September 2010, the results of which are presented in two companion manuscripts. The first manuscript summarizes new epidemiologic data highlighting the bidirectional relation between depression and epilepsy and related methodological issues in studying this relationship. An examination of the neurobiologic aspects of primary mood disorders, mood disorders in PWE and pathogenic mechanisms of epilepsy derived from studies in animal models and humans is allowing a better understanding of the complex relation between the two conditions. In the first manuscript, we review data from animal models of epilepsy in which equivalent symptoms of depression and anxiety disorders develop and, conversely, animal models of depression in which the kindling process is facilitated. Data from structural and functional neuroimaging studies in humans provide a further understanding of potential common pathogenic mechanisms operant in depression and epilepsy that may explain their high comorbidity. The negative impact of depression on the control of seizure disorders has been documented in various studies. In this manuscript, these data are reviewed and potential mechanisms explaining this phenomenon are proposed.

Consensus statement: the evaluation and treatment of people with epilepsy and affective disorders.

Affective disorders in people with epilepsy (PWE) have become increasingly recognized as a primary factor in the morbidity and mortality of epilepsy. To improve the recognition and treatment of affective disorders in PWE, an expert panel comprising members from the Epilepsy Foundations Mood Disorders Initiative have composed a Consensus Statement. This document focuses on depressive disorders in particular and reviews the appearance and treatment of the disorder in children, adolescents, and adults. Idiosyncratic aspects of the appearance of depression in this population, along with physiological and cognitive issues and barriers to treatment, are reviewed. Finally, a suggested approach to the diagnosis of affective disorders in PWE is presented in detail. This includes the use of psychometric tools for diagnosis and a stepwise algorithmic approach to treatment. Recommendations are based on the general depression literature as well as epilepsy-specific studies. It is hoped that this document will improve the overall detection and subsequent treatment of affective illnesses in PWE.

Depression after status epilepticus: behavioural and biochemical deficits and effects of fluoxetine

Depression represents one of the most common comorbidities in patients with epilepsy. However, the mechanisms of depression in epilepsy patients are poorly understood. Establishment of animal models of this comorbidity is critical for both understanding the mechanisms of the condition, and for preclinical development of effective therapies. The current study examined whether a commonly used animal model of temporal lobe epilepsy (TLE) is characterized by behavioural and biochemical alterations involved in depression. Male Wistar rats were subjected to LiCl and pilocarpine status epilepticus (SE). The development of chronic epileptic state was confirmed by the presence of spontaneous seizures and by enhanced brain excitability. Post-SE animals exhibited increase in immobility time under conditions of forced swim test (FST) which was indicative of despair-like state, and loss of taste preference in saccharin solution consumption test which pointed to the symptomatic equivalence of anhedonia. Biochemical studies revealed compromised serotonergic transmission in the raphe-hippocampal serotonergic pathway: decrease of serotonin (5-HT) concentration and turnover in the hippocampus, measured by high performance liquid chromatography, and decrease of 5-HT release from the hippocampus in response to raphe stimulation, measured by fast cyclic voltammetry. Administration of fluoxetine (FLX, 20 mg/kg/day for 10 days) to naive animals significantly shortened immobility time under conditions of FST, and inhibited 5-HT turnover in the hippocampus. In post-SE rats FLX treatment led to a further decrease of hippocampal 5-HT turnover; however, performance in FST was not improved. At the same time, FLX reversed SE-induced increase in brain excitability. In summary, our studies provide initial evidence that post-SE model of TLE might serve as a model of the comorbidity of epilepsy and depression. The finding that behavioural equivalents of depression were resistant to an antidepressant medication suggested that depression in epilepsy might have distinct underlying mechanisms beyond alterations in serotonergic pathways.

Psychiatric and Medical Comorbidity and Quality of Life Outcomes in Childhood-Onset Epilepsy

OBJECTIVE: We compared associations of epilepsy remission status and severity as well as psychiatric and other comorbidities with child and parent-proxy reports of health-related quality of life (HRQoL) in adolescents previously diagnosed with epilepsy. METHODS: In a prospective, community-based study of newly diagnosed childhood epilepsy, HRQoL of 277 children was assessed 8 to 9 years after diagnosis by using child and parent-proxy versions of the Child Health Questionnaire (CHQ). Multiple linear regression models adjusted for age and gender were used to compare associations of epilepsy remission and “complicated” epilepsy (secondary to an underlying neurologic insult or epileptic encephalopathy) status and psychiatric and other comorbidities with HRQoL. RESULTS: Mean age of epilepsy onset was 4.4 years (SD: 2.6). At the 9-year reassessment, children were, on average, 13.0 years old (SD: 2.6); 64% were seizure-free for 5 years, 31% were taking antiepileptic drugs, and 19% had a complicated epilepsy. Prevalence of comorbidities at follow-up were 26% psychiatric diagnosis; 39% neurodevelopmental spectrum disorder (NDSD); 24% chronic medical illness; and 15% migraine. In multivariable analysis, having a psychiatric disorder was broadly associated with child (6 of 11 scales) and parent-proxy (7 of 12 scales) HRQoL (P ≤ .0125). Five-year remission and complicated epilepsy status had few or no associations with HRQoL. Although parent-proxy HRQoL was strongly associated with NDSD (6 of 11 scales), child-reported HRQoL was not (2 of 11 scales). CONCLUSIONS: Psychiatric comorbidities are strongly associated with long-term HRQoL in childhood-onset epilepsy, which suggests that comprehensive epilepsy care must include screening and treatment for these conditions, even if seizures remit.

Reduced white matter integrity in attention-deficit hyperactivity disorder

We used diffusion tensor imaging to investigate fractional anisotropy (FA), a measure of fiber tract integrity, in attention-deficit hyperactivity disorder (ADHD). Using a tract-based atlasing approach on six-direction diffusion tensor imaging data, we examined FA within the cingulum, corpus callosum, corticospinal tract, fornix, optic radiations, superior longitudinal fasciculus, uncinate fasciculus, and the superior and inferior occipitofrontal fasciculi in an all-male sample of 17 children and adolescents with ADHD and 16 age-matched controls. ADHD patients had significantly lower FA in the corticospinal tract (P=0.02) and the superior longitudinal fasciculus (P=0.017) compared with controls. Results support that disruptions in motor and attentional networks may contribute toward ADHD pathophysiology. Future research may clarify how ADHD subtype and psychiatric comorbidities affect diffusion measures.