The original cohort consisted of 613 children of whom 501 (81.7%) participated in the 9-year interview and had completed, usable interviews. Of those who were not included, 28 were actively followed but declined to participate in the interview, 70 had already been lost prior to this phase of the study, 13 had died prior to the time of the interview, and one interview had to be excluded.
In the interviewed group, 247 (49.3%) were female. The average ages at onset of epilepsy and at time of participating in the interview were 5.8 years (SD=4.0) and 15.3 years (SD=4.2). The interviews were targeted to be done approximately 9 years after initial diagnosis of epilepsy. The mean interval was 9.5 years (SD=1.4, range 6.6 to 15.1). The epilepsy was classified as uncomplicated in 342 (68.3%) of the included cohort.
One or more psychiatric disorders was reported in 152 (30.3%) including 80 with internalizing disorders (depression (N=67), anxiety (N=25), OCD (N=14), bipolar disorder (N=6) or schizophrenia (N=2)) and 111 with externalizing disorders (ADHD (N=104), CD (N=22), or ODD (N=5)). Multiple psychiatric disorders were reported in 57 (11.4%) study subjects including 39 who had both externalizing and internalizing disorders. One or more neurodevelopmental spectrum disorders was reported in 209 (41.7%) including developmental delay (N=160), language problem (N=112), dyslexia (N=14), learning disorder (N=135), and autistic spectrum disorder (ASD, N=26). Multiple neurodevelopmental spectrum disorders were reported in 145 (28.9%).
Special education or related services had been received by 296 (59.1%) of the interviewed cohort, including 144 (90.6%) in the complicated group and 152 (44.4%) in the uncomplicated group (p<0.0001). Of subjects with reported neurodevelopmental spectrum disorders, 100% in the complicated group and 75/79 (95%) in the uncomplicated group had received special services.
Comparison of complicated and uncomplicated epilepsy
Both neurodevelopmental and psychiatric disorders were more common in children with complicated than with uncomplicated epilepsy (). The associations with psychiatric disorders were almost entirely due to externalizing disorders which occurred in 62 (18.1%) of the uncomplicated and 49 (30.8%) of the complicated group (p=0.002).
Psychiatric and neurodevelopmental spectrum disorders in complicated versus uncomplicated epilepsy.
Association between neurodevelopment and psychiatric disorders ()
Overall, 115/349 (33.0%) with no psychiatric disorders had neurodevelopmental disorders versus 94/152 (61.8%) of those with any psychiatric disorders (p<0.0001). This relationship was stronger for externalizing than for internalizing disorders. Within the complicated epilepsy group, however, there was no association between neurodevelopmental disorders and psychiatric disorders overall or separately for internalizing or externalizing disorders. By contrast, for the uncomplicated group, psychiatric disorders and neurodevelopmental disorders were strongly associated (p<0.0001). This was observed for both internalizing and for externalizing disorders but was stronger for externalizing.
Overall and separately within complicated and uncomplicated epilepsy groups, internalizing and externalizing disorders were strongly associated with each other. In the full group, 35% with versus 11% without externalizing disorders also had internalizing disorders (p<0.0001). Within the complicated group, the corresponding figures were 31% versus 11% (p=0.002), and within the uncomplicated group, the figures were 39% versus 10% (p<0.0001).
Within the complicated group, 9/22 (41%) with depression had anxiety versus 4/137 (3%) of those without depression (p<0.0001). In the uncomplicated group, the comparable figures were 6/45 (13%) and 6/297 (2%) (p=0.002). ADHD co-occurred with depression or anxiety. Within the complicated group, 12/46 (26%) of those with ADHD had depression or anxiety versus 14/113 (12%) of those without ADHD (p=0.03). The corresponding percentages in the uncomplicated group were 21/58 (36%) and 30/284 (11%) (p<0.0001).
Associations between psychiatric disorders and neurodevelopmental spectrum disorders.
Because some of the subgroups were too small for more detailed analysis within the complicated group, further analyses focused primarily on the uncomplicated group (N=342; ). Within this group, we found some fairly large differences in the factors associated with having internalizing versus externalizing disorders. In particular, older age, both at onset and at interview, were strongly correlated with internalizing but not with externalizing disorders or neurodevelopmental spectrum disorders. Although a history of having failed trials of at least two AEDs (pharmacoresistance) was not associated with greater proportions having psychiatric or neurodevelopmental spectrum disorders in this uncomplicated epilepsy group, not being in five-year remission at the time of the interview and, to a lesser extent, never having been five-years seizure-free, were significantly associated with a greater proportion reporting both internalizing and neurodevelopmental disorders but not externalizing disorders. Of the additional variables we considered, only male sex was strongly associated with externalizing disorders but not with neurodevelopmental disorders.
Association between clinical factors and psychiatric and neurodevelopmental disorders in the portion of the cohort with uncomplicated epilepsy.
To summarize these complex inter-relationships, we performed a series of logistic regression analyses to identify independent factors correlated with internalizing, externalizing, and neurodevelopmental spectrum disorders (). We selected age at interview rather than age at onset for these models as this made sense in light of what is known of the epidemiology of these disorders in general.
Results of logistic regression analyses to identify the factors that had independent associations with neurodevelopmental, internalizing, and externalizing disorders.
The main factors correlated with internalizing disorders were externalizing disorders (p<0.0001) and older age at interview (p=0.0003). After adjustment for these two factors, 5-year remission status at the time of interview was associated with a 43% lower prevalence of internalizing disorder (p=0.04), 96% of which was depression and/or anxiety. The main factors associated with externalizing disorders were internalizing disorders (p<0.0001), neurodevelopmental spectrum disorders (p<0.0001), and male gender (p<0.0001). Finally, neurodevelopmental spectrum disorders were associated with externalizing disorders (p<0.0001) and 5-year remission status at the time of the interview (p=0.0007).