|Year : 2015 | Volume
| Issue : 3 | Page : 124-131
Depression among school aged epileptic children and their siblings
Marwa Abd El-Maksoud, Hamdy Bedair, Hanan Azouz, Heba Abou El-Wafa MD
Neuropsychiatry and Pediatric Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
|Date of Submission||15-Mar-2014|
|Date of Acceptance||14-May-2015|
|Date of Web Publication||30-Sep-2015|
Heba Abou El-Wafa
Department of Neuropsychiatry, Alexandria University, 21511 Alexandria
Source of Support: None, Conflict of Interest: None
Researches on children and adolescents with epilepsy have revealed a high incidence of psychological and behavioral difficulties. For a longtime, patients and physicians tended to focus solely on the control of epileptic seizures, while disregarding the presence of comorbid psychiatric symptoms and disorders. Recognition of their negative impact in the life of patients with epilepsy in recent years has highlighted the need for the early identification of psychiatric symptoms.
Aim of the work
The work aimed to study the prevalence of depression in school aged epileptic children and their siblings and to study the possible risk factors of depressive disorders in those children with epilepsy and their siblings.
Patients and methods
The study included 150 school children divided into three groups: epileptic children, their siblings, and a healthy control group. They have been all subjected to history taking, neurological examination, psychiatric interview, electroencephalography, and psychometric assessment using Children's Depression Inventory, Arabic form.
We found a significant relationship between the prevalence of depression and focal seizures (P < 0.001) especially frontal and temporal lobe epilepsy; however, we did not find a statistically significant relationship between depression and other seizures related risk factors. There was a significantly (P = 0.002) poor school performance among epileptic children (42%) compared with their siblings (16%) and the control children (12%), and also there was a significant relationship between poor school performance in epileptic children and high prevalence of depression (P = 0.025) among these children.
There is no great impact of epilepsy on the social or psychological life of the siblings especially among young children. Despite the high prevalence of depression among young epileptic children, it was not statistically significant compared with the control children. Moreover, there is a significant relationship between focal seizures and depression especially temporal and frontal lobe epilepsy. Depression as a comorbidity in epileptic children further compromises their school performance.
Keywords: anxiety, depression, epilepsy, psychiatric, school performance, seizure
|How to cite this article:|
El-Maksoud MA, Bedair H, Azouz H, El-Wafa HA. Depression among school aged epileptic children and their siblings. Egypt J Psychiatr 2015;36:124-31
|How to cite this URL:|
El-Maksoud MA, Bedair H, Azouz H, El-Wafa HA. Depression among school aged epileptic children and their siblings. Egypt J Psychiatr [serial online] 2015 [cited 2021 Sep 28];36:124-31. Available from: http://new.ejpsy.eg.net/text.asp?2015/36/3/124/166349
| Introduction|| |
Various investigations focusing on the prevalence of psychopathology in pediatric epilepsy have documented that children with epilepsy have an estimated overall risk of 21-60% for childhood psychopathology (Ott et al., 2001, 2003). This is at least three to six times higher than the risk for psychopathology in the general pediatric population (i.e. 6.6%) and among children with a chronic medical condition not involving the central nervous system (i.e. 11.6%) (Ekinci et al., 2009). Prevalence rates of psychiatric comorbidities have been found to be significantly higher in focal epilepsy, particularly in temporal lobe epilepsy (TLE) or in frontal lobe epilepsy. Depression in patients with epilepsy frequently differs from those of patients without epilepsy and is commonly classified as 'atypical'. The characteristic of depressive disorders in epilepsy is the temporal relation of their symptoms to that of seizure occurrence; thus symptoms can be classified as preictal (preceding seizures by up to 2 days), ictal (being an expression of the actual seizures or the aura), interictal (occurring independently from seizures), and postictal (occurring any time within the first 5 days following seizures) (Morales et al., 2008). Suicidality (completed suicide, suicide attempt, and suicidal ideation), is significantly more frequent among people with epilepsy than in the general population. Yet, it remains under-recognized and untreated (Rafnsson et al., 2001; Jones et al., 2003; Christensen et al., 2007).
