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Autism and Epilepsy: Organic Connections?
LETTERS TO THE EDITOR
mother agreed he would normally have shaken off without difficulty. Although he had some history of "taking things hard," including tearfulness, the degree of upset at this time was different. He did not appear otherwise depressed, nor did he acknowledge depressed or irritable feelings. He noted that the wish to die persisted: "I couldn't put it out of my mind." He was distressed at not knowing what to do about this feeling. In the meantime, he noted a decrease in feeling that he had to read sentences over and over. Clomipramine was reduced to 25 mg/day without recurrence of the suicidal ideation during 4 months of follow-up and with complete relief from obsessive and compulsive symptoms. The seriousness of the symptom and its relevance to the possible induction of self-destructive ideation or behavior by fluoxetine make this report of interest. Although fluoxetine and clomipramine are not structurally related, they both increase serotonin activity through blocking reuptake. The possible mechanisms of acute suicidality have been recently debated by King et al. (l99Ia, b) and by Fuller and Beasley (1991). This appears to be the first report of new suicidality in a patient taking clomipramine.
among autistic subjects (Gillberg and Steffenburg, 1987) and of psychosis among epileptics (McKenna et aI., 1985), but an association of the two in monozygotic twins is rare. There has been much discussion of the relations between autism and epilepsy, which seem on the latest evidence to be the outcome of a common cerebral dysfunction (Olsson et aI., 1988). Our cases evidence the concordance in the twins of two pathological conditions (autism and epilepsy), probably of heterogeneous genetic origin with different involvement of genetic and nongenetic factors in the two patients. In both subjects, there was interaction between hereditary factors (family history of psychiatric illness) and homogeneous acquired factors (pre- and perinatal distress). Our report confirms the data of Vukicevic and Siegel (1990) on the primary importance of suboptimal factors in the fetal or neonatal periods to normal neuropsychic development. Similar remarks apply to the multifactorial pathogenesis of epilepsy, for it has recently been recognized that genetic factors are involved even in partial epilepsy (Ottman et aI., 1989). One last point regarding the EEG abnormalities recorded from the left temporal lobe: a left temporal EEG focus is considered to be most frequently associated with psychosis in adults (Perez et aI., 1985).
Gordon Harper, M.D. The Children's Hospital Boston, Massachusetts
Prof. Carlo Lenti Universita Degli Studi Di Milano Milan, Italy
REFERENCES
REFERENCES
Fuller, R. F. & Beasley, C. M., Jr. (1991), Fluoxetine mechanism of action. J. Am. Acad. Child Adolesc. Psychiatry, 30:849 (letter). King, R. A., Riddle, M. A., Chappell, P. B., Hardin, M. T., Anderson, G. M., Lombroso, P. & Scahill, Z. (199Ia), Emergence of selfdestructive phenomena in children and adolescents during fluoxetine treatment. J. Am. Acad. Child Adolesc. Psychiatry, 30: 179-186. - - Anderson, G. M., Rasmusson, A. & Riddle, M. A. (l99Ib), Fluoxetine mechanism of action. J. Am. Acad. Child Adolesc. Psychiatry, 30:849-850 (letter).
Gillberg, C. & Steffenburg, S. (1987), Outcome and prognostic factors in infantile autism and similar conditions. J. Autism Dev. Disord., 17:271-275. McKenna, P. J., Kanej, M. & Parrish, K. (1985), Psychotic syndromes in epilepsy. Am. J. Psychiatry, 142:895-904. Olsson, I., Steffenburg, S. & Gillberg, C. (1988), Epilepsy in autism and autistic-like conditions: a population-based study. Arch. Neural., 45:666-668. Ottman, R., Annegers, J. E., Hauser, W. A. & Kurland, L. T. (1989), Seizure risk in offspring of parents with generalized versus partial epilepsy. Epilepsia, 30:157-161. Perez, M. M., Trimble, M. R., Murray, N. M. F. & Reider, I. (1985), Epileptic psychosis: an evaluation of PSE profiles. Br. J. Psychiatry, 146:155-163. Vukicevic, J., Siegel, B. (1990), Pervasive developmental disorder in monozygotic twins. J. Am. Acad. Child Adolesc. Psychiatry, 29:897-900.
