Familial autism

Aldred S, Moore KM, Rtzgerald M, Waring RH. Plasma amino add levels in children with autism and their families. / Autism Dev Disord. 2003 33 93-97. 

Patients tend to believe that medications from nature are non-toxic, non-addicted, and non-invasive. Therefore complementary medicines are usually used in common, less severe, and chronic mental disorders such as sleep disorders, neurasthenia, and anxiety disorders. It is also applied in incurable conditions, for example dementias, autism, and schizophrenia, when doctors and families have tried desperately all means and finally turned to complementary medicine as the last hope. 

Based on existing findings, there are many important hypotheses in pediatric psychopharmacogenetics. Selective serotonin transporter inhibitors have been shown to have efficacy in double-blind studies in children and/ or adolescents in the treatment of autism, major depression, OCD, and anxiety disorders. Given the association of the serotonin transporter promoter variant with SSRI treatment response in adult depression (Smeraldi et ah, 1998), all of the SSRI-responsive phenotypes should be tested for promoter variant influence on response using family-based or population-based controlled association studies. The report of strong 5-HTTLPR allelic effects on SSRI-induced mania (Mundo et ah, 2000) is of special interest given frequent SSRI-induced activation in children. 

Maestrini, E., Lai, C., Marlow, A., Matthews, N., Wallace, S., Bailey, A., Cook, E., Weeks, D., Monaco, A., and International Molecular Genetics of Autism Consortium. (1999) Serotonin transporter (S-HTT) and gamma-aminobuyric acid receptor subunit beta-3 (GABRB3) gene polymorphisms are not associated with autism in the IMGSA families. Am J Med Genet (Neuropsychiatr Genet), 88 492-496. 

De Jaco, A., Comoletti, D., Kovarik, Z., Gaietta, G., Radic, Z., Lockridge, O., Ellisman, M.H., Taylor, P. (2006). A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the a,heta-hydrolase fold protein family. J. Biol. Chem. 281 9667-76. 

Recently, Campbell et al. (2009) have reported that disrupted MET gene signaling may contribute to increased risk for autism spectrum disorder that includes familial GI dysfunction. A functional variant in the promoter of the gene encoding the MET receptor tyrosine kinase has been associated with ASD, and MET protein expression has been found to be decreased in the temporal lobe cortex in ASD postmortem brain tissue. MET is a pleiotropic receptor that is known to function in both brain development and GI repair. Thus, the identification of medical disorders in ASD individuals, in this case GI disorders, may not only improve quality of life for those affected with ASD but may lead to improved or more precise definition of genetic and phenotypic subtypes in this complex heterogeneous disorder. 

Bolton, P, MacDonald, H, Pickles, A, Rios, P et al. (1994) A case-controlled family history study of autism. J Child Psychol Psychiatry 35 877-900. 

Campbell, DB, Buie, TM, Winter, H, Bauman, ML, SutcUffe, JS, Perrin, JM and Levitt, P (2009) Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions. Pediatrics 123 1018-1024. 

Kogan, MD, Strickland, BB, Blumberg, SJ, Singh, GK, Perrin, JM and van Dyck, PC (2008) A national profile of health care experiences and family impact of autism spectmm disorder among children in the United States, 2005-2006. Pediatrics 122 1149-1158. 

Lauritsen, MB, Pedersen, CB, and Mortensen, PB. (2005) Effects of familial risk factors and place of birth on the risk of autism a nationwide register-based study. J Child Psychol Psychiatry. 46 963-971. 

Spiker D, Lotspeich LJ, Dimiceh S, Myers RM, Risch N (2002) Behavioral phenotypic variation in autism multiplex families evidence for a continuous severity gradient. Am J Med Genet 114 129-136. 

Pickles A, Bolton P, Macdonald H, Bailey A, Le Couteur A, Sim CH, Rutter M (1995) Latent-class analysis of recurrence risks for complex phenotypes with selection and measurement error a twin and family history study of autism. Am J Hum Genet 57 717-726. 

Acknowledgments The authors would like to thank the families for generous donation of patient brain samples and the Autism Tissue Program for assistance in obtaining samples. A.H. is funded by a NIMH predoctoral fellowship FMH078377 and the research discussed was funded by NIH R01HD048799 awarded to J.M.L. 

Yirmiya N, Rosenberg C, Levi S, Salomon S, Shulman C, Nemanov L, Dina C, Ebstein RP (2006) Association between the arginine vasopressin la receptor (AVPRla) gene and autism in a family-based study mediation by socialization skiUs. Mol Psychiatry 11 488 94. 

Loss-of-function mutations in members of the Neuroligin (NL) family of trans-synaptic cell adhesion molecules have been implicated in human autism and mental retardation (Chih et al., 2004 Comoletti et al., 2004 Jamain et al 2003 Laumonnier et al., 2004 Yan et al, 2005). At the time of writing, neuroligin mutations represent owe of only a few independently replicated, functional, genetic mutation links to idiopathic autism not associated with a broader neuropsychiatric syndrome (Chih et al., 2004 Comoletti et al., 2004 Jamain et al., 2003 Laumonnier et al., 2004 Yan et al., 2005). 

---