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Epileptic, organic and genetic vulnerabilities for timing of the development of interictal psychosis

  • Naoto Adachi (a1), Nozomi Akanuma (a2), Masumi Ito (a3), Masaaki Kato (a3), Tsunekatsu Hara (a4), Yasunori Oana (a5), Masato Matsuura (a6), Yoshiro Okubo (a7) and Teiichi Onuma (a8)...

Abstract

Background

Age at the first psychotic episode and an interval between the onset of epilepsy and that of psychosis reflect developmental processes of interictal psychosis. However, factors relating to these indices remain unknown.

Aims

To identify clinical variables that are associated with the timing of the development of interictal psychosis.

Method

In 285 adults with epilepsy with interictal psychosis, effects of epileptic (epilepsy type), organic (intellectual functioning) and genetic (family history of psychosis) variables on timing of the development of psychosis were examined.

Results

The mean interval between the onset of epilepsy and that of psychosis was 14.4 years. Some psychosis occurred within a few years of the first seizure. Generalised epilepsy, normal intellectual function and a positive family history of psychosis were associated with early onset of psychosis.

Conclusions

Early development of interictal psychosis in people with epilepsy may reflect other individual vulnerabilities to psychosis rather than epilepsy-related damage.

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Copyright

Corresponding author

Naoto Adachi, Adachi Mental Clinic, Kitano 7-5-12, Kiyota, Sapporo 004-0867, Japan. Email: adacchan@tky2.3web.ne.jp

Footnotes

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Declaration of interest

None.

Footnotes

References

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2 Trimble, MR, Schmitz, B. The psychoses of epilepsy/schizophrenia. In Epilepsy: A Comprehensive Textbook (eds Engel, J Jr, Pedley, TA): 2071–81. Lippincott-Leven, 1997.
3 Mellers, J, Toone, BK, Lishman, WA. A neuropsychological comparison of schizophrenia and schizophrenia-like psychosis of epilepsy. Psychol Med 2000; 30: 325–35.
4 Matsuura, M, Adachi, N, Muramatsu, R, Kato, M, Onuma, T, Okubo, Y, et al. Intellectual disability and psychotic disorders of adult epilepsy. Epilepsia 2005; 46 (suppl 1): 11–4.
5 Qin, P, Xu, H, Laursen, TM, Vestergaard, M, Moriensen, PB. Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study. BMJ 2005; 331: 23–5.
6 Adachi, N, Matsuura, M, Okubo, Y, Oana, Y, Takei, N, Kato, M, et al. Predictive variables of interictal psychosis in epilepsy. Neurology 2000; 55: 1310–4.
7 Adachi, N, Matsuura, M, Hara, T, Oana, Y, Okubo, Y, Kato, M, et al. Psychoses and epilepsy: are interictal and postictal psychoses distinct clinical entities? Epilepsia 2002; 43: 1574–82.
8 Adachi, N, Onuma, T, Hara, T, Matsuura, M, Okubo, Y, Kato, M, et al. Frequency and age-related variables in interictal psychoses in localization-related epilepsies. Epilepsy Res 2002; 48: 2531.
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Epileptic, organic and genetic vulnerabilities for timing of the development of interictal psychosis

  • Naoto Adachi (a1), Nozomi Akanuma (a2), Masumi Ito (a3), Masaaki Kato (a3), Tsunekatsu Hara (a4), Yasunori Oana (a5), Masato Matsuura (a6), Yoshiro Okubo (a7) and Teiichi Onuma (a8)...
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Author's Reply

Naoto Adachi, Psychiatrist
12 May 2010

We thank Professors Craddock and Owen for the insightful comments on the possible molecular genetic basis of the relation between epilepsy and psychosis. In most clinical studies of psychosis in epilepsy patients, individual psychotic vulnerabilities are rarely concerned, compared to epilepsy-related factors. However, several large studies have recently demonstrated genetic vulnerabilities to psychosis even in epilepsy patients.1,2 Our recent work3 also demonstrated various factors, i.e., genetic, organic, and epilepsy-related, associated with the development ofinterictal psychosis in epilepsy patients.