Siblings have less psychological problems than their brothers or sisters with epilepsy but they were more disturbed than children in the general population. Interestingly, siblings of children with chronic epilepsy are more affected than those of the newly diagnosed children (Otero, 2009). Despite the recognition of the relative frequent comorbidity of depression in epilepsy and its negative impact on the patients' quality of life, they usually go undetected and untreated (Quinn et al., 2006). Early detection allows the physician to choose the proper anti epileptic drugs (AED) in conjunction with other therapeutic interventions necessary to cause an optimal remission of seizures and psychiatric comorbidity (Morales et al., 2008).
In the present study, we studied the prevalence of depression in school aged epileptic children and their siblings and its possible risk in those children with epilepsy and their siblings.
| Aim of the work|| |
The work aimed to study the prevalence of depression in school aged epileptic children and their siblings and to study its possible risk factors in those children with epilepsy and their siblings.
| Patients and methods|| |
This cross-sectional study was conducted on 100 children who have been recruited from El-Shatby neurology outpatient clinic and neurology outpatient clinic of health insurance institution (Semoha clinic) and 50 control children who were recruited from Shawkat El-Tagrebya preparatory school. The children were divided into three groups:
All children were undergoing the following: firstly: history taking, child psychiatric interview according to the DSM-IV-TR; 10 full neurological and physical examination and informed consent. Secondly: psychometric assessment using Kovac Children's Depression Inventory (CDI), Arabic form.
- Group 1: Include 50 school children (index participants) diagnosed with idiopathic epilepsy, aged 6-10 years, received antiepileptic medication and having one sibling or more. Children showing clinical evidences of neurological deficit, chronic medical or surgical disorders, and abnormal imaging findings were excluded.
- Group 2: Include 50 siblings to the index participants matched for age and living in contact with their sibling at the same socioeconomic status and having no chronic medical or surgical disorders.
- Group 3: Include 50 normal control children (the sample was obtained from Shawkat El-Tagrebya primary school) matched for age, sex, socioeconomic status with the index participants and having no chronic medical or surgical disorders.
All the epileptic children were undergoing the following:
Full history of epileptic seizures include the following: age of onset (first attack), last attack, frequency of attacks, preictal (aura), type of seizures, postictal events, duration of seizures, and response to therapy and medication (monotherapy or polytherapy). Electroencephalography will be conducted only if there were no recent ones in the last 6 months.
Data were analyzed using software package version 18.0 (SPSS Inc., Chicago, Illinois, USA). Test of normality was applied on the data by using Kolmogorov-Smirnov test, Shapiro-Wilk test also D'Agstino. Quantitative data were expressed using range, mean, SD, and median while qualitative data were expressed in frequency and percent. Qualitative data were analyzed using χ2 -test and also exact tests such as Fisher exact and Monte Carlo were applied to compare different groups. Quantitative data were analyzed using Student t-test to compare between two groups while F-test (analysis of variance) was used to compare the three categories of outcome. Not normally distributed quantitative data were analyzed using Mann-Whitney test for comparing two groups. P value was assumed to be significant at 0.05.
| Results|| |
Descriptive data of the three studied groups:
As regard to the sex and age of children in this study it is shown in [Table 1].
The family history as regard the consanguinity, epilepsy, psychiatric disorders, and marital status is shown in [Table 2].
|Table 2 Comparison between epileptics and control group according to family history of consanguinity, epilepsy, psychiatric, mental disorder and family marital status |
Click here to view
Clinical data studied among epileptic children including the age of onset of seizures, the type of seizure, response to medication and medications are shown in [Table 3].
The distribution of the studied cases according to drugs used in the epileptic group is shown in [Table 4].
|Table 4 Distribution of studied cases according to drugs used in the epileptic group |
Click here to view
Assessment of the school performance of the three studied groups using the school grades records is shown in [Table 5].
|Table 5 Comparison between the three studied groups according to school performance |
Click here to view
The prevalence of depression among the three studied groups
Using the Kovac CDI, [Table 6] shows the comparison between the three studied groups as regard depression [Table 7].
|Table 6 Comparison between the three studied groups according to Children's Depression Inventory score |
Click here to view
|Table 7 Relation between Children's Depression Inventory and demographic data |
Click here to view
Possible risk factors of depression in epileptic children in our study
[Table 8] shows the relation between degree of depression and demographic data of the studied group.
|Table 8 Relation between Children's Depression Inventory and demographic data |
Click here to view
[Table 9] as well shows the relation between the degree of depression and family history as regard family history of epilepsy, consanguinity, marital status, and psychiatric disorders.
|Table 9 Relation between Children's Depression Inventory and family history of consanguinity, family history of epilepsy, marital status, and history of psychiatric/mental disorder |
Click here to view
[Table 10] shows the relation between the degree of depression and the clinical data of the studied epileptic children as regard type of seizures, response to therapy, medications, and age of onset of seizure.
|Table 10 Relation between Children's Depression Inventory and clinical data of the studied epileptic children |
Click here to view
The relation between the degree of depression and medications used is shown in [Table 11].
