Depressive and obsessive-compulsive symptoms in hyperserotonemic parents of children with autistic disorder

Cook, Edwin H.; Charak, David; Arida, Janet; Spohn, Julie A.; Roizen, Nancy; Leventhal, Bennett L.

doi:10.1016/0165-1781(94)90117-1

Cited by 56 publications

(20 citation statements)

References 20 publications

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“…This result has been replicated by several groups [Hoshino et al, 1984;Anderson et al, 1987;Cook et al, 1990], and extended with the recognition that blood serotonin is also elevated in the first degree relatives of these children Piven et al, 1999;Cook et al, 1994;Leboyer et al, 1999]. How the abnormalities of blood serotonin might be related to brain serotonin, however, is not well understood.…”

Section: Altered Prenatal Serotonin-evidence For a Role In Autismsupporting

confidence: 50%

Serotonin in autism and pediatric epilepsies

Chugani

2004

Ment. Retard. Dev. Disabil. Res. Rev.

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Serotonergic abnormalities have been reported in both autism and epilepsy. This association may provide insights into underlying mechanisms of these disorders because serotonin plays an important neurotrophic role during brain development-and there is evidence for abnormal cortical development in both autism and some forms of epilepsy. This review explores the hypothesis that an early disturbance in the serotonin system affects cortical development and the development of thalamocortical innervation, and is a potential mechanism, common to autism and pediatric epilepsies associated with cortical dysplasia. An argument is made that cortical malformation leads to abnormalities of thalamocortical connectivity, and that serotonin plays a critical role in this process. Finally, a role for altered metabolism of the serotonin precursur, tryptophan, in both epilepsy and autism is discussed. Key Words: serotonin; autism; epilepsy; tryptophan; cortical development; kynurenine E pilepsy is more common among autistic children than in the general population; conversely, autism (or milder pervasive developmental disorders) is more common in epileptic children than in the general population. There is evidence for abnormalities of the neurotransmitter serotonin in both epilepsy and autism. The role of serotonin in brain development is briefly reviewed here and then the evidence considered for a role of an altered serotonin system in these developmental disorders. We hypothesize that serotonergic abnormalities during prenatal and early postnatal development may lead to changes in thalamocortical connectivity, which results in a predisposition for autism and epilepsy. In addition, we discuss the involvement of aberrant metabolism of tryptophan-the metabolic precursor of serotonin-as a potential mechanism for alterations in serotonin availability.

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Section: Altered Prenatal Serotonin-evidence For a Role In Autismsupporting

confidence: 50%

Serotonin in autism and pediatric epilepsies

Chugani

2004

Ment. Retard. Dev. Disabil. Res. Rev.

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“…Others have implied that autism in some forms may represent a variant in the genetic expression of depression (Cook et al 1994, Smalley et al 1995. Ghaziuddin and Greden (1998) consider depression to be a distinct, presumably incidental, condition in some children with autism/pervasive developmental disorder, but they have not related this to the incidence of major affective disorder in the families nor to the etiology of autism.…”

Section: Discussionmentioning

confidence: 99%

“…C 11 -alpha-methyltryptophan PET (C 11 -AMT PET) scans showed decreased serotonin synthesis in one cerebral hemisphere (primarily left) of boys with autism, and bilaterally in girls (Chugani et al 1997(Chugani et al , 1999). Brain serotonin is similarly disordered in major affective disorders in adults (Cook et al 1994, Drevets et al 1999). In addition, the beneficial effects of treatment of autism with antidepressant SSRIs and other agents used to treat major affective disorders fits the concept of the fundamental identification of autism with affective disorder.…”

Section: Discussionmentioning

confidence: 99%

Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement

DeLong

Ritch

Burch

2002

Develop Med Child Neuro

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One hundred and twenty‐nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow‐up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

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“…Depletion of the 5-HT precursor, tryptophan, induced a worsening of autistic symptoms in some, but not all, patients (McDougle et al 1996a). There is evidence for increased whole blood serotonin not only in patients with autism (Hoshino et al 1984;Anderson et al 1987), but also in their first degree relatives (Piven et al 1991;Cook et al 1994;Leboyer et al 1999). Of interest, parents of autistic patients with increased whole blood serotonin scored higher on ratings of repetitive behavior than parents without elevated whole blood serotonin (Cook et al 1994).…”

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confidence: 99%

The Relationship between Repetitive Behaviors and Growth Hormone Response to Sumatriptan Challenge in Adult Autistic Disorder

Hollander

2000

Neuropsychopharmacology

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Autism is heterogeneous with respect to clinical symptoms and etiology. To sort out this heterogeneity in autismAutism is heterogeneous with respect to clinical symptoms and etiology. To sort out this heterogeneity in autism, one might determine whether specific neurobiological markers vary in parallel to key clinical symptoms. Autism is characterized by three unique behavioral dimensions: social impairment, communication difficulties and rigid, restricted interests, and repetitive behaviors. One recent study explored the relationship between repetitive behaviors in autism and D8/17, a B-lymphocyte antigen marker expressed at increased levels in patients with rheumatic fever, as well as in patients with neuropsychiatric disorders characterized by repetitive behaviors such as Sydenham's chorea, Tourette's syndrome and obsessivecompulsive disorder. Of interest, obsessive compulsive disorder (OCD) occurs with increased frequency in first degree relatives of autistic patients and is associated with the broader phenotype of autism (Bolton et al. 1998). D8/17 expression was found to be significantly positively correlated with the severity of repetitive behaviors as measured by the Yale-Brown Obsessive Compulsive Scale-compulsivity subscale in childhood and adolescent autism . We have hypothesized that repetitive behaviors in autism may also be related to serotonergic (5-HT) dysfunction (Hollander et al. 1998).Pharmacological treatment studies support a role of 5-HT in autistic disorders. (Mehlinger et al. 1990) and sertraline (Steingard et al. 1997) have documented efficacy in treating both global autistic symptoms as well as symptoms of repetitive behaviors and restricted interests in up to 60% of patients treated.Several biological studies have also suggested 5-HT dysregulation in autistic patients, however the findings have not been uniform, but rather replicated in subgroups of patients. For example, contradictory results in linkage disequilibrium analyses of two common alleles (long and short) of the 5HT transporter (5HTT) gene have been reported. While there was linkage between the short allele and a narrowly defined group of autistic probands (Cook et al. 1997), an association between the long allele and a more broadly defined group of autistic probands has also been reported (Klauck et al. 1997).Pharmacological challenge studies with 5-hydroxytryptophan and fenfluramine have demonstrated reduced prolactin response in some patients with autism (Hoshino et al. 1984;McBride et al. 1989), however age, gender, and racial/ethnic factors may account for some of the heterogeneity. Depletion of the 5-HT precursor, tryptophan, induced a worsening of autistic symptoms in some, but not all, patients (McDougle et al. 1996a). There is evidence for increased whole blood serotonin not only in patients with autism (Hoshino et al. 1984;Anderson et al. 1987), but also in their first degree relatives (Piven et al. 1991;Cook et al. 1994;Leboyer et al. 1999). Of interest, parents of autistic patients with increased whole blood ser...

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Depressive and obsessive-compulsive symptoms in hyperserotonemic parents of children with autistic disorder

Cited by 56 publications

References 20 publications

Serotonin in autism and pediatric epilepsies

Serotonin in autism and pediatric epilepsies

Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement

The Relationship between Repetitive Behaviors and Growth Hormone Response to Sumatriptan Challenge in Adult Autistic Disorder

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