Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study is to test the hypothesis that major affective and/or anxiety disorders are increased among relatives of autistic probands compared with controls. Among 36 families with an autistic child, 23 (64%) have a first degree relative diagnosed with major depressive disorder and 14 (39%) have a first degree relative diagnosed with social phobia. These rates are significantly greater than the 19% and 5%, respectively, found among 21 families with a child having a genetic condition, tuberous sclerosis complex, or a seizure disorder but no autism. The frequency of major depression among the 96 first degree relatives of autistic probands is 37.5% compared with 11.1% found among 45 relatives of control probands. The frequency of social phobia, 20.2%, is approximately 10 times more common than that found among the relatives of the control probands (2.4%). Elevated rates of both major depression and social phobia are found among parents and siblings in the families with an autistic child. Furthermore, 64% of parents affected with a major depression had the onset of the first depressive episode prior to the birth of the autistic child and all parents with social phobia had the onset of condition prior to the birth of the autistic child. Family patterns differ depending on the intellectual level of the autistic child; specifically, social phobia is significantly greater among the first degree relatives of non-retarded autistic probands than among relatives of individuals with autism and comorbid mental retardation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autism, affective disorders, and social phobia. 748 30

The frequency and clinical presentation of autism in 28 probands with tuberous sclerosis complex (TSC) are reported and risk factors that may influence the development of autism in TSC are examined. Eight probands meet ICD-10 and DSM-IV criteria for autism, an additional 4 meet criteria for pervasive developmental disorder (PDD). Twelve TSC probands with autism/PDD are compared to 16 TSC probands without these conditions for factors which may underlie the association of autism and TSC. A specific seizure type, infantile spasms, as well as mental retardation, are increased in the TSC, autistic/PDD group. Furthermore, rates of social phobia and substance abuse are elevated among first-degree relatives of TSC probands with autism compared to first-degree relatives of TSC probands without autism. Implications of these findings in understanding the association of autism and TSC are discussed.
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PMID:Autism in tuberous sclerosis complex. 958 71

The fragile X mental retardation gene, FMR1, contains a polymorphic CGG repeat in the 5'-untranslated region of exon 1. Once unstable, this repeat is capable of expansion across generations. Women who carry a premutation allele (55-199 repeats) are at risk of passing on a full mutation allele (>200 repeats) to their offspring. A full mutation leads to the most common form of inherited intellectual disability, fragile X syndrome (FXS). Mounting evidence suggests that premutation carriers may be vulnerable to symptoms of anxiety and depression. The goal of this study was to test the hypothesis that among women who carry a premutation, the stress of raising a child with FXS would be moderated by genetic factors influencing endogenous cortisol responses, which could in turn modulate anxiety and depression symptoms. To this end, we genotyped single nucleotide polymorphisms (SNPs) at the corticotrophin releasing hormone receptor 1 locus (CRHR1) in 460 women. Participants completed self-report questionnaires assessing symptoms of depression [Centers for Epidemiological Studies Depression Scale (CESD)], anxiety [State-Trait Anxiety Inventory (STAI) and Social Phobia and Anxiety Inventory (SPAI)], and mood [Positive and Negative Affect Schedule (PANAS)]. Results indicate a statistically significant interaction between CRHR1 genotype and the status of raising a child with FXS to predict social anxiety symptoms reported on the SPAI (rs7209436, P = 0.0001). Our data suggest that genetic variants in CRHR1 that associate with differential cortisol activation may also modulate levels of anxiety related to the stress of raising a child with FXS among women who carry an FMR1 premutation.
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PMID:Depression and anxiety symptoms among women who carry the FMR1 premutation: impact of raising a child with fragile X syndrome is moderated by CRHR1 polymorphisms. 2257 56

The fragile X mental retardation 1 gene (Fmr1) is polymorphic for CGG trinucleotide repeat number in the 5'-untranslated region, with repeat lengths <45 associated with typical development and repeat lengths >200 resulting in hypermethylation and transcriptional silencing of the gene and mental retardation in the fragile X Syndrome (FXS). Individuals with CGG repeat expansions between 55 and 200 are carriers of the fragile X premutation (PM). PM carriers show a phenotype that can include anxiety, depression, social phobia, and memory deficits. They are also at risk for developing fragile X-associated tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder characterized by tremor, ataxia, cognitive impairment, and neuropathologic features including intranuclear inclusions in neurons and astrocytes, loss of Purkinje cells, and white matter disease. However, very little is known about dendritic morphology in PM or in FXTAS. Therefore, we carried out a Golgi study of dendritic complexity and dendritic spine morphology in layer II/III pyramidal neurons in primary visual cortex in a knock-in (KI) mouse model of the PM. These CGG KI mice carry an expanded CGG trinucleotide repeat on Fmr1, and model many features of the PM and FXTAS. Compared to wild-type (WT) mice, CGG KI mice showed fewer dendritic branches proximal to the soma, reduced total dendritic length, and a higher frequency of longer dendritic spines. The distribution of morphologic spine types (e.g., stubby, mushroom, filopodial) did not differ between WT and KI mice. These findings demonstrate that synaptic circuitry is abnormal in visual cortex of mice used to model the PM, and suggest that such changes may underlie neurologic features found in individuals carrying the PM as well as in individuals with FXTAS.
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PMID:Abnormal dendrite and spine morphology in primary visual cortex in the CGG knock-in mouse model of the fragile X premutation. 2261 20