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Epilepsy & Behavior 11 (2007) 92–97

Interactions between seizure frequency, psychopathology,and severity of intellectual disability in a population

with epilepsy and a learning disability q

Howard Ring a,*, Asif Zia b, Steve Lindeman b, Karen Himlok a

a Developmental Psychiatry Section, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge CB2 2AH, UKb Cambridgeshire and Peterborough Mental Health Partnership NHS Trust, Peterborough, UK

Received 28 February 2007; revised 30 March 2007; accepted 2 April 2007Available online 22 May 2007

Abstract

Despite observations associating lower IQ and psychopathology in epilepsy, the possible differential effects of varying severity oflearning (intellectual) disability (LD) on the manifestation of psychopathology in people with LD and epilepsy have not been clarified.In this study of retrospectively collected data describing the epilepsy, learning disability, and psychopathology of 175 patients withepilepsy and LD over a 3-month period, we observed that 65 patients had no recent seizures, whereas 110 had experienced at leastone seizure in the preceding 3 months. We found that depression and psychoses were more common in those with no seizures in thepreceding 3 months, but that which of these psychiatric states was manifest was related to the severity of LD. Psychosis rates were higherin those with mild LD, whereas depression rates were higher in those with severe LD.� 2007 Elsevier Inc. All rights reserved.

Keywords: Epilepsy; Psychosis; Depression; Learning disability

1. Introduction

The relationship between epilepsy and psychiatricpathology is well established. Both affective disorders andpsychoses have been reported to occur at increased fre-quency in people with epilepsy [1,2]. This association is wellrecognized in those with a learning disability (LD) (some-times referred to as intellectual disability), who also tendto have more severe epilepsy [3–8].

Several mechanisms potentially underlying the associa-tion between epilepsy and psychopathology have beendescribed, including the direct consequences of epilepticbrain activity [9] and lower IQ [10] leading to interictal

1525-5050/$ - see front matter � 2007 Elsevier Inc. All rights reserved.

doi:10.1016/j.yebeh.2007.04.002

q The clinical data collection on which this article is based was funded bygrants from UCB Pharma and Pfizer.

* Corresponding author. Fax: +44 01223 746122.E-mail address: har28@cam.ac.uk (H. Ring).

and postictal psychiatric states, antiepileptic drug (AED)effects [11,12], and a biological but poorly understood reci-procal relationship between epileptic severity and behav-ioral symptoms that has been described in relation torelative or absolute reductions in seizure frequency (‘‘alter-native psychoses’’) or epileptogenic EEG activity (‘‘forcednormalisation’’) (see Krishnamoorthy et al. [13] and Wolf[14] for reviews of this topic). However, despite observa-tions suggesting a link between lower IQ and psychopa-thology in epilepsy and the observed frequency andseverity of epilepsy and psychopathology in those withLD [15], many studies of the relationship between seizuresand psychopathology either have excluded people with LDor have not examined the potential differential effects ofvarying severity of LD on the manifestation of psychopa-thology. We have therefore investigated the nature of psy-chopathology in a group of patients with LD and epilepsy,ascertained from community LD health services.

Table 1Comparisons between those with and without recent seizures

No seizuresin past3 months(N = 65)

At least oneseizure in past3 months(N = 110)

Age 41.2 39.6

Gender (male) 57% 54%

Epilepsy duration (years) 24.6 26.3

Epilepsy syndrome, where knownIdiopathic generalized (N = 70) 72% 74%Focal (N = 24) 28% 26%

Number of AEDs prescribeda 1.4 2.1

Severity of LDb

Mild 31% 14%Moderate 20% 15%Severe 46% 65%Profound 3% 6%

a t(171) = �5.438, P < 0.001.b Pearson’s v2(4) = 10.846, P = 0.028.

H. Ring et al. / Epilepsy & Behavior 11 (2007) 92–97 93

2. Method

This observational study collected data describing the epilepsy, learn-ing disability, and any psychopathology manifest by patients under thecare of community LD teams in one county of England. Consent to pro-vide these data was obtained from those patients with the capacity tomake this decision; for those unable to give consent, assent was soughtfrom their prime carer. The study was approved by the local research eth-ics committee.