There was a significant relationship (P = 0.025) between depression in epileptic children and poor school performance as shown in [Table 12].
|Table 12 Relation between Children's Depression Inventory and school performance |
Click here to view
| Discussion|| |
In the current study, the prevalence of depression among the siblings of the epileptic children was: two of the 50 siblings had mild depression (4%) on CDI scale. This was consistent with the result of another study by Wood et al. (2008) as 37 siblings (aged 6-18 years) of children with intractable epilepsy were surveyed regarding anxiety, depression, and quality of life, by both self-report (Revised Children's Manifest Anxiety Scale; CDI) and parental report (Child Behavior Checklist). No sibling had a score in the clinical range on the CDI in their study. The study concluded that siblings of children with intractable epilepsy are functioning well overall and have a good quality of life.
It was found that, there is no increase in the prevalence of depression among the siblings of epileptic children compared with the control group. Although we expected greater psychological impacts on the life of siblings of epileptic children, these results could be explained by a number of suggestions including the following:
As regard to the prevalence of depression among epileptic children in this study, there were nine cases (18%) of the 50 children with epilepsy aged 7-10 years having the score of mild depression on CDI scale, while six children (12%) of the matched control group had mild depression. Although there was a higher prevalence of depression among the epileptic children compared with the control group, there was no statistically significant relationship between the prevalence of depression and epilepsy. These results were consistent with Turkish study conducted by Bilgic et al. (2006); the study assessed the prevalence of depression among 30 patients between the ages of 8-16 years with primary idiopathic epilepsy, using CDI scores. The level of depressive symptoms was higher in the epileptic group than in the control group but not statistically significant.
- There might be a denial from those children to express their feelings especially in front of their parents.
- They have not been neglected by their overburdened parents, as most of the parents in our study were educated and with average socioeconomic status and with intact family structure.
- We also noticed while interviewing the siblings that some of them, especially the older ones, were very supportive and believed that their siblings with epilepsy will get better, whereas the younger siblings did not fully understand the nature of his brother's or sister's illness.
- All the siblings included in this study had no chronic medical or surgical conditions that exclude the emotional impact of the chronic illness.
However in contrast to this study, Jones et al. (2007) in 2007 studied children aged 8-18 years with recent onset epilepsy (<1 year in duration) of idiopathic etiology (n = 53) and a healthy comparison group (n = 50) and showed significantly higher rates of depressive disorders (22.6 vs. 4%, P < 0.01) compared with the comparison group using 4th ed. DSM-IV Axis I disorders. Similarly Baki et al. (2004) in 2004 studied 35 children and adolescents with seizures (age range = 7-19 years), 35 sex-matched healthy controls (age range = 8-17 years), in a cross-sectional analysis. Patients with epilepsy had higher CDI scores (mean ± SD = 12.48 ± 6.35) than controls (9.31 ± 5.11) (P < 0.05).
The variations between these results and the results of the other studies could be explained by a number of factors, which may affect the prevalence of depression. First: the age of epileptic children in the current study was 7-10 years to exclude the effect of puberty, whereas the other studies have included both children and adolescents in their subjects. Supporting this explanation, Oguz et al. (2002) noted more symptoms of depression in adolescents (12-18 years of age) with epilepsy as compared with children 9-11 years of age. The study applied CDI to 35 patients with epilepsy aged 9-18 years and to 35 healthy children who served as the control group. Both study and control groups were divided into two age groups: 9-11 years and 12-18 years. Depression scores (16.65 ± 8.32 and 8.15 ± 3.15, P < 0.05) were significantly higher in the 12-18 year age group of epileptic children than in the control group. Thome-Souza et al. (2004) also found a predominance of depression in adolescents and found that age was an important predictive factor. Second: prevalence of depression can vary due to the use of different ratings and diagnostic instruments and scales. Third: most of epileptic children in this study were on classic AEDs, 28% of them were on carbamazepine. Affective problems are rare complications of treatment with carbamazepine due to the antidepressant properties of it, which is chemically related to the tricyclic antidepressants (Schmitz, 2006).