Psychoses in patients with any CNS adversity, not only epilepsy but also other brain disorders, can be diagnosed as “Organic Psychosis”. The international criteria for mental disorders, either the ICD-10 or the DSM4, recognise the traditional dichotomy, i.e. functional and organic psychosis. However, since such CNS adversities are not invariably associated with the development of psychotic states, other additional conditions are required to generate psychotic symptoms. It is known that psychoses after brain injury occur more frequently in people with a familylording of psychoses.4 Thus, individual (possibly constitutional) vulnerability to psychosis can be considered as a contributing factor to the development of the “Organic Psychosis” and its severity.

As for classification systems for mental disorders, many limitations of the Kraepelinian dichotomy between schizophrenia and affective disorders have been concerned.5 Likewise, there appear to be limitations of the dichotomous view of organic and non-organic. The concept of organicpsychosis has been useful to classify and manage patients, but it appears too simplistic to explain complex pathogenesis in such patients. It may bethe time to reconceptualise psychoses in patients with or without diagnosable brain disorders.

Naoto Adachi1,2, Nozomi Akanuma2,3, Masumi Ito2, Masaaki Kato2, Tsunekatsu Hara4, Yasunori Oana5, Masato Matsuura6, Yoshiro Okubo3, Teiichi Onuma2

1Adachi Mental Clinic, Sapporo, Japan; 2National Centre Hospital for Mental, Nervous and Muscular Disorders, N.C.N.P., Kodaira, Japan; 3Department of Neuropsychiatry, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan; 4Komagino Hospital, Hachioji, Japan; 5Department of Neuropsychiatry, School of Medicine, Tokyo Medical University, Tokyo, Japan; 6Department of Neuropsychiatry, Nihon UniversitySchool of Medicine, Tokyo, Japan

Correspondence; Naoto Adachi, Adachi Mental Clinic, Kitano 7-5-12, Kiyota, Sapporo 004-0867, Japan. (adacchan@tky2.3web.ne.jp)

Declaration of Interest: None

References:1)Adachi N, Matsuura M, Hara T, Oana Y, Okubo Y, Kato M, Onuma T. Psychoses and epilepsy: are interictal and postictal psychoses distinct clinical entities? Epilepsia 2002; 43:1574-82.

2)Qin P, Xu H, Laursen TM, Vestergaard M, Moriensen PB. Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study. Br Med J 2005; 331:23-5.

3)Adachi N, Akanuma N, Ito M, Kato M, Hara T, Oana Y, Matsuura M, Okubo Y, Onuma T:Epileptic, organic, and genetic vulnerabilities for timing of the development of onset of interictal psychosis. Brit J Psychiatry 2010; 196,212-6.

4)Corcoran C, Malaspina D. Traumatic brain injury and risk for schizophrenia. Int J Mental Health 2001; 30: 17-32.

5)Craddock N, Owen MJ. The Kraepelinian dichotomy – going, going…butstill not gone. Brit J Psychiatry 2010; 196: 92-5.
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Conflict of interest: None Declared

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Molecular genetics and the relationship between epilepsy and psychosis

Nick Craddock, Professor of Psychiatry
22 March 2010

We read with interest the paper by Adachi et al (1) in which they conclude that early development of interictal psychosis in people with epilepsy may reflect individual vulnerabilities to psychosis, including genetic, rather than being driven by epilepsy-related damage.

As they point out, their conclusion challenges traditional assumptions about the relationship between epilepsy and psychosis, many ofwhich have been based on relatively sparse data. It is of interest that recent molecular genetic findings in psychosis suggest that the co-morbidity of psychotic symptoms and epilepsy is a product of shared underlying biological mechanisms. For example, specific genomic structuralvariants (copy number variants) have been described that predispose to schizophrenia, epilepsy, as well as some other “neurodevelopmental” phenotypes such as autism and learning disability (2). Individuals with such structural variants do not typically have both schizophrenia and epilepsy but rather some with a variant have schizophrenia, others have epilepsy, while yet others have a different phenotype or are unaffected. This means that the relationship cannot be caused simply by “toxic” effects of epileptic seizures on the brain. Rather the finding strongly suggests that one or more genes, the function of which is disturbed by thestructural variant, play(s) a role in the pathogenesis of both epilepsy and psychosis. A second recent observation of potential interest concerns genes encoding ion channels. Ion channelopathies are known to underlie some epilepsies so it is of great interest that variation within the gene CACNA1C (encoding a subunit of the L-type voltage-dependent calcium channel) is associated with schizophrenia as well as recurrent depression and bipolar disorder (3,4). This suggests that ion channel dysfunction maybe also be involved in mood and psychotic illness. Again, this provides support for the possibility that some individuals might experience both psychosis and epilepsy at least in part because of an underlying vulnerability to both.

It is likely that as the understanding of brain function increases wewill move closer to understanding the complexities, multiple associations and co-morbidities that commonly occur in psychiatric illness. A sufficient number of adequately trained psychiatrists working within appropriate services will be vital for translating this knowledge into benefits for patients (5).

Nick Craddock* PhD, FRCPsych, Michael J. Owen PhD, FRCPsych

MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom

*Correspondence: Nick Craddock, MRC Centre for Neuropsychiatric Genetics and Genomics, Henry Wellcome Building, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, United Kingdom. (Email:craddockn@cardiff.ac.uk)

Declaration of interest: The authors declare no competing interests.

References

1. Adachi N, Akanuma N, Ito M, Kato M, Hara T, Oana Y, Matsuura M, Okubo Y, Onuma T. Epileptic, organic and genetic vulnerabilities for timing of the developmentof interictal psychosis. Br J Psychiatry. 2010 Mar;196:212-6.

2. Craddock N, Owen MJ. The Kraepelinian dichotomy - going, going... but stillnot gone. Br J Psychiatry. 2010 Feb;196(2):92-5.

3. Ferreira MA, O'Donovan MC, Meng YA, et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet. 2008 Sep;40(9):1056-8.

4. Green EK, Grozeva D, Jones I, et al. The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry. 2009 Jul 21. [Epub ahead of print] PubMed PMID: 19621016.

5. Bullmore E, Fletcher P, Jones PB. Why psychiatry can't afford to be neurophobic. Br J Psychiatry. 2009 Apr;194(4):293-5.
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Conflict of interest: None Declared

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Interictal Psychosis

Marco Procopio, Consultant Psychiatrist
17 March 2010

Adachi et al (1) analysed a large cohort of patients fulfilling diagnostic criteria for both schizophrenia and epilepsy. The findings in their study are interesting, also in the light of the literature on seasonality of birth in both pathologies.There is a robust body of evidence showing that the chronological distribution of births in patientssuffering from schizophrenia is different from that in the general population (2), and similar results have been found when analysing cohortsof patients suffering from epilepsy (3, 4). These results are suggestive ofenvironmental aetiological agents acting during the intrauterine neurodevelopment in both disorders. It can be therefore hypothesised that common factors could have a causal effect during the development in utero for both schizophrenia and epilepsy, as suggested in the concept of "continuum of reproductive casualty" described by Knobloch and Pasamanick (5). The strength of this hypothesis is confirmed by the finding in the study by Adichi et al that, in the great majority of the patients they studied, the aetiology was unknown, or secondary to migration disorders.

1. Adachi N, Akanuma N, Ito M, Kato M, Hara T, Oana Y, et al. Epileptic, organic and genetic vulnerabilities for timing of the development of interictal psychosis. Br J Psychiatry 2010; 196: 212-216.

2. Bradbury TN, Miller GA. Season of birth in schizophrenia: A reviewof evidence, methodology, and etiology. Psychological Bulletin 1985; 98(3): 569-594.

3. Procopio M, Marriott PK, Williams P. Season of birth: aetiologicalimplications for epilepsy. Seizure 1997; 6:99-105.

4. Procopio M, Marriott PK, Davies RJ. Seasonality of birth in epilepsy: a Southern Hemisphere study. Seizure 2006; 15:17-21.

5. Pasamanick B, Knobloch H. Seasonal Variation in Complications of Pregnancy. Obstetrics & Gynecology 1958; 12(1): 110-112.
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Conflict of interest: None Declared

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