Participants were ascertained from those being actively managed bytheir local community LD team. A trained researcher identified thosepatients who had epilepsy in addition to LD by reviewing their clinical notesand checking with LD team clinicians. For each identified and consenting/assenting participant, a trained researcher collected information regardingtheir epilepsy, their learning disability, and any psychiatric diagnosis pres-ent over the 3 months preceding the date of data collection. This informa-tion was gathered using a structured data collection form retrospectivelyfrom clinical notes and contemporaneously from interviews with the LDservice, general practitioner, any involved specialist hospital services, anda carer who was familiar with the participant’s recent state. The informationobtained was entered onto an Excel database and subsequently analyzedusing SPSS. The severity of LD described was that which had previouslybeen determined by each participant’s community LD team, most oftenby use of the Weschler Adult Intelligence Scale. In the United Kingdom,to have been eligible for clinical LD services in the first place, individualsneed to have a measured Full Scale IQ 670. The IQ bands associated withthe descriptions of LD severity used in this study were those routinelyemployed in UK clinical practice: mild = 50–70, moderate = 35–50,severe = 20–35, and profound <20. The learning disabilities in thesepatients were all part of a pervasive developmental disability, and individ-uals with acquired or limited specific intellectual deficits were not includedin the study sample. The epilepsy diagnoses used in the study were thosereported in the participants’ clinical notes, where necessary clarified by fur-ther perusal of available clinical, EEG, and imaging data by the authors.The great majority of participants in the study lived with and were closelysupported by family or paid carers. Seizure frequency was determined byinterviewing the participants’ carers, the majority of whom had previouslyattended epilepsy training days on which they had been taught how to rec-ognize and record seizure frequencies and types. Although some patientsmay have also experienced unobserved seizures, because all the patientsin the study were under the care of specialist LD teams whose members rou-tinely inquired about the patients’ epilepsy, we think it likely that the seizurerecording was relatively accurate. The psychopathology descriptionsemployed—depression, psychosis, challenging behaviour, and self-injuri-ous behaviour—were based on clinical descriptions obtained from the clin-ical notes or from health care professionals who knew the patients. The termdepression was used to describe subjectively reported or objectively notedsigns or symptoms of low mood, whereas the term psychosis was used todescribe psychotic phenomena such as hallucinations and delusions, butdid not include peri-ictal confusional states. The psychiatric accounts wereclinical descriptions and did not necessarily meet relevant ICD/DSM crite-ria for formal psychiatric diagnoses. To obtain an overall measure of cur-rent seizure severity, the study population was divided into those whohad no reported seizures over the 3 months prior to the time of data collec-tion and those who had experienced at least one seizure over this period.

3. Results

Altogether, data were obtained describing 175 individu-als with a LD who also had a diagnosis of epilepsy. The agerange of the study population was 16–72, with a mean of 40(SD = 11), and 56% of the sample were male. A wide rangeof different etiologies for the LD were noted, the most fre-quent of which were cerebral palsy in 18% and Down’s syn-drome in 5%. In 36% no clear cause of LD could beidentified. Overall, the mean duration of epilepsy in the

sample was 26 years (SD = 17, range = 1–71). The meanmonthly seizure frequency over the 3 months precedingthe study was 7.2, with a range of 0 to 90 seizures permonth. Of the 175 patients considered in this study, 65had not experienced any seizures in the 3 months prior tothe study, whereas 110 had experienced at least one seizure.The mean monthly seizure frequency of those with at leastone seizure in these 3 months was 11.4. The type of epilepsysyndrome present could be established in 56% of the studypopulation, with almost all having either an idiopathic gen-eralized epilepsy (70 individuals) or a focal epilepsy (24individuals) syndrome. There were no significant differ-ences between those who had had and those who had nothad seizures in the preceding 3 months with respect tothe proportions with an idiopathic generalized comparedwith a focal epilepsy syndrome. Relevant descriptors ofthose with and without any seizures in the 3 months pre-ceding the study are contrasted in Table 1.

As shown in Table 1, while those with and withoutrecent seizures were similar in terms of age, gender distribu-tion, and duration of their epilepsy, those with recent sei-zures, on average, were prescribed more AEDs and hadless mild and more severe LD.

To investigate the relationship between seizure fre-quency and psychopathology, we identified which partici-pants had experienced a psychotic disorder, anonpsychotic depressive disorder, challenging behaviour,or self-harm over the same 3-month period preceding thestudy that the seizure frequency data described. The psy-chopathology reported in this group of patients isdescribed in Table 2.