As regard to the sex difference among the epileptic children with depression, in our study, we found that 66% of the epileptic children with depression were males, whereas 33% were females. Similarly 63% of the epileptic children with no depression were males and 36% were females. We concluded that most of our sample group of epileptic children and control children were males and there was no significant relationship between sex and depression among epileptic children.
Consistent with our result, Hoare and Kerley (1991) and Baki et al. (2004) found no relationship between sex and depression in children and adolescents with epilepsy. However, Bilgic et al. (2006) found adolescent boys to have more emotional problems and suggested that, in epilepsy, male sex may be a risk factor for emotional symptoms. Stores (1978) suggested a higher rate of depressive complaints in boys. Although the underlying reason for this is unknown, he proposed that it may be related to higher expectations from men in society, which in turn, may cause more stigmatization.
As regard to the relationship between the prevalence of depression and age of onset of seizures, this study showed no significant relationship, as the mean age of onset of seizures among children with depression was 3.22 years which was not significantly different from the mean age of onset of epileptic children with no depression (3.19 years).
Consistent with these findings, Austin et al. (2001, 2002), Oguz et al. (2002), Baki et al. (2004), and Thome-Souza et al. (2004) did not support early onset seizures as being a risk factor for depression. However, a study conducted by Bromfield et al. (1992) on school placement suggested that depression and anxiety problems may be more common in children with a later age of onset of epilepsy.
One possible explanation of these results is that, the mean age of onset of seizures among epileptic children in the current study was 3 years and it is assumed that younger children are less aware of their disorder and, thus, less affected. Previous studies have suggested that children with seizure onset after 5 years of age typically display behavioral problems more often than cognitive deficits (Hermann et al., 1980; Sabbagh et al., 2006), whereas early age at onset of epilepsy is known to be associated with poor cognitive outcome (Meador et al., 2001; Elger et al., 2004).
Investigations on the relationship between seizure type and depression in the current study as a possible risk factor have shown that most of the cases (89%) of epileptic children with focal seizures had depression compared with 5% with no depression. So significant relationship between depression and focal seizures (P < 0.001) was found. Consistent with these results, Caplan et al. (2005) used mood self-report scales for 100 children with complex partial seizures (CPSs), 71 children with childhood absence epilepsy, and 93 normal children, aged 5-16 years. They reported significantly higher rates of depression in children with CPS as compared with children with childhood absence epilepsy. Thome-Souza et al. (2004) demonstrated that, in comparison with generalized seizures, focal seizures are associated with a higher risk of psychopathology in children. On the basis of the electroencephalographic findings of the epileptic children with focal seizures in the current study, there were four cases with frontal lobe localization and three cases of epileptic foci in the temporal lobe. The high prevalence of depression among patients with frontal lobe epilepsy has been explained by a bulk of evidence based studies by many authors; using PET and single-photon emission computed tomographic scans. They suggested that the hippocampus belongs to the limbic-frontal-subcortical network involved in the pathophysiology of major depressive disorder. Indeed, decreased hippocampal volume, blood flow and glucose metabolism were reported by Bremner et al. (2000) and Kennedy et al. (2001) in patients with major depressive disorder. Therefore, it is not surprising that seizure disorders of frontal lobe origin may also be associated with mood-altering symptoms (Sheline et al., 1999, 2003).
Brain and brainstem changes of serotoninergic 5-hydroxytryptophan (5-HT) 1A receptor density have been reported in patients with major depressive disorder as well as in patients with TLE using PET and the selective antagonist radiotracers. These changes (combination of decreased extracellular concentration of 5-HT and number of 5-HT 1A receptors) in the most depressed patients would be consistent with the relationship between TLE and depression (Toczek et al., 2003; Savic et al., 2004).
