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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Celiac disease (CD) long has been associated with neurologic and psychiatric disorders including cerebellar ataxia, peripheral neuropathy, epilepsy, dementia, and depression. Earlier reports mainly have documented the involvement of the nervous system as a complication of prediagnosed CD. However, more recent studies have emphasized that a wider spectrum of neurologic syndromes may be the presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology. These include migraine, encephalopathy, chorea, brain stem dysfunction, myelopathy, mononeuritis multiplex, Guillain-Barre-like syndrome, and neuropathy with positive antiganglioside antibodies. The association between most neurologic syndromes described and gluten sensitivity remains to be confirmed by larger epidemiologic studies. It further has been suggested that gluten sensitivity (as evidenced by high antigliadin antibodies) is a common cause of neurologic syndromes (notably cerebellar ataxia) of otherwise unknown cause. Additional studies showed high prevalence of gluten sensitivity in genetic neurodegenerative disorders such as hereditary spinocerebellar ataxia and Huntington's disease. It remains unclear whether gluten sensitivity contributes to the pathogenesis of these disorders or whether it represents an epiphenomenon. Studies of gluten-free diet in patients with gluten sensitivity and neurologic syndromes have shown variable results. Diet trials also have been inconclusive in autism and schizophrenia, 2 diseases in which sensitivity to dietary gluten has been implicated. Further studies clearly are needed to assess the efficacy of gluten-free diet and to address the underlying mechanisms of nervous system pathology in gluten sensitivity.
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PMID:Neurologic presentation of celiac disease. 1582 33

Motor and phonic tics are most frequently due to Tourette syndrome, but there are many other causes of tics. We analyzed data on 155 patients with tics and co-existent disorders (101M/54F; mean age 40.5 +/- 20.2 years). Fourteen (9.0%) patients had tics associated with an insult to the basal ganglia, such as head trauma (N = 4, 2.5%), stroke (N = 2, 1.2%), encephalitis (N = 3, 1.9%) and other causes. In addition, certain drugs, toxins, and post-infectious causes were associated with tics. Rarely, peripheral injury can cause movement disorders, including tics (N = 1, 0.6%). Pervasive developmental disorders, including Asperger's syndrome (N = 13, 8.3%), mental retardation (N = 4, 2.5%), autism (N = 3, 1.9%), and Savant's syndrome (N = 1, 0.6%), also may be associated with tics, as noted in 21 of the 155 patients (13.5%). Genetic and chromosomal disorders, such as Down's syndrome 5 (3.2%), neuroacanthocytosis (N = 2, 1.2%), and Huntington's disease (N = 1, 0.6%), were associated with tics in 16 patients (10.3%). We have also examined the co-existence of tics and other movement disorders such as dystonia (N = 31, 20.0%) and essential tremor (N = 17, 10.9%). Sixteen (10.3%) patients presented psychogenic tics, and one (0.6%) psychogenic tics and dystonia; conversely, Tourette syndrome preceded the onset of psychogenic dystonia (N = 1, 0.6%), and psychogenic tremor (N = 1, 0.6%) in two patients. Finally, 12 (7.7%) patients had tics in association with non-movement related neurological disorders, such as static encephalopathy (N = 2, 1.2%) and seizures (N = 3, 1.9%). To understand the physiopathology of tics and Tourette syndrome, it is important to recognize that these may be caused or associated with other disorders.
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PMID:Secondary tics and tourettism. 1596 46

Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role in motor and cognitive function. However, the impairment of emotional processes in neurologic and psychiatric pathologies involving the dopaminergic system (Parkinson disease, schizophrenia, autism, Attention Deficit Hyperactivity Disorder, Huntington disease, frontal lobe lesions), as well as the influence that administration of dopaminergic agonists/antagonists exert on the processing of emotion, suggest a role for DA in emotional processes. Moreover, emotional processes are dependent upon a variety of structures, the majority of which form part of the limbic system and are subject to DA innervation. In reviewing the literature, the amygdala emerges as a brain structure critical for emotional processing. It may also be implicated in deficits in emotional recognition found in two major disorders where DA's implication is clear: Parkinson disease and schizophrenia. In addition, the amygdala's response to emotional tasks is likely to be altered by the administration of both agonist and antagonist dopaminergic drugs. Experimental studies reinforce the idea of a dopaminergic contribution to emotional response, as suggested by biochemical, pharmacologic, and lesion experiments. Although the implication of the dopaminergic system in emotional processing appears to be clearly documented, the contribution of specific DA receptor subtypes, or of the DA cotransmitters cholecystokinin and neurotensin, or even glutamate, is, however, still unclear. Altogether, these observations suggest that DA has, undoubtedly, a direct and/or indirect role in the full emotional process.
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PMID:Dopaminergic contribution to the regulation of emotional perception. 1623 63