Examining the prevalence of psychopathological statesin those with and without any seizures in the 3 months pre-ceding the study demonstrated that the proportion of thosewith no seizures who had experienced psychopathology

Table 2Psychopathology observed in 175 patients with LD and epilepsy

Psychopathology Frequency in study population

None 76 (43%)Depressive disorder 46 (26%)Psychotic disorder 20 (11%)Challenging behavior 32 (18%)Self-injury 14 (8%)

Note. Four patients were reported to have both a psychotic disorder and adepressive disorder and were classified as having a psychotic disorder inthese analyses. Six participants were recorded as having both a depressivedisorder and self-injurious behavior or challenging behavior, whereas fourparticipants were recorded as having both a psychotic disorder and self-injurious behavior or challenging behavior. In the analyses, challengingbehavior and self-injurious behavior are counted independently of anycomorbid depression or psychosis.

94 H. Ring et al. / Epilepsy & Behavior 11 (2007) 92–97

was significantly higher than the proportion of those withseizures who had experienced psychopathology(P = 0.007, Fisher’s exact test). Examination of Table 3reveals that both psychosis and depressive disorderoccurred at increased frequency in those with no seizuresin the preceding 3 months, whereas challenging behaviorand self-injurious behavior occurred at similar ratesregardless of recent seizure frequency.

As noted in Table 1, those with no recent seizures hadhigher rates of mild LD and lower rates of severe LD thanthose who were experiencing continuing seizures. Toaddress the question of whether there was a relationshipbetween severity of LD and rates of psychopathology inthose with and without recent seizures, the frequencies ofpsychosis and depression were examined with respect tothe presence or absence of recent seizures in those withmild or severe LD (Table 4). (Those with moderate or pro-

Table 3Rates of psychopathology in those with and without recent seizures

Psychosis(%)

Depressivedisorder(%)

Challengingbehavior(%)

Self-injury(%)

No seizures inprevious 3 months,N = 65

15 34 18 9

Any seizures inprevious3 months, N = 110

9 22 19 7

Table 4Rates of depression and psychosis in those with mild and severe LD withrespect to whether they had experienced recent seizures

Mild LD Severe LD

1. No recent seizuresDepression diagnosed 6/20 (30%) 12/29 (41%)Psychosis diagnosed 7/20 (35%) 1/29 (3%)

2. At least one seizure in past 3 monthsDepression diagnosed 5/15 (33%) 11/71(15%)Psychosis diagnosed 2/15 (13%) 5/71 (7%)

found LD were not included in these analyses, as these lev-els of LD occurred at similar rates in those with andwithout recent seizures).

Examination by hierarchical log-linear analysis of thedata summarized in Table 4 demonstrates a borderline sig-nificant (P = 0.054) three-way interaction between severityof LD (mild or severe LD), seizure status (presence orabsence of any seizures in the 3 months prior to the study),and diagnosis of depression or psychosis. Subsequently,2 · 2 table analyses of these data separately for those withand those without continuing seizures were performed.These demonstrated that for those with no recent seizures,psychosis rates were higher in those with mild LD than inthose with severe LD, whereas those with severe LD hadhigher rates of depression than those with mild LD (Fish-er’s exact test, P = 0.03). However, for those with at leastone seizure in the 3 months preceding the study, therewas no significant difference in psychosis or depressionrates between those with mild and those with severe LD.

To establish whether the presence of depression or psy-chosis was particularly associated with any AED, the fre-quencies with which each AED was prescribed werecompared between those with and without these psychopa-thologies. Altogether across the study cohort, 13 differentAEDs were prescribed, most commonly sodium valproate,carbamazepine, and lamotrigine. No AED was found to beprescribed more often in association with either depressionor psychosis or in those with no seizures in the preceding 3months compared with those with at least one seizure overthis time.

To explore whether, in those with continuing seizures,there was an association between seizure frequency andpsychopathology rates, we compared rates of depressionand psychosis in those with one to four seizures per monthand those with more than four seizures per month (where 4was the median number of seizures per month in those withcontinuing seizures). We found no difference in the propor-tions of those with psychosis (respectively 11% vs 8% inthose with more or less than the median number). Therewas a weak trend toward significance (v2 test, P = 0.095)for more frequent depression (in 28%) in those with moreas opposed to those with less than the median number (inwhom there was depression in 14%).