In contrast to these results, Dunn et al. (1999) Oguz et al. (2002), and Baki et al. (2004) are not supporting a significant relationship between seizure type and depression in the study group of children with epilepsy. Ott et al. (2001) examined psychopathology in 48 children with CPSs, 39 children with primary generalized epilepsy with absence, and 59 nonepileptic children, aged 5-16 years. They found no difference in rates of depression between the two groups on the Schedule for Affective Disorders and Schizophrenia for School-Age Children.
Frequency and/or recurrence of seizures is another proposed risk factor for depression in children with epilepsy. There were 78% of epileptic children with mild depression having uncontrolled seizures and 22% of them had controlled seizures. While among epileptic children with no depression, there were 20 cases (49%) with uncontrolled seizures. No significant relationship between frequency of seizures and the prevalence of depression in epileptic children in this study could be detected.
Consistent with this study, Thome-Souza et al. (2004), Caplan et al., Schmitz (2006), Baki et al. (2004), and Bilgic et al. (2006) found no association between seizure frequency and the risk for general psychopathology and affective disorders. These findings are supported by a review of the literature (Plioplys et al., 2007) that suggested psychopathology and emotional problems cannot be independently predicted by seizure frequency.
However in contrast to the findings of this study, Turky et al. (2008) showed that seizure frequency was significantly associated with emotional problems and depression. Austin et al. (2002) found a significant relationship between frequent seizures and internalizing problems and depression in children. Explanation for these findings included the possibility that both seizures and emotional problems are caused by an underlying neurological disorder, that is, seizure per se does not disrupt behavior and emotions.
The findings of this study can be explained by the younger age group of epileptic children in the current study compared with the adolescents included in the previously mentioned studies. We believe that the older the child, the greater is the child's perception of the changes in his or her daily life induced by the recurrence of seizures and the difference from peers. As regard to the potential risk of emotional side effects of treatment regimens, the current study showed no relationship between polytherapy and the prevalence of depression. It was found that 77% of epileptic children with depression were on polytherapy, whereas 80% of the epileptic children with no depression were on polytherapy.
Consistent with these results, Austin et al. (2002), Thome-Souza et al. (2004), and Caplan et al. (2005) have offered equivocal results, suggesting no significant difference in rates of depression between children on monotherapy and those on polytherapy. However, in contrast, Sabbagh et al. (2006) found a significant relationship between polytherapy and behavior problems in school-aged children with epilepsy. Hermann et al. (2000) also described behavior problems in patients on polytherapy, and Oguz et al. (2002) found that polytherapy was a significant predictor for the presence of depression in both children and adolescents with epilepsy.
It is hypothesized that antiepilepsy medication may have an effect on rates of psychiatric symptoms in epileptic patients. However in the current study, the majority of the cases with depression and anxiety were on classic antiepileptic medication mostly sodium valproate (77-80%) and carbamazepine (33-34%). There was no significant relationship between AEDs and depression in epileptic children in our study.
Consistent with this study, Dunn et al. (1999), Kessler et al. (2001), Oguz et al. (2002), Williams et al. (2003), Caplan et al. (2005), Alwash et al., and Austin et al. (1992) reported that, AEDs have not been found to be consistent predictors of mood problems and depression. However, depression and increased suicidality have been associated with the use of phenobarbital in children with epilepsy. Newer AEDs, such as levetiracetam and topiramate have been found to increase the risk of depressive symptoms in patients with epilepsy (Jones et al., 2007). However, this could not be revised in the current study due to economic reasons as most of the epileptic children received their medications from health insurance institutions where classic AEDs are used commonly, whereas the new AEDs used by the cases are usually expensive and not frequently used by our study group. So there was no significant number of cases on new AEDs to compare with.
Familial factors have also been found to be an important predictive factor for depression. This could not be supported by the current study, as no significant relationship between depression and family history of psychiatric and mental disorders was found. In contrast to this study, it has been well documented that depression is a familial illness (Mitchell et al., 1989), and children of parents with depression are up to eight times more likely to develop depression than children of parents without depression (Wickramaratne and Weissman, 1998). This relationship appears to hold true for patients with epilepsy as well. Plioplys (2003) found that, family history of depression has been reported in up to 50% of patients with epilepsy and depression. However, the low prevalence of psychiatric disorders among the families of the epileptic children in this study could be due to cultural beliefs that ignore or deny the diagnosis of psychiatric troubles.