Autism and Epilepsy: Organic Connections? To the Editor: We read with interest the report of Vukicevic and Siegel (1990) on pervasive developmental disorders in monozygotic twins. We report a similar case of autism and epilepsy in male monozygotic twins. Case report: An aunt of the twins' mother suffers from chronic psychosis and is hospitalized in a psychiatric institution. A brother of the father has a primary affective disorder. There was probable fetal damage, as a result of a threatened miscarriage at the 36th week and complete detachment of the placenta at the 39th week, and definite neonatal distress. Born by cesarean section, the first twin presented an Apgar score of 7 at I minute and 9 at 5 minutes; the second twin had a score of 3 at I minute and 5 at 5 minutes. Psychomotor development was delayed in both boys, and they did not learn to walk until 2 years of age. They never learned to speak, and frorv the first years of life, they displayed the characteristic symptoms of autism: lack of social interaction and ability to play, stereotyped behaviors, and so on. The first twin began to have complex partial seizures at age II, and these recurred monthly. The second twin had a similar seizure 8 months later, with a single recurrence after 6 months. Kariotyping with search for fragile X, magnetic resonance imaging, and tests for abnormalities ofthe sugar, amino acid, and mucopolysaccharide metabolism revealed nothing abnormal. Only a CT brain scan revealed signs of atrophy in both twins. EEG showed spike activity over the temporal and central regions of the left hemisphere, more evident in the second twin. Numerous studies have demonstrated a high frequency of epilepsy
370
Biological Liability in Families with Autism To the Editor: Piven et al. (1990, 1991) have provided a well-designed comprehensive study of psychiatric disorders in adult siblings and parents of autistic probands. Our family history studies support their findings, extending the findings to second-degree relatives, which strengthens one hypothesis that some of the psychiatric symptomatology may be an expression of underlying biological liability in families with autism. One study was designed using the mother of the autistic probands as the main informant for autistic probands, siblings, and seconddegree family members, i.e., grandparents, aunts and uncles, nieces and nephews. Family history was obtained using a family history questionnaire that included questions pertaining to medical and psychiatric illness, medication usage, and learning disabilities. When a sibling or other family member was identified, diagnosed, or treated for psychiatric illness, a first-person structured psychiatric interview, the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) was conducted (Spitzer and Endicott, 1978). Diagnoses were made using research diagnostic criteria (Spitzer and Robins, 1978). When family members were deceased or unavailable, a secondJ. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992
mother agreed he would normally have shaken off without difficulty. Although he had some history of "taking things hard," including tearfulness, the degree of upset at this time was different. He did not appear otherwise depressed, nor did he acknowledge depressed or irritable feelings. He noted that the wish to die persisted: "I couldn't put it out of my mind." He was distressed at not knowing what to do about this feeling. In the meantime, he noted a decrease in feeling that he had to read sentences over and over. Clomipramine was reduced to 25 mg/day without recurrence of the suicidal ideation during 4 months of follow-up and with complete relief from obsessive and compulsive symptoms. The seriousness of the symptom and its relevance to the possible induction of self-destructive ideation or behavior by fluoxetine make this report of interest. Although fluoxetine and clomipramine are not structurally related, they both increase serotonin activity through blocking reuptake. The possible mechanisms of acute suicidality have been recently debated by King et al. (l99Ia, b) and by Fuller and Beasley (1991). This appears to be the first report of new suicidality in a patient taking clomipramine.
among autistic subjects (Gillberg and Steffenburg, 1987) and of psychosis among epileptics (McKenna et aI., 1985), but an association of the two in monozygotic twins is rare. There has been much discussion of the relations between autism and epilepsy, which seem on the latest evidence to be the outcome of a common cerebral dysfunction (Olsson et aI., 1988). Our cases evidence the concordance in the twins of two pathological conditions (autism and epilepsy), probably of heterogeneous genetic origin with different involvement of genetic and nongenetic factors in the two patients. In both subjects, there was interaction between hereditary factors (family history of psychiatric illness) and homogeneous acquired factors (pre- and perinatal distress). Our report confirms the data of Vukicevic and Siegel (1990) on the primary importance of suboptimal factors in the fetal or neonatal periods to normal neuropsychic development. Similar remarks apply to the multifactorial pathogenesis of epilepsy, for it has recently been recognized that genetic factors are involved even in partial epilepsy (Ottman et aI., 1989). One last point regarding the EEG abnormalities recorded from the left temporal lobe: a left temporal EEG focus is considered to be most frequently associated with psychosis in adults (Perez et aI., 1985).