4. Discussion

4.1. Major findings

This study, of 175 patients with epilepsy and a learning(intellectual) disability characterized by an IQ of 670,observed that rates of psychosis and depression were higherin those with no recent seizures than in those with ongoingseizures. In addition, an interaction between the level ofLD and the nature of the psychiatric symptoms presentwas also noted, but only in those with no seizures in theprevious 3 months. Those with mild LD and no recent sei-zures had higher rates of psychosis, whereas those with

H. Ring et al. / Epilepsy & Behavior 11 (2007) 92–97 95

severe LD and no recent seizures had higher rates ofdepression. These relationships between seizure frequencyand LD severity were not observed for more general mark-ers of psychological distress—challenging and self-injuri-ous behaviors. As far as the authors are aware, thisdetailed relationship between severity of LD and psychopa-thology in relation to seizure frequency has not previouslybeen reported.

4.2. Relationship of these findings to other relevant research

4.2.1. Psychopathology in people with epilepsy and LD

Rates of depression and psychoses observed overall inthis study resembled those reported in a Scottish popula-tion with epilepsy and LD by Espie et al. [6], who describedpossible affective or neurotic disorder in 29% of their sam-ple (compared with possible depression in 26% of thecurrent sample) and possible psychotic disorder in 10% oftheir sample (compared with possible psychosis in 11% ofthe current sample). In both that research and the currentstudy, the rates of psychosis observed were lower thanthe 24% reported in a Japanese population by Matsuuraet al. [7], but higher than the 4.4% reported in an Englishpopulation by Deb et al. [16] This wide range of prevalenceof psychosis may in part relate to differences in the diagnos-tic processes and definitions employed in these studies(although both Espie et al. [6] and Deb et al. [16] usedthe Psychiatric Assessment Schedule for Adults with Devel-opmental Disabilities [17] (PAS-ADD) and ICD-10 crite-ria). However, the results of the current study suggestthat differences in overall rates of psychosis between studiesmay also relate both to differences in the relative propor-tions of those with occasional, frequent, or currently no sei-zures and to the relative proportions of those with mild asopposed to more severe LD in the study populations.Although in the current study the most significant findingwas of more psychopathology in those with no recent sei-zures, Espie et al. [6] found that increasing seizure fre-quency predicted psychiatric cases. Although whenconsidering only those with at least one seizure we did notea small trend toward more depression in those with greaterseizure frequency, overall our results give an impression ofthe relationship between epilepsy and psychopathology dif-ferent from that described by Espie et al. This differencemay in part be related to the observation that in the currentstudy, 37% of participants had experienced no recent sei-zures, whereas in the study population described by Espieet al. [6], just 12% experienced seizures at a rate of less thanone per month, leading to a smaller proportion of casesfrom which such observations could be made. The rate ofseizure freedom in the current study may be higher becauseour participants were recruited only from community LDservices, whereas Espie and colleagues also recruited partic-ipants from specialist epilepsy services, in which those withmore severe epilepsy are likely to be concentrated. Withrespect to the relationship between psychopathology andseverity of LD in people with epilepsy, as noted above, this

has not been much explored, although Adachi et al. [9]reported that rates of psychosis were observed across alltheir participants to be higher in those with mild than inthose with severe LD. However, those authors definedsevere LD simply as an IQ <70, which in UK services isthe cutoff for entry to the description of LD, with thosehaving an IQ >70 not being considered to have LD [18].In the current study, we demonstrated distinct relation-ships between seizure frequency and psychopathology inthose whose IQ fell into mild (IQ = 50–70) and severe(IQ = 20–35) categories of LD.

4.2.2. The relationship between psychopathology and severity

of LD in those without epilepsy

The pattern observed in those with no recent seizures, ofmore depression associated with severe LD and more psy-chosis with mild LD, differs from results reported inpatients with LD but no epilepsy, for whom varying resultshave been obtained. Holden and Gitlesen [19] reportedincreased rates of both depression and psychosis in thosewith moderate compared with those with severe or pro-found LD and concluded that prevalence of psychiatric ill-ness decreases with increasing severity of LD. Morerecently, however, in a community-based epidemiologicalstudy, Cooper et al. looked for but did not find a relation-ship between prevalence of depression and severity of LD[20]. However, it has also been pointed out that reportsof low prevalence rates of psychiatric disorders, at leastin children with epilepsy and the most severe intellectualimpairment, may arise as a consequence of the difficultyin identifying psychiatric symptoms in those with moresevere LD [21]. Overall, however, in the current study psy-chotic symptoms were observed in 20% of our participants,compared with the rate of clinically diagnosed psychoticdisorders of 4.4% in a community sample of people withLD, 39% of whom had mild LD and 19% severe LD [22],suggesting that compared with the study of patients withsevere LD but no epilepsy, we have not significantly under-diagnosed psychotic symptoms in this group. Factors thatmay help explain the distribution of psychopathologyobserved in the current study could therefore include issuesrelated to diagnosis of psychopathology in those withdiffering severities of LD or to some aspect of the partici-pants’ chronic epileptic disorder.