It is found that prevalence of poor school performance is significantly higher in epileptic children compared with matched siblings and control group (P = 0.004). Also significant relationship between poor school performance and depression among epileptic children was found (P = 0.025). Certainly, it is reasonable to expect that academic underachievement is likely to increase the probability of emotional distress in children and adolescents who suffer from cognitive difficulties. This is illustrated well in a study completed by Caplan et al. (2005) who found higher rates of affective disorders in children with epilepsy who had lower verbal abilities. Such cognitive inefficiencies can interfere with the child's ability to perform, thus increasing the chances of severe frustration and anxiety. It has been also shown that, early age of onset of epilepsy (the mean age was 3 years in our study) is known to be associated with poor cognitive outcome (Meador et al., 2001; Elger et al., 2004), another recent study suggested that antiepileptic drugs also can induce clinically meaningful adverse cognitive and behavioral side effects (Bromley et al., 2011).
| Acknowledgements|| |
Conflicts of interest
| References|| |
Austin JK, Risinger MW, Beckett LA (1992). Correlates of behavior problems in children with epilepsy. Epilepsia 33:1115-1122.
Austin JK, Harezlak J, Dunn DW, Huster GA, Rose DF, Ambrosius WT (2001). Behavior problems in children before first recognized seizures. Pediatrics 107:115-122.
Austin JK, Dunn DW, Caffrey HM, Perkins SM, Harezlak J, Rose DF (2002). Recurrent seizures and behavior problems in children with first recognized seizures: a prospective study. Epilepsia 43:1564-1573.
Baki O, Erdogan A, Kantarci O, Akisik G, Kayaalp L, Yalcinkaya C (2004). Anxiety and depression in children with epilepsy and their mothers. Epilepsy Behav 5:958-964.
Bilgic A, Yilmaz S, Tiras S, Deda G, Kilic EZ (2006). Depression and anxiety symptom severity in a group of children with epilepsy and related factors. Turk J Psychiatry 17:165-172.
Bromfield EB, Altshuler L, Leiderman DB, Balish M, Ketter TA, Devinsky O, et al
. (1992). Cerebral metabolism and depression in patients with complex partial seizures. Arch Neurol 49:617-623.
Bromley RL, Leeman BA, Baker GA, Meador KJ (2011). Cognitive and neuro-developmental effects of antiepileptic drugs. Epilepsy Behav 22:9-16.
Caplan R, Siddarth P, Gurbani S, Hanson R, Sankar R, Shields WD (2005). Depression and anxiety disorders in pediatric epilepsy. Epilepsia 46:720-730.
Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E (2007). Epilepsy and risk of suicide: a population-based case-control study. Lancet Neurol 6:693-698.
Dunn DW, Austin JK, Huster GA (1999). Symptoms of depression in adolescents with epilepsy. J Am Acad Child Adolesc Psychiatry 38:1132-1138.
Ekinci O, Titus JB, Rodopman AA, Berkem M, Trevathan E (2009). Depression and anxiety in children and adolescents with epilepsy: prevalence, risk factors, and treatment. Epilepsy Behav 14:8-18.
Elger CE, Helmstaedter C, Kurthen M (2004). Chronic epilepsy and cognition. Lancet Neurol 3:663-672.
Hermann BP, Schwartz MS, Karnes WE, Vahdat P (1980). Psychopathology in epilepsy: relationship of seizure type to age at onset. Epilepsia 21:15-23.
Hermann BP, Seidenberg M, Bell B (2000). Psychiatric comorbidity in chronic epilepsy: identification, consequences, and treatment of major depression. Epilepsia 41:Suppl 2:31-41.
Hoare P, Kerley S (1991). Psychosocial adjustment of children with chronic epilepsy and their families. Dev Med Child Neurol 33:201-215.
Jones JE, Hermann BP, Barry JJ, Gilliam FG, Kanner AM, Meador KJ (2003). Rates and risk factors for suicide, suicidal ideation, and suicide attempts in chronic epilepsy. Epilepsy Behav 43:31-38.
Jones JE, Watson R, Sheth R, Caplan R, Koehn M, Seidenberg M, Hermann B (2007). Psychiatric comorbidity in children with new onset epilepsy. Dev Med Child Neurol 49:493-497.