Acetylcholinesterase inhibitors (AChEIs) are currently being evaluated as adjunctive therapy for the cognitive dysfunction of schizophrenia. This core symptom of schizophrenia has often been attributed to impaired attention and abnormal sensory motor gating, features that are also found in Huntington's Disease, autism, and several other psychiatric and neurological disorders. The ability to improve prepulse inhibition (PPI) of the acoustic startle response may predict the efficacy of compounds as cognitive enhancers. In this study, PPI was disrupted in Wistar rats in three pharmacologic models: dopamine receptor agonism by apomorphine, NMDA receptor antagonism by MK801, or muscarinic acetylcholine receptor antagonism by scopolamine. We then evaluated the commonly used AChEIs, donepezil (0.5, 1.0, or 2.0mg/kg) and galantamine (0.3, 1.0, or 3.0mg/kg) for the capacity to improve PPI in each model. Under vehicle conditions, the prepulse stimuli (75, 80 and 85dB) inhibited the startle response to a 120dB auditory stimulus in a graded fashion. Galantamine (depending on dose) improved PPI deficits in all three PPI disruption models, whereas donepezil ameliorated PPI deficits induced by scopolamine and apomorphine, but was not effective in the MK801 model. These results indicate that some AChEIs may have the potential to improve cognition in schizophrenia by improving auditory sensory gating.
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PMID:Galantamine and donepezil attenuate pharmacologically induced deficits in prepulse inhibition in rats. 1704 31

Autism is a pervasive developmental disorder, with characteristics including impairments in reciprocal social interaction, impaired communication, and repetitive/stereotyped behaviors. Despite decades of research, the etiology of autism remains elusive. Thus, it is important that we pursue all avenues, in attempting to understand this complicated disorder. One such avenue is the development of animal models. While autism may be uniquely human, there are behavioral characteristics of the disorder that can be established in animal models. Evidence supports a genetic component for this disorder, and over the past few decades the mouse has been a highly valuable tool for the elucidation of pathways involved in many human disorders (e.g., Huntington's disease). As a first step toward establishing a mouse model of autism, we studied same-sex social behavior in a number of inbred mouse strains. In Study 1, we examined intra-strain social behavior of male pairs after one mouse had 15 min prior exposure to the testing chamber. In Study 2, we evaluated intra-strain and inter-strain social behavior when both mice were naive to the testing chamber. The amount and type of social behavior seen differed between these studies, but overall there were general inbred strain differences in social behavior. Some strains were highly social, e.g., FVB/NJ, while others displayed low levels of social behavior (e.g., A/J, BTBR T+tf/J). These strains may be useful in future genetic studies to determine specific genes involved in mouse social behavior, the findings of which should in turn help us to determine some of the genes involved in human social behavior and its disorders (e.g., autism).
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PMID:Assessing autism-like behavior in mice: variations in social interactions among inbred strains. 1709 58

The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.
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PMID:Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids. 1807 18

Different pathologies of the central and peripheral nervous system show sex differences in their incidence, symptomatology and/or neurodegenerative outcome. These include Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple sclerosis, traumatic brain injury, stroke, autism, schizophrenia, depression, anxiety disorders, eating disorders and peripheral neuropathy. These sex differences reveal the need for sex-specific neuroprotective strategies. This review article and other manuscripts published in this issue of Hormones and Behavior analyze possible sex-specific therapeutic strategies based on neuroactive steroids. In particular in our introductory article, the possibility that sex differences in the levels or in the action of neuroactive steroids may represent causative factors for sex differences in the incidence or manifestation of pathologies of the nervous system is considered.
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PMID:Sex-specific therapeutic strategies based on neuroactive steroids: In search for innovative tools for neuroprotection. 1952 84

Tens of thousands of subjects may be required to obtain reliable evidence relating disease characteristics to the weak effects typically reported from common genetic variants. The costs of assembling, phenotyping, and studying these large populations are substantial, recently estimated at three billion dollars for 500,000 individuals. They are also decade-long efforts. We hypothesized that automation and analytic tools can repurpose the informational byproducts of routine clinical care, bringing sample acquisition and phenotyping to the same high-throughput pace and commodity price-point as is currently true of genome-wide genotyping. Described here is a demonstration of the capability to acquire samples and data from densely phenotyped and genotyped individuals in the tens of thousands for common diseases (e.g., in a 1-yr period: N = 15,798 for rheumatoid arthritis; N = 42,238 for asthma; N = 34,535 for major depressive disorder) in one academic health center at an order of magnitude lower cost. Even for rare diseases caused by rare, highly penetrant mutations such as Huntington disease (N = 102) and autism (N = 756), these capabilities are also of interest.
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PMID:Instrumenting the health care enterprise for discovery research in the genomic era. 1960 38