4.3. Possible explanations of the findings

The observations reported in Table 1 indicate thatwithin the study population, ongoing seizures were, notsurprisingly, associated with more severe epilepsy, reflectedin prescription of more AEDs. In addition, also as wouldbe predicted from previous observations, there were pro-portionately more people with a severe or profound LDin the group with continuing seizures. However, we alsonoted that there were higher rates of psychopathology inthose with no recent seizures. This group comprised pro-portionately fewer people with a severe or profound LD.

96 H. Ring et al. / Epilepsy & Behavior 11 (2007) 92–97

It is therefore important to consider whether the higherrates of psychopathology in the seizure-free group couldhave arisen as a consequence of issues related to the detec-tion of psychiatric symptoms in those with the lowest IQs.

As noted above, it is widely accepted that it is more dif-ficult to make psychiatric diagnoses in people with severeLD, who generally lack the language abilities to verballydescribe their psychological experiences, than it is in peoplewith mild or moderate LD [23]. In addition, for those at themost severe end of the LD spectrum, it remains unclearwhether behavioral disturbances that appear to indicatepsychological distress reflect psychological states that arecongruent with the depressive and psychotic statesdescribed in those with higher IQs. The diagnosis of psy-chotic states may be particularly problematic in this con-text. This difficulty could have contributed in this studyto higher rates of depression, and particularly of psychosisin the group with no recent seizures, which contained pro-portionately fewer people with a severe or profound LD.However, examination of Table 4 reveals that the higherrate of psychosis in the group with ‘‘no recent seizures’’was accounted for by higher psychosis rates not amongthose with severe LD (3% in those without vs 7% in thosewith recent seizures) but rather in those with mild LD (35%in those with vs 13% in those without recent seizures), inwhom the diagnosis is reasonably straightforward and reli-able. Considering depression, in this case the higher rate inthose with no recent seizures is accounted for by theincreased diagnosis of depression among those with severeLD in the patients with no recent seizures (41%) comparedto those with ongoing seizures and severe LD (15%). Henceit seems unlikely that the increased rates of psychopathol-ogy in those with no recent seizures, compared with thosewith ongoing seizures, can be explained purely as a conse-quence of the higher proportion of those with more severeLD in the ongoing seizure group.

It is, however the case that if only the ‘‘no recent sei-zures’’ group is considered, the higher rates of psychosisin those with mild compared with those with severe LDmay have been more strongly related to the difficulties inidentifying psychotic symptoms in those with more severeLD. Although in the current study we cannot formallyquantify the potential size of this effect, looking again atTable 4, at the rates of psychosis among those with contin-uing seizures, note that the ratio of psychotic symptoms inthose with mild versus those with severe LD is approxi-mately 2:1. In those with no recent seizures, however, theequivalent ratio is approaching 12:1. It is therefore possiblethat some other factor, in addition to the relative propor-tions of those with mild and severe LD in the two groups,is contributing to the increased rates of psychopathology inthose with no recent seizures.

Other articles exploring the association betweenincreased psychopathology and relative or absolute reduc-tions in seizure frequency or epileptogenic EEG activityhave considered the possibility of a direct physiological link(described as alternative psychoses (AP) or forced normal-

ization (FN) [13,14]) between decreased epileptic activityand the development of psychopathology. The majorityof prior reports of AP/FN have been in the form of smallcase series and anecdotal reports, most often describingpsychosis, with depression less frequently recognized as apossible manifestation of this phenomenon. [14,24]. How-ever, as discussed below, the design of the current studydoes not provide any account of the temporal relationshipbetween reduction in seizure frequency and development ofpsychopathology that would address the possibility of AP/FN being a mechanism in this study.