Kessler RC, Avenevoli S, Ries Merikangas K (2001). Mood disorders in children and adolescents: an epidemiologic perspective. Biol Psychiatry 49:1002-1014.
Meador KJ, Gilliam FG, Kanner AM, Pellock JM (2001). Cognitive and behavioral effects of antiepileptic drugs. Epilepsy Behav 2:1-17.
Mitchell J, McCauley E, Burke P, Calderon R, Schloredt K (1989). Psychopathology in parents of depressed children and adolescents. J Am Acad Child Adolesc Psychiatry 28:352-357.
Morales IG, Mayor P, Kanner AM (2008). Psychiatric comorbidities in epilepsy. Review article. Neurologist 14:15-25.
Oguz A, Kurul S, Dirik E (2002). Relationship of epilepsy-related factors to anxiety and depression scores in epileptic children. J Child Neurol 17:37-40.
Otero S (2009). Psychopathology and psychological adjustment in children and adolescents with epilepsy. World J Pediatr 5:12-17.
Ott D, Caplan R, Guthrie D, Siddarth P, Komo S, Shields WD, et al. (2001). Measures of psychopathology in children with complex partial seizures and primary generalized epilepsy with absence. J Am Acad Child Adolesc Psychiatry 40:907-914.
Ott D, Siddarth P, Gurbani S, Koh S, Tournay A, Shields WD, Caplan R (2003). Behavioral disorders in pediatric epilepsy: unmet psychiatric need. Epilepsia 44:591-597.
Plioplys S (2003). Depression in children and adolescents with epilepsy. Epilepsy Behav 4:39-45.
Plioplys S, Dunn DW, Caplan R (2007). 10-year research update review: psychiatric problems in children with epilepsy. J Am Acad Child Adolesc Psychiatry 46:1389-1402.
Quinn H, Nikolov B, Jovine L, et al.
(2006). How do persons with epilepsy react when they are referred for symptoms of depression? 2006 annual meeting of the American Epilepsy Society
. California, USA: San Diego.
Rafnsson V, Olafsson E, Hauser WA, Gudmundsson G (2001). Cause-specific mortality in adults with unprovoked seizures. A population-based incidence cohort study. Neuroepidemiology 20:232-236.
Sabbagh SE, Soria C, Escolano S, Bulteau C, Dellatolas G (2006). Impact of epilepsy characteristics and behavioral problems on school placement in children. Epilepsy Behav 9:573-578.
Savic I, Lindström P, Gulyás B, Halldin C, Andrée B, Farde L (2004). Limbic reductions of 5-HT1A receptor binding in human temporal lobe epilepsy. Neurology. 62:1343-1351.
Schmitz, B (2006). Effects of antiepileptic drugs on mood and behavior. Epilepsia 47: Suppl 2:28-33.
Sheline YI, Sanghavi M, Mintun MA, Gado MH (1999). Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci. 19:5034-5043.
Sheline YI, Gado MH, Kraemer HC (2003). Untreated depression and hippocampal volume loss. Am J Psychiatry 160:1516-1518.
Stores G (1978). School-children with epilepsy at risk for learning and behavior problems. Dev Med Child Neurol 20:502-508.
Thome-Souza S, Kuczynski E, Assumpção F Jr, Rzezak P, Fuentes D, Fiore L, Valente KD (2004). Which factors may play a pivotal role on determining the type of psychiatric disorder in children and adolescents with epilepsy? Epilepsy Behav 5:988-994.
Toczek MT, Carson RE, Lang L, Ma Y, Spanaki MV, Der MG, et al. (2003). PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy. Neurology 60:749-756.
Turky A, Beavis JM, Thapar AK, Kerr MP (2008). Psychopathology in children and adolescents with epilepsy: an investigation of predictive variables. Epilepsy Behav 12:136-144.
Wickramaratne PJ, Weissman MM (1998). Onset of psychopathology in offspring by developmental phase and parental depression. J Am Acad Child Adolesc Psychiatry 37:933-942.
Williams J, Steel C, Sharp GB (2003). Anxiety in children with epilepsy. Epilepsy Behav 4:729-732.
Wood LJ, Sherman E, Hamiwka LD, Blackman M, Wirrell E (2008). Depression, anxiety, and quality of life in siblings of children with intractable epilepsy. Epilepsy Behav 13:144-148.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11], [Table 12]