Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies have shown abnormal pituitary hormone responses to neuroendocrine agonists in autistic subjects. Two probes (clonidine and L-Dopa) were used to investigate neuroendocrine responses through changes in growth hormone levels. Seven medication-free autistic subjects (ages 6.6 to 19.1) were evaluated and compared to 14 normal controls. Growth hormone was collected at 30-min intervals during the entire study. Clonidine was administered first (dose: 0.15 mgm2), and samples were collected for 180 min. L-Dopa was then administered (dose: 250 mg for subjects less than 70 lb and 500 mg for subjects greater than 70 lb), and samples were collected for 120 min. There was no difference in the amplitude of the clonidine or L-Dopa peak growth hormone responses in the control versus the autistic subjects. In the autistic subjects, the L-Dopa-stimulated growth hormone peak was delayed and the clonidine growth hormone peak was premature. A statistical difference with the control subjects was found when consideration was given to both the premature response of growth hormone to clonidine and the delayed response to L-Dopa (p = .01, Fisher's Exact Test). These findings suggest possible abnormalities of both dopaminergic and noradrenergic neurotransmission in subjects with autism.
J Autism Dev Disord 1990 Dec
PMID:Growth hormone response to L-dopa and clonidine in autistic children. 227 68

Sequencing studies have implicated haploinsufficiency of ARID1B, a SWI/SNF chromatin-remodeling subunit, in short stature (Yu et al., 2015), autism spectrum disorder (O'Roak et al., 2012), intellectual disability (Deciphering Developmental Disorders Study, 2015), and corpus callosum agenesis (Halgren et al., 2012). In addition, ARID1B is the most common cause of Coffin-Siris syndrome, a developmental delay syndrome characterized by some of the above abnormalities (Santen et al., 2012; Tsurusaki et al., 2012; Wieczorek et al., 2013). We generated Arid1b heterozygous mice, which showed social behavior impairment, altered vocalization, anxiety-like behavior, neuroanatomical abnormalities, and growth impairment. In the brain, Arid1b haploinsufficiency resulted in changes in the expression of SWI/SNF-regulated genes implicated in neuropsychiatric disorders. A focus on reversible mechanisms identified Insulin-like growth factor (IGF1) deficiency with inadequate compensation by Growth hormone-releasing hormone (GHRH) and Growth hormone (GH), underappreciated findings in ARID1B patients. Therapeutically, GH supplementation was able to correct growth retardation and muscle weakness. This model functionally validates the involvement of ARID1B in human disorders, and allows mechanistic dissection of neurodevelopmental diseases linked to chromatin-remodeling.
 ...
PMID:Arid1b haploinsufficient mice reveal neuropsychiatric phenotypes and reversible causes of growth impairment. 2869 22