Finally, we did not identify associations between otherepilepsy-related variables and specific psychiatric symp-toms. In common with Espie at al. [6] and Deb [25], inthe current study it was noted that seizure type did not pre-dict psychiatric state. With respect to AED use, althoughthere is an extensive literature relating the use of AEDsto the generation of psychopathology [11,12,26], in the cur-rent study the increased rates of depression and psychosiswere not related to the prescription of any specific AEDs.Conversely, some AEDs have efficacy as mood stabilizers[18]. However, in the current study, the AEDs most oftenprescribed; sodium valproate, carbamazepine, and lamotri-gine, which are also those AEDs most widely prescribed asmood stabilizers, were used with similar frequencies inthose with and without psychoses or depression and inthose with continuing seizures and those who wereseizure-free.

4.4. Study limitations

Most importantly, seizure frequency was obtained onlyfor the 3-month period preceding the date of data collec-tion. We do not have data on any EEG changes thatmay or may not have been associated with seizure absence,nor are there data describing when the last recorded seizureoccurred in those who had been seizure-free for at least 3months, or when the psychiatric symptoms reported werefirst observed. These factors mean that we cannot formallydescribe the periods of seizure freedom with psychopathol-ogy as either forced normalization or alternative psychosesaccording to the criteria formulated by Krishnamoorthyand Trimble [27]. Another limitation of this study is thatthe data were obtained largely retrospectively, albeitmostly from contemporaneously prepared clinical records.The group studied were suffering from a wide range ofbrain disorders, and it is therefore not possible to relatecognitive or psychiatric states observed to specific neuro-pathological processes. In addition, the epilepsy and psy-chopathology descriptions were derived from a relativelylarge number of different clinicians, and as the criteria usedin the current study to define the presence of a particularpsychopathological state were based on clinical descrip-tions and diagnoses by these clinicians, it is likely that dif-ferent diagnostic processes were employed across the studycohort. It is also important to emphasize that psychiatricdescriptions employed in this study, although based on

H. Ring et al. / Epilepsy & Behavior 11 (2007) 92–97 97

specific signs and symptoms, are clinical accounts and notformal ICD or DSM diagnoses. Nevertheless, there is noevidence that these diagnostic processes differed systemati-cally according to whether or not participants had experi-enced a recent seizure, and as noted above, rates ofdepression and psychosis observed in this study resembledthose previously reported by Espie et al. [6].

5. Conclusions

We suggest that the results of this study indicate thatin a proportion of those with LD and chronic epilepsy,seizure freedom is associated with the manifestation ofpotentially serious psychiatric symptoms. Our findingthat the form in which this psychopathology manifestsis related to the level of overall functional brain distur-bance as reflected by LD severity resembles observationsby Wolf [14] made in the context of forced normaliza-tion. He suggested that, although active inhibitory pro-cesses lead to both reduction of seizure activity anddevelopment of enhanced vulnerability to the develop-ment of psychopathology, a range of individual factorsdetermine the actual occurrence and form of the psycho-pathology. Applying this model, it is the different biolog-ical and environmental associations of mild as opposedto severe LD that lead toward either depression or psy-chosis. Although the current study can only speculativelypropose this model as a possible explanation of the clin-ical observations reported, we believe that these observa-tions suggest that future research could usefullyprospectively investigate the effects of alterations in sei-zure frequency on the development of specific psycho-pathological states in patients with different magnitudesof LD severity.

Acknowledgments

We are grateful to the patients and the CommunityTeams and Carers of the patients whose data contributedto this study. The authors are also grateful to Dr. PeterWatson (MRC Cognition and Brain Unit, University ofCambridge) for statistical advice and to UCB Pharmaand Pfizer for funding our data collection.

References

[1] Bredkjaer S, Mortensen P, Parnas J. Epilepsy and non-organic non-affective psychosis: national epidemiologic study. Br J Psychiatry1998;172:235–8.

[2] Vuilleumier P, Jallon P. Epilepsy and psychiatric disorders: epidemi-ological data. Rev Neurol 1998;154:305–17.

[3] McGrother C, Bhaumik S, Thorp C, et al. Epilepsy in adults withintellectual disabilities: prevalence, associations and service implica-tions. Seizure 2006;15:376–86.

[4] Adachi N, Matsuura M, Okubo Y, et al. Predictive variables ofinterictal psychosis in epilepsy. Neurology 2000;55:1310–4.