Gordon Harper, M.D. The Children's Hospital Boston, Massachusetts
Prof. Carlo Lenti Universita Degli Studi Di Milano Milan, Italy
REFERENCES
REFERENCES
Fuller, R. F. & Beasley, C. M., Jr. (1991), Fluoxetine mechanism of action. J. Am. Acad. Child Adolesc. Psychiatry, 30:849 (letter). King, R. A., Riddle, M. A., Chappell, P. B., Hardin, M. T., Anderson, G. M., Lombroso, P. & Scahill, Z. (199Ia), Emergence of selfdestructive phenomena in children and adolescents during fluoxetine treatment. J. Am. Acad. Child Adolesc. Psychiatry, 30: 179-186. - - Anderson, G. M., Rasmusson, A. & Riddle, M. A. (l99Ib), Fluoxetine mechanism of action. J. Am. Acad. Child Adolesc. Psychiatry, 30:849-850 (letter).
Gillberg, C. & Steffenburg, S. (1987), Outcome and prognostic factors in infantile autism and similar conditions. J. Autism Dev. Disord., 17:271-275. McKenna, P. J., Kanej, M. & Parrish, K. (1985), Psychotic syndromes in epilepsy. Am. J. Psychiatry, 142:895-904. Olsson, I., Steffenburg, S. & Gillberg, C. (1988), Epilepsy in autism and autistic-like conditions: a population-based study. Arch. Neural., 45:666-668. Ottman, R., Annegers, J. E., Hauser, W. A. & Kurland, L. T. (1989), Seizure risk in offspring of parents with generalized versus partial epilepsy. Epilepsia, 30:157-161. Perez, M. M., Trimble, M. R., Murray, N. M. F. & Reider, I. (1985), Epileptic psychosis: an evaluation of PSE profiles. Br. J. Psychiatry, 146:155-163. Vukicevic, J., Siegel, B. (1990), Pervasive developmental disorder in monozygotic twins. J. Am. Acad. Child Adolesc. Psychiatry, 29:897-900.
Autism and Epilepsy: Organic Connections? To the Editor: We read with interest the report of Vukicevic and Siegel (1990) on pervasive developmental disorders in monozygotic twins. We report a similar case of autism and epilepsy in male monozygotic twins. Case report: An aunt of the twins' mother suffers from chronic psychosis and is hospitalized in a psychiatric institution. A brother of the father has a primary affective disorder. There was probable fetal damage, as a result of a threatened miscarriage at the 36th week and complete detachment of the placenta at the 39th week, and definite neonatal distress. Born by cesarean section, the first twin presented an Apgar score of 7 at I minute and 9 at 5 minutes; the second twin had a score of 3 at I minute and 5 at 5 minutes. Psychomotor development was delayed in both boys, and they did not learn to walk until 2 years of age. They never learned to speak, and frorv the first years of life, they displayed the characteristic symptoms of autism: lack of social interaction and ability to play, stereotyped behaviors, and so on. The first twin began to have complex partial seizures at age II, and these recurred monthly. The second twin had a similar seizure 8 months later, with a single recurrence after 6 months. Kariotyping with search for fragile X, magnetic resonance imaging, and tests for abnormalities ofthe sugar, amino acid, and mucopolysaccharide metabolism revealed nothing abnormal. Only a CT brain scan revealed signs of atrophy in both twins. EEG showed spike activity over the temporal and central regions of the left hemisphere, more evident in the second twin. Numerous studies have demonstrated a high frequency of epilepsy
370
Biological Liability in Families with Autism To the Editor: Piven et al. (1990, 1991) have provided a well-designed comprehensive study of psychiatric disorders in adult siblings and parents of autistic probands. Our family history studies support their findings, extending the findings to second-degree relatives, which strengthens one hypothesis that some of the psychiatric symptomatology may be an expression of underlying biological liability in families with autism. One study was designed using the mother of the autistic probands as the main informant for autistic probands, siblings, and seconddegree family members, i.e., grandparents, aunts and uncles, nieces and nephews. Family history was obtained using a family history questionnaire that included questions pertaining to medical and psychiatric illness, medication usage, and learning disabilities. When a sibling or other family member was identified, diagnosed, or treated for psychiatric illness, a first-person structured psychiatric interview, the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) was conducted (Spitzer and Endicott, 1978). Diagnoses were made using research diagnostic criteria (Spitzer and Robins, 1978). When family members were deceased or unavailable, a secondJ. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992