The research planning agenda for DSM-V examined possible similarities in phenomenology, comorbidity, familial and genetic features, brain circuitry, and treatment response between obsessive-compulsive disorder (OCD) and several related disorders that are characterized by repetitive thoughts or behaviors. Such data support a re-examination of the DSM-IV-TR classification of OCD and the anxiety disorders, with possible inclusion of a group of obsessive-compulsive spectrum disorders (OCSDs) in DSM-V. Various disorders were systematically examined for inclusion in such a grouping, and later a smaller number were determined to meet threshold criteria for inclusion in the OCSDs. The disorders that were originally examined included OCD, obsessive-compulsive personality disorder (OCPD), Tourette's syndrome (TS) and other tic disorders, Sydenham's chorea, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), trichotillomania (TTM), body dysmorphic disorder (BDD), autism, eating disorders, Huntington's and Parkinson's disease, impulse control disorders, as well as substance and behavioral addictions. Certain disorders such as BDD, OCPD, TS, and TTM share many commonalities with OCD in phenomenology, comorbidity, familial and genetic features, brain circuitry, and treatment response. Other disorders, such as the impulse control disorders (ICDs) share some common features with OCD, but also differ in many ways as well. The articles presented in this issue of Psychiatry Research are a result of this international collaboration, which examined diagnostic and classification issues of OCSDs for DSM-V in a conference titled "The Future of Psychiatric Diagnosis: Refining the Research Agenda: Obsessive-Compulsive Behavior Spectrum" held in June 2006 at the American Psychiatric Association's headquarters in Arlington, VA.
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PMID:Cross-cutting issues and future directions for the OCD spectrum. 1981 39

Meta-analysis of genomic coordinates of SNP variations identified in genome-wide association studies (GWAS) of up to 712,253 samples (comprising 221,158 disease cases, 322,862 controls, and 168,233 case/control subjects of obesity GWAS) reveals that 39% of SNPs associated with 22 common human disorders are located within intergenic regions. Chromatin-state maps based on H3K4me3-H3K36me3 signatures show that many intergenic disease-linked SNPs are located within the boundaries of the K4-K36 domains, suggesting that SNP-harboring genomic regions are transcribed. Here we report identification of 13 trans-regulatory RNAs (transRNAs) 100 to 200 nucleotides in length containing intergenic SNP sequences associated with Crohn's disease, rheumatoid arthritis, type 1 diabetes, vitiligo, hypertension and multiple types of epithelial malignancies (prostate, breast, ovarian and colorectal cancers). We demonstrate that NALP1 loci intergenic SNP sequence, rs2670660, is expressed in human cells and may contribute to clinical manifestations of autoimmune and autoimflammatory phenotypes by generating distinct allelic variants of transRNAs. Stable expression of allele-specific sense and anti-sense variants of transRNAs markedly alters cellular behavior, affect cell cycle progression, and interfere with monocyte/macrophage transdifferentiation. On a molecular level, forced expression of allele-specific sense and anti-sense variants of transRNAs asserts allele-specific genome-wide effects on abundance of hundreds microRNAs and mRNAs. Using lentiviral gene transfer, microarray and Q-RT-PCR technologies, we identify rs2670660 allele-specific gene expression signatures (GES) which appear useful for detecting the activated states of innate immunity/inflammasome pathways in approximately 700 clinical samples from 185 control subjects and 350 patients diagnosed with nine common human disorders, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, Huntington disease, autism, Alzheimer disease, obesity, prostate and breast cancers. Microarray analysis of clinical samples demonstrates that rs2670660 allele-specific GES are engaged in patients' peripheral blood mononuclear cells (PBMC) which encounter pathological conditions in coherent tissues of a human body during immune surveillance and homeostasis monitoring. These data indicate that expression of transRNAs encoded by specific intergenic sequences can trigger activation of innate immunity/inflammasome pathways and contribute to clinical development of autoinflammatory and autoimmune syndromes. Documented in this work single-base substitution-driven molecular and biological antagonisms of intergenic SNP-containing transRNAs suggest a guiding mechanism of selection and retention of phenotype-compatible intergenic variations during evolution. According to this model, random genetic variations which generate transRNAs asserting antagonistic phenotype-altering effects compared to ancestral alleles will be selected and retained as SNP variants.
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PMID:Identification of intergenic trans-regulatory RNAs containing a disease-linked SNP sequence and targeting cell cycle progression/differentiation pathways in multiple common human disorders. 1992 86


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