[5] Deb S, Hunter D. Psychopathology of people with mental handicapand epilepsy: II. Psychiatric illness. Br J Psychiatry 1991;159:826–30.

[6] Espie C, Watkins J, Curtices L, et al. Psychopathology in peoplewith epilepsy and intellectual disability: an investigation ofpotential explantory variable. J Neurol Neurosurg Psychiatry2003;74:1485–92.

[7] Matsuura M, Adachi N, Maramatsu R, et al. Intellectual disabilityand psychotic disorders of adult epilepsy. Epilepsia 2005;46(Suppl. 1):11–4.

[8] Rodin E, editor. The prognosis of people with epilepsy. Springfield,IL: Charles C Thomas; 1968. p. 156–74.

[9] Adachi N, Matsuura M, Hara T, et al. Psychoses and epilepsy: areinterictal and postictal psychoses distinct clinical entities? Epilepsia2002;43:1574–82.

[10] Umbricht D, Degreef G, Barr W, et al. Postictal and chronicpsychoses in patients with temporal lobe epilepsy. Am J Psychiatry1995;152:224–31.

[11] Besag F. Behavioural effects of the new anticonvulsants. Drug Saf2001;24:513–36.

[12] Schmitz B. Effects of antiepileptic drugs on mood and behaviour.Epilepsia 2006;47(Suppl. 2):28–33.

[13] Krishnamoorthy E, Trimble M, Sander J, et al. Forced normalisa-tion at the interface between epilepsy and psychiatry. Epilepsy Behav2002;3:303–8.

[14] Wolf P. Acute behavioral symptomatology at disappearance ofepileptiform EEG abnormality: paradoxical or forced normalization.In: Smith B, Treiman D, Trimble M, editors. Advanced Neurology55: Neurobehavioural problems in epilepsy. New York: RavenPress; 1991. p. 127–42.

[15] Van der Feltz-Cornelis C. Treatment of interictal psychiatric disorderin epilepsy: III. Personality disorder, aggression and mental retarda-tion. Acta Neuropsychiatr 2002;1:49–54.

[16] Deb S, Thomas M, Bright C. Mental disorder in adults withintellectual disability: 1. Prevalence of functional psychiatric illnessamong a community-based population aged between 16 and 64 years.J Intell Disabil Res 2001;45:495–505.

[17] Moss S, Ibbotson B, Professer H, et al. Validity of the PASS-ADDfor detecting psychiatric symptoms in adults with learning disability(mental retardation). Social Psychiatry Psychiatr Epidemiol1997;32:344–54.

[18] Dunn R, Frye M, Kimbrell T, et al. The efficacy and use ofanticonvulsants in mood disorders. Clin Neuropharmacol1998;21:215–35.

[19] Holden B, Gitlesen J. The association between severity of intellectualdisability and psychiatric symptomatology. J Intell Disabil Res2004;48:556–62.

[20] Cooper SA, Smiley E, Morrison J, Williamson A, Allan L. Anepidemiological investigation of affective disorders with a population-based cohort of 1023 adults with intellectual disabilities. Psychol Med2007;5:1–10.

[21] Steffenberg E, Steffenberg S. Epilepsy and other neuropsychiatricmorbidity in mentally retarded children. In: Sillanpaa M et al.,editors. Epilepsy and mental retardation. Petersfield: WrightsonBiomedical; 1999. p. 47–59.

[22] Cooper SA, Smiley E, Morrison J, Williamson A, Allan L. Mental ill-health in adults with intellectual disabilities: prevalence and associ-ated factors. Br J Psychiatry 2007;190:27–35.

[23] Moss S. Assessment: conceptual issues. In: Bouras N, editor.Psychiatric and behavioural disorders in developmentaldisabilities and mental retardation. Cambridge: Univ. Press;1999. p. 18–37.

[24] Barry J, Huynh N, Lembke A. Depression in individuals withepilepsy. Curr Treat Options Neurol 2000;2:571–85.

[25] Deb S. Electrophysiological correlates of psychopathology in indi-viduals with mental retardation and epilepsy. J Intell Disabil Res1995;39:129–35.

[26] Trimble M. New antiepileptic drugs and psychopathology. Neuro-psychobiology 1998;38:149–51.

[27] Krishnamoorthy E, Trimble M. Forced normalization: clinical andtherapeutic relevance. Epilepsia 1999;40(Suppl. 10):S